Tecomella undulata Improves Insulin Sensitivity by Attenuating Inflammation and Oxidative Stress in Experimental NASH

Abstract

Background and AimThe pathophysiology of NASH is complex owing to its diverse pathological drivers, and until recently, there were no approved drugs for this disease. Tecomella undulata is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. Experimental ProcedureMice fed with chow diet and normal water (CDNW) or western diet and sugar water (WDSW) for 12 weeks were randomized to receive vehicle control, Saroglitazar, or Tecomella undulata for an additional 12 weeks. Insulin resistance, lipid profiles, histological analysis, and liver enzymes were assessed. The oxidative stress, ER and inflammatory markers were determined by quantitative RT-PCR (qRT-PCR) and western blot analysis. Results and ConclusionThe administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in WDSW mice but had no effect on CDNW mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced ER stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were on par with Saroglitazar, the approved drug used to treat human NASH and positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH in humans.