Background: The gut microbiota plays important roles in the occurrence and development of obesity and diabetes through participating in nutrient absorption and metabolism. Microecological regulation is likely to be key to understanding the effects of Chinese medicine. The Linggui Zhugan (LGZG) formula is a well-known Chinese medicine for controlling obesity in the clinic. However, its pharmacological effects and mechanism of action in diabetes require further exploration. Objective: To evaluate the effects of LGZG on body weight, glycemic control, lipid levels and gut microbiota in high-fat diet-induced diabetic mice. Methods: High-fat diet-induced diabetic mice were subjected to an 8-week protocol of LGZG administration. We then evaluated the pharmacological effects of LGZG and its influence on gut microbes in fecal samples using the 16S rRNA-based microbiome profiling technique. Results: LGZG administration significantly reduced body weight and body fat mass in diabetic mice. Compared with the high-fat diet control group, LGZG favorably influenced blood glucose control, decreased blood glucose levels and increased glucose tolerance, accompanied by an improvement in lipid metabolism. Furthermore, the global community composition and relative abundance of many taxa differed between mice fed chow or a high-fat diet. As expected, LGZG supplementation altered the general community structure of gut microbiota, the Firmicutes/Bacteroidetes ratio, and the relative abundance of certain bacteria, such as Bacteroides, Lactobacillus, Oscillospira and Helicobacter. Conclusion: LGZG effectively controlled obesity and relieved insulin resistance, which may be closely related to its impact on gut microbiota.

Background: Traditional Chinese medicine (TCM) has been used to treat diabetic complications including diabetic retinopathy for many years. Objectives: This review was performed to systematically assess the efficacy and safety of TCM for treating non- proliferative diabetic retinopathy (NPDR). Methods: Retrieval from 7 electronic databases was conducted to determine eligible trials published until March 1, 2018. Randomized controlled trials of NPDR that comparing compound Chinese medicine containing the therapeutic method of activating blood and remove stasis versus controls were included for analysis. Primary outcomes were progression of retinopathy. Secondary outcomes included visual acuity, mean defect of visual field, micro-aneurysms, hemorrhage areas, exudates, capillary nonperfusion areas, hemorheological indicators, oscillatory potentials (Ops), glycated haemoglobin (HbA1c), and adverse events. Data extraction and quality assessment were performed. Results expressing as risk ratios (RRs) or mean differences (MD) were analyzed with a fixed- or random- effect model. I ² statistics were used to assess heterogeneity. Results: A total of 33 trials and 3373 participants were included. Findings revealed that no included studies reported the progression of retinopathy. Compared with conventional medicine, TCM was significantly better at improving visual acuity (MD, −0.10; 95% confidence interval [CI] −0.16 to −0.05) and Ops (MD, −4.68, 95% CI −8.51 to −0.85), and reducing the mean defect of visual field (MD, −1.43; 95%CI, −2.17 to −0.68), micro-aneurysms (MD, −4.51; 95% CI, −6.23 to −2.79), hemorrhage areas (MD, −0.62; 95% CI, −1.06 to −0.19), plasma viscosity (MD, −0.10; 95% CI, −0.20 to 0.00), and HbA1c (MD, −0.22; 95% CI, −0.42 to −0.03). Compared with placebo, TCM was also associated with a decline in the number of microaneurysms (MD, −4.35; 95% CI, −6.25 to −2.45), exudates (MD, −0.17; 95% CI −0.31 to −0.03), capillary nonperfusion areas (MD, −0.18; 95% CI, −0.31 to −0.04), and HbA1c (MD, −0.88; 95% CI, −1.44 to −0.32). Compared with blank groups, TCM was superior at decreasing the mean defect of visual field (MD, −0.87; 95% CI −0.95 to −0.79) and the numbers of micro-aneurysms (MD, −3.35; 95% CI, −4.73 to −1.97). Adverse events were also assessed. Conclusion: Activating blood compound Chinese herbal medicine could help to improve visual acuity, micro-aneurysms and HbA1c. Further trials are needed to provide more reliable evidence.

Background: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and remains the leading cause of blindness in adults. Retinal inflammation is playing a crucial role in the development of DR, and targeting inflammatory mediators is a promising strategy for controlling DR. Here, we investigated compound Chinese medicine Luo Tong formula (LTF) alleviated retinal inflammatory responses in a STZ-induced diabetic rat model. Methods: Sprague–Dawley rats were divided into four groups: control, streptozotocin-induced diabetic, LTF-treated diabetic, and calcium dobesilate (CaD)-treated diabetic rats. Blood samples were collected for blood glucose examination. Hematoxylin–eosin and periodic acid-Schiff staining were conducted for light microscopy observations. Retinal cell apoptosis was detected using the TUNEL assay. Proteins expression was quantified by Western blotting and/or immunohistochemistry, and gene expression was assessed by real-time PCR. Results: Diabetic rats showed significant increases in the expression of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB), and the phospho-p38 mitogen-activated protein kinase (p-p38-MAPK)/p38 MAPK ratio compared to control rats. LTF treatment significantly improved both retinal and pancreatic pathological injury, LTF treatment also inhibited inducible the p-p38 MAPK/p38 MAPK ratio and NF-κB activation and decreased the subsequent induction of the retinal expression of proinflammatory mediators TNF-α, IL-1β, MCP-1 and ICAM-1 compared to diabetic rats. LTF also exhibited a protective effect on islet function. Conclusions: LTF before the onset of DR can alleviate retinal pathological injury, LTF may play an anti-inflammatory role by inhibiting p38-MAPK and then inhibiting NF-κB pathway. But further studies are needed to confirm this conclusion. Trial registration This is an animal experiment, trial registration is not necessary.

Background. Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic β-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. Methods. MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. Results. Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. Conclusion. BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).

Background: Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. Methods/design: This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin–creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. Discussion: We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration: ClinicalTrials.gov, NCT03009864. Registered January 2017.