TABLE 2.

In vitro, in vivo studies and mechanism of action for treating diabetes with fenugreek and diosgenin.

Plant/Part and Location	Bioactive compound/Extract	Study	Clinical trial	Mode of action/Inference	Reference
Trillium govanianum, India	Sitagliptin, Diosgenin, Borassoside, Protodioscin	In vitro	−	Borassoside E (IC50 7.15 ± 1.78°μM), protodioscin (IC50 6.72 ± 0.04°μM), and diosgenin (IC50 12.75 ± 2.70°μM) inhibiting the activity of α-amylase, α-glucosidase, and dipeptidyl peptidase IV, respectively.	(100)
Gnidia glauca (Leaves, stems and flowers), Dioscorea bulbifera (Bulbs) Maharashtra, India	Petroleum ether, ethyl acetate and methanol extracts of plant	In vitro	−	Petroleum ether extract of G. glauca flower inhibit α-amylase by 78.56% and ethyl acetate extract of D. bulbifera bulbs inhibit α-amylase by 73.39%. Can use to treat type II diabetes mellitus.	(101)
Fenugreek (Trigonella foenum-graecum L. seed), London	Crude ethanolic extract B, further sub-fractions of B (saponin-free C, saponin D and sapogenin E) and a gum fiber fraction F	In vitro	−	Inhibited glucose-uptake at 0.33 and/or 3.3°mg/mL (p < 0.001).	(63)
Fenugreek (Trigonella foenumgraecum) seeds, India	80% ethanol by UAE method for 5 min produced 13.78 g diosgenin equivalent/100 g	In vitro	−	Inhibit α-amylase (IC50 crude = 371.7°μg/ml, IC50 defat = 370.5°μg/ml). Diosgenin assist in delaying glucose diffusion.	(48)
Fenugreek seed and Balanites fruit, Egypt	Methanolic extract	α-amylase (in vitro), starch absorption (in vivo)	STZ-diabetic rats (50 mg/kg) normal (n = 10) and diabetic groups (n = 45)	Fenugreek extract administrated STZ-diabetic mice, and decreased liver glucose-6-phosphatase activity, restored liver glycogen content, cut blood glucose levels by 58% and inhibit intestinal α-amylase activity.	(102)
Trigonella foenum-graecum	Saponin fraction contains diosgenin	In vivo	Four-week-old male KK-Ay/Ta Jcl mice administrated high-fat diet supplemented with 0.5 or 2.0% fenugreek	In HepG2 cells, diosgenin (5 and 10°μmol/L) reduced TG accumulation and the expression of genes related to lipogenesis and helpful for the controlling of diabetes-related hepatic dyslipidemias.	(103)
Fenugreek seed, Hungary	Diosgenin	In vivo	Diosgenin in three different doses (1°mg/bw kg, 10°mg/bw kg, and 50 mg/bw kg) and fenugreek seed (0.2 g/bw kg) were administered orally for 6 weeks to Male Wistar rats.	Rats given 1 mg/kg diosgenin with fenugreek seed showed better peripheral insulin sensitivity as evidenced by higher insulin sensitivity index and high metabolic clearance rates of insulin. Fenugreek seed regulates hormones in synchronised action with IGF-1, which is crucial for maintaining appropriate blood sugar levels.	(95)
Fenugreek seed, Puducherry, India	Methanolic extract contain trigonelline and diosgenin	In vivo	Male Sprague–Dawley rats (8−10 weeks with 150−200 g BW) administering STZ (dose of 35 mg/kg BW). Group 1 = control (NPD), Group 2 = T2DM model rats (HFD followed by STZ administration), Group 3, 4, 5 T2DM rats were given 300 mg FSE/kg BW, 40 mg of trigonelline/kg BW, 60 mg of diosgenin/kg BW, respectively.	Rats treated with FSE (217.11 ± 2.36 mg/dL), trigonelline (275.13 ± 24.88 mg/dL), and diosgenin (218.32 ± 37.9 mg/dL) showed significant reduction in glucose levels as compared to T2DM group (506.94 ± 7.06 mg/dL). T2DM rats showed two- to threefold increase in ER chaperones Bip, protein disulfide isomerase (PDI), as well as ER stress-related proapoptotic markers CHOP, Caspase12, and Caspase3 in the liver, and increased lipid peroxidation (LPO) and decreased antioxidant levels.	(104)
India	Diosgenin	In vivo	Male albino Wistar rats (BW = 150−180g) fed with HFD and administered with STZ (35 mg kg–1), Group 1: Control, Group 2: Diabetic control, Group 3: Diabetic rats administered with diosgenin (60 mg kg–1b.w–1), Group 4: Diabetic rats administered with glyclazide (5 mg kg–1 b.w–1).	Administration of diosgenin to HFD-STZ diabetic rats depicted a decrease in body weight gain, blood glucose (118.9 ± 9.92 mg/dL), insulin (14.65 ± 2.4°μU ml–1), insulin resistance (2.01 ± 0.32) and modulated lipid profile in plasma and tissues as compared to HFD-STZ Diabetic control rats.	(105)
Fenugreek, India	Diosgenin	In vivo	Male Wistar rats (BW = 150−180 g) administrated 55 mg/kg streptozotocin with three different doses (15, 30, and 60 mg/kg BW) of diosgenin	Rats given 30 mg/kg BW diosgenin had lower serum Glucose 6-phosphatase levels (106.1 ± 2.9) compared to diabetic rats (155.0 ± 6.3) and higher hexokinase levels (15.8 ± 2.03) compared to diabetic rats (8.09 ± 2.1), which improved glycogen metabolism and lowered blood glucose levels.	(84)
China	Diosgenin	In vivo	Female mice were administered orally with DSG (10 mg/kg b.w. and 20 mg/kg b.w) using an intra-gastric tube	Diosgenin decreases gestational diabetes in db/ + pregnant mice, by improvements in glucose and insulin resistance, a decline in fasting blood glucose and insulin levels, and an increase in hepatic glycogen content.	(106)
Fenugreek seed, India	−	In vivo	Sixty patients having Type 2 diabetes divided into two groups. Group 1 = 30 patients received 10°gm of fenugreek seeds soaked in hot water every day, Group 2 = 30 patients didn’t received fenugreek seeds.	Reduction in fasting blood glucose levels in the 5th month in the study group (P = 0.0421) while significant reduction in HbA1C in the 6th month (P = 0.0201)	(107)