PREGNACIN PLUS SOFTGEL CAPSULES (Each softgel capsule contains Vit D3/ Vit E/Vit C/Vit B1/Vit B2/ Vit B3/Vit B9/Vit B12/Vit B7/ Vit B5/Vit K3/Vit B6/Iron/Magnesium/Zinc/Iodine/Copper/Selenium/Ginger extract/Natural mixed Carotenoids 10mcg/4mg/70mg/3mg/2mg/20mg/400mcg/6mcg/150mcg/6mg/70mcg/10mg/17mg/150mg/15mg/140mcg/1mg/30mcg/10mg/2mg)

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

• Vitamin A deficiency
• Age-related macular degeneration
• Skin protection against UV radiation
• Antioxidant support

Dosage

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

Adults: Refer to specific product guidelines as carotenoid dosing can vary based on formulation and indication.

Mechanism of action

Carotenoids exert their effects primarily through their antioxidant activity, scavenging free radicals and reducing oxidative stress. They can also modulate cell signaling pathways, influencing gene expression related to immune responses and cellular growth. Some carotenoids, such as beta-carotene, can be converted into retinol (vitamin A) in the body, which is essential for vision, growth, and immune function.

Pharmacodynamics

Carotenoids have been shown to impact various biological processes, including the modulation of inflammation and the enhancement of immune responses. They may also contribute to the maintenance of healthy visual function by protecting retinal cells from oxidative damage. The antioxidant effects of carotenoids can reduce the risk of chronic diseases associated with oxidative stress, such as cardiovascular diseases and certain types of cancer.

Pharmacokinetics

Carotenoids are absorbed in the intestine and transported in the bloodstream bound to lipoproteins. Their bioavailability can be influenced by dietary fat intake, as they are fat-soluble compounds. Once absorbed, carotenoids are metabolized in the liver, where they can be stored or converted into active forms such as retinol. Elimination occurs primarily via bile and feces, with a variable half-life depending on the specific carotenoid.

Pregnancy

Carotenoids are generally considered safe during pregnancy, but high doses should be avoided. They play a role in fetal development, particularly in vision and immune function.

Breast-feeding

Carotenoids are excreted in breast milk, but they are generally regarded as safe during breastfeeding. Adequate intake is beneficial for both mother and infant.

Storage

Store in a cool, dry place away from light. Keep tightly closed to protect from moisture.

Formulations

• Capsules
• Soft gels
• Powders
• Liquid formulations

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

• 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

• Nausea and vomiting (including motion sickness and morning sickness)
• Gastrointestinal discomfort
• Osteoarthritis
• Inflammation
• Cold and flu symptoms

Dosage

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

Adults: Refer to established guidelines for specific dosing; typically, doses range from 1 to 3 grams of dried ginger per day.

Mechanism of action

The active components of ginger, particularly gingerols, exert their effects primarily through the inhibition of pro-inflammatory cytokines and enzymes, such as cyclooxygenase and lipoxygenase. This action helps to reduce inflammation and pain. Additionally, ginger enhances gastrointestinal motility and has antiemetic properties, which are beneficial in treating nausea.

Pharmacodynamics

Ginger exhibits anti-inflammatory, antioxidant, and antinausea effects. Its ability to modulate the immune response and inhibit platelet aggregation contributes to its cardiovascular protective effects. The antiemetic properties of ginger are particularly effective in reducing nausea and vomiting associated with motion sickness and chemotherapy.

Pharmacokinetics

Ginger is rapidly absorbed in the gastrointestinal tract, with its active components being metabolized in the liver. The bioavailability of ginger compounds may vary, with gingerols being converted into shogaols during processing or heating. The elimination half-life and specific metabolic pathways have not been extensively studied, but the effects can be observed within 30 minutes to 2 hours after ingestion.

Contra-indications

• Gallstones
• Bleeding disorders
• Allergy to ginger or other plants in the Zingiberaceae family

Adverse effects

• Gastrointestinal disturbances (nausea, diarrhea, heartburn)
• Allergic reactions (skin rash, itching)
• Increased risk of bleeding

Interactions

• Anticoagulants (e.g., warfarin, aspirin)
• Antiplatelet agents
• Certain antihypertensives
• Diabetes medications (may enhance effects)

Precautions

• Use with caution in patients with diabetes, hypertension, or gallbladder disease
• Consult a healthcare provider before use in pregnancy or lactation

Pregnancy

Generally considered safe in food amounts, but high doses should be avoided due to potential effects on uterine contractions.

Breast-feeding

Considered safe in food amounts, but high doses should be avoided.

Storage

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

Formulations

• Dried ginger powder
• Ginger root (fresh)
• Ginger tea
• Ginger extract (liquid or capsule)
• Ginger oil

Indications

• Iodine deficiency
• Goiter
• Hypothyroidism
• Thyroiditis
• Fibrocystic breast disease

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines based on age and weight.

Adults: Refer to the BNF for appropriate dosing guidelines based on condition and clinical judgment.

Mechanism of action

Molecular iodine inhibits the induction and promotion of carcinogenesis in mammary tissues and has shown beneficial effects in fibrocystic breast disease. It temporarily decreases thyroid hormone production through the acute Wolff-Chaikoff effect, followed by a return to normal hormone synthesis due to down regulation of the sodium-iodide symport. This mechanism can lead to a transient hypothyroid state in some individuals with underlying thyroid conditions.

Pharmacodynamics

Iodine is vital for the synthesis of thyroid hormones thyroxine (T4) and triiodothyronine (T3). It affects the metabolism of amine-derived hormones and plays a role in amino acid metabolism. The acute excess of iodide can lead to decreased circulating levels of T4 and T3 in susceptible individuals, while most people can escape this effect and maintain normal thyroid function.

Pharmacokinetics

Iodine is absorbed primarily in the gastrointestinal tract and is distributed throughout the body, particularly in the thyroid gland, where it is concentrated for hormone synthesis. The kidney plays a significant role in the excretion of excess iodine. The half-life of iodine in the body varies and can be influenced by dietary intake and underlying health conditions.

Adverse effects

• Hypothyroidism
• Hyperthyroidism
• Iodine allergy
• Gastrointestinal disturbances

Interactions

• Thyroid hormones
• Antithyroid drugs
• Lithium
• Diuretics

Precautions

• Use with caution in patients with thyroid dysfunction
• Monitor thyroid function periodically during treatment
• Pregnant or breastfeeding women should consult a healthcare provider before use

Pregnancy

Iodine is essential for fetal thyroid hormone synthesis, but excessive iodine intake should be avoided.

Breast-feeding

Iodine is excreted in breast milk; consult a healthcare provider regarding supplementation.

Storage

Store in a cool, dry place away from light.

Formulations

• Iodine solution
• Iodine tincture
• Potassium iodide tablets

Dosage

Children: Refer to specific drug guidelines as paediatric dosing must be determined based on the individual drug and condition being treated.

Adults: Refer to specific drug guidelines as dosing can vary widely based on the exact medication and its intended use.

Mechanism of action

The mechanism of action of mixed drugs can vary widely, often involving multiple pathways. For example, some may act as agonists or antagonists at certain receptors, while others may inhibit enzymes or modulate neurotransmitter levels. This complexity allows mixed drugs to have a broad spectrum of effects, which can be beneficial in treating conditions that require multifaceted approaches.

Pharmacodynamics

Pharmacodynamics of mixed drugs also varies significantly. Their effects can be dose-dependent, with lower doses potentially providing different therapeutic effects than higher doses. The interactions with various receptors and pathways can lead to synergistic or antagonistic effects, influencing the overall therapeutic outcome. Side effects and therapeutic efficacy must be carefully monitored.

Pharmacokinetics

Pharmacokinetics of mixed drugs includes absorption, distribution, metabolism, and excretion, which are influenced by the drug's chemical structure and route of administration. Many mixed drugs are absorbed rapidly and have wide distribution in body tissues. Metabolism can occur in the liver, often involving cytochrome P450 enzymes, and excretion may be renal or hepatic, depending on the drug's properties. The half-life can vary, affecting dosing schedules and potential for drug interactions.

Pregnancy

Consult with a healthcare provider regarding use during pregnancy, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Breast-feeding

Consult with a healthcare provider regarding use during breastfeeding, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Storage

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

Indications

• Pain relief
• Inflammatory conditions
• Dental applications
• Antifungal treatments
• Antioxidant support

Dosage

Children: Refer to specific product guidelines for pediatric dosing as it may vary based on formulation and intended use.

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

Mechanism of action

The exact mechanism of action of eugenol is not fully understood. However, it has been shown to interrupt action potentials, contributing to its analgesic properties. Eugenol exhibits anti-inflammatory effects by modulating the activity of polymorphonuclear leukocytes, which release inflammatory mediators. Additionally, eugenol has demonstrated antioxidant activity, protecting cells from oxidative stress. It has been observed to inhibit the formation of malondialdehyde in irradiated thymocytes, suggesting a protective role against oxidative damage.

Pharmacodynamics

Eugenol exhibits several pharmacological properties, including analgesic, anti-inflammatory, antipyretic, neuroprotective, antifungal, and antioxidant effects. Its ability to inhibit reactive oxygen species generation and modulate inflammatory mediators contributes to its therapeutic potential in managing pain and inflammation. The dose-dependent effects of eugenol on respiratory inhibition of mitochondria highlight its impact on cellular energy metabolism, further extending its pharmacodynamic profile.

Pharmacokinetics

Eugenol is rapidly absorbed and distributed throughout the body following administration. It undergoes extensive metabolism in the liver, with various metabolic pathways including conjugation and oxidation. The elimination half-life and specific pharmacokinetic parameters can be influenced by the route of administration and individual patient factors. The exact pharmacokinetics of eugenol in humans require further elucidation through clinical studies.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Skin irritation
• Allergic reactions

Precautions

• Use with caution in individuals with liver disease or gastrointestinal disorders.
• Caution is advised in patients who are pregnant or breastfeeding.

Pregnancy

Eugenol should be used with caution during pregnancy due to insufficient data on safety.

Breast-feeding

Eugenol is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Essential oil
• Topical preparations

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

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

Molecular iodine is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rats.It has also been shown to have beneficial effects in fibrocystic human breast disease. An acute iodide excess (above the preexisting dietary intake) transiently decreases the production of thyroid hormones in the thyroid gland; this is referred to as the acute Wolff-Chaikoff effect. In normal people, this is followed by a return to normal levels of hormone synthesis, referred to as escape from the acute Wolff-Chaikoff effect, without a significant change in circulating hormone levels. Escape is thought to be the result of down regulation of the sodium-iodide symport (NIS), the iodide transporter in the thyroid gland, resulting in a decrease in the intrathyroidal iodine and the resumption of normal hormone synthesis. An acute or chronic excess of iodide can also decrease circulating T4 and T3 levels and induce a hypothyroid state in some people who have underlying thyroid disorders. These effects are the result of a failure to escape from the acute Wolff-Chaikoff effect. Most people who experience iodine-induced hypothyroidism recover when the excess iodine intake is discontinued.

Mechanism of action

The exact mechanism of action of eugenol is unknown. However, eugenol has been shown to interrupt action potentials, which may be involved in its anti-pain activity. Research has also shown eugenol to have anti-inflammatory, neuroprotective, antipyretic, antioxidant, antifungal and analgesic properties. ... Thymocyte suspension was irradiated by gamma-rays, and the malondialdehyde (MDA) formation was measured with the thiobarbituric acid reactive species (TBARS) method. The results showed an increase in MDA in irradiated (2 Gy) thymocytes, which was inhibited in samples treated with increasing concentrations of eugenol (10-200 uM) prior to irradiation. The concentration of eugenol required to inhibit half of the MDA formation (IC(50)) in irradiated thymocytes was 100 uM. A dose-dependent increase in the generation of ROS was observed in irradiated thymocytes (0.5-200 cGy) as measured by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA), which was inhibited by eugenol administered before irradiation. Respiratory inhibition of isolated rat liver mitochondria by eugenol was dose related and uncoupled oxidative phosphorylation from electron transfer. Polymorphonuclear leukocytes (PMNL) play an important role in the modulation of inflammatory conditions in humans. PMNL cells recruited at the site of inflammation, release inflammatory mediators such as leukotrienes, proteolytic enzymes and reactive oxygen species. Among these, leukotrienes are implicated in pathophysiology of allergic and inflammatory disorders like asthma, allergic rhinitis, arthritis, inflammatory bowel disease and psoriasis. 5-lipoxygenase (5-LO) is the key enzyme in biosynthetic pathway of leukotrienes. Our earlier studies showed that spice phenolic active principles significantly inhibit 5-LO enzyme in human PMNLs. In this study we have further characterized the inhibitory mechanism of eugenol, the active principle of spice-clove on 5-LO enzyme and also its effect on leukotriene C((4)) (LTC(4)). Substrate dependent enzyme kinetics showed that the inhibitory effect of eugenol on 5-LO was of a non-competitive nature. Further, eugenol was found to significantly inhibit the formation of LTC(4) in calcium ionophore A23187 and arachidonic acid (AA) stimulated PMNL cells. These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells. The Ca(2+)-activated Cl(-) channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(-) conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol), the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(-) conductance with single-site IC(50)~150 uM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(-) channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities. For more Mechanism of Action (Complete) data for EUGENOL (21 total), please visit the HSDB record page.