Background: Accumulated experimental evidence suggests that resveratrol may have an effect on diabetic nephropathy by inhibiting inflammation and decreasing oxidative stress. However, the credibility of the evidence for this practice is unclear. Thus, we aimed to perform a systematic review and meta-analysis of animal studies to evaluate the antioxidant and anti-inflammatory properties of resveratrol when used in the treatment of diabetic nephropathy.Methods: Electronic bibliographic databases including PubMed, EMBASE, and Web of Science were searched for relevant studies. The methodological quality of animal studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Risk of Bias (SYRCLE’s RoB) tool. A meta-analysis was performed based on the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.4 software. This study was registered within International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42021293784.Results: Thirty-six qualified studies involving 726 animals were included. There was a significant association of resveratrol with the levels of blood glucose (BG), serum creatinine (Scr), blood urea nitrogen (BUN), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and interleukin-1β (IL-1β). Nevertheless, resveratrol treatment did not effectively decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, more remarkable antioxidant and hypoglycemic effects were observed in type 2 diabetic nephropathy rather than in type 1 diabetic nephropathy based on subgroup analysis.Conclusion: In this meta-analysis, resveratrol can exert its antioxidant activities by reducing the levels of MDA and recovering the activities of SOD, CAT, GSH, and GPx. With regard to pro-inflammatory cytokines, resveratrol had a positive effect on the reduction of IL-1β. However, the analysis indicated that resveratrol had no effect on IL-6 and TNF-α levels, probably because of the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatory properties of resveratrol, but its relationship with the levels of some inflammatory cytokines such as IL-6 and TNF-α in animals with diabetic nephropathy needs further elucidation.

Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-clinical animal data to assess the current evidence for rhein effects and mechanisms in treating diabetic nephropathy.Methods: The databases of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP information database, Wanfang Data Information Site, and Chinese Biomedical Literature were searched for this review. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A metaanalysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 12.0 software. This study was registered with PROSPERO, number CRD42018105220.Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P < 0.05), serum creatinine (Scr) (P < 0.05), urine protein (P < 0.05), kidney tubules injury index (P < 0.05), relative area of kidney collagen (P < 0.05), transforming growth factor-β 1 (P < 0.05), malondialdehyde (P < 0.05), and superoxide dismutase (P < 0.05) compared with that in the control group. No significant association between rhein and endothelin (P > 0.05) was found. Subgroup analysis showed that the hypoglycemic effect of rhein on type 2 diabetic nephropathy was better than on type 1 diabetic nephropathy (P < 0.05).Conclusions: These findings suggested that rhein has beneficial effects on animal models of diabetic nephropathy, and that the mechanisms are mostly involved with ameliorating levels of TGF-β 1 , renal fibrosis, metabolism, and oxidative stress status. However, some factors such as possible publication bias, methodological quality, and sample size may affect the accuracy of positive findings. These limitations suggested Frontiers in Pharmacology | www.frontiersin.org Rhein for Diabetic Nephropathy Hu et al.that a cautious interpretation of the positive results of this systematic review and metaanalysis is necessary. Therefore, high methodological quality and well-reported animal experiments are needed in future research.

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Citri Reticulatae Pericarpium (CRP), also known as “chenpi”, is the most common qi-regulating drug in traditional Chinese medicine. It is often used to treat cough and indigestion, but in recent years, it has been found to have multi-faceted anti-cancer effects. This article reviews the pharmacology of CRP and the mechanism of the action of flavonoids, the key components of CRP, against cancers including breast cancer, lung cancer, prostate cancer, hepatic carcinoma, gastric cancer, colorectal cancer, esophageal cancer, cervical cancer, bladder cancer and other cancers with a high diagnosis rate. Finally, the specific roles of CRP in important phenotypes such as cell proliferation, apoptosis, autophagy and migration–invasion in cancer were analyzed, and the possible prospects and deficiencies of CRP as an anticancer agent were evaluated.

Introduction: Hyperglycemia is closely associated with the occurrence of diabetic complications, especially for patients with type 2 diabetes mellitus. Clinical trials indicated that walking exercise could improve glycemic control in patients with type 2 diabetes mellitus, but it is difficult to draw definitive and reliable conclusions due to the small sample size and possible exaggerated efficacy of various individual clinical trials. Therefore, we will conduct systematic review and meta-analysis to assess the current evidence for the efficacy of walking on glycemic control. Methods and analysis: The databases of PubMed, EMBASE, Web of Science and Cochrane Library will be searched for this review. Cochrane risk-of-bias assessment tool will be applied to assess the risk of bias of included studies. A meta-analysis will be performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 14.0 software. Subgroup analysis will be conducted to investigate the sources of heterogeneity. Sensitivity analysis will be performed to assess the reliability and stability of the meta-analysis. Publication bias and small-study effects will be evaluated by a funnel plot and Eggers test if there are at least 10 studies. Additionally, the quality of evidence for this review will be assessed by Grades of Recommendations Assessment, Development and Evaluation (GRADE). Results: This systematic review and meta-analysis will be to assess the efficacy of walking exercise on glycemic control. Conclusion: We will provide strong evidence to determine whether walking can improve glycemic control in patients with type 2 diabetes mellitus. This study is supposed to provide references for clinical trials and patients with type 2 diabetes mellitus. Ethics and dissemination: This study does not require ethical approval. The results of this review will be published in a peer reviewed journal. INPLASY registration number: INPLASY202090046.