Puerarin

Puerarin, an isoflavone extracted from Radix puerariae, is a 5-HT2C receptor antagonist.

In Vitro:Puerarin inhibits the expression of LPS-induced iNOS, COX-2 and CRP proteins and also suppresses their mRNAs from RT-PCR experiments in RAW264.7 cells. The inhibition of iNOS, COX-2 and CRP expression is due to a dose-dependent inhibition of phosphorylation and degradation of I-κB, which resulted in the reduction of p65NF-κB nuclear translocation. The effect of puerarin-mediated inhibition of LPS-induced iNOS, COX-2 and CRP expression is attributed to suppressed NF-κB activation at the transcriptional level[1]. Puerarin is a novel open-channel blocker of IK1, which may underlie the antiarrhythmic action of puerarin. Puerarin competes with barium, an open-channel blocker of IK1, to inhibit IK1 currents[2].

In Vivo:Both genistein and puerarin effectively alleviate hepatic damage induced by chronic alcohol administration through potential antioxidant, anti-inflammatory, or anti apoptotic mechanisms. However, genistein is more effective than puerarin in decreasing levels of malondialdehyde (1.05±0.0947 vs. 1.28±0.213 nmol/mg pro, p< 0.05), tumor necrosis factor α (3.12±0.498 vs. 3.82±0.277 pg/mg pro, p < 0.05), interleukin-6 (1.46±0.223 vs. 1.88±0.309 pg/mg pro, p < 0.05), whereas puerarin is more effective than genistein in ameliorating serum activities or levels of alanine transaminase (35.8±3.95 vs. 42.6±6.56 U/L, p < 0.05) and low-density lipoprotein cholesterol (1.12±0.160 vs. 1.55±0.150 mmol/L, p < 0.05) [3]. Early-stage renal damages can be significantly improved by puerarin, possibly via its suppression of ICAM-1 and TNF-α expression in diabetic rat kidneys[4].

References:
[1]. Hu W, et al. Puerarin inhibits iNOS, COX-2 and CRP expression via suppression of NF-κB activation in LPS-induced RAW264.7 macrophage cells. Pharmacol Rep. 2011;63(3):781-9. [2]. Zhang H, et al. Puerarin: a novel antagonist to inward rectifier potassium channel (IK1). Mol Cell Biochem. 2011 Jun;352(1-2):117-23. [3]. Zhao L,et al. Protective Effects of Genistein and Puerarin against Chronic Alcohol-Induced Liver Injury in Mice via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. J Agric Food Chem. 2016 Sep 28;64(38):7291-7. [4]. Pan X, et al. Effect of Puerarin on Expression of ICAM-1 and TNF-α in Kidneys of Diabetic Rats. Med Sci Monit. 2015 Jul 23;21:2134-40.

Puerarin ameliorates oxidative stress in a rodent model of traumatic brain injury.[Pubmed:24079811]

J Surg Res. 2014 Jan;186(1):328-37.

BACKGROUND: A wealth of evidence has suggested that oxidative stress is involved in the secondary brain injury after traumatic brain injury (TBI). Recently, numerous in vivo and in vitro studies were reported that Puerarin could inhibit oxidative stress through the activation of phosphatidylinositol 3-kinase (PI3K)-Akt pathway. It is unknown, however, whether Puerarin can provide neuroprotection and reduce oxidative stress after TBI. The present study investigated the effects of Puerarin on the TBI-induced neurodegeneration, oxidative stress, and the possible role of PI3K-Akt pathway in the neuroprotection of Puerarin, in a rat model of TBI. MATERIALS AND METHODS: Rats were randomly distributed into various subgroups undergoing the sham surgery or TBI procedures. Puerarin (200 mg/kg) was given intraperitoneally at 10 min before injury and PI3K-Akt pathway inhibitor LY294002 was also administered intracerebroventricular in one subgroup. All rats were killed at 24 h after TBI for examination. RESULTS: Our data indicated that Puerarin could significantly reduce TBI-induced neuronal degeneration, accompanied by the partial restoration of the redox disturbance and enhanced expression of phospho-Akt in the pericontusional cortex after TBI. Moreover, PI3K-Akt pathway inhibitor LY294002 could partially abrogate the neuroprotection of Puerarin in rats with TBI. CONCLUSIONS: These results indicate that Puerarin can ameliorate oxidative neurodegeneration after TBI, at least in part, through the activation of PI3K-Akt pathway.

The effect of puerarin against IL-1beta-mediated leukostasis and apoptosis in retinal capillary endothelial cells (TR-iBRB2).[Pubmed:25593509]

Mol Vis. 2014 Dec 31;20:1815-23. eCollection 2014.

PURPOSE: Blood-retinal barrier (BRB) breakdown, the early hallmark of diabetic retinopathy (DR), is thought to depend on retinal inflammation and cell damage. The proinflammatory factor interleukin-1beta (IL-1beta) was demonstrated to cause inflammation as well as cell apoptosis during the process of BRB breakdown. This study extensively evaluated the protective effect of Puerarin, a major active component extracted from the traditional herb Radix puerariae, against IL-1beta-induced cell dysfunction in TR-iBRB2 cells, a retinal capillary endothelial cell line. METHODS: TR-iBRB2 cells were pretreated with IL-1beta (10 ng/ml) for 24 h and then exposed to Puerarin (0, 10, 25, and 50 muM) for another 24 h. Leukocyte endothelial adhesion was assessed through a cell-based assay using lymphoblastoid cells. Cell apoptosis was evaluated with flow cytometry, and the expression of adhesion molecules and apoptosis-related molecules was assessed with western blot analysis. RESULTS: Our data showed that Puerarin attenuated IL-1beta-mediated leukostasis and cell apoptosis in TR-iBRB2 cells. Furthermore, Puerarin strikingly prevented IL-1beta-induced molecular events of the upstream and downstream signaling pathways involved in this cellular process. CONCLUSIONS: These findings may significantly contribute to better understanding of the protective effect of Puerarin, in particular for DR, as well as provide novel insights into the potential application of this compound in DR therapy.

Puerarin attenuates airway inflammation by regulation of eotaxin-3.[Pubmed:25530546]

Immunol Lett. 2015 Feb;163(2):173-8.

Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of many diseases in the clinical practice. The present study aimed to determine the protective effects and the underlying mechanisms of Puerarin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and Puerarin (10 mg/kg, 20 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Th1/Th2 cytokines were measured by enzyme-linked immunosorbent assay, eotaxin-3 was evaluated by western blotting. Our study demonstrated that, compared with model group, Puerarin inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-gamma level in bronchoalveolar lavage fluid; histological studies demonstrated that Puerarin substantially inhibited OVA-induced eosinophilia in lung tissue compared with model group. Western blotting studies demonstrated that Puerarin substantially inhibited eotaxin-3 compared with model group. Our findings support Puerarin can prevent some signs of allergic asthma in the mouse model.

Puerarin ameliorates hepatic steatosis by activating the PPARalpha and AMPK signaling pathways in hepatocytes.[Pubmed:25605057]

Int J Mol Med. 2015 Mar;35(3):803-9.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the hepatic manifestation of metabolic syndrome and is the leading cause of chronic liver disease. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Puerarin is a herbal product widely used in Asia, and is believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. The present study was designed to investigate the effects and mechanisms of action of Puerarin in reducing lipid accumulation in oleic acid (OA)-treated HepG2 cells. Hepatocytes were treated with OA with or without Puerarin to observe lipid accumulation by Oil Red O staining. We also examined hepatic lipid contents (e.g., triacylglycerol and cholesterol) following treatment with Puerarin. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), peroxisome proliferator-activated receptor alpha (PPARalpha) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) protein and mRNA expression, respectively. Our results revealed that Puerarin suppressed OA-induced lipid accumulation, and reduced the triacylglycerol and cholesterol levels. Furthermore, Puerarin decreased the expression levels of lipogenic enzymes, such as FAS and SREBPs, and increased the expression levels of PPARalpha, which are critical regulators of hepatic lipid metabolism through the AMPK signaling pathway. These results indicate that Puerarin has the same ability to activate AMPK, and reduce SREBP-1 and FAS expression, thus inhibiting hepatic lipogenesis and increasing hepatic antioxidant activity. We found that Puerarin exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in hepatocytes. Therefore, Puerarin extract may have therapeutic benefits in the treatment of fatty liver and lipid-related metabolic disorders.

Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats.[Pubmed:16472823]

Life Sci. 2006 Jun 20;79(4):324-30.

Hypercholesterolemia is a dominant risk factor for the development and progression of atherosclerosis and cardiovascular diseases. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular diseases. Pueraria lobata is employed clinically to treat cardiovascular diseases in China. In the present study, the atheroscleroprotective potential of the herb's major active compound, Puerarin, was investigated by monitoring serum lipid profile and major enzyme expressions on cholesterol homeostasis in Sprague-Dawley rats fed with control diet, hypercholesterolmic diet or hypercholesterolmic diet plus administration of Puerarin (300 mg/kg/day, p.o.) for 4 weeks. Puerarin markedly attenuated the increased total cholesterol induced by hypercholesterolmic diet in both serum and liver. It caused a significant reduction in the atherogenic index. Expression of mRNA for hepatic 7alpha-hydroxylase (CYP7A1) was significantly enhanced but not for those of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and lanosterol 14alpha-demethylase (CYP51). To further explore the atheroscleroprotective potential of Puerarin, acetylcholine induced endothelium-dependent vasorelaxation and endothelial nitric oxide synthase (eNOS) expression on isolated thoracic aortas were analyzed. Animals administered with Puerarin suppressed the hypercholesterolemic diet induced impairment of eNOS expression, whereas there was no significant difference in the endothelium-dependent vasorelaxation among various groups of animals. These data indicated that Puerarin reduced the atherogenic properties of dietary cholesterol in rats. Its hypocholesterolemic function may be due to the promotion of cholesterol and bile acids excretion in liver. Whether Puerarin targets directly on cholesterol homeostasis or both cholesterol homeostasis and endothelial function remains to be determined.

Puerarin protects PC12 cells against beta-amyloid-induced cell injury.[Pubmed:18675923]

Cell Biol Int. 2008 Oct;32(10):1230-7.

beta-Amyloid protein (Abeta), a major protein component of brain senile plaques in Alzheimer's disease, is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. In this study, the protective effect of Puerarin, an isoflavone purified from the radix of the Chinese herb Pueraria lobata, on Abeta-induced rat pheochromocytoma (PC12) cultures was investigated. Although exposure of PC12 cells to 50 microM Abeta25-35 caused significant viability loss and apoptotic rate increase, pretreatment of the cells with Puerarin for 24h reduced the viability loss and apoptotic rate. Puerarin (1 microM) significantly inhibited Abeta25-35-induced apoptosis of PC12 cells. Preincubation of the cell with Puerarin also restored the ROS and mitochondrial membrane potential levels that had been altered as a result of Abeta25-35 treatment. Puerarin was also found to increase the Bcl-2/Bax ratio and reduce caspase-3 activation. These results suggest that Puerarin could attenuate Abeta25-35-induced PC12 cell injure and apoptosis and could also promote the survival of PC12 cells. Therefore, Puerarin may act as an intracellular ROS scavenger, and its antioxidant properties may protect against Abeta25-35-induced cell injury.