Kudzu (Pueraria lobata)

Pharmacology:

• Constituents: The active constituents of kudzu include daidzin, daidzein, puerarin, genistin, genistein, tectorigenin, glycitin, tectoridin, 6"-O-xylosyltectoridin, 6"-O-xyloglycitin, biochanin A, and spinasterol.^{42,48,49,50,51,52,53,54,5}
• Two oleanane-type triterpene saponins named pedunsaponins B2 and C3 were isolated from the roots of Pueraria peduncularis.⁵⁵ Their structures were determined to be 3-O-(6-O-methyl)-beta-glucuronopyranosyl-3beta,15alpha-dihydroxyolean-12-en-16-one (2), and 3-O-beta-glucopyranosyl-(1 --> 3)-beta-glucuronopyranosyl-3beta,15alpha-dihydroxyoleana-12-en-16-one (3).
• Alcohol effects: The isoflavones daidzein, genistein, formononetin and biochanin A isolated from kudzu root have shown to be potent reversible human alcohol dehydrogenase (ADH) isoenzyme inhibitors in vitro. The isoflavones produced a competitive inhibition of gamma(g)2-g2-ADH-isoenzyme with respect to ethanol and an uncompetitive inhibition of gamma(g)2-g2-ADH-isoenzyme with respect to NAD+. The most potent inhibitor was genistein with an effective concentration of 0.1micromole. Although flavones such as apigenin, kaempferol, 7-hydroxyflavone, and galangin also demonstrated ADH-inhibiting activity, the effects were more pronounced with isoflavones. No effects were seen in B1B1-ADH isoenzymes and B2B2-ADH isoenzymes when concentrations up to 20micromoles were used.⁴¹
• The isoflavones in kudzu root extract may suppress alcohol intake and alcohol withdrawal symptoms in animals, although the mechanism is unclear.^42,56,39,57
• Kudzu may decrease peak blood alcohol levels due to delayed gastric emptying, exposing alcohol to a longer time for first-pass metabolism in the stomach.^43,44 Slowed gastric emptying may prolong the effects of alcohol.
• Kudzu may contribute to alleviating the adverse effects of ethanol ingestion by enhancing the lipid metabolism as well as the hepatic antioxidant defense system.⁵⁸ Kudzu may also have an appetite suppressant effect for alcohol.⁵⁹
• The flowers of kudzu exhibit protective effects against ethanol-induced apoptosis in human neuroblastoma cells by inhibiting the expression of a protease, caspase-3 that is responsible for proteolytic cleavage of many proteins.⁶⁰
• Anti-bacterial effects: Arrowroot tea (Puerariae radix) inhibited microbial growth of both Gram-negative and Gram-positive food borne pathogens in various foods, especially liquid foods.⁶¹
• Anti-cancer effects: Genistein, biochanin A and daidzein appear to have cytotoxic activity.^62,51 Preliminary research results suggest that biochanin A and genistein inhibit the cell growth of stomach cancer cell lines in vitro through activation of a signal transduction pathway for apoptosis.⁶³ The constituent tectorigenin demonstrated antiproliferative activity against human cancer (HL-60) cells by the induction of differentiation in the cells and a reduction in the expression of Bcl-2, an antiapoptotic protein.⁵¹
• Anti-inflammatory effects: Kudzu has the ability to decrease prostaglandin E2 and tumor necrosis factor (TNF)-alpha release, both of which are involved in inflammatory process.¹
• Antioxidant effects: Kudzu and its constituents may have antioxidant activity.^64,40,2,3 Pueraria lobata has shown more potent antioxidant activity than that of Pueraria thomsonii likely due to its higher contents of isoflavonoids.⁶⁵
• Puerarin may protect neurons against oxidative stress.⁶⁶ It appears to block apoptosis in its early stages via the regulation of anti- and pro-apoptotic proteins, as well as by the attenuation of caspase-3 activation in H₂O₂-induced PC12 cells.
• Puerarin promoted the activity of super oxide dismutase in the brain, liver, and serum in animal studies.^67,68
• Anti-thrombotic effects: In clinical and animal studies, Pueraria lobata has displayed antithrombotic activity.^{19,20,21,22,23,24,18,25,26} It may inhibit the increase of platelet aggregation and blood viscosity.^22,24,25,26 Puerarin can increase superoxide dismutase activity, decrease lipoprotein level and enhance the activity of fibrinolysis.¹⁹
• Cardiovascular effects: Early preclinical and animal research suggests kudzu has a protective effect against myocardial ischemia and may increase cardiac function.^{13,69,70,22,4,71,72,73,11,29,74} Animal research suggests that puerarin may reduce both systolic and diastolic blood pressure, and diminish myocardial oxygen consumption.³⁷
• The kudzu constituent, daidzein, may have antiarrhythmic properties.^35,36,37,38 These effects may be related to its inhibition of Na+ or Ca2+ influx and its blocking beta-adrenergic receptor.^{75,76,71,36,37}
• Kudzu increased nitric oxide content in heart, brain, liver, and kidney.^77,78
• Puerarin may have vasorelaxant properties, possibly by blocking beta-adrenergic receptors.^15,28,45
• Puerarin decreases plasma renin and angiotensin II activity.²⁷
• Cytochrome P450 system effects: Early research suggests that kudzu inhibits and induces cytochrome P450 isoenzymes; however, it is unclear which CYP isoenzymes are affected and to what degree.⁴⁰
• Estrogenic effects: Isoflavone constituents have both estrogenic and antiestrogenic activity.^{79,80,81,31,32,46,82,16,47,48,33,34}
• Based on lab and animal research, puerarin, genistin, glycetein, and daidzein are considered phytoestrogens.^83,80,82 These phytoestrogens may have additive or synergistic effects with each other.^12,33
• Based on an open label trial, Pueraria mirifica is thought to be involved in alleviating symptoms such as hot flashes and night sweats in perimenopausal women¹⁷ and affecting cognitive function in postmenopausal women.
• Hepatic effects: Puerarin showed potent hepatoprotective activity, but did not inhibit beta-glucuronidase; however, daidzein, which is produced by human intestinal bacteria, potently inhibited beta-glucuronidase.^6,7
• Hypoglycemic effects: Based on animal studies, kudzu and its constituents may have hypoglycemic effects.^8,9,10 Puerarin has increased glucose utilization to lower plasma glucose.⁸⁴ It has also activated alpha1-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose.^85,30
• Compounds that target the peroxisome proliferator-activated receptors PPARalpha and PPARgamma are used to correct dyslipidemia and to restore glycemic balance, respectively.⁸⁶ Because the majority of diabetic patients suffer from atherogenic lipid abnormalities in addition to insulin resistance, ligands are required that can activate both PPARalpha and PPARgamma. Pueraria thomsonii significantly activated PPARalpha and PPARgamma and bioassay-guided fractionation isolated daidzein as the PPAR-activating compound. However, daidzein was not as potent as other common isoflavones.
• Neurologic effects: Kudzu may provide protection for neurons.^87,14,88
• Daidzin may act by inhibiting serotonin and dopamine metabolism.⁸⁹
• Puerarin showed an improvement effect against the memory impairment in the modeling aging-mice induced by D-galactose.⁶⁸
• Based on animal studies, puerarin reduced flow velocities of both the middle cerebral artery and anterior cerebral artery; cerebral blood flow was enhanced due to dilatation of the intracranial arteries.^90,91
• Osteoporotic effects: In animal studies, Pueraria lobata increased bone mineral density.³⁴ Puerarin has also suppressed bone resorption and promoted bone formation in animal studies.^14,46

Pharmacodynamics/Kinetics:

• Absorption: Puerarin is rapidly, but incompletely, absorbed from the gastrointestinal tract.^52,92
• Bioavailability: Plasma daidzin concentration-time curves determined the crude extract daidzin has approximately 10 times greater bioavailability than the pure compound based on an animal study.⁵⁰
• Experimental results demonstrated that the excretive amounts of puerarin reached its maximum three hours after ingesting puerarin.⁹³
• Distribution: Puerarin is distributed widely in the body.⁹²
• Metabolism: When puerarin or daidzin were incubated for 24 hours with human intestinal bacteria, two metabolites, daidzein and calycosin, were produced from them, respectively.⁹⁴ The metabolic time course of puerarin was as follows: at an early time, puerarin was converted to daidzin, and then calycosin. The metabolic time course of daidzin by human intestinal bacteria was also similar to that of puerarin. Puerarin and daidzin were transformed to their aglycones by the bacteria producing beta-glucuronidase, C-glycosidase and beta-glycosidase, respectively.²¹
• Kudzu may decrease peak blood alcohol levels due to delayed gastric emptying, exposing alcohol to a longer time for first-pass metabolism in the stomach.^43,44
• Elimination: Puerarin is eliminated at a fairly rapid rate. The blood level of puerarin following intravenous administration in rats was found to decrease in the elimination phase with a half-life of 18 minutes.⁹²

References

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