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Fenugreek seed extract and its phytocompounds- trigonelline and diosgenin arbitrate their hepatoprotective effects through attenuation of endoplasmic reticulum stress and oxidative stress in type 2 diabetic rats

Mayakrishnan, Tharaheswari, Nakkala, Jayachandra Reddy, Jeepipalli, Syam Praveen Kumar, Raja, Kumar, Khub Chandra, Varshney, Mohan, Vasanth Kumar, Sadras, Sudha Rani
European food research & technology 2015 v.240 no.1 pp. 223-232
antioxidants, apoptosis, blood serum, c-peptide, chemical constituents of plants, diosgenin, endoplasmic reticulum, fenugreek, food research, glycogen, hepatoprotective effect, high fat diet, hyperglycemia, insulin resistance, lipid peroxidation, liver, mechanism of action, noninsulin-dependent diabetes mellitus, oxidative stress, protein disulfide-isomerase, proteins, rats, streptozotocin, triacylglycerols, trigonelline
Fenugreek seed and some of its phytoconstituents are known to possess hypoglycemic and hypolipidemic properties but their mode of action in insulin target tissues remains to be elucidated. As hepatic insulin resistance contributes to the development of type 2 diabetes mellitus (T2DM), the protective effects of fenugreek seed extract (FSE) and two of its phytoconstituents-trigonelline and diosgenin were evaluated in T2DM rats with special focus on changes in endoplasmic reticulum (ER) stress and oxidative stress markers in liver. Trigonelline and diosgenin content in FSE were quantified by HPTLC. T2DM was induced in male Sprague–Dawley rats by feeding high-fat diet and administration of low-dose streptozotocin. T2DM rats exhibited hyperglycemia and significantly reduced serum C-peptide levels. Liver damage in T2DM rats was marked by significantly elevated levels of liver marker enzymes in serum, liver triglycerides (TGs), and reduced liver glycogen and was further confirmed by histological analysis. T2DM rats also displayed twofold–threefold increase in the levels of ER chaperones Bip, protein disulfide isomerase (PDI) as well as ER stress associated proapoptotic markers CHOP, Caspase12 and Caspase3 in liver along with elevated lipid peroxidation (LPO) and reduced antioxidant levels. Promisingly, FSE, trigonelline, and diosgenin were found to exhibit protective effects individually and brought about significant reduction in serum enzymes, liver TGs, LPO, expression of liver ER stress marker proteins, and significant increase in liver glycogen content and antioxidants. Histological analysis also supported their protective effects suggesting that FSE and its phytoconstituents alleviate T2DM associated liver damage by normalizing ER stress and oxidative stress.