Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and dysfunction of RyR2 in the heart of streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms. METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed. RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats. CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.

The inhibitory effects of Xiao-Gao-Jiang-Zhuo-containing serum on adipogenesis in 3T3-L1 preadipocytes.

BACKGROUND: Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro. METHODS: Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes. RESULTS: XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells. CONCLUSION: XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity.

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats.

CONTEXT: Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax ginseng C.A. Meyer (Araliaceae)]. OBJECTIVE: This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-ß, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed. RESULTS: There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-ß (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-ß (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury. DISCUSSION AND CONCLUSIONS: These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.

Probiotics for the improvement of metabolic profiles in patients with metabolic-associated fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

Objective: This meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy of probiotics in the treatment of metabolic-associated fatty liver disease (MAFLD) mainly in terms of liver function, glucose and lipid metabolism, and inflammation. Methods: RCTs were searched on PubMed, Web of Science, Embase, and the Cochrane Library until June 2022. A meta-analysis was performed on the therapeutic efficacy of probiotics on liver function, glucose and lipid metabolism, and inflammatory biomarkers by using RevMan 5.4 software. Results: A total of 772 patients from 15 studies were included in the analysis. The methodological quality varied across studies. We found that adding probiotic therapies could reduce the levels of alanine aminotransferase [mean difference (MD): -11.76 (-16.06, -7.46), p < 0.00001], aspartate aminotransferase (MD: -9.08 (-13.60, -4.56), p < 0.0001], γ-glutamyltransferase [MD: -5.67 (-6.80, -4.54), p < 0.00001] and homeostasis model assessment-insulin resistance [MD: -0.62 (-1.08, -0.15), p = 0.01], in patients with MAFLD compared with those in control individuals. However, there was no statistically significant improvement in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, C-reactive protein and tumor necrosis factor α among patients with MAFLD. Subgroup analyses showed that other key factors, such as age, participants' baseline body mass index, and the duration of intervention, may influence probiotic therapy outcomes. Conclusion: There is promising evidence that probiotic supplementation can reduce liver enzyme levels and regulate glycometabolism in patients with MAFLD. Further rigorous and long-term trials exploring these novel therapeutic perspectives are warranted to confirm these results.

Effects of Berberine on Diabetes and Cognitive Impairment in an Animal Model: The Mechanisms of Action.

Diabetes is a group of metabolic disorders with an increased risk of developing cognitive impairment and dementia. The hippocampus in the forebrain contains an abundance of insulin receptors related to cognitive function and plays an important role in the pathophysiology of neurodegenerative disorders. Berberine from traditional Chinese medicine has been used to treat diabetes and diabetic cognitive impairment, although its related mechanisms are largely unknown. In this study, a STZ diabetes rat model feeding with a high-fat diet was used to test the effects of berberine compared with metformin. Oral glucose tolerance and hyperinsulinemic-euglycemic clamp were used for glucose metabolism and insulin resistance. The Morris water maze was used to observe the compound effects on cognitive impairment. Serum and hippocampal [Formula: see text]-amyloid peptide (A[Formula: see text], Tau and phosphorylated Tau protein deposition in the hippocampi were measured. The TUNEL assay was used to detect the neuronal apoptosis, supported by histomorphological changes and transmissional electron microscopy (TEM) image. Our data showed that the diabetic rats had a significantly cognitive impairment. In addition to improving glucose metabolism and reducing insulin resistance, berberine significantly improved the cognitive function in the rat. Berberine also effectively decreased the expression of hippocampal tau protein, phosphorylated Tau, and increased insulin receptor antibodies. Moreover, berberine downregulated the abnormal phosphorylation of A[Formula: see text] and Tau protein and improved hippocampal insulin signaling. The TUNEL assay confirmed that berberine reduced hippocampal neuronal apoptosis supported by TEM. Thus, berberine significantly improved the cognitive function in diabetic rats by changing the peripheral and central insulin resistance. The reduction of neuronal injury, A[Formula: see text] deposition, abnormal phosphorylation of Tau protein, and neuronal apoptosis in the hippocampus were observed as the related mechanisms of action.

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats.

Rhizoma coptidis (Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal's depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.