Hypolipidemic and antioxidant potential of Trigonella foenum-graecum leaf extract via MAPK/JNK signaling pathway in high-fat diet-induced obese rats

Objective: To determine the qualitative and quantitative phytochemical components in the aqueous leaf extract of Trigonella foenum-graecum L. (AqE-TFG) and evaluate its therapeutic potential against high-fat diet-associated dyslipidemia in high-fat diet-induced obese rats. Methods: A total of 24 healthy adult male albino rats were randomly divided into 4 groups ( n =6): Group 1 (normal control), Group 2 (untreated dyslipidemic control), Group 3 and 4 (low and high dose treatments of AqE-TFG 250 mg/kg and 500 mg/kg). Blood samples were collected for the estimation of lipid profile, oxidative markers, biochemical parameters, and histopathology of adipose tissue. Gene expression analysis was performed using qRT PCR. Results: AqE-TFG showed antioxidant activity (IC 50 = 4.82 μg/mL). HPLC analysis showed the presence of sinapic acid, p -coumaric acid, gallic acid, salicylic acid, kaempferol, ferulic acid, chlorogenic acid, quercetin, and HB acid. AqE-TFG remarkably inhibited body weight gain and restored the lipid profile. Furthermore, AqE-TFG elevated superoxide dismutase and catalase levels. Besides, AqE- TFG significantly downregulated mRNA expression levels of dual oxidase-related genes ( Duox, Duoxa-1, Duox2 ) and downstream MAPK/JNK signaling cascade genes ( MAPK8, Traf4, Traf6 ). Adipose tissue histology showed well-organized, intact adipocytes in treatment groups. Conclusions: AqE-TFG has both preventive and therapeutic effects against high-fat diet-induced dyslipidemia. AqE-TFG could enhance antioxidant defense and restore histopathological lesions via MAPK/JNK signaling pathway.