Puerarin: Preparation, Pharmacological Action and Application Studies

General Description

As one of three major isoflavonoid compounds,[1]puerarin with strong biological activities[2] was isolated from Gegen in the late 1950s.Currently, there are three main dosage forms of puerarin for clinica applications, that is, injection, tablet, and capsule.[1] Its bioavailability in vivo is often limited by its insolubility. A novel transglycosylase increases the solubility of puerarin [100-fold, by converting it to puerarin glycosides.[2]It has been demonstrated to possess a wide spectrum of pharmacological effects such as vasodilation, cardioprotection, neuroprotection, antioxidant, anticancer, antiinflammation, alleviation of pain, promotion of bone formation, inhibition of alcohol intake, and attenuation of insulin resistance. It is suggested that puerarinmay be a valuable therapy option for the prophylaxis and treatment of various diseases, including arrhythmia, diabetes and diabetic complications, PD, AD, osteonecrosis, hyperlipidemia, endometriosis, and cancer.[1] Puerarin and its glycosides do not have significant toxic effects, at least in rodents, either in vitro or in vivo at doses of up to 250 mg/kg per day.[2]

Figure 1 Puerarin powder

Preparation

β-D-glucopyranosyl-2,6-dimethoxybenzene, was obtained by coupling of a lithiated aromatic reagent with pyranolactone. Condensation of p-methoxybenzaldehyde gave the chalcone. The protected chalcone was cyclized to 7,4’-di-O-methylpuerarin in the presence of Tl(NO3 ). Demethylation of 7,4’-di-O-methylpuerarin was accomplished by refluxing with TMSI in CH3 CN to give puerarin.[3]

Pharmacological Action

1.Vasodilatory activity:Puerarin has the vasodilatory action and acts as a significant part in the modulation of vascular tone. And the vasorelaxant effect conducted by puerarin was dependent on the activation of endothelium. The endotheliumdependent vasodilation induced by puerarin was related to NO production, whereas the endotheliumindependent relaxation involved the K+ channels opening.[1]

2.Cardioprotective activity:The cardioprotective effect of puerarin against ischemia and reperfusion injury in isolated ventricular myocytes was carried out through activation of mitochondrial ATP-sensitive potassium channels and inhibition of the opening of mitochondrial permeability transition pores. Besides, puerarin attenuated hydrogen peroxide (H2O2)-elicited myocyte death and decreased the level of reactive oxygen species (ROS) in isolated ventricular myocytes.[1]

3.Inhibition of ischemia and reperfusion injury:Puerarin significantly inhibited brain infarct size and increased hypoxia-inducible factor-1α, inducible nitric oxide synthase (iNOS), TNF-α, and active caspase-3 protein expression levels in MCAOstimulated ischemic area,administration of puerarin (50 and 100 mg/kg) decreased edema volume, and glutamate (Glu) and aspartate (Asp) levels but enhanced neurological function.[1]

4.Antidiabetic activity and inhibition of diabetic complications:Antidiabetes.Intravenous administration of puerarin dose-dependently lowered the blood glucose level. Puerarin (100 μM)markedly suppressed H2O2-induced viability loss and apoptotic index in pancreatic islets. Additionally, pretreatment with puerarin improved H2O2-induced reduction in basal and glucose-stimulated insulin production but blocked H2O2induced free radicals production and stimulated activities of superoxide dismutase (SOD) and catalase in the isolated pancreatic islets, suggesting the protective effect of puerarin on pancreatic islets against oxidative stress associated with the antioxidative activity.[1]

5.The puerarin has an effect of inhibition of diabetic ocular complications, inhibition of diabetic vascular complications and amelioration of diabetic nephropathy. the protective effect of puerarin against vascular complications in DM.[1]

6.Antiinflammatory activity:The puerarin exhibited the antiinflammatory activity by inhibiting the level of IL-8.[1]

7.Anti-Parkinsons disease activity:Puerarin pretreatment enhanced Akt phosphorylation in both MPP+-induced and non-MPP+-induced cells, modulated mitochondrial membrane potential, and prevented MPP+induced apoptosis, which were effectively abolished by LY294002.[1]

8.Anti-Alzheimers disease activity:The potential use of puerarin on ADassociated neuroapoptosis and disorders of cognitive function.Thus, puerarin might act as a scavenger of intracellular ROS and protect neurons against apoptosis stimulated by oxidative stress.[1]

9.Antiosteoporotic activity:puerarin stimulated bone gain through promoting osteoblast differentiation in an ER-mediated manner and might be a preventive and therapeutic candidate against postmenopausal osteoporosis.[1]

10.Inhibition of alcohol-induced disorders:The cell viability, cellular lipid accumulation, and the expression of microtubule-associated protein 1 light chain 3 in ethanol-incubated hepatocytes were restored after puerarin treatment.[1]

11.Antioxidant activity: Puerarin scavenged both superoxide anion induced by riboflavin-light and hydroxyl radical induced by Fenton reaction, suppressed oxidative erythrocyte hemolysis and the level of MDA caused by H2O2 in erythrocytes, and alleviated oxidative modification of LDL elicited by ultraviolet ray and cupric sulfate, suggesting its antiperoxidation effect and the potential use for prevention of atherosclerosis.[1]

12.Phytoestrogenic activity:Puerarin could interfere with tissue invasion ofESCs and angiogenesis of ectopic endometrial tissues induced by E2. In addition, puerarin inhibited cell apoptosis, tumor-related gene expression, and angiopoiesis in endometriotic tissue of patients with endometriosis. Therefore, puerarin might be an ideal therapeutic agent for endometriosis.[1]

13.Anticancer activity and induction of apoptosis:Puerarin is an ideal candidate as an antitumor agent owing to its induction of apoptosis in various types of human cancer cells. Administration of puerarin dose-dependently and time-dependently inhibited colon cancer HT-29 cellular growth, suppressed c-myc and Bcl-2 expression, enhanced Bax expression and caspase-3 activation, and subsequently induced apoptosis in HT-29 cells.[1]

Application

It has been widely used in the treatment of cardiovascular diseases, cerebrovascular disorders, cancer, Parkinson’s disease (PD), Alzheimer’s disease (AD), and diabetes and diabetic complications. It also exerts protective actions against fever, inflammation, hyperlipidemia, osteonecrosis, alcohol-induced disorders, and oxidative damage. The beneficial effects of puerarin on various medicinal purposes may be due to its abilities to inhibit calcium influx, improve microcirculation, reduce insulin resistance, scavenge oxygen free radicals, counteract cell death, inhibit alcohol intake, and so on.Puerarin has been used for the therapy of diabetes mellitus (DM) in China since the 1990s. It also has analgesic and antipyretic effects.In addition, It might be useful for the treatment of polycystic syndrome and could be used in the management of hypoxia-induced pulmonary hypertension.[1]

References

[1]Zhou YX,et al. Puerarin: a review of pharmacological effects[J]. Phytotherapy Research, 2014, 28(7): 961-975.

[2]Chung HJ, et al. Toxicological evaluation of the isoflavone puerarin and its glycosides[J]. European Food Research and Technology. 2009, 230: 145-153.

[3]Lee DYW,et al.Total synthesis of puerarin, an isoflavone C-glycoside[J]. Tetrahedron letters, 2003, 44(36): 6857-6859.

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