Dendrobium mixture (DM) is a patented Chinese herbal medicine indicated which has anti-inflammatory and improved glycolipid metabolism. However, its active ingredients, targets of action, and potential mechanisms are still uncertain. Here, we investigate the role of DM as a prospective modulator of protection against non-alcoholic fatty liver disease (NAFLD) induced by type 2 diabetes mellitus (T2DM) and illustrate the molecular mechanisms potentially involved. The network pharmacology and TMT-based quantitative protomics analysis were conducted to identify potential gene targets of the active ingredients in DM against NAFLD and T2DM. DM was administered to the mice of DM group for 4 weeks, and db/m mice (control group) and db/db mice (model group) were gavaged by normal saline. DM was also given to Sprague-Dawley (SD) rats, and the serum was subjected to the palmitic acid-induced HepG2 cells with abnormal lipid metabolism. The mechanism of DM protection against T2DM-NAFLD is to improve liver function and pathological morphology by promoting peroxisome proliferator-activated receptor γ (PPARγ) activation, lowering blood glucose, improving insulin resistance (IR), and reducing inflammatory factors. In db/db mice, DM reduced RBG, body weight, and serum lipids levels, and significantly alleviated histological damage of liver steatosis and inflammation. It upregulated the PPARγ corresponding to the prediction from the bioinformatics analysis. DM significantly reduced inflammation by activating PPARγ in both db/db mice and palmitic acid-induced HepG2 cells.
Introduction: Yu Nu compound (YNJ) is a traditional Chinese medicine widely utilized to treat type 2 diabetes possibly through mediating autophagy. Abnormal podocyte autophagy and apoptosis could result in podocyte loss in diabetics nephropathy (DN). The mechanism of Yu Nu compound in DN is still unclear. Therefore, the study aims to investigate the effects of Yu Nu compound and analyze the potential mechanism. Methods: Goto-Kakizaki (GK) rats were administered using YNJ with different doses once a day by gavage for 4 weeks. The renal cortex injury was observed by HE staining and electron microscope. Cell apoptosis of renal cortex was analyzed by TUNNEL staining. The mTOR, autophagy-related proteins and apoptosis-related proteins were detected by Western blot or real-time PCR in vivo and vitro. MPC5 cells were exposed to high glucose (HG, 30mM) for 12h to simulate podocyte injury in DN. MPC5 cells were treated by serum containing YNJ with different dosages. Cell activities and apoptosis were, respectively, detected through Cell Counting Kit-8 (CCK8) assay and flow cytometry. Results: The results showed that the medium dose of YNJ had better effects on decreasing blood glucose and improving renal injury in GK rats, followed by decreasing mTOR levels. The autophagy levels were enhanced in renal cortex, accompanied with the increase of cell apoptosis in vivo. Besides, the proteins regulating autophagy and apoptosis were significantly modulated by YNJ in GK rats. Then, we found that the decreasing endogenous mTOR could reverse the effects of YNJ on podocyte apoptosis and autophagy in vivo. Discussion: The study suggested that YNJ recovered normal autophagy and suppressed apoptosis through regulating mTOR. The maintenance of normal basal autophagic activity possibly based on the effect of YNJ on multiple target was essential for maintaining podocyte function.
Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut–brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation.
Background: Yu Nu compound (YNJ) is a traditional Chinese medicine widely utilized to treat type 2 diebetes, which has been reported to regulate autophagy. Abnormal podocyte autophagy and apoptosis could result in podocyte loss in diabetics nephropathy (DN). The mechanism of Yu Nu compound in DN is still unclear. Therefore, the study aims to investigate how Yu Nu compound exerts effects on DN rats.Methods: GK rats were administered using YNJ with different dose once a day by gavage for 4 weeks. The renal cortex injury was observed by HE and electron microscope. Cell apoptosis of renal cortex was analyzed by tunnel staining. The mTOR, autophagy-related proteins and apoptosis-related proteins were detected by Western blot or Real-time PCR in vivo and vitro. MPC5 cells were exposed to high glucose (HG, 30mM) for 12h for simulating podocytes injury in DN. MPC5 cells were treated by serum containing YNJ with different dosage. Cell activities and apoptosis were respectively detected through CCK8 assay and Flow cytometry.Results: The results showed that the medium dose of YNJ has better effects on decreasing blood glucose and improving renal injury in GK rats, followed by decreasing mTOR levels. The autophagy levels were enhanced, accompanied with the increase of cell apoptosis in vivo and vitro. The decreasing endogenous mTOR could reverse the effects of YNJ on cell apoptosis and autophagy.Conclusion : the study suggested that YNJ reduced the excessive autophagy and suppressed apoptosis through regulating mTOR. The maintenance of normal basal autophagic activity possibly based on the effect of YNJ on multiple target was essential for maintaining podocytes function.
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