Dendrobium mixture ameliorates type 2 diabetes mellitus with non-alcoholic fatty liver disease through PPAR gamma: An integrated study of bioinformatics analysis and experimental verification

Abstract

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.

Sclareol ameliorates liver injury by inhibiting nuclear factor-kappa B/NOD-like receptor protein 3-mediated inflammation and lipid metabolism disorder in diabetic mice

“…Growing evidence shows that NAFLD is a common feature observed in T1DM, T2DM, and even cardiovascular diseases. 7 , 40 , 41 These diseases are all associated with an increased burden of inflammation. 16 , 41 - 43 Inflammation is a crucial contributor to the development of liver injury in diabetes by promoting the secretion of pro-inflammatory cytokines, such as TNFα and IL-6.…”

Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway

“…The study design for the animal model and experimental intervention followed our previous study [ 15 ]. Ten male non-diabetic db/m mice (8 weeks of age, weighing 18–20 g) and 20 male obese and T2DM db/db mice (8 weeks of age, weighing 36–38 g) were purchased from Changzhou cavens experimental animal Co., Ltd.…”

“…After anesthesia, the intact liver tissues were removed, washed and fixed in 4 % paraformaldehyde/phosphate-buffered saline. The histological staining of liver follows the steps in our previous study [ 15 ]. The specimens were embedded in paraffin and cut into thin slices (5 μm thick).…”

“…The method follows a previous study [ 15 ]. Frozen sections of liver tissue obtained from mice and crawling slices of HepG2 cells treated with various post-administration DM serum were subjected to fractionation using 60 % isopropanol for 10 min.…”

“…It has also been demonstrated potential in mitigating complications associated with diabetic nephropathy [ 13 ] and diabetic cognitive dysfunction [ 14 ], in animals. Our recent study has highlighted the therapeutic potential DM in ameliorating T2DM with NAFLD in an integrated study of bioinformatics analysis and experimental verification [ 15 ]. The underlying molecular mechanism was associated with peroxisome proliferator-activated receptor ϒ (PPAR-ϒ) activation.…”