PALMIGES CAPSULES (Each Capsules contains Palmitoylethanolamide/Genistein/Daidzen 300mg/4mg/50mg)

Indications

• Menopausal symptoms
• Hormonal balance
• Bone health
• Potential protective effects against hormone-related cancers

Dosage

Children: Refer to established guidelines or consult healthcare providers for appropriate dosing.

Adults: Refer to established guidelines or consult healthcare providers for appropriate dosing.

Mechanism of action

Daidzein exerts its effects mainly through its structural similarity to estrogen, allowing it to bind to estrogen receptors. This binding activates estrogen receptor signaling pathways, which can modulate gene expression and produce estrogen-like biological effects. Additionally, daidzein can influence various signaling pathways, including those involved in apoptosis and cell proliferation, which are relevant in cancer prevention and management.

Pharmacodynamics

Daidzein demonstrates estrogenic activity by binding to estrogen receptors (ERs), specifically ERα and ERβ. This binding can lead to various physiological effects such as the regulation of bone metabolism, modulation of lipid profiles, and influence on the menstrual cycle. Its antioxidant properties also contribute to cellular protection against oxidative stress, which is implicated in chronic disease development.

Pharmacokinetics

After oral administration, daidzein is absorbed in the gastrointestinal tract and undergoes extensive metabolism in the liver, primarily via glucuronidation and sulfation. Peak plasma concentrations are typically reached within 1 to 2 hours after ingestion. The half-life of daidzein is variable, influenced by factors such as the individual's metabolic rate and the presence of other dietary components. It is excreted mainly in urine in conjugated forms.

Pregnancy

Limited data on safety in pregnancy; use with caution and only if potential benefits outweigh risks.

Breast-feeding

Not known if excreted in human milk; exercise caution and consult a healthcare provider.

Storage

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

Indications

• Breast cancer prevention
• Prostate cancer prevention
• Cardiovascular health in postmenopausal women
• Improvement of glucose metabolism

Dosage

Children: Refer to specific guidelines and consult the BNF for Children for appropriate dosing information.

Adults: Refer to specific guidelines and consult the BNF for appropriate dosing information.

Mechanism of action

Genistein may inhibit cancer cell growth by blocking enzymes required for cell growth. It interacts with nuclear estrogen receptors to alter transcription of cell-specific genes, potentially decreasing cardiovascular risk in postmenopausal women. It is also proposed to improve glucose metabolism by inhibiting islet tyrosine kinase activity and insulin release. Its anticarcinogenic activity may stem from several mechanisms, including upregulation of apoptosis, inhibition of angiogenesis, inhibition of DNA topoisomerase II, and inhibition of protein tyrosine kinases. Genistein's weak estrogenic activity may contribute to its anti-prostate cancer effects, while its anti-estrogenic properties may explain its potential benefits in breast cancer.

Pharmacodynamics

Genistein exhibits a range of pharmacodynamic effects, including modulation of cellular signaling pathways involved in growth, apoptosis, and angiogenesis. Its weak estrogenic activity allows it to mimic estrogen, possibly influencing hormone-sensitive cancers. The compound's antioxidant properties also contribute to its protective effects against oxidative stress, while its ability to enhance nitric oxide availability may improve vascular function.

Pharmacokinetics

Genistein is absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It undergoes extensive metabolism, primarily in the liver, where it is conjugated to glucuronides and sulfates. The elimination half-life is variable but generally ranges from 5 to 8 hours. Excretion occurs mainly through urine. Factors such as diet, gut microbiota, and genetic variations can influence its pharmacokinetics.

Pregnancy

Genistein should be used with caution during pregnancy due to its weak estrogenic activity, which may affect fetal development.

Breast-feeding

Due to limited data on the excretion of genistein in human milk, breastfeeding mothers are advised to consult healthcare professionals before use.

Storage

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

Formulations

• Tablets
• Capsules
• Powder

Indications

• Chronic pain syndromes
• Neuropathic pain
• Inflammatory conditions
• Pain associated with multiple sclerosis
• Fibromyalgia

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines. The safety and efficacy in children should be evaluated by a healthcare professional.

Adults: Refer to the BNF for specific dosing recommendations. Generally, starting doses range from 300 mg to 1200 mg per day, divided into two or three doses.

Mechanism of action

Palmitoylethanolamide exerts its effects primarily through the activation of peroxisome proliferator-activated receptors (PPARs), particularly PPAR-alpha. This activation leads to a reduction in inflammation and pain by modulating the release of pro-inflammatory cytokines and enhancing the body’s natural pain-relieving mechanisms. PEA is also thought to inhibit the activity of mast cells and microglia, contributing to its analgesic and neuroprotective effects.

Pharmacodynamics

Palmitoylethanolamide has been shown to exhibit anti-inflammatory and analgesic effects in various preclinical and clinical studies. It acts on the endocannabinoid system, although it does not bind directly to cannabinoid receptors. Instead, it influences endocannabinoid signaling and has been implicated in reducing inflammatory responses and promoting homeostasis in pain pathways.

Pharmacokinetics

Palmitoylethanolamide is absorbed well when administered orally, with peak plasma concentrations typically occurring within 1-3 hours. It is metabolized primarily in the liver and has a half-life that supports sustained therapeutic effects. The elimination of PEA from the body occurs mainly through hepatic metabolism and renal excretion. The pharmacokinetics of PEA can be influenced by factors such as dosage form and patient-specific variables.

Pregnancy

There is insufficient data regarding the use of palmitoylethanolamide in pregnancy. Caution is advised.

Breast-feeding

Limited data is available on the excretion of palmitoylethanolamide in human milk. Caution should be exercised when administered to a nursing woman.

Storage

Store at room temperature, in a tightly closed container, away from moisture and direct light.

Formulations

• {'formulation': 'Capsules', 'strength': 'Various strengths available'}
• {'formulation': 'Powder', 'strength': 'Various strengths available'}

Mechanism of action

Genistein may inhibit cancer cell growth by blocking enzymes required for cell growth. Genistein may decrease cardiovascular risk in postmenopausal women by interacting with the nuclear estrogen receptors to alter the transcription of cell specific genes. In randomized clinical trials, genistein was seen to increase the ratio of nitric oxide to endothelin and improved flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. In addition, genistein may have beneficial effects on glucose metabolism by inhibiting islet tyrosine kinase activity as well as insulin release dependent on glucose and sulfonylurea. Several mechanisms have been proposed for genistein's putative anticarcinogenic activity. These include upregulation of apoptosis, inhibition of angiogenesis, inhibition of DNA topoisomerase II and inhibition of protein tyrosine kinases. Genistein's weak estrogenic activity has been suggested as another mechanism for genistein's putative anti-prostate cancer activity. In addition to the above mechanisms, other mechanisms of genistein's putative anti-prostate cancer activity include inhibition of nuclear factor (NF)-Kappa B in prostate cancer cells, downregulation of TGF (transforming growth factor)-beta and inhibition of EGF (epidermal growth factor)-stimulated growth. Genistein's anti-estrogenic action may be another possible mechanism to explain its putative anti-breast cancer activity. In the final analysis, the mechanism of genistein's putative anticarcinogenic activity is unclear. A number of studies have shown that genistein can interact with topoisomerase II in vitro. ... Genistein (3.7 M) stabilizes the topoisomerase II-DNA complex. ... stimulating topoisomerase II dependent DNA cleavage (in the ranges 80-370 M and 12.5-250 M, respectively). ... Genistein 50 M) inhibited unwinding of DNA by topoisomerase II in primary hematopoietic cells and stimulated strand breakage. ...The effect of genistein on the DNA cleavage and ATP hydrolysis steps of the topoisomerase II catalysed reactions /was investigated and/ genistein inhibited enzyme-catalysed ATP hydrolysis with an IC50 of 7 M. However, genistein did not stimulate DNA cleavage. Further studies ... showed that genistein (50 M) and daidzein (100 M) induced cleavage of the MLL gene in primary hematopoietic cells. Further in vitro experiments suggested that inhibition of topoisomerase II catalysed re-ligation of DNA strand breaks as the mechanism of action. Genistein has been found to have a number of antioxidant activities. It is a scavenger of reactive oxygen species and inhibits lipid peroxidation. It also inhibits superoxide anion generation by the enzyme xanthine oxidase. In addition, genistein, in animal experiments, has been found to increase the activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalase and glutathione reductase. Genistein has weak estrogenic activity as measured in in vivo and in vitro assays. In vivo, its estrogenic activity is one-third that of glycitein and four times greater than that of daidzein. For more Mechanism of Action (Complete) data for GENISTEIN (9 total), please visit the HSDB record page.