Sources and Composition
Pueraria lobata (Technically Pueraria Montana variant Lobata) is a Traditional Chinese Medicine for the purposes of menopausal symptoms and the associated comorbidities (osteoporosis and cardiac impairment), hangover therapy, and as a general health preservation agent; it is commonly referred to as either Kudzu or Kadzu or Gegen; the term Pueraria Radix (Root of Pueraria) almost exclusively refers to this plant rather than the other bioactive herb Pueraria Mirifica; despite the aforementioned herb being a more potent estrogenic agent, Pueraria Lobata is one of the more popular phytoestrogenic herbs in mainland China.
Puerarin appears to have its absorption increased linearly with increasing concentrations up to 102.7μg/mL without a changing Papp value, suggesting that passive diffusion mediates absorption at lower concentrations with a possible active transport mechanism. It is mostly absorbed in the Ileum, and the active efflux component appears to be mediated by MRP1 (2.6-fold absorption when inhibited by MK-571) as well as P-Glycoprotein (1.8-fold absorption when inhibited by Vermapril).
When Puerarin is incubated with either Angelica dahurica basic extract (450μg/mL) or its volatile oils (0.72μl/mL) the absorption of Puerarin is increased 1.7-fold and 3.6-fold respectively; suggesting that Angelica dahurica contains both MRP1 and Pgp inhibitors, and is in accordance with traditional combination therapy of these two herbs.
Puerarin appears to be fairly well absorbed from the intestines at low concentrations, and is effluxed by both MRP and Pgp; combination therapy with Angelica dahurica can enhance absorption of Puerarin
Following oral administration of Pueraria Lobata alongside two other herbs (Danshen and Ligusticum chuanxiong in even ratios), a large oral dose of the ethanolic extract detected both soy isoflavones (Genistein and Daidzein) reaching serum, with a variety of Daidzein conjugates including Puerarin also being detected in serum. This study also confirmed the presence of Methoxypuerarins (3' and 4') and both Formononetin and Glycitein, and noted that diglycosides of Daidzein and one of Formononetin were not detected as Phase II metabolites.
The kinetics of Puerarin (after 7.5g/kg water extract of the decoction) were a half-life of 46.9 minutes (β-Half life of 925.7min) and AUC of 790.3μ min/mL; a Cmax of 1.41ug/mL (3.39umol/L) and a Tmax of 18.5 minutes; suggesting rapid absorption. These parameters are somewhat similar to those achieved with the combination formula GegenQinlian, and similar absorption properties were noted with the other Daidzin-based bioactives.
It was noted that diglycoside metabolites (two Daidzin diglycosides and one Formononetin) were not detected as Phase II Metabolites.
Supplemental dosages of Pueraria Lobata appear to increase circulating levels of isoflavones
When mice are fed a consistent diet containing 0.2% Kudzu root (25.3% Puerarin, 7.07% Daidzin, 0.8% Daidzein), serum levels can be detected of Daidzein (208-883nM) and its glycoside Puerarin (4.57-10.44nM), Dihydrodaidzein (65.36-751nM) and the endogenous metabolite Equol (8,286-29,300nM) are also detected as well as Formononetin (143+/-68nM); the range noted in this study was due to serum levels of both obese and lean mice being measured with obese mice eating more overall.
It is possible most bioactivity of Pueraria Lobata is vicariously through Daidzein and Equol, which would make its bioactivities markedly similar to dietary soy isoflavones (good source of Daidzein, with benefits somewhat linked to endogenous production of Equol)
A study in menopausal women given 100mg of Kudzu isoflavones daily noted that both Kudzu treatment and Hormone Replacement Therapy (HRT; 0.625mg CEE and 5mg MPA) noted an improvement on the scores on the MMSE rating scale.
Delayed recall was improved in HRT and not in control, and Kudzu was intermediate to these two conditions yet not significantly different from either. Attention span, Motor speed, and flexible thinking were noted to be increased with Kudzu.
May have some cognitive enhancing properties in menopausal women
Kudzu has been tested for its interactions with menopausal symptoms using a supplement standardized for 100mg Isoflavones for a period of 3 months, but has failed to demonstrate a reduction of symptoms (although in this study hormone replacement therapy with 0.625mg CEE/5mg MPA also failed, the authors suspected that the low baseline symptoms were to blame).
Has once failed to reduce menopausal symptoms
It should be noted that the related herb, Pueraria Mirifica, is more commonly touted to be catered to menopause rather than Kudzu
In vitro, Puerarin has been noted to have beta-adrenoreceptor antagonistic properties at 0.1-3umol/L concentrations and has shown these effects following intravenous administration of 100mg/kg isolated Puerarin (cat) and inhibited the effects of beta-adrenergic agonists (ephedrine and isoproterenol) on cardic tissue.
Lipids and Cholesterol
In obese mice given 0.2% of the diet as Kudzu root for 8 months, Kudzu root failed to significantly modify triglycerides or total cholesterol relative to control.
A study using 100mg Kudzu isoflavones daily for 3 months in menopausal women (otherwise health) noted that there was no change in a lipid panel (cholesterol, triglycerides, or Apolipoproteins) that was significantly different than placebo; the active control of Hormone Replacement Therapy exerted benefit.
Interactions with Glucose Metabolism
0.2% of Kudzu root in the diet of obese mice for 8 months is associated with a decrease in fasting glucose (from 183+/-14 to 148+/-11mg/dl; 19% decrease) and improvements in both glucose tolerance (oral glucose tolerance test) as well as insulin tolerance (indicative of insulin sensitivity). Lean mice fed Kudzu in a similar manner experience improvements in glucose tolerance to a smaller magnitude (not statistically significant) with no improvement to insulin tolerance.
Skeletal Mass and Bone Metabolism
In ovariectomized mice given 5-20% of the diet as Pueraria Lobata root for 4 weeks, bone mineral density (of the femur) was increased with 20% Kuduz in the diet being as effective as the active control of 17β-estradiol with another study replicating 20% and 17β-estradiol being equally effective with both increased bone mass beyond baseline and 10% of the diet appearing to normalize bone losses relative to control. 5mg/kg of Puerarin in isolation also appears to exert anti-osteroporotic effects in ovarectomized mice over 8 weeks of feeding, suggesting that this is the active component.
At multiple times, interventions which note improvements in bone mass and serum biomarkers of bone metabolism have failed to find increases of uterine weight (indicative of estrogenicity) either with the Kudzu plant or isolated Puerarin.
Appears to increase bone mineral density, although at least one study suggests that this is distinct from estrogenic effects
Interactions with Fat Mass
0.2% of the diet as Kudzu root for 8 months in obese mice was associaed with an attenuation of the rise of adiponectin seen in the obese control, which brought serum concentrations to a level similar to lean control. This study did not note any alterations in food intake nor body weight associated with Kudzu.
In ovariectomized rats given 100mg/kg of Pueraria Lobata flavones (exact molecules not stated, 'flavone' in this study treated as one entity) daily for 5 weeks noted that the weight gain associated with ovariectomy (research model for menopause) was attenuated, although not to the degree as the active control of 1mg/kg estrogen. Similar results have been noted in obese ovariectomized mice given 80mg or Pueraria Lobata daily, where weight gain assocaited with menopause was attenuated with comparable potency to 0.25mg estradiol.
Inflammation and Immunology
A polysaccharide from Pueraria Lobata (PLP) has been reported to increased nitric oxide release from macrophages and increase MHC-II expression from dendritic cells, although with minimal efficacy in increasin splenic cell proliferation. This polysaccharide appears to activate monocytic, but not lymphatic, immune cells and concentration-dependently stimulated up to 300ug/mL although never exceeding the active control of LPS.
When looking at the mechanisms, it was noted that PLP-stimulated dendritic cells were characterized by increased NF-kB translocation and increased expression of all MAPKs (p38, JNK, and ERK).
Interactions with Hormones
In a study on ovariectomized mice, Pueraria Lobata can induce a dose-dependent activation of Estrogenic activity mediated via ERα, with activation at 1mcg/mL increasing up to 6-fold at maximal activation at 25mcg/mL; it was noted that Pueraria Lobata, as well as Licorice, were both simply agonists and not Selective Estrogen Receptor Modulators (SERMs) in this study, and that the EC50 of Pueraria Lobata (5.5µg/mL) was greater than that of licorice (EC50 16µg/mL).
Puerarin (daidzein-8-C glucoside) up to 100uM does not bind to either subset of the estrogen receptor. As daidzein itself has affinity, it appear the 8C glucoside prevents binding via steric hindrance.
In vitro, Pueraria Lobata is estrogenic with affinity for the alpha subset (ERα)
In a study assessing the estrogenicity of Pueraria Lobata against three strains of Pueraria Mirifica, 10-1000mg/kg oral ingestion for these herbs resulted in a failure of Kudzu to induce vaginal cornification (indicative of biologically relevant estrogenicity); Pueraria Mirifica as well as injections of estrogen were both successful in inducing vaginal cornification while 1mg/kg Genistein (one of the two soy isoflavones) also failed. In mice given up to 20% the diet as Kuduz for 4 weeks, there was no noticeable increase in uterine weight when compared to control and a lack of uterine/vaginal effects were replicated with 80mg of the herb extract daily in ovarectomized mice.
When investigating breast tissue, oral ingestion of 40-320mg of Pueraria Lobata in mice bearing breast cancer tumors (MCF-7) failed to find any evidence of Pueraria Lobata stimulating tumor growth, which usually occurs with ERα activation (and occurred in the positive control group of estradiol).
One study has hypothesized that estrogenic effects are localized to adipose (or at least, not female sex organs) as some genetic biomarkers downstream of estrogen activation (downregulation of CD8B and CD79B, upregulation of GPX3 and MUP; estrogen but not Pueraria Lobata influenced Leptin and LCN2) were noted to be upregulated by Pueraria Lobata in the same mice where no uterine effects were noted.
A lack of estrogenic effect has been noted on female sex organs including mammary tissue, which is thought to be either due to a lack of estrogenicity overall (and some bioactives merely mimicking it by chance) or localized estrogenicity that does not occur in sex organs
Interactions with Organ Systems
90 or 180mg/kg isolated Puerarin alongside a chronically high alcohol containing diet (36% of calories) noted that while Puerarin failed to modify the (increased with ethanol) weights of the liver Puerarin was associated with less fatty liver buildup, inflammation, and serum liver enzymes.
Protective effects have been noted with Puerarin in regards to toxin and alcohol-induced liver fibrosis, and 200-800mg/kg of Puerarin in rats fed CCL4 (hepatotoxin) noted dose-dependent protective effects and reduced oxidation and inflammation as assessed by liver histology.
The leaves of Pueraria Lobata (sometimes termed Pueraria flos) are used in Traditional Chinese Medicine for the purposes of hangover prevention and commonly used alongside Ginseng radix, Amomi Fructus rotundus, and Citri reticulatae Pericarpium.
The root extract, which is not traditionally used, appears to inhibit the Aldehyde dehydrogenase (ALDH) enzyme (similar to the pharmaceutical Disulfiram) which is thought to reduce tolerance and create an aversion to alcohol from a build-up of acetaldehyde. Reduced activity of the ALDH enzyme (Homozygote ALDH2*2) occurs to a greater degree in Asian populations and is known to increase the frequency of intolerance to alcohol consumption.
It has been noted in a review that the ALDH inhibitor Disulfiram has been linked to both alcohol aversion (as intended) and euphora from alcohol and cocaine; studies investigating the interactions of Pueraria flos and euphoria from alcohol are lacking.
The leaf extract of Kudzu appears to enhance acetaldehyde clearance from the body and possibly aid in the reduction of hangovers (in accordance with traditional claims) while the root extract may confer the opposite effects and increase insensitivity to alcohol by inhibiting the enzyme that degrades acetaldehyde
Salvia Miltiorrhiza (Danshen) appears to have been used alongside Pueraria Lobata (Gegen) for the purpose of cardiovascular health, under the combination name of DG (Danshen-Gegen) which is a 7:3 ratio of Danshen to Gegen dry weight.
In activated macrophages, concentration-dependent antiinflammatory effects were noted on nitric oxide, iNOS and PGE2 (weak inhibition of COX2) while cytokine release was attenuated in a dose dependent manner on IL-6 and IL-1β, with the latter cytokine noting full suppression to levels below control at 1mg/mL; TNF-α was not highly affected, and these effects were thought to be due to NF-kB inhibition. The anti-inflammatory effects of the herb combination, in regards to LPS-stimulated macrophages, is synergistic (combination index 0.75) as the IC50 value of either herb (1.01 and 1.10mg/mL) is less potent than that of the combination (IC50 0.50mg/mL). The anti-artherogenic effects as assessed by foam cell formation was merely additive while the inhibitory effect of either herb on vascular smooth muscle cells (vSMCs) appeared to antagonize each other when in combination.
The combination formula appears to have vasorelaxant properties mediated via potassium channel activation at a concentration of 1-7mg/mL (IC50 value of 895+/-121μg/mL), and coincubation with potassium channel inhibitors reduced the maximal relaxation by 20-37%.
Appears to be synergistic in regards to reducing inflammation, and additive in regards to reducing artherogenic formation; both conclusions based on in vitro research currently
When Puerarin is incubated with either Angelica dahurica basic extract (450μg/mL) or its volatile oils (0.72μl/mL) in vitro with intestinal cells, the absorption of Puerarin is increased 1.7-fold and 3.6-fold respectively; this suggests that Angelica dahurica can enhance the absorption of Puerarin from Pueraria Lobata.
Angelica Dahurica may increase the absorption of Puerarin from Pueraria Lobata, and thus enhance bioactivities of any action in the body related to Puerarin