Pueraria July 11, 2018 – Posted in: Pueraria Mirifica
Common Name(s): Kwao Krua , White Kwao Krua , Kwao Keur , Kwao Kruea
Uses
Most commercial products containing pueraria are available as rejuvenating, antiaging, or skin-lightening creams or gels, as beauty soaps, or as capsules or tablets for increasing appetite, enlarging breasts, modulating hair growth or regrowth, and other rejuvenating purposes. However, there is no literature to support these uses. The medical literature documents the plant’s use primarily for menopause, but also for cancer and osteoporosis.
Dosing
Commercial products are available in topical (creams, gels, and soaps) or oral (capsules or tablets) dosage forms. Some clinical studies used 200 to 400 mg (extracted from the root or tuber) by mouth per day. Commercial manufacturers suggest 250 mg (root or tuber) by mouth every morning and evening. For breast enlargement, manufacturers recommend a twice-daily topical application to the breast area for 3 to 5 minutes until fully absorbed.
Contraindications
Avoid use if hypersensitive to any of the components of the product. Because of its phytoestrogen-like effects, use pueraria with caution if diagnosed with estrogen-dependent neoplasia, pulmonary embolism, liver dysfunction or disease, or anemia.
Pregnancy/Lactation
Avoid use during pregnancy and lactation because of the lack of clinical data and the plant’s phytoestrogen activity.
Interactions
None were documented.
Adverse Reactions
Because of pueraria’s estrogen-like effect, use with caution in patients with asthma, diabetes mellitus, epilepsy, migraine, or systemic lupus erythematosus. Use with caution in patients with abnormal triglycerides or hypercalcemia.
Toxicology
No data.
Botany
The plant species Pueraria mirifica belongs to the Fabaceae, or bean, subfamily, and its tuberous roots contain several phytoestrogens. Pueraria mirifica is a woody vine commonly found in forests throughout Thailand, with 28 cultivars presently documented. The tuberous root varies in size depending on soil condition but may weigh as much as 100 kg. The plant’s palmate-type leaves are ovate or straightforward and contain 3 leaflets in 1 petiole. The blue-to-purple flowers are composed of 5 petals and bloom from February to March.
History
The plant species is abundant in phytoestrogens, and postmenopausal women in Thailand have consumed it for more than 100 years citing its beneficial estrogen effects. In traditional Thai medicine, it is common to use Pueraria mirifica as a skin moisturizer, to improve regrowth of hair, to improve body flexibility and sexual performance, and to firm and enlarge the breasts. Commercial products containing pueraria are continually introduced into the world market and have become popular in Thailand, Korea, and Japan. Most commercial products are available as topical rejuvenating, antiaging, or skin-lightening creams or gels, as beauty soaps, or as capsules or tablets for increasing appetite, enlarging breasts, modulating hair growth or regrowth, and other rejuvenating purposes. Since 1999, domestic and global demand for the raw materials from Pueraria mirifica roots or tubers has increased, resulting in the intense harvesting of the plant from the forests of Thailand.
Chemistry
Isoflavones, coumestans, and lignans are the 3 main classes of phytoestrogens. The tuberous roots of Pueraria mirifica primarily contain the active component miroestrol and its derivative, deoxymiroestrol. The tuberous roots of Pueraria mirifica also include daidzin, daidzein, genistin, genistein, puerarin, mirificoumestan, kwakhurin, coumestrol, mirificin, and 2 steroids, estrone, and estriol. The manufacture and synthesis of miroestrol are documented. Deoxymiroestrol was isolated and identified as the most active phytoestrogen of the plant.
Thin-layer chromatography analysis has documented varying amounts of phytoestrogens collected from Pueraria mirifica in different locations in Thailand. One of the challenges of large-scale manufacturing of Pueraria mirifica for drugs and cosmetics is resolving these variations in lots.
Uses and Pharmacology
Cancer
Spinasterol, an active cytotoxic component of Pueraria mirifica, was active against certain gynecological cancer cell lines and activates estrogen receptors ER-alpha and ER-beta. The ethanol extract had antiproliferative effects on breast cancer cell lines MCF-7, ZR-75-1, MDA-MB-231, SK-BR-3, and Hs578T. Another component, known as PE-D, affected the growth in a dose-dependent and time-dependent manner on some breast cancer cell lines (MCF-7, MDAMB-231), and on the growth of ovarian (2774) and cervical cancer cells (HeLa). The estrogenic effects of some components in Pueraria mirifica are compared with estradiol, a primary estrogen in humans. The rank order of phytoestrogen potency are deoxymiroestrol; miroestrol; 8-prenylnaringenin; coumestrol; genistein/equol; daidzein; resveratrol. Pueraria mirifica also had an estrogenic effect on a human HepG2 hepatoma cell line that contained an estrogen receptor and a luciferase reporter gene; this evidence indicates that metabolic activation of Pueraria mirifica promotes estrogenic activity. Another study also documents that estrogenic activity may result from metabolic activation of liver enzymes.
Animal data
The proposed mechanism of action involves strong competitive binding of the plant’s phytoestrogens to ER-alpha and or synthesis suppressor of ER-alpha.
Pretreatment of rats with Pueraria mirifica (1,000 mg/kg body weight per day tuberous root powder) resulted in decreased virulence of rat mammary tumor development from 7,12-dimethylbenz( a )anthracene (7,12-DMBA). Histopathological analysis of the mammary tumor tissues revealed lower ER-alpha, ER-beta, and ER-alpha/ER-beta profile.
Menopause
Animal data
In rabbits, Pueraria mirifica improved endothelial function through a nitric oxide pathway, decreased contractile responses to norepinephrine, and increased responses to estradiol. The plant caused no changes in lipid profile or liver enzymes. In male and female gonadectomized rats, Pueraria mirifica had estrogen-like activity and affected accessory sex organs. It increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in both sexes. The mechanisms of action involving direct stimulation of the accessory sex organs and suppression of the hypothalamic-pituitary-gonadal axis. Overall activity was more potent in female rats than in male rats. Studies in mice found that Pueraria mirifica does not affect male fertility or the hypothalamus-pituitary-testis axis. The testis, epididymis, and seminal vesicle all had normal histopathology in Pueraria mirifica -treated male mice.
1. Pueraria mirifica may significantly alter the length of menstrual cycles and suppress ovulation by reducing serum levels of gonadotropins. The length of the menstrual cycle increased in monkeys treated with Pueraria mirifica 10 and 100 mg/day of root extract and disappeared entirely in monkeys treated with root extract 1,000 mg/day. Serum FSH, LH, estradiol, progesterone, and immunoreactive-irinhibin were lower in a dose-dependent manner during treatment. During the posttreatment period, only monkeys treated with Pueraria mirifica 10 and 100 mg/day of extract recovered from the changes in menstrual cycle length and hormone levels. Other studies document similar activity for the Pueraria mirifica 1,000 mg/day dose of root extract and the direct correlation in dose with gonadotrophin levels.
The plant had a dose-dependent estrogenic effect on rat vaginal cornification. Pueraria mirifica phytoestrogens at a dose of root extract 1,000 mg/day decreased serum parathyroid hormone and calcium levels in aged menopausal monkeys and, thus, may be beneficial in treating bone loss caused by estrogen deficiency. Pueraria mirifica had an estrogenic action in old menopausal monkeys by changing the sexual skin area around the perineum to the base of the tail to a reddish pigmentation. FSH may be a candidate marker for the study of Pueraria mirifica‘s estrogenic effects in female monkeys if changes in urinary hormones are used as an indicator.
Clinical data
In a 24-week randomized, double-blind, placebo-controlled trial of 51 postmenopausal women, oral Pueraria mirifica exhibited estrogenicity on vaginal tissue, alleviated vaginal dryness symptoms and dyspareunia, improved signs of vaginal atrophy, and restored atrophic vaginal epithelium. In another clinical trial of 51 postmenopausal women 46 to 60 years of age, Pueraria mirifica tuberous root had an estrogen-like effect on the bone turnover rate at a dose of 20, 30, and 50 mg/day for a 24-week period. Phase 1 to 3 trials in Thailand compared the estrogenic effect of Pueraria mirifica to conjugated equine estrogen in relieving climacteric symptoms in perimenopausal women.
In small clinical trials, the administration of Pueraria mirifica crude extract improved hot flushes, frustration, sleep disorder, skin dryness, high blood cholesterol, amenorrhea, and other menopause-related symptoms in women. There was no change in blood cells or liver and renal function.
Other pharmacologic activity
Antioxidant
Some of the isoflavonoids in Pueraria mirifica had antioxidant activity similar to that of alpha tocopherol, or vitamin E. Pueraria mirifica decreased neuronal cell death in a time- and dose-dependent manner against neurotoxic agents in an Alzheimer disease model in vitro. Mechanism of action may be associated with an effect on synaptic density by inducing synaptophysin expression via the estrogen receptor.
Osteoporosis
In sex-hormone–deficient male rats, treatment with Pueraria mirifica root powder completely inhibited bone loss in long bones and axial bones. At higher doses, it increased bone density without affecting accessory sex organs. In a similar study, Pueraria mirifica completely inhibited bone loss in long bones and axial bones in estrogen-deficient female rats. However, the highest dose of Pueraria mirifica root powder (1,000 mg/kg body weight per day) caused an undesired adverse reaction of increased uterine weight.
Insecticide
The active ingredients from the root of Pueraria mirifica had lethal properties during various growth cycles against the yellow fever mosquito ( Aedes aegypti ) and other mosquito species with disease-spreading abilities.
Dosage
Commercial products are available as topical creams, gels, and soaps, or in oral capsule and tablet dosage forms. Some clinical studies used 200 to 400 mg extract from root or tuber orally per day. Commercial manufacturers suggest a dosage of 250 mg of active ingredients from the root orally every morning and evening. For topical products, manufacturers recommend a twice-daily topical application to the breast area for 3 to 5 minutes until fully absorbed.
Pregnancy/Lactation
Avoid use during pregnancy and lactation because of the lack of clinical data and the plant’s phytoestrogen activity.
Interactions
Phytoestrogens have estrogen-like effects. Theoretically, drug interactions may occur with the following:
Corticosteroids (eg, prednisone)
May increase pharmacologic and toxicologic effects.
Hydantoins (eg, phenytoin)
May affect the concentration of these medications.
Thyroid hormones (eg, levothyroxine)
May decrease serum free thyroxine concentrations.
Drug/Laboratory tests
Increased triglyceride levels may occur.
Adverse Reactions
Because of the estrogen-like effect of Pueraria mirifica, use with caution in patients with asthma, diabetes mellitus, epilepsy, migraine, or systemic lupus erythematosus. Also, use with caution in patients with abnormal triglycerides or hypercalcemia.
Toxicology
High doses of Pueraria mirifica caused general and genotoxicity in animals. Rats treated with aqueous and ethanolic root extracts of Pueraria mirifica had significantly lower body weight gain and lowered packed red cell volume; the plant also had mutagenic activity. A root extract dosage of 100 mg/kg had adverse effects on mating efficiency and reproduction in female mice. No estrogen hormone activities were found in egg and chicken meat tissue or rats. The median lethal dose for oral consumption of Pueraria mirifica root powder in mice was 2,000 mg/kg body weight per day.