Tao Liang

Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function.

This study was designed to evaluate the potential effects of puerarin (PR), an effective isoflavonoid compound purified from Pueraria lobata, in treating hepatic fibrosis (HF) rats induced by carbon tetrachloride (CCl(4), 2 mL kg(-1) d(-1)). Compared to model control, PR treatment effectively lowered the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) in HF rats. Masson stained analysis showed that the condition of HF rats was mitigated. Meanwhile, the tumor necrosis factor alpha (TNF-α), nuclear factor-kappa B (NF-κB) expressions were significantly down-regulated at protein level by PR intervention. Additionally, the activity of superoxide dismutase (SOD) was elevated, while the content of malondialdehyde (MDA) was lessened in liver tissue. As revealed by immunohistochemistry assay, PR therapy resulted in reduced production of transforming growth factor-βl (TGF-βl). Moreover, it also was attributed to decreased mRNA level of inducible nitric oxide synthase (iNOS) using RT-PCR analysis. These findings demonstrate that puerarin successfully reverses hepatotoxicity in CCl(4)-induced HF rats via the underlying mechanisms of regulating serum enzymes and attenuating TNF-α/NF-κB pathway for anti-inflammation response, as well as improving metabolic function in liver tissue.

Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-γ expression and inhibition of PI3K/Akt pathway.

Hepatic fibrosis (HF) is a chronic disease, which primarily leads to liver unregulated metabolism. In this study, we aimed to investigate the therapeutic effects of puerarin (PR), an active ingredient from kudzu root, on CCl4-induced HF rats. PR effectively ameliorated the liver metabolic function, resulting in reduced serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total-bilirubin (T-bilirubin), extracellular matrix (ECM) contents and increased levels of albumin, total-protein (T-protein) in HF rats. Similarly, pathological examination showed that the CCl4-lesioned liver was mitigated by PR treatments. Meanwhile, we also detected significantly reduced levels of hydroxyproline (Hyp), type III precollagen (PCIII) and collagen I (Col I) in the liver tissue of HF rats, whereas the peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression was effectively increased. Moreover, the expression of tissue inhibitor of metal protease-1 (TIMP-1) was decreased, while the expression of matrix metalloproteinase-2 (MMP-2) was increased. In addition, the expression of p-PI3K and p-Akt was significantly down-regulated by PR treatments. Taken together, PR could attenuate the CCl4-induced toxicity in the hepatocytes of HF rats. It played a protective role in the liver tissue probably through regulating the PPAR-γ expression and blocking the PI3K/Akt pathway to inhibit the excessive deposition of collagen.

Protective effect of cinnamon polyphenols against STZ-diabetic mice fed high-sugar, high-fat diet and its underlying mechanism

This study was designed to investigate the potential effects of 14days intragastrically given of cinnamon polyphenols (CPS) in treating diabetic mice induced by intraperitoneal injection of streptozotocin (150mgkg(-1)) and fed high-sugar, high-fat diet. The diabetic mice model was successfully established through determining on fasting blood-glucose (FBG) test. As revealed by glucose oxidase (GOD) and radioimmunoassay (RIA), both dimethyldiguanide (DC, 0.6gkg(-1)d(-1)) and CPS (0.3, 0.6, 1.2gkg(-1)d(-1)) treatments significantly resulted in down-regulation of blood glucose and insulin levels in serum, while the levels of oxidative stress markers were markedly lowered through ELISA assay. Meanwhile, the pathological damage in islet with pancreatic beta cells was ameliorated by treatment of CPS at different doses, as shown in HE stain. At the same time, the treatments also caused notable reduction of iNOS, NF-κB expressions showing in Western blot analysis. These findings demonstrate that cinnamon polyphenols can exert the hypoglycemic and hypolipidemic effects through the mechanisms that may be associated with repairing pancreatic beta cells in diabetic mice and improving its anti-oxidative capacity, as well as attenuating cytotoxicity via inhibition of iNOS, NF-κB activation.

Anti-diabetic effect of ramulus mori polysaccharides, isolated from Morus alba L., on STZ-diabetic mice through blocking inflammatory response and attenuating oxidative stress

Diabetes mellitus is a clinically complex disease characterized by the dysfunctions of pancreas. In this study, we investigated the therapeutic effects of ramulus mori polysaccharides (RMP) on diabetic mice induced by streptozotocin. Our results showed that body weight and insulin level were notably increased after metformin and RMP treatments, while the blood glucose was lowered. HE-staining assay showed that the treatments mitigated the pathological lesions in pancreas tissue. In addition, the expression levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6) and cyclo-oxygenase-2 (COX-2) were effectively reduced in pancreas tissue by the treatments, respectively. We also found that upon these treatments, the activities of manganese superoxide dismutase (MnSOD) and glutathione reductase (GSH-Rd) were increased; the content of malonaldehyde (MDA) was decreased in pancreas tissue; and the mRNA expression of heme oxygenase-1 (HO-1) was markedly increased in pancreas tissue. Taken together, these results suggest that RMP plays the blood glucose-lowering and metabolism-normalizing roles, and it may improve the function of pancreas through inhibiting the inflammatory response and attenuating the oxidative stress in pancreas tissue.

Puerarin attenuates neuronal degeneration and blocks oxidative stress to elicit a neuroprotective effect on substantia nigra injury in 6-OHDA-lesioned rats.

In the present study, we aimed to investigate the protective effect of puerarin (PR) on the substantia nigra (SN) of 6-hydroxydopamine (6-OHDA)-lesioned rats. Our results show that glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were increased, while the malonaldehyde (MDA) content was reduced in the SN following PR treatment. Furthermore, examination of specific immunostaining revealed that histopathological lesions in SN tissue were alleviated. Similarly, the mRNA level of heme oxygenase-1 (HO-1) was notably decreased, and the expression of NAD(P)H: quinone oxidoreductase-1 (NQO-1) mRNA was increased. As revealed by Western blot analysis, PR therapy contributed to a marked expression of DJ-1 and superoxide dismutase-2 (SOD2) at the protein levels in the SN of 6-OHDA-lesioned rats. Taken together, these findings suggest that puerarin effectively exerts its neuroprotective action against 6-OHDA-induced Parkinsonian rats through the enhancement of antioxidant capability and attenuation of oxidative stress injury, thereby inhibiting neurodegeneration in SN tissue.

Phenolic and Lignan Glycosides from the Butanol Extract of Averrhoa carambola L. Root

Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside (1), benzyl-1-O- β-D-glucopyranoside (2), (+)-5-methoxyisolariciresinol 3α-O- β-D-gluco-pyranoside (3), (+)-isolariciresinol 3α-O- β-D-glucopyranoside (4), koaburaside (5), (+)-lyoniresinol 3α-O- β-D-glucopyranoside (6), (−)-lyoniresinol 3α-O- β-D-glucopyranoside (7), (−)-5-methoxyisolariciresinol 3α-O- β-D-glucopyranoside (8), (−)-isolariciresinol 3α-O- β-D-glucopyranoside (9), 3,5-dimethoxy-4-hydroxyphenyl 1-O-β-apiofuranosyl (1→6)-O-β-D-glucopyranoside (10), 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl (1→6)-β-gluco-pyranoside (11), methoxyhydroquinone-4- β -D-glucopyranoside (12), (2S)-2-O- β-D-gluco-pyranosyl-2-hydroxyphenylacetic acid (13), 3-hydroxy-4-methoxyphenol 1-O -β-D-apio-furanosyl-(1→6)-O - β-D-glucopyranoside (14) and 4-hydroxy-3-methoxyphenol 1-O -β-D-apiofuranosyl-(1→6)-O - β-D-glucopyranoside (15) were isolated from this plant for the first time.

Puerarin, isolated from Kudzu root (Willd.), attenuates hepatocellular cytotoxicity and regulates the GSK-3β/NF-κB pathway for exerting the hepatoprotection against chronic alcohol-induced liver injury in rats.

Puerarin (PR) has been utilized as a phytomedicine to managing liver disease in China. Thus, this study aimed to evaluate the potential PR-mediated hepatoprotective role against chronic alcohol-induced liver injury in rats. The results indicated that serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and pro-inflammatory cytokines were significantly reduced following PR treatment, while the albumin (ALB) level was increased. Meanwhile, intrahepatic contents of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) were elevated. Pathological examination showed that alcohol-lesioned hepatocytes were mitigated through the PR treatment. In addition, the endogenous levels of glycogen synthase kinase-3β (GSK-3β) at the protein level and β-catenin expression at the mRNA level were notably down-regulated, whereas the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB) proteins in the liver tissue were effectively decreased following the PR treatment. Together, these findings demonstrate that PR mediates hepatoprotection against alcohol-induced liver injury. The mechanisms underlying the cytoprotective effects of PR are associated with inhibiting immunotoxicity in hepatocytes and regulating the GSK-3β/NF-κB pathway, thereby maintaining metabolic homeostasis in the liver tissue.

Hepatoprotective effects of Yulangsan polysaccharide against isoniazid and rifampicin-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCEnYulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra, which is used as an hepatic protection, anti-aging and memory improving agent. In this study, the hepatoprotective effects of YLSPS against isoniazid (INH) or rifampicin and isoniazid (RFP+INH)-induced liver injury were investigated in mice.nnnMATERIALS AND METHODSnThe liver injury was induced by intragastric administration of INH or RFP+INH daily for 10 days. During the experiment, the model group received INH or RFP+INH only, and the normal control group received an equal volume of saline. Treatment groups received not only INH or RFP+INH but also the corresponding drugs, DDB (200mg/kg/day) or YLSPS (100, 200, and 400mg/kg/day) 2h after the administration of INH or RFP+INH.nnnRESULTSnAnalysis experiments showed that YLSPS significantly alleviated liver injury as indicated by the decreased levels of ALT and AST and the increased levels of SOD, GSH and GSH-Px. Moreover, YLSPS could effectively reduce the pathological tissue damage. The research on the mechanisms underlying the hepatoprotective effect showed that YLSPS was able to reduce lipid peroxidation and activate the anti-oxidative defense system.nnnCONCLUSIONnOur results show that YLSPS is effective in attenuating hepatic injury in the INH or RFP+INH-induced mouse model, and could be developed as a new drug for treatment of liver injury.

Puerarin improves metabolic function leading to hepatoprotective effects in chronic alcohol-induced liver injury in rats.

Puerarin (PR), an active component extracted from the kudzu root, has been widely used as an ethno-medicine to treat hepatopathy in China. Therefore, the aim of the present study was to investigate the hepatoprotective action of PR in chronic alcohol-induced liver injury in rats. Data showed that the serum levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were elevated following PR administration. In addition, the levels of endogenous CYP2E1, CYP1A2, and CYP3A proteins in liver tissue were also gradually decreased following PR treatment. Histopathological examinations suggested that alcohol-induced hepatocellular lesions were mitigated by PR treatment. Collectively, these data indicate that PR contributes to cytoprotection against alcohol-induced liver lesions through improving metabolic function.

Puerarin, isolated from Pueraria lobata (Willd.), protects against diabetic nephropathy by attenuating oxidative stress.

In this study, we evaluated the effect of puerarin (PR) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced diabetic mice. The fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (Scr), as well as 24-hour urine protein levels were effectively ameliorated in DN mice treated with PR (20, 40, 80mg/kg/day). Furthermore, PR treatment markedly resulted in down-regulation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in kidney. Interestingly, the activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) were increased by PR. An improvement in kidney tissue damage could be observed after PR administration. Further ultrastructural investigation revealed a dramatically ameliorative effect of PR on mitochondrial damage. Meanwhile, the silent information regulator 1 (SIRT1), forkhead box protein O1 (FOXO1) and alpha subunit of peroxisome proliferators-activated receptor-gamma coactivator-1 (PGC-1α) expressions were significantly up-regulated at protein level by PR administration in renal cortex. However, the protein expression of nuclear-factor kappa B (NF-κB) was down-regulated in PR groups. Our present study demonstrates the hypoglycemic and renal protective effects of PR in DN mice, which support its anti-diabetic property. PR exerts its renal protection effect probably via the mechanism of attenuating SIRT1/FOXO1 pathway for renal protection.