The hypoglycemic activity of fenugreek may be associated with the galactomannan fiber and saponin components that reduce gastrointestinal glucose and cholesterol absorption, and increase bile acid excretion ⁽¹⁴⁾. 4-Hydroxyisoleucine, an amino acid constituent, potentiates insulin secretion in non-insulin-dependent diabetic rats when administered intraperitoneally ⁽¹⁵⁾. In addition to lower fasting and postprandial glucose levels, fenugreek-treated diabetic rats had higher hemoglobin, GSH, and plasma antioxidant levels and lower glycosylated hemoglobin, plasma lipids, and TBARS levels than diabetic controls ⁽⁴⁾. Dietary fenugreek also normalizes the activities of glucose and lipid-metabolizing enzymes in diabetic rats ⁽³⁾. Other animal studies suggest dietary fenugreek increases serum T4, liver GSH, glyoxalase I, and GST activities, and decreases T3 levels and T3/T4 ratio ^{(17) (18) (19)}. In humans, fenugreek intake was associated with an increase in molar insulin binding sites of erythrocytes, which may enhance glucose utilization ⁽¹⁶⁾.

Fenugreek has also been studied for its anticancer potential. In MCF-7 estrogen receptor-positive breast cancer cells, a fenugreek extract induced cell cycle arrest and apoptosis ⁽⁹⁾. Dioscin, a steroidal saponin isolated from fenugreek, suppressed cell viability of ovarian cancer cells by regulating VEGFR2, PI3K, phosphorylated AKT and phosphorylated p38 MAPK signaling pathways ⁽³⁹⁾.

In a case report of serotonin syndrome likely caused by an interaction between fenugreek and sertraline, the authors point to animal studies that posit 4-hydroxyisoleucine may increase serotonin turnover in the brain ⁽⁴⁷⁾.