Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

Abstract

BackgroundPre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity.MethodsObese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR).ResultsThe results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat.ConclusionsTaken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.

Erchen Decoction Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats

“…This has sparked a resurgence in the targeting of BAT to treat obesity and type 2 diabetes. Many traditional Chinese medicine drugs have been shown to activate BAT to prevent metabolic disorders in high-fat diet-fed mice and rats [29][30][31]. According to the theory of TCM, highfat diet-induced Pi deficiency leads to skeletal muscle dysfunction, while ECD increases Pi and has beneficial metabolic effects on high-fat diet-fed mice partially due to the upregulation of the protein levels of lipoprotein lipase in skeletal muscle.…”

Potential lipolytic regulators derived from natural products as effective approaches to treat obesity

“…All of these reduce neutral lipids in the cytosol and increase FFA release. Madecassoside ( 94 ), tanshinone 1 ( 95 ), triptolide ( 58 ), crocin ( 96 ), guggulsterone ( 97 ), bilobalide ( 98 ), α-cubebenoate ( 99 , 100 ), betulinic acid ( 93 ), fucoxanthinol ( 101 ), widdrol ( 102 ), ginkgolide C ( 103 ), and illudins C2 and C3 ( 104 ) could all potentially treat obesity either by inhibiting adipocyte differentiation and lipogenesis or by increasing lipolysis. The LDAP ( 88 – 90 ), PKA ( 89 , 90 ), AMPK ( 96 , 98 ), and PKC-MEK-ERK ( 102 ) pathways are involved in the lipolytic mechanisms induced by these compounds ( Table 3 ).…”