STILEGE TABLETS

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase is involved in the degradation of propionate, crucial for fat and protein metabolism. The lack of vitamin B12 results in the accumulation of methylmalonyl CoA, contributing to neurological manifestations. Additionally, it is vital for the synthesis of methionine from homocysteine, and its deficiency can lead to functional folate deficiency, which impacts red blood cell formation.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities associated with pernicious anemia, such as megaloblastic indices, gastrointestinal lesions, and neurological damage. It is essential for growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. The drug significantly impacts fat and carbohydrate metabolism, as well as protein synthesis. Rapidly dividing cells, such as those in the bone marrow, have a high demand for vitamin B12. Parenteral administration of cyanocobalamin can quickly reverse the anemia and gastrointestinal symptoms of vitamin B12 deficiency, while also preventing the progression of related neurological damage.

Pharmacokinetics

Cyanocobalamin is absorbed in the intestine, primarily in the ileum, via specific transport mechanisms that may be impaired in individuals with intrinsic factor deficiency (as seen in pernicious anemia). Once absorbed, it is widely distributed in body tissues, with significant concentrations found in the liver, kidneys, and heart. The vitamin is stored in the liver, where it can be released into circulation as needed. Cyanocobalamin undergoes conversion to its active forms, methylcobalamin and adenosylcobalamin, which are utilized in various metabolic processes. The elimination half-life is variable, but it is generally excreted via urine as metabolites

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

• Folic acid may interact with cyanocobalamin, especially in cases of megaloblastic anemia caused by folate deficiency.

Precautions

• Should not be given alone for pernicious anemia.
• Use caution in patients with Leber's disease, as it may worsen optic atrophy.

Pregnancy

Cyanocobalamin is essential during pregnancy as it helps prevent neural tube defects. It is advised that females of childbearing potential take 5 mg of folic acid daily before conception and throughout pregnancy.

Breast-feeding

Cyanocobalamin is generally considered safe during breastfeeding, but it is advised to monitor the infant for any adverse effects.

Storage

Store in a cool, dry place, away from direct sunlight. Protect from moisture.

Formulations

• Tablet: 1000 micrograms
• Tablet: 500 micrograms
• Tablet: 100 micrograms
• Oral solution: 50 micrograms per ml
• Solution for injection: 1000 micrograms per ml

Indications

• Vitamin C deficiency
• Scurvy
• Adjunct therapy in iron overload conditions

Dosage

Children: Child 1 month–3 years: 125–250 mg daily in 1–2 divided doses; Child 4–11 years: 250–500 mg daily in 1–2 divided doses; Child 12–17 years: 0.5–1 g daily in 1–2 divided doses.

Adults: 500 mg daily, taken in 1-2 divided doses, depending on the clinical condition and dietary needs.

Mechanism of action

Ascorbic acid functions primarily as a reducing agent, facilitating enzymatic reactions in the body, including the hydroxylation of proline and lysine in collagen synthesis. It also plays a role in the absorption of iron from the gastrointestinal tract and enhances the immune response.

Pharmacodynamics

Ascorbic acid is crucial for the maintenance of connective tissue and is involved in the metabolism of several amino acids. Its antioxidant properties help to mitigate oxidative stress and may play a role in reducing the risk of chronic diseases.

Pharmacokinetics

Ascorbic acid is absorbed in the intestines and is widely distributed throughout the body. The renal clearance of ascorbic acid is dose-dependent, with higher doses leading to increased excretion. The half-life varies but is generally around 15 to 30 minutes in healthy individuals, with tissue saturation levels influencing its retention.

Contra-indications

• Hypercalcaemia
• Hyperoxaluria
• Patients with cardiac dysfunction

Adverse effects

• Abdominal pain
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Weight loss
• Polyuria
• Sweating
• Thirst
• Vertigo

Interactions

• Increases risk of cardiovascular adverse effects with iron chelators
• Increases risk of cardiovascular adverse effects with deferiprone
• Increases risk of cardiovascular adverse effects with desferrioxamine

Precautions

• Use with caution in patients with iron overload
• Monitor for symptoms of overdose

Pregnancy

High doses teratogenic in animals but therapeutic doses unlikely to be harmful.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Ascorbic acid 50 mg tablets
• Ascorbic acid 100 mg tablets
• Ascorbic acid 200 mg tablets
• Ascorbic acid 250 mg tablets
• Ascorbic acid 500 mg capsules

Indications

• Selenium deficiency
• Supportive therapy in conditions requiring antioxidant support
• Potential adjunct in cancer prevention strategies

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Initially 100–500 micrograms daily, adjusted according to response and serum levels.

Mechanism of action

Selenium is metabolized to selenophosphate and selenocysteine, which are essential for the synthesis of selenoproteins. This process involves the incorporation of selenium into proteins through a specialized tRNA that recognizes the RNA sequence UGA, which is facilitated by SECIS structures and SBP-2 proteins. Key selenoproteins, like glutathione peroxidases, help protect cells from oxidative damage, thus playing a significant role in reducing the risk of diseases such as atherosclerosis and certain cancers.

Pharmacodynamics

Selenium is incorporated into various selenoproteins that perform essential functions, including antioxidant activity, redox balance, and regulation of thyroid hormones. Its role in antioxidant defense mechanisms is particularly important for protecting cells against reactive oxygen species (ROS). Selenium supplementation has been linked to improved immune function and potential cancer prevention.

Pharmacokinetics

Selenium is absorbed through the gastrointestinal tract, and its bioavailability can vary based on the source and form of selenium. Once absorbed, it is distributed to various tissues, where it is incorporated into selenoproteins. Selenium is primarily excreted through urine, and its half-life can depend on dietary intake and individual metabolism. Selenium status can be assessed through blood levels of selenoproteins and selenium itself.

Adverse effects

• Nausea
• Anaemia
• Aplastic anaemia
• Skin reactions
• Gastrointestinal disorders

Precautions

• Selenium supplementation should not be given unless there is good evidence of deficiency.
• Use caution in patients with a history of hypersensitivity to selenium or its compounds.

Pregnancy

Limited information is available regarding selenium supplementation during pregnancy. Consult specialist sources for guidance.

Breast-feeding

Limited information is available; the effect of selenium on copper levels in milk is conflicting, and its impact on the infant is unknown.

Storage

After opening, store in a refrigerator (2–8°C).

Formulations

• Tablets (e.g., L-Selenomethionine 200 micrograms, SelenoPrecise 100 micrograms)
• Capsules (e.g., Trientine dihydrochloride 250 mg)
• Injection solutions (e.g., Sodium selenite 50 micrograms per 1 ml)

Indications

• Symptomatic relief of mild to moderate osteoarthritis of the knee

Dosage

Children: Refer to the BNF for Children for

Adults: 200–400 mg daily, maximum 6.5 mg/kg per day, or 1250 mg once daily, or 1500 mg once daily dissolved in at least 250 mL of water; review treatment if no benefit after 2–3 months.

Mechanism of action

The mechanism of action of glucosamine in joint health is not entirely clear, but it is believed to involve several pathways. Glucosamine is a precursor for glycosaminoglycans, which are essential for cartilage integrity. It may also reduce inflammation by inhibiting interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), which could improve symptoms of arthritis and joint pain. Upon uptake by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, further contributing to glycosaminoglycan synthesis.

Pharmacodynamics

Glucosamine is theorized to provide essential building blocks for the synthesis of glycosaminoglycans, potentially slowing the progression of osteoarthritis and alleviating joint pain. Although some studies have indicated modest improvements in joint pain and function among users, the overall evidence remains inconclusive. Glycosaminoglycans are critical for maintaining cartilage elasticity, strength, and flexibility, which are vital for joint health.

Pharmacokinetics

After oral administration, glucosamine is absorbed in the gastrointestinal tract and transported into the bloodstream, where it is metabolized into various forms, including glucosamine-6-phosphate. The exact pharmacokinetics, such as absorption rate and half-life, remain largely undefined, and much of the data is derived from animal studies. Further research is required to clarify its pharmacokinetic profiles in humans.

Adverse effects

• Constipation
• Diarrhoea
• Fatigue
• Gastrointestinal discomfort
• Headache
• Nausea
• Flushing
• Skin reactions

Interactions

• Glucosamine + warfarin: Severe (increases anticoagulant effect)
• Glucosamine + coumarins: Severe (increases anticoagulant effect)
• Glucosamine + acenocoumarol: Unknown (decreases anticoagulant effect)
• Glucosamine + coumarins: Unknown (decreases anticoagulant effect)

Precautions

• Asthma
• Impaired glucose tolerance
• Predisposition to cardiovascular disease

Pregnancy

Safety during pregnancy has not been established; consult with a healthcare provider.

Breast-feeding

Safety during breastfeeding has not been established; consult with a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Alateris®
• Dolenio®
• Glusartel®

Indications

• Cognitive impairment
• Dementia
• Memory enhancement
• Anxiety
• Peripheral vascular disease

Dosage

Children: Safety and efficacy in children have not been established. Use is not generally recommended without professional guidance.

Adults: Refer to specific product guidelines, as Ginkgo biloba is available in various forms including tablets, extracts, and teas. Typical doses range from 120 to 240 mg per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of Ginkgo biloba is not fully understood, but it is believed to enhance cerebral blood flow and improve circulation by inhibiting platelet-activating factor (PAF) and promoting vasodilation through nitric oxide release. Additionally, the antioxidant properties of flavonoids and terpenoids may protect neurons from oxidative stress and free radical damage.

Pharmacodynamics

Ginkgo biloba exhibits several pharmacodynamic effects, including increased blood flow to the brain, improved oxygen utilization, and enhanced glucose metabolism. It may also modulate neurotransmitter systems, including serotonin and dopamine, which could contribute to its effects on mood and cognitive function. The anti-inflammatory properties may further aid in neuroprotection.

Pharmacokinetics

Ginkgo biloba extracts are well-absorbed after oral administration. The bioavailability of its active constituents varies, and peak plasma concentrations occur within 1 to 4 hours post-ingestion. The elimination half-life of ginkgo flavonoids is approximately 4 to 5 hours, and metabolites are primarily excreted in urine. Factors such as age, health status, and concurrent medications can affect its pharmacokinetics.

Adverse effects

• Headache
• Dizziness
• Gastrointestinal upset
• Allergic skin reactions
• Palpitations

Interactions

• Anticoagulants (e.g., warfarin)
• Antiplatelet agents (e.g., aspirin)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Certain antidepressants (e.g., selective serotonin reuptake inhibitors)

Precautions

• Use with caution in patients with bleeding disorders
• Monitor for potential interactions with other medications
• Discontinue use prior to surgery to reduce bleeding risk

Pregnancy

Not recommended due to insufficient safety data.

Breast-feeding

Lack of sufficient data, caution is advised.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablets
• Capsules
• Liquid extracts

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Asthma
• Inflammatory bowel disease
• Chronic inflammatory conditions

Dosage

Children: Refer to established guidelines for appropriate dosing, as specific doses can vary based on formulation and clinical condition.

Adults: Refer to established guidelines for appropriate dosing, as specific doses can vary based on formulation and clinical condition.

Mechanism of action

Boswellic acids inhibit the enzyme 5-lipoxygenase, which is involved in the production of leukotrienes, inflammatory mediators. By blocking this pathway, boswellia reduces inflammation and may alleviate pain associated with conditions like arthritis and asthma.

Pharmacodynamics

Boswellia exhibits anti-inflammatory, analgesic, and potentially immunomodulatory effects. Its action on leukotriene synthesis is significant in conditions characterized by excessive inflammation. The anti-inflammatory effects may help in reducing symptoms of chronic inflammatory diseases, such as osteoarthritis and rheumatoid arthritis.

Pharmacokinetics

Boswellia is absorbed in the gastrointestinal tract and its bioavailability may be enhanced when taken with fatty meals. The metabolism and excretion pathways of boswellic acids are not fully elucidated, but they are believed to undergo hepatic metabolism. Their half-life may vary, necessitating multiple doses for sustained effects.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Skin rash
• Allergic reactions

Interactions

• May interact with anticoagulants and antiplatelet drugs, increasing the risk of bleeding
• Potential interaction with NSAIDs, which may enhance gastrointestinal side effects

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor for allergic reactions, especially in patients with known sensitivities to resins or similar compounds

Pregnancy

Boswellia is generally not recommended during pregnancy due to a lack of safety data.

Breast-feeding

Insufficient information is available on the excretion of boswellia in human milk; caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Capsules
• Tablets
• Extracts
• Topical preparations

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Joint pain
• Cartilage repair
• Tissue engineering

Dosage

Children: Dosage for cartilage-related conditions in paediatric patients should be determined by a healthcare professional, taking into account the child's age, weight, and specific clinical situation.

Adults: Dosage for cartilage-related conditions is highly variable and should be determined by a healthcare professional based on individual patient needs and clinical guidelines.

Mechanism of action

Cartilage does not have a specific pharmacological mechanism of action as it is a biological tissue rather than a drug. However, it contributes to joint stability and mobility by reducing friction between bones during movement and absorbing shock. The chondrocytes within cartilage are responsible for maintaining the extracellular matrix, which is essential for the tissue's resilience and function.

Pharmacodynamics

The pharmacodynamics of cartilage is primarily related to its role in joint health and function. It helps to distribute loads across joint surfaces and acts as a cushion to protect bones from impact. The degradation of cartilage, often seen in conditions like osteoarthritis, leads to pain and decreased mobility due to increased friction and bone-on-bone contact. Cartilage also plays a role in the inflammatory response within joints, influencing the severity of conditions like rheumatoid arthritis.

Pharmacokinetics

As cartilage is a biological tissue, it does not have traditional pharmacokinetic properties like absorption, distribution, metabolism, and excretion observed in drugs. However, factors such as age, mechanical stress, and nutritional status can affect the health and maintenance of cartilage. The healing process of cartilage is slow due to its avascular nature, meaning it has limited blood supply and, therefore, a limited capacity for regeneration.

Pregnancy

Data on the safety of cartilage supplements during pregnancy is limited. It is advisable to consult a healthcare provider before use.

Breast-feeding

There is insufficient data on the safety of cartilage supplements during breastfeeding. Consultation with a healthcare provider is recommended.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Vitamin D deficiency
• Rickets
• Osteomalacia
• Osteoporosis
• Hypoparathyroidism

Dosage

Adults: The usual adult dose for vitamin D deficiency is 800 to 2000 IU daily, depending on the severity of deficiency and clinical condition. Higher doses may be used under medical supervision.

Mechanism of action

Cholecalciferol is converted to its active forms, 25-hydroxyvitamin D in the liver and 1,25-dihydroxyvitamin D in the kidneys. These metabolites enhance the intestinal absorption of calcium and phosphorus, increase serum calcium levels, and mobilize these minerals from bone. This process is regulated by parathyroid hormone, which influences calcium and phosphate metabolism, particularly in the kidneys.

Pharmacodynamics

The pharmacodynamics of cholecalciferol involve its conversion to active metabolites that play a significant role in calcium and phosphorus homeostasis. The metabolites facilitate intestinal absorption of these minerals, promote bone mineralization, and influence renal reabsorption. The onset of action occurs within 10 to 24 hours following administration, as metabolic activation is required for its biological effects.

Pharmacokinetics

Cholecalciferol is absorbed in the gastrointestinal tract, and its absorption is enhanced by the presence of dietary fats. It is transported in the bloodstream bound to vitamin D-binding protein. Once in the liver, it undergoes hydroxylation to form 25-hydroxyvitamin D, which is further converted in the kidneys to the active form, 1,25-dihydroxyvitamin D. The elimination half-life of cholecalciferol varies, typically spanning several days, and it is primarily excreted in bile and urine.

Adverse effects

• Hypercalcemia
• Hypercalciuria
• Nausea
• Vomiting
• Constipation
• Weakness
• Fatigue

Interactions

• May enhance the effects of thiazide diuretics, leading to increased risk of hypercalcemia
• Anticonvulsants may increase metabolism of vitamin D, leading to reduced effectiveness
• Cholestyramine may reduce absorption of vitamin D

Precautions

• Monitor serum calcium levels in patients with renal impairment
• Caution in patients with a history of hypercalcemia or hyperparathyroidism
• Use with caution in patients taking other medications that affect calcium metabolism

Pregnancy

Cholecalciferol can be used during pregnancy if indicated, as vitamin D is essential for fetal bone development.

Breast-feeding

Cholecalciferol is excreted in breast milk, but is generally considered safe during breastfeeding.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Capsules
• Tablets
• Liquid formulations

Indications

• Osteoarthritis
• Joint pain
• Cartilage repair
• Joint health maintenance

Dosage

Children: Refer to healthcare professionals for guidance on dosing in children, as specific pediatric dosing information is not well established.

Adults: Refer to specific product labeling and consult healthcare professionals for guidance on dosing, as dosages can vary based on formulations and clinical guidelines.

Mechanism of action

Chondroitin works primarily by providing the building blocks necessary for the synthesis of glycosaminoglycans, which are critical components of cartilage. It is thought to inhibit the enzymes that break down cartilage, thereby promoting cartilage repair while also exhibiting anti-inflammatory properties. Additionally, chondroitin may enhance the retention of water in the cartilage, improving its elasticity and resilience.

Pharmacodynamics

Chondroitin has been shown to modulate inflammatory responses within the joints and may help to improve joint mobility and reduce pain associated with osteoarthritis. Its effects on cartilage metabolism are believed to contribute to its therapeutic benefits, although the clinical efficacy may vary among individuals. The anti-inflammatory properties may also contribute to a reduction in joint swelling and discomfort.

Pharmacokinetics

Chondroitin is poorly absorbed from the gastrointestinal tract, with bioavailability ranging from 12% to 36%. It is distributed in the extracellular matrix of cartilage and other connective tissues. Metabolism of chondroitin is not well understood, but it is believed to be metabolized in the liver. The elimination half-life in humans is not well defined, and it is primarily excreted via urine as metabolites. The effects of food on its absorption are still under investigation.

Adverse effects

• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Headache
• Skin reactions

Interactions

• Anticoagulants (e.g., warfarin) - may increase the risk of bleeding
• NSAIDs - may affect the efficacy of these medications

Precautions

• Use with caution in patients with a history of bleeding disorders
• Caution is advised in patients undergoing surgery due to potential bleeding risk
• Patients with shellfish allergies should consult a physician as some chondroitin supplements are derived from marine sources

Pregnancy

There is insufficient reliable information regarding the safety of chondroitin during pregnancy. It is advisable to avoid use unless prescribed by a healthcare professional.

Breast-feeding

It is not known if chondroitin is excreted in human milk. Caution is advised for nursing mothers considering its use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Capsule
• Tablet
• Powder
• Liquid

Indications

• Type 2 diabetes mellitus
• Dyslipidemia
• Metabolic syndrome
• Antioxidant support
• Anti-inflammatory conditions

Dosage

Children: Specific dosing for children should be determined by a healthcare professional based on individual circumstances and clinical guidelines.

Adults: Dosage varies based on formulation and indication. Commonly, 1-6 grams of powdered cinnamon can be used daily, though specific recommendations should be based on clinical guidelines and individual patient needs.

Mechanism of action

Cinnamon exerts its effects primarily through the modulation of insulin signaling pathways. Cinnamaldehyde enhances insulin sensitivity and may stimulate glucose uptake by cells. It also has antioxidant properties, which help in reducing oxidative stress. Additionally, components of cinnamon may inhibit enzymes involved in carbohydrate digestion, leading to a reduction in postprandial blood glucose levels.

Pharmacodynamics

Cinnamon demonstrates several pharmacodynamic effects, including anti-inflammatory, antioxidant, and antimicrobial activities. Its active compounds can help regulate blood glucose levels, improve lipid profiles by reducing triglycerides and LDL cholesterol, and exhibit potential benefits in metabolic syndrome and type 2 diabetes management.

Pharmacokinetics

The bioavailability of cinnamon compounds varies, but cinnamaldehyde is rapidly absorbed and metabolized in the liver. Its metabolites can be detected in plasma, and the half-life varies based on the dose and formulation. The onset of action for cinnamon extract may vary, and continuous consumption is often required to achieve significant clinical effects. Cinnamon is generally well-tolerated, with minimal adverse effects reported.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Liver toxicity (with excessive consumption of Cassia cinnamon)

Precautions

• High doses may cause liver damage due to coumarin content in Cassia cinnamon.
• Caution in individuals with liver disease.

Pregnancy

Cinnamon is generally considered safe in food amounts during pregnancy, but high doses should be avoided.

Breast-feeding

Cinnamon is likely safe in food amounts while breastfeeding, but excessive use should be avoided.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Ground cinnamon
• Cinnamon sticks
• Cinnamon oil
• Cinnamon extract

Indications

• Bone health support
• Joint pain relief
• Weight management
• Anti-inflammatory effects
• Antioxidant support

Dosage

Children: Refer to specific product guidelines for dosing recommendations, as there are no standardized doses established.

Adults: Refer to specific product guidelines for dosing recommendations, as there are no standardized doses established.

Mechanism of action

Cissus quadrangularis exhibits several mechanisms of action, primarily attributed to its active compounds such as flavonoids, phenolic compounds, and triterpenoids. These compounds are known to possess anti-inflammatory, antioxidant, and analgesic properties. Cissus may promote the synthesis of collagen, thereby aiding in bone and connective tissue health. Additionally, it may modulate the activity of certain enzymes involved in metabolic processes, contributing to its weight management effects.

Pharmacodynamics

The pharmacodynamic effects of cissus are primarily related to its anti-inflammatory and analgesic properties. It is thought to inhibit the production of pro-inflammatory cytokines and increase antioxidant activity, which can alleviate pain and inflammation. Furthermore, the plant may play a role in regulating lipid metabolism and reducing oxidative stress, which can benefit overall metabolic health.

Pharmacokinetics

The pharmacokinetics of cissus are not extensively studied. However, it is generally understood that the active compounds in cissus are absorbed in the gastrointestinal tract, with their bioavailability influenced by various factors including formulation and individual metabolism. The elimination half-life and specific metabolic pathways remain largely unknown and require further research to clarify.

Adverse effects

• Gastrointestinal disturbances
• Headache
• Dizziness
• Allergic reactions

Interactions

• May enhance the effects of anticoagulants
• Potential interaction with antihyperglycemic agents

Precautions

• Use with caution in patients with diabetes
• Avoid use in pregnant or breastfeeding women unless advised by a healthcare professional

Pregnancy

Limited data on safety during pregnancy; consult a healthcare professional before use.

Breast-feeding

Insufficient data on safety during breastfeeding; consult a healthcare professional before use.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder
• Capsules
• Tinctures

Indications

• Skin aging and wrinkle reduction
• Joint pain and osteoarthritis
• Tendon and ligament injuries
• Bone health
• Wound healing

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing based on the indication and formulation used.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing based on the indication and formulation used.

Mechanism of action

Collagen exerts its effects primarily by providing the necessary amino acids, such as glycine, proline, and hydroxyproline, that are crucial for the synthesis of new collagen in the body. It is thought to stimulate fibroblast proliferation, which leads to increased collagen production and improved tissue repair. Additionally, collagen may enhance the hydration of the skin and improve its elasticity.

Pharmacodynamics

Collagen supplementation may promote the synthesis of new collagen and improve the integrity of the extracellular matrix. This can lead to improved skin hydration, elasticity, and the reduction of wrinkles. In joint health, collagen may help reduce inflammation and pain, contributing to improved mobility and function. The effects can vary based on the source of collagen (bovine, porcine, marine) and the form of administration (powder, liquid, capsules).

Pharmacokinetics

After oral administration, collagen peptides are absorbed in the gastrointestinal tract and enter the bloodstream. They can be transported to various tissues where they may be incorporated into the extracellular matrix. The half-life of collagen peptides is relatively short, and they are metabolized in the liver and other tissues. The bioavailability of collagen can vary based on the formulation and the presence of other dietary components.

Adverse effects

• Allergic reactions
• Skin rash
• Itching
• Gastrointestinal disturbances
• Nausea

Precautions

• Use with caution in individuals with fish allergies if derived from fish sources
• Monitor for allergic reactions

Pregnancy

Collagen is generally considered safe during pregnancy, but consult a healthcare professional before use.

Breast-feeding

Collagen is likely safe during breastfeeding, but consult a healthcare professional before use.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Powder
• Capsules
• Liquid

Indications

• Copper deficiency
• Occipital Horn Syndrome
• Menke's disease
• Contraception (via copper IUD)

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Refer to the relevant clinical guidelines and BNF for specific dosing information.

Mechanism of action

Copper is absorbed from the gastrointestinal tract via high affinity copper uptake proteins and low affinity copper uptake proteins, likely being reduced to the Cu1+ form prior to transport. Inside enterocytes, it binds to the copper transport protein ATOX1, which facilitates its transport to copper transporting ATPase-1 on the Golgi membrane for incorporation into the Golgi apparatus. Once in systemic circulation, copper binds primarily to ceruloplasmin, albumin, and alpha 2-macroglobulin. It acts as a cofactor in a variety of oxidase enzymes and also influences sperm motility when released from copper IUDs, contributing to its contraceptive effect.

Pharmacodynamics

Copper is essential for the activity of many enzymes and plays a vital role in processes such as iron metabolism, neurotransmitter synthesis, and antioxidant defense. Copper ions, particularly when released from intrauterine devices, have been shown to decrease sperm viability, thereby impacting fertility.

Pharmacokinetics

Copper is absorbed from the gut and is predominantly transported in the plasma bound to proteins such as ceruloplasmin and albumin. The absorption efficiency can vary; however, a significant portion of dietary copper is usually absorbed. The body regulates copper levels through hepatic excretion and storage mechanisms, ensuring homeostasis. Excess copper can lead to toxicity, while deficiency results in various health issues.

Pregnancy

Copper is considered essential during pregnancy, but excessive intake should be avoided due to potential toxicity.

Breast-feeding

Copper is excreted in breast milk, and adequate maternal intake is important for infant development.

Storage

Store in a cool, dry place, away from moisture and heat.

Indications

• Anti-inflammatory therapy
• Antioxidant support
• Adjunctive treatment in cancer
• Cholagogic agent
• Supportive treatment for metabolic syndrome

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric populations.

Adults: Refer to the BNF for specific dosing guidelines as doses may vary based on formulation and clinical indication.

Mechanism of action

Curcumin acts as a scavenger of reactive oxygen species, including hydroxyl radicals, superoxide anions, and singlet oxygen, which leads to the inhibition of lipid peroxidation and protection against peroxide-induced DNA damage. It exerts anti-inflammatory effects by modulating key signaling molecules involved in inflammation, notably inhibiting protein kinases, c-Jun/AP-1 activation, and cyclooxygenase (COX)-2 expression and activity. This multifaceted mechanism contributes to its anti-carcinogenic properties and therapeutic activity against various diseases.

Pharmacodynamics

In animal studies, curcumin has demonstrated significant effects, such as increasing bile flow and inhibiting edema formation in models of inflammation. It has also shown to decrease cell proliferation in cancerous tissues, increase apoptosis, and enhance micro-vessel density in tumor models. Furthermore, curcumin may enhance biliary excretion and inhibit platelet aggregation in vitro, indicating its potential role in cardiovascular health.

Pharmacokinetics

Curcumin undergoes extensive metabolism and has low bioavailability due to poor absorption. It is rapidly conjugated and excreted, primarily in the form of glucuronides and sulfates. The pharmacokinetic profile can be influenced by factors such as formulation, dosage, and the presence of other compounds that enhance its absorption.

Pregnancy

Curcumin should be used with caution during pregnancy. Limited data is available on its safety, and it is advisable to consult healthcare providers before use.

Breast-feeding

Curcumin is excreted in breast milk, and caution is advised when used during breastfeeding. Consultation with healthcare providers is recommended.

Storage

Store in a cool, dry place away from light. Ensure the container is tightly closed.

Formulations

• Curcumin capsules
• Curcumin powder
• Curcumin tinctures
• Curcumin topical formulations

Indications

• General wellness support
• Anti-inflammatory effects
• Antioxidant activity
• Digestive aid
• Support for immune function

Dosage

Children: Paediatric dosing should be determined based on the specific extract and its intended use. Consultation with a healthcare provider is recommended for accurate dosing.

Adults: Dosage varies widely depending on the specific extract and formulation. It is essential to follow the manufacturer's instructions or consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action of herbal extracts can vary significantly based on their constituents. Commonly, they exert their effects through multiple pathways including modulation of neurotransmitter systems, interference with inflammatory processes, or direct antioxidant activity. Some extracts may activate certain receptors or inhibit enzymes related to disease processes.

Pharmacodynamics

The pharmacodynamics of extracts is complex due to the presence of multiple active compounds which can have synergistic or antagonistic effects. These compounds may influence cellular signaling pathways, alter gene expression, or modulate immune response. The overall pharmacological profile is determined by the specific composition of the extract, its concentration, and the biological target it interacts with.

Pharmacokinetics

The pharmacokinetics of extracts involves absorption, distribution, metabolism, and excretion of the active compounds. Generally, herbal extracts are absorbed in the gastrointestinal tract, with bioavailability influenced by factors such as formulation, the presence of food, and individual metabolic differences. Compounds may undergo hepatic metabolism, and elimination can occur through urine or feces, depending on their chemical nature.

Pregnancy

Consult a healthcare professional before use, as the safety of the extract during pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use, as the safety of the extract during breastfeeding has not been established.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Folate deficiency
• Megaloblastic anemia
• Prevention of neural tube defects in pregnancy
• Supplementation in patients on certain medications (e.g., methotrexate)

Dosage

Children: Refer to the BNF for Children for appropriate pa

Adults: Refer to specific guidelines or the BNF for appropriate adult dosing based on the indication.

Mechanism of action

Folate functions as a coenzyme in the conversion of homocysteine to methionine, a process that is vital for DNA synthesis and repair. It is involved in the one-carbon metabolism pathway, where it acts as a carrier of one-carbon units necessary for the synthesis of purines and thymidylate, thus supporting the production of nucleotides and DNA. This mechanism is particularly important in rapidly dividing cells.

Pharmacodynamics

Folate is critical for the formation of red blood cells and the proper functioning of the nervous system. It aids in the production of nucleic acids, which are essential for cell proliferation. Folate deficiency can lead to impaired DNA synthesis, resulting in megaloblastic anemia characterized by the presence of large, immature red blood cells in the bloodstream. Adequate folate levels are also associated with reduced risk of neural tube defects in developing fetuses.

Pharmacokinetics

Folate is absorbed in the proximal part of the small intestine, primarily in the jejunum, and is transported in the bloodstream bound to plasma proteins. It undergoes hepatic metabolism and is stored mainly in the liver. The elimination half-life varies, but dietary folate can be retained in the body for several weeks. Excess folate is excreted through the urine. The bioavailability of folate from food sources is lower compared to synthetic folic acid found in supplements.

Interactions

• folates+fluorouracil: Severe (increases risk of toxicity)
• folates+antiepileptics: Moderate (decreases concentration)
• folates+fosphenytoin: Moderate (decreases concentration)
• folates+phenobarbital: Moderate (decreases concentration)
• folates+phenytoin: Moderate (decreases concentration)
• folates+primidone: Moderate (decreases concentration)
• sulfasalazine+folates: Unknown (decreases absorption)

Pregnancy

Folate is essential for fetal development and is often recommended to prevent neural tube defects.

Breast-feeding

Folate is generally safe during breastfeeding, as it is important for both maternal and infant health.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Tablets
• Injection

Indications

• Cognitive enhancement
• Memory disorders
• Tinnitus
• Peripheral vascular disease
• Anxiety
• Age-related macular degeneration

Dosage

Children: Safety and efficacy have not been established in children, so refer to specific guidelines if considering use in paediatric populations.

Adults: Refer to specific product guidelines, typically ranging from 120 to 240 mg of standardized ginkgo extract per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of ginkgo is not fully understood, but it is thought to involve several pathways. Ginkgo extracts contain flavonoids and terpenoids, which are believed to contribute to its pharmacological effects. These compounds may enhance cerebral blood flow by dilating blood vessels and reducing blood viscosity. Ginkgo also has antioxidant properties that help protect against oxidative stress, and it may modulate neurotransmitter systems, particularly those involving serotonin and dopamine.

Pharmacodynamics

Ginkgo exhibits various pharmacodynamic effects, including vasodilation, increased blood flow, and improved neurotransmission. It is noted for its ability to enhance cognitive function, particularly in older adults with mild cognitive impairment. The antioxidant properties of ginkgo help mitigate damage caused by free radicals, potentially reducing the risk of neurodegenerative diseases. Its effects on blood circulation can also alleviate symptoms associated with peripheral vascular disease.

Pharmacokinetics

Ginkgo is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-3 hours. It undergoes extensive metabolism in the liver, primarily via cytochrome P450 enzymes. The elimination half-life of ginkgo components can vary, generally ranging from 4 to 12 hours. The bioavailability of ginkgo extracts can be influenced by formulation and individual patient factors, including age and health status.

Contra-indications

• Hypersensitivity to ginkgo or any of its components
• Active bleeding disorders
• Concurrent use with anticoagulants or antiplatelet agents

Adverse effects

• Gastrointestinal upset
• Headache
• Dizziness
• Allergic skin reactions
• Palpitations

Interactions

• Increased risk of bleeding when used with warfarin, aspirin, or other anticoagulants
• Potential interaction with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants
• May affect the metabolism of certain drugs metabolized by cytochrome P450 enzymes

Precautions

• Use with caution in patients with a history of seizures
• Monitor for bleeding complications in patients with bleeding disorders
• Discontinue use prior to surgical procedures to reduce bleeding risk

Pregnancy

Limited data available, caution advised; consult healthcare provider.

Breast-feeding

Insufficient reliable information available regarding safety; consult healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Ginkgo biloba extract (standardized)
• Ginkgo leaf tablets
• Ginkgo capsules
• Ginkgo tinctures

Indications

• Fatigue
• Stress management
• Cognitive enhancement
• Immune support
• General well-being

Dosage

Children: Refer to specific product guidelines, as dosing in children should be determined by a healthcare professional.

Adults: Refer to specific product guidelines, as dosing can vary based on formulation and intended use.

Mechanism of action

Ginseng is thought to exert its effects through several mechanisms, including modulation of the hypothalamic-pituitary-adrenal (HPA) axis, enhancement of antioxidant activity, and regulation of neurotransmitter levels. Ginsenosides, the active compounds in ginseng, may influence cellular signaling pathways, promote neuroprotection, and enhance immune responses.

Pharmacodynamics

The pharmacodynamic effects of ginseng are attributed primarily to its active constituents, ginsenosides, which interact with various receptors and enzymes in the body. These interactions can lead to increased energy metabolism, improved cognitive function, enhanced physical performance, and modulation of the immune system. Ginseng may also exhibit adaptogenic properties, helping the body to maintain homeostasis under stress.

Pharmacokinetics

Ginsenosides undergo extensive metabolism in the body, primarily by the liver. Bioavailability can vary significantly based on the specific ginsenoside and the method of administration. Ginseng is usually administered orally, with effects typically observed within several hours after ingestion. The elimination half-life of ginsenosides can vary based on the specific compound and individual metabolism, with some studies suggesting that effects may persist for several hours to days.

Adverse effects

• Insomnia
• Headache
• Gastrointestinal disturbances
• Nervousness
• Hypertension
• Allergic reactions

Interactions

• May interact with anticoagulants (e.g., warfarin)
• May enhance the effects of caffeine
• May affect insulin levels and blood sugar control
• Potential interaction with immunosuppressants

Precautions

• Use with caution in patients with hypertension
• May cause sleep disturbances; avoid use before bedtime
• Should be used cautiously in patients with diabetes
• Consult a healthcare provider before use in individuals with autoimmune conditions

Pregnancy

Limited data available. Generally not recommended due to potential hormonal effects.

Breast-feeding

Limited data available. Consult a healthcare provider before use.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Dried root
• Powdered extract
• Capsules
• Tinctures
• Teas

Indications

• Wound healing
• Skin ulceration
• Burns
• Psoriasis
• Dermatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age and condition.

Adults: Refer to the BNF for specific formulations and dosing guidelines, as dosages may vary based on the condition being treated and the formulation used.

Mechanism of action

While there is no well-controlled data to formally substantiate the method of action, ongoing studies suggest that allantoin may induce a histological wound healing profile in animal models, leading to improved reestablishment of normal skin. This includes increased vasodilation, inflammatory cell presence, angiogenesis, fibroblast proliferation, and collagen deposition in treated wounds compared to untreated ones.

Pharmacodynamics

There is limited controlled data regarding the pharmacodynamic properties of allantoin. However, studies indicate that allantoin may possess moisturizing and keratolytic effects, increasing the extracellular matrix's water content and enhancing the desquamation of dead skin cells. These activities can promote cell proliferation and facilitate wound healing.

Pharmacokinetics

Specific pharmacokinetic data for allantoin in humans is limited. However, it is known to be applied topically, which suggests local absorption at the site of application. Systemic absorption is considered minimal due to its low molecular weight and hydrophilicity.

Pregnancy

There is limited data on the safety of allantoin in pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Allantoin is generally considered safe during breastfeeding, but caution is recommended. Consult a healthcare professional before use.

Storage

Store at room temperature, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Topical cream
• Gel
• Ointment

Indications

• Osteoarthritis of the knee
• Viscosupplementation for joint pain
• Dry eye syndrome
• Ocular surgeries (e.g., cataract surgery)
• Wound healing

Dosage

Adults: Refer to specific guidelines or literature for adult dosing recommendations, as they can vary based on

Mechanism of action

Hyaluronate acts by increasing the viscosity and elasticity of synovial fluid in joints, leading to improved lubrication and shock absorption. It binds to water molecules, thus enhancing the hydration of tissues. In the context of osteoarthritis, it helps to restore the normal viscoelastic properties of the joint fluid, which can help alleviate pain and improve joint function. In ocular applications, it serves to lubricate the surface of the eye, aiding in the comfort and healing of the cornea.

Pharmacodynamics

Hyaluronate's pharmacodynamic effects are primarily related to its hydrophilic nature and its ability to form a gel-like consistency when mixed with water. This property allows it to provide mechanical support and cushioning in joints, reducing friction and wear in the articular cartilage. It also plays a role in cell signaling and tissue hydration, influencing cell proliferation and migration in wound healing.

Pharmacokinetics

Hyaluronate is administered via injection or topical application, depending on the indication. After injection into the joint space, it can remain for several weeks, but its half-life is influenced by factors such as the degree of synovial fluid viscosity and the presence of inflammation. Systemic absorption is minimal, and it is primarily metabolized by hyaluronidase enzymes found in various tissues, leading to fragmentation and clearance from the body. In ocular formulations, its retention time on the eye surface can vary based on the formulation and the presence of preservatives.

Contra-indications

• Hypersensitivity to hyaluronate or any component of the formulation
• Infection at the injection site
• Active skin diseases

Adverse effects

• Injection site reactions (pain, swelling, redness)
• Allergic reactions
• Joint effusion
• Increased joint pain
• Headache

Precautions

• Use with caution in patients with bleeding disorders
• Careful consideration in patients with a history of allergic reactions
• Not recommended for intra-articular injection in patients with active infections

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed and the potential benefits justify the risks.

Breast-feeding

It is not known if hyaluronate is excreted in human milk. Use with caution and only if clearly needed.

Storage

Store at 2-25 degrees Celsius. Protect from light. Do not freeze.

Formulations

• Sodium hyaluronate injection
• Hyaluronic acid gel

Indications

• Manganese deficiency
• Bone health and development
• Antioxidant support
• Enzyme cofactor in metabolic processes

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations.

Adults: Refer to specific clinical guidelines or the BNF for appropriate dosing recommendations.

Mechanism of action

Manganese serves as a cofactor for several enzymes, including manganese superoxide dismutase (MnSOD), which protects cells from oxidative stress by catalyzing the dismutation of superoxide radicals into oxygen and hydrogen peroxide. It also participates in the activation of enzymes involved in carbohydrate, fat, and protein metabolism.

Pharmacodynamics

Manganese plays a role in various biochemical pathways, particularly in the metabolism of amino acids, cholesterol, glucose, and carbohydrates. It is crucial for bone formation and the maintenance of cartilage. Manganese also aids in the synthesis of glycosyltransferases, which are important for the formation of glycoproteins and proteoglycans.

Pharmacokinetics

Manganese is absorbed primarily in the small intestine, with absorption efficiency influenced by dietary factors and the presence of competing minerals. It is transported in the bloodstream bound to proteins such as alpha-2-macroglobulin and transferrin. Manganese is stored in the liver, pancreas, and bones, and is excreted primarily through bile and to a lesser extent in urine. Its half-life in the human body is not well defined due to its trace nature and variable absorption.

Pregnancy

Manganese is classified as a dietary mineral that is essential for human health, but excessive intake should be avoided during pregnancy as it may affect fetal development.

Breast-feeding

Manganese is present in breast milk, and normal dietary intake is considered safe during breastfeeding. However, excessive supplementation should be avoided.

Storage

Store in a cool, dry place, away from direct light and moisture.

Indications

• Cardiovascular disease prevention
• Hypertriglyceridemia
• Rheumatoid arthritis
• Inflammatory bowel disease
• Cognitive decline and dementia
• Mood disorders

Dosage

Adults: Dosage varies based on the condition being treated. For general health, a common recommendation is 250-500 mg of combined EPA and DHA

Mechanism of action

Omega fatty acids exert their effects through various mechanisms, including the modulation of inflammatory pathways and the synthesis of specialized pro-resolving mediators. They are incorporated into cell membranes, affecting membrane fluidity and receptor function. Omega-3 fatty acids can also decrease the production of pro-inflammatory eicosanoids and increase anti-inflammatory mediators, promoting a balanced inflammatory response.

Pharmacodynamics

The pharmacodynamics of omega fatty acids involve their role in cellular signaling, gene expression, and lipid metabolism. Omega-3 fatty acids, particularly EPA and DHA, have been shown to influence the resolution of inflammation and enhance endothelial function. They also play a role in neuroprotection and cognitive function, with evidence suggesting that adequate omega-3 intake is associated with reduced risk of neurodegenerative diseases.

Pharmacokinetics

Omega fatty acids are absorbed in the intestine through the action of bile salts and pancreatic enzymes. Once absorbed, they are transported via chylomicrons into the lymphatic system and then into the bloodstream. They are distributed throughout the body, particularly in the brain and heart. The half-life of omega fatty acids can vary, with some studies suggesting an elimination half-life of several days to weeks, depending on the specific fatty acid and individual metabolism. They undergo beta-oxidation for energy production and can be converted into eicosanoids, which mediate various physiological functions.

Adverse effects

• Nausea
• Diarrhea
• Fishy aftertaste
• Allergic reactions
• Increased bleeding risk

Interactions

• Anticoagulants may increase the risk of bleeding when combined with omega-3 fatty acids
• Antihypertensive medications may have additive effects on blood pressure

Precautions

• Use cautiously in patients with bleeding disorders
• Monitor patients on anticoagulants for signs of increased bleeding
• Consider the source of omega-3 fatty acids, as some may contain contaminants

Pregnancy

Generally considered safe when used in recommended amounts, but high doses should be avoided due to potential bleeding risk.

Breast-feeding

Considered safe; omega-3 fatty acids can be beneficial for both mother and infant.

Storage

Store in a cool, dry place, away from light. Refrigeration may be required for some formulations to maintain stability.

Formulations

• Capsules
• Softgels
• Liquid oil
• Fortified foods

Indications

• Hormone replacement therapy
• Diabetes management
• Metabolic disorders
• Cancer treatment
• Pain management
• Antimicrobial therapy

Dosage

Children: Paediatric dosing is also variable and should be determined based on specific guidelines for each peptide. Refer to paediatric dosing references for the appropriate dosages.

Adults: Dosage varies widely based on the specific peptide and condition being treated. Refer to specific product guidelines for appropriate dosing.

Mechanism of action

Peptides exert their effects by binding to specific receptors on the surface of target cells, which activates intracellular signaling pathways. This interaction can lead to various physiological responses, including modulation of enzyme activity, gene expression, and cellular metabolism.

Pharmacodynamics

The pharmacodynamic properties of peptides depend on their structure and the specific receptors they target. Peptides can exhibit high selectivity for their receptors, leading to minimal off-target effects. Dose-dependent responses are common, with many peptides showing a threshold effect below which no significant biological response is observed.

Pharmacokinetics

Peptides typically have a short half-life due to rapid degradation by proteolytic enzymes in the bloodstream. Their absorption can vary based on the route of administration, with oral bioavailability often being poor. For parenteral administration, factors such as the site of injection and formulation can influence their pharmacokinetic profile. Distribution is generally limited to the extracellular fluid, and elimination is primarily via renal pathways.

Pregnancy

Peptides should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when administering peptides during breastfeeding, as the effects on a nursing infant are not well studied.

Storage

Peptides should be stored at 2-8 degrees Celsius, protected from light and moisture. Once reconstituted, they should be used promptly or stored as recommended by the manufacturer.

Indications

• Enhancement of bioavailability of other drugs
• Potential anti-inflammatory agent
• Antioxidant
• Neuroprotective agent
• Possible anticancer properties

Mechanism of action

Piperine enhances the bioavailability of various compounds by inhibiting certain drug-metabolizing enzymes, particularly cytochrome P450 enzymes, thereby reducing their metabolism and increasing their absorption in the gastrointestinal tract. It also influences various transport proteins, which can affect the pharmacokinetics of drugs.

Pharmacodynamics

Piperine exhibits various pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective activities. It has been shown to modulate multiple signaling pathways involved in inflammation and oxidative stress, potentially contributing to its therapeutic effects.

Pharmacokinetics

Piperine is well absorbed after oral administration, with its bioavailability enhanced due to its ability to inhibit metabolic enzymes. It is metabolized primarily in the liver, with a relatively short half-life which can vary based on the presence of food and other substances.

Pregnancy

Piperine should be used with caution during pregnancy; consult healthcare professionals before use.

Breast-feeding

Limited information is available regarding piperine use during breastfeeding; consult healthcare professionals before use.

Storage

Store in a cool, dry place, away from direct sunlight.

Indications

• Depression
• Anxiety disorders
• Sleep disorders
• Seasonal affective disorder

Dosage

Children: Refer to established guidelines for specific dosing recommendations for children, as data on pediatric dosing is limited.

Adults: Refer to established guidelines for specific dosing recommendations, as dosages may vary based on formulation and specific condition being treated.

Mechanism of action

Quadrangularis exerts its effects primarily through the modulation of neurotransmitters in the brain, particularly serotonin, dopamine, and norepinephrine. Hyperforin is believed to inhibit the reuptake of these neurotransmitters, leading to increased levels in the synaptic cleft. Additionally, hypericin has been shown to exhibit anti-inflammatory and antiviral properties, which may contribute to its overall therapeutic profile.

Pharmacodynamics

The pharmacodynamic effects of quadrangularis include its ability to elevate mood, reduce anxiety, and improve sleep quality. The herb may also have neuroprotective effects, potentially benefiting cognitive function. Side effects can include gastrointestinal disturbances, fatigue, and photosensitivity, particularly with prolonged use.

Pharmacokinetics

Quadrangularis is bioavailable following oral administration, with peak plasma concentrations typically occurring within 1 to 2 hours. The herb is metabolized in the liver, primarily by cytochrome P450 enzymes, and its metabolites are excreted via urine. The half-life of active components can vary, influencing dosing frequency and duration of action.

Pregnancy

The safety of quadrangularis during pregnancy has not been established. It is advisable to avoid use unless clearly needed.

Breast-feeding

Information on the excretion of quadrangularis in breast milk is not available. Use with caution and consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Joint pain
• Inflammation
• Vitamin C deficiency
• Antioxidant support

Dosage

Children: There is no specific paediatric dosage established; refer to product-specific guidelines or consult a healthcare professional for appropriate dosing.

Adults: There is no specific adult dosage established; refer to product-specific guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

The exact mechanism of action of rosehips is not fully understood. However, they are believed to exert anti-inflammatory effects primarily due to their high content of vitamin C, flavonoids, and other antioxidants. These compounds may inhibit the production of pro-inflammatory cytokines and reduce oxidative stress, contributing to their therapeutic effects.

Pharmacodynamics

Rosehips have been observed to have anti-inflammatory, antioxidant, and immune-boosting properties. The vitamin C content supports collagen synthesis and may contribute to the maintenance of healthy connective tissues. Additionally, the phenolic compounds present in rosehips may modulate inflammatory pathways, providing potential benefits in conditions such as osteoarthritis and rheumatoid arthritis.

Pharmacokinetics

The pharmacokinetics of rosehips are not well-studied, but the bioavailability of vitamin C and other soluble compounds is generally high when ingested. Absorption occurs in the gastrointestinal tract, with peak plasma concentrations typically reached within a few hours. The metabolites are likely excreted primarily through the kidneys. The pharmacokinetics of rosehip extracts can vary depending on the formulation and preparation method.

Adverse effects

• Gastrointestinal upset
• Diarrhea
• Nausea
• Allergic reactions

Precautions

• Use with caution in individuals with a history of allergies to rose family plants
• Consult a healthcare provider before use in patients with chronic medical conditions or those taking other medications

Pregnancy

Limited information is available on the safety of rosehips during pregnancy. Consult a healthcare provider before use.

Breast-feeding

Limited information is available on the safety of rosehips during breastfeeding. Consult a healthcare provider before use.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Dried fruit
• Powder
• Capsules
• Teas
• Extracts

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Joint pain
• Inflammatory bowel disease
• Chronic respiratory conditions

Dosage

Children: Refer to established guidelines and consult a healthcare professional for appropriate dosing based on specific conditions.

Adults: Refer to established guidelines and consult a healthcare professional for appropriate dosing based on specific conditions.

Mechanism of action

Boswellia serrata contains boswellic acids, which inhibit the 5-lipoxygenase enzyme, leading to a reduction in the synthesis of leukotrienes. This action decreases inflammation and pain associated with various conditions, particularly those affecting the joints. Boswellic acids may also modulate the immune response and possess analgesic properties.

Pharmacodynamics

The pharmacodynamic effects of Boswellia serrata are primarily attributed to its anti-inflammatory and analgesic properties. By inhibiting leukotriene synthesis, it reduces the inflammatory response in the body. Additionally, Boswellia serrata may enhance circulation and improve joint mobility while reducing stiffness and swelling in affected areas.

Pharmacokinetics

Boswellia serrata is absorbed in the gastrointestinal tract, though the bioavailability may vary based on formulation and presence of other compounds. The active boswellic acids are metabolized in the liver, and excretion primarily occurs via the kidneys. The half-life of boswellic acids can vary, but they generally remain in the system long enough to exert their therapeutic effects.

Pregnancy

There is insufficient reliable information regarding the safety of serrata during pregnancy. It is advisable to avoid use unless specifically directed by a healthcare professional.

Breast-feeding

There is limited data on the excretion of serrata components in human milk. Caution is advised, and it is best to consult with a healthcare provider before use during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and moisture. Keep out of reach of children.

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Cancer
• Cardiovascular diseases
• Skin disorders

Dosage

Children: Refer to specific product guidelines and consult a healthcare provider for appropriate dosing in children.

Adults: Refer to specific product guidelines, as dosages may vary widely depending on the formulation and intended use.

Mechanism of action

The exact mechanism of action of shark cartilage is not fully understood. It is believed to work by inhibiting angiogenesis, the process through which new blood vessels form from pre-existing vessels, which is crucial for tumor growth and metastasis. The compounds within shark cartilage may also modulate immune responses and exhibit anti-inflammatory effects.

Pharmacodynamics

Shark cartilage is thought to exert its effects through various biological pathways, primarily by interacting with the immune system and influencing cellular communication. It may have anti-inflammatory effects that reduce swelling and pain, particularly in joint disorders. Additionally, its potential anti-cancer properties are attributed to its ability to inhibit the growth of blood vessels that supply tumors.

Pharmacokinetics

The pharmacokinetics of shark cartilage have not been well-studied. It is generally consumed as an oral supplement, and its bioavailability may vary depending on the formulation. The components of shark cartilage, including glycosaminoglycans, are likely to be absorbed through the gastrointestinal tract, but the extent of absorption and metabolism remains unclear. Further research is needed to elucidate the pharmacokinetic profile of shark cartilage.

Pregnancy

There is limited data on the safety of shark products during pregnancy. Consult healthcare providers for personalized advice.

Breast-feeding

Limited data on the safety of shark products during breastfeeding. Consult healthcare providers for personalized advice.

Storage

Store in a cool, dry place away from direct sunlight. Ensure proper sealing to maintain freshness.

Mechanism of action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

Mechanism of action

The mechanism of action of glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time. When taken up by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, the natural precursor of glycosaminoglycans (GAGs) that contain N-acetylglucosamine (keratan sulfate and Hyaluronan) and those that have N-acetylgalactosamine (heparan sulfate and chondroitin sulfate). These GAGs are polysaccharides composed of hexosamines and monosaccharides (e.g., galactose and glucuronic acid) arranged as a linear chain of repeating disaccharide units (such as the glucuronic acid and N-acetylgalactosamine-6-sulfate of chondroitin sulfate). With the exception of hyaluronan, GAGs do not exist alone in nature but are attached to specific "core" proteins, and the composite structures are called proteoglycans (protein-glycosaminoglycans). Both hyaluronan and many different kinds of proteoglycans (such as aggrecan, versican, and syndecan) are abundant throughout the body where they perform diverse functions.

Pharmacodynamics

The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.

Mechanism of action

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality. The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS). The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein. Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function. Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach. /Selenium/ Selenium status can also influence thyroid hormone function via the deiodinase enzymes. Selenium is a critical component of the deiodinase enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, triiodothyronine (T3). Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the thyroid during the conversion of T4 to T3. /Selenium/ Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low in the organism. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation. Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be an additional mechanism for intermediate- or chronic-duration toxicity. Skin, hair, and nail damage are significant indicators of chronic selenium overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur in certain amino acids, including the disulfide bridges that pr

Pharmacodynamics

Selenium is incorporated into many different selenoproteins which serve various functions throughout the body.

Mechanism of action

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight. Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions. Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma. In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in en

Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys.

Mechanism of action

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2. It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor. Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown. The reason for the less severe reaction when the foreign body is at a distance from the retina has been proposed to be ... that near the retina & its blood vessels there is greater oxygen tension than at a distance, which causes metallic copper to oxidize to toxic copper compounds more rapidly close to or in contact with the retina than at a distance. Furthermore, the abscess formation that is characteristic of copper undergoing oxidation close to the retina & choroiod can be attributed to attraction of polymorphonuclear leukocytes from these nearby vascular tissues, which become heavily infiltrated. Liquefaction & disorganization of the vitreous body has been explained on the basis of copper catalysis of oxidation of ascorbic acid, leading to depolymerization of the hyaluronic acid of the vitreous humor. Changes in protein & hexosamine content have also been related to decrease in viscosity of the vitreous humor. Increased content of amino acids in the vitreous humor has been consistent with proteolysis of the vitreous body, but decreased concentration in the aqueous humor has suggested suppression of secretion of amino acids by the ciliary body under the influence of copper.

Pharmacodynamics

Copper is incorporated into many enzymes throughout the body as an essential part of their function. Copper ions are known to reduce fertility when released from copper-containing IUDs.

Mechanism of action

Curcumin acts as a scavenger of oxygen species, such as hydroxyl radical, superoxide anion, and singlet oxygen and inhibit lipid peroxidation as well as peroxide-induced DNA damage. Curcumin mediates potent anti-inflammatory agent and anti-carcinogenic actions via modulating various signalling molecules. It suppresses a number of key elements in cellular signal transduction pathways pertinent to growth, differentiation, and malignant transformation; it was demonstrated _in vitro_ that curcumin inhibits protein kinases, c-Jun/AP-1 activation, prostaglandin biosynthesis, and the activity and expression of the enzyme cyclooxygenase (COX)-2. Curcumin, a polyphenolic natural product, exhibits therapeutic activity against a number of diseases, attributed mainly to its chemical structure and unique physical, chemical, and biological properties. It is a diferuloyl methane molecule [1,7-bis (4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione)] containing two ferulic acid residues joined by a methylene bridge. It has three important functionalities: an aromatic o-methoxy phenolic group, alpha, beta-unsaturated beta-diketo moiety and a seven carbon linker. Extensive research in the last two decades has provided evidence for the role of these different functional groups in its crucial biological activities. A few highlights of chemical structural features associated with the biological activity of curcumin are: The o-methoxyphenol group and methylenic hydrogen are responsible for the antioxidant activity of curcumin, and curcumin donates an electron/ hydrogen atom to reactive oxygen species. Curcumin interacts with a number of biomolecules through non-covalent and covalent binding. The hydrogen bonding and hydrophobicity of curcumin, arising from the aromatic and tautomeric structures along with the flexibility of the linker group are responsible for the non-covalent interactions. The alpha, beta-unsaturated beta-diketone moiety covalently interacts with protein thiols, through Michael reaction. The beta-diketo group forms chelates with transition metals, thereby reducing the metal induced toxicity and some of the metal complexes exhibit improved antioxidant activity as enzyme mimics. New analogues with improved activity are being developed with modifications on specific functional groups of curcumin... The present study demonstrates that curcumin acts as pro-oxidant and sensitizes human lung adenocarcinoma epithelial cells (A549) to apoptosis via intracellular redox status mediated pathway. Results indicated that curcumin induced cell toxicity (light microscopy and MTT assay) and apoptosis (AnnexinV-FITC/PI labeling and caspase-3 activity) in these cells. These events seem to be mediated through generation of reactive oxygen species (ROS) and superoxide radicals (SOR) and enhanced levels of lipid peroxidation. These changes were accompanied by increase in oxidized glutathione (GSSG), reduced glutathione (GSH) and gamma-glutamylcysteine synthetase (gamma-GCS) activity, but decrease in GSH/GSSG ratio. The induction of apoptosis and decrease in GSH/GSSG ratio was also accompanied by sustained phosphorylation and activation of p38 mitogen activated protein kinase (MAPK). On the other hand, addition of N-acetyl cysteine (NAC), an antioxidant, blocked the curcumin-induced ROS production and rescued malignant cells from curcumin-induced apoptosis through caspase-3 deactivation. However, L-buthionine sulfoximine (BSO), a GSH synthesis blocking agent, further enhanced curcumin-induced ROS production and apoptosis in A549 cells. Decreased GSH/GSSG ratio seems to be a crucial factor for the activation of MAPK signaling cascade by curcumin. The study therefore, provides an insight into the molecular mechanism involved in sensitization of lung adenocarcinoma cells to apoptosis by curcumin. Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activiti

Pharmacodynamics

Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120%. In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density. Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility. Curcumin inhibited arachidonic acid-induced platelet aggregation _in vitro_.

Mechanism of action

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Pharmacodynamics

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.