Anti-hypoglycemic and hepatocyte-protective effects of hyperoside from Zanthoxylum bungeanum leaves in mice with high-carbohydrate/high-fat diet and alloxan-induced diabetes

Abstract

The development of diabetes mellitus (DM) is accompanied by hyperglycemia-induced oxidative stress. Hyperoside is a major bioactive component in Zanthoxylum bungeanum leaves (HZL) and is a natural antioxidant. However, the effects of HZL on DM and its mechanisms of action remain undefined. The present study evaluated the anti-hypoglycemic and hepatocyte-protective effects of HZL in mice with diabetes induced by a high-carbohydrate/high-fat diet (HFD) and alloxan. We also aimed to eludicate the underlying mechanisms. Our resutls demonstrated that the administration of HZL significantly reduced body weight gain, serum glucose levels and insulin levels in diabetic mice compared with the vehicle-treated mice. In addition, the levels of dyslipidemia markers including total cholesterol, triglyceride and low-density lipoprotein cholesterol in the HFD-treated mice were markedly decreased. Further experiments using hepatocytes from mice revealed that HZL significantly attenuated liver injury associated with DM compared with vehicle treatment, as evidenced by lower levels of alanine aminotransferase and aspartate aminotransferase in serum and by lower levels of lipid peroxidation, nitric oxide content and inducible nitric oxide synthase activity in liver tissues. Nuclear factor-κB (NF-κB) and mitogen-associated protein kinase (MAPK) signaling pathways were investigated to elucidate the molecular mechanisms responsible for the protective effects of HZL against diabetic liver injury. The results indicated that HZL inhibited the phosphorylation of p65/NF-κB, MAPK (including p38, JNK and ERK1/2) and activating transcription factor 3 protein expression, with an additional suppression of Bax, cytochrome c, caspase-9 and caspase-3 in the liver tissues of diabetic mice. Taken together, our findings suggest that HZL, which was effective in inhibiting oxidative stress-related pathways may be beneficial for use in the treatment of DM.

Hyperoside protects against cerebral ischemia-reperfusion injury by alleviating oxidative stress, inflammation and apoptosis in rats

“…Hyperoside, also known as quercetin-3-O-b-D-galactopyranoside, is found in the fruit or whole plant of Hypericaceae, Rosaceae, Campanulaceae and Celastraceae plants, and belongs to the group of flavonol glycosides, with hepatoprotective, anticancer, bacteriostatic and memory-improving properties [7][8][9]. In addition, hyperoside can protect against myocardial I/R injury by inhibiting endoplasmic reticulum stress and activating the Nrf2 signalling pathway [10].…”

Simultaneous Enrichment and Separation of Four Flavonoids from Zanthoxylum bungeanum Leaves by Ultrasound‐Assisted Extraction and Macroporous Resins with Evaluation of Antioxidant Activities

“…In our previous studies, according to the results of the structure–activity relationship of nine flavonoids from Z. bungeanum leaves (Zhang, Wang, Yang, Zhou, & Zhang, ) and the correlation between the chromatographic fingerprint and antioxidant activity of the 22 subsequent fractions of Z. bungeanum leaves ethanol extracts (Zhang, Luo, Wang, He, & Li, ; Zhang, Luo, & Wang, ), it was found that quercitrin, hyperoside, rutin, and afzelin were the dominant flavonoids, which played a major role in antioxidant and antimicrobial activity. Furthermore, hyperoside from Z. bungeanum leaves also exerts many bioactivities, such as antiproliferative effects against SW620 (Zhang, Dong, Zhang, & Zhang, ) and antihyperglycemic and hepatocyte‐protective effects (Zhang, Wang, Dong, Yu, & Zhang, ). Therefore, in view of these benefits, it is necessary to establish a simple, low‐cost and efficient purification method for the four flavonoids from Z. bungeanum leaves.…”

Effect of Hyperoside on the Inhibition of Adipogenesis in 3t3-L1 Adipocytes

“…This cell line is a well-defined in vitro model for studying the adipogenesis mechanism. In the literature, both in vivo and in vitro anti-obesity activity of hyperoside has not been studied sufficiently (13,14). In vitro models allow the investigation of the effects of the molecule on both preadipocytes and adipocytes at the molecular level.…”