TABLE 2.

Characteristics of selected studies on the effects of Piper sarmentosum Roxb. on diabetes mellitus.

Study design	Plant source	Plant parts	Type of extract	Phyto-chemical(s)	Results	Outcomes	References
In vitro study. Antidiabetic activity was measured using α-glucosidase inhibitory activity.	Selangor, Malaysia	Leaf	Ethanol	Catechin. Naringin	PS at 1,000 μg/ml did not inhibit α-glucosidase activity.	PS has no antidiabetic activity.	Sallehuddin et al. (2020)
In vitro study. Antidiabetic activity was evaluated by α-glucosidase and α-amylase inhibitory activity.	Chiangrai province, Thailand	Leaf	Aqueous	Caffeic acid p-Coumaric acid.	PS showed α-glucosidase inhibitory activity but did not show inhibition against α -amylase activity.	PS has antidiabetic effect by inhibiting α-glucosidase activity.	Wongsa et al. (2012)
In vivo animal study. Twenty-four male, Sprague Dawley rats were divided into four groups (n = 6) including non-diabetic control, non-diabetic treated with PS (0.125 g/kg/day), untreated diabetic (induced with single intramuscular injection of 50 mg/kg STZ) and diabetic treated with PS (0.125 g/kg/day). Treatment with PS was started 4 weeks after STZ injection, for a total of 28 days via intragastric tube. SBP was measured using tail-cuff method. The rat’s liver was collected for morphological analysis.	Negeri Sembilan, Malaysia	Leaf	Aqueous		-PS decreased the SBP of streptozotocin-induced diabetic rats (p < 0.05). -Compared to untreated diabetic rats, treatment with PS increased the liver weight (6.03 ± 0.39 g vs. 10.23 ± 0.27 g, p < 0.05) and reversed the diabetes-induced degenerative changes in the liver tissues as evidenced by absence of nuclear deformation in the of hepatocytes, less hyperemic areas in the sinusoids and less necrosis and vacuolization in the liver.	PS has a positive effect on diabetes and its complications.	Thent and Das (2015)
In vivo animal study. Fifty adult male mice (ICR strain, 8-week-old) were randomly divided into five groups (n = 6 for References group and n = 11 for diabetic groups) including non-diabetic control, untreated diabetic (induced with intraperitoneal injection of 6 mg/100 g BW STZ), diabetic treated with glibenclamide (1 mg/100 g BW/day orally as positive control), diabetic treated with PS1 (60 mg/100 g BW/day orally) and diabetic treated with PS2 (100 mg/100 g BW). Treatments were administered for 21 days. Fasting blood glucose (FBG) level was measured by glucometer via blood from the tail artery. Plasma was analysed for insulin levels. Pancreas was also assessed histologically.	Khon Kaen Province, Thailand	Leaf	Aqueous		Compared with untreated diabetic rats, diabetic rats treated with PS had: - Greater change in FBG (+46.01% vs. -32.75%). - Higher insulin level (14.19 ± 2.95 IU/L vs. 21.36 ± 2.53 IU/L, p < 0.05). - Increase in size and decrease in number of dead cells in the pancreatic islets. - PS was as potent as glibenclamide in increasing insulin level.	PS has hypoglycemic activities by increasing insulin secretion and improving pancreatic islet function.	Luangpirom et al. (2014)
In vivo animal study. Eighteen male Sprague Dawley rats were randomly divided into three groups (n = 6) including nondiabetic control, untreated diabetic (induced with single intramuscular injection of 50 mg/kg STZ) and diabetic treated with PS (0.125 g/kg/day orally). Treatment with PS was started 10 days following STZ induction and continued for 28 days. Body weight and kidney weight index were recorded. FBG was measured using glucometer from the tail vein. Kidneys were collected for histomorphometric and histological analysis.	Selangor, Malaysia	Leaf	Aqueous		- PS did not have significant effect on the body weight, kidney weight index and FBG of diabetic rats. - PS attenuated the histological changes in the diabetic rat’s kidney as evidenced by less contracted glomeruli, mild inflammatory cells infiltration, reduced urinary space size and absence of glomerular membrane thickening.	Antihyperglycemic activity of PS prevents further progression of diabetic nephropathy.	Hussan et al. (2013)
In vivo animal study. Twenty-four male Sprague Dawley rats were randomly divided into four groups (n = 6) including nondiabetic control (normal saline), nondiabetic treated with PS (0.125 g/kg/day orally), untreated diabetic (induced with single intramuscular injection of 50 mg/kg STZ) and diabetic treated with PS (0.125 g/kg/day orally). Treatments were administered for 28 days. The rat’s cardiac and aortic tissues were collected for histological analysis.	Negeri Sembilan, Malaysia	Leaf	Aqueous		Treatment of diabetic mice with PS caused less degenerative changes in the myocardium and aortic tissues as evidenced by lack of connective tissue deposit in the myocardium, reduced tunica media thickness, reduced tunica intima to tunica media ratio and less disruption of elastic fibre in the tunica media layer of the aorta.	PS has beneficial effect on diabetes by reducing degenerative changes in the myocardium and aorta.	Thent et al. (2012a)
In vivo animal study Thirty-two male Sprague Dawley rats were randomly divided into four groups (n = 8) including nondiabetic control (normal saline), nondiabetic treated with PS (0.125 g/kg/day orally), untreated diabetic (induced with single intramuscular injection of 50 mg/kg STZ) and diabetic treated with PS (0.125 g/kg/day orally). Treatments were started 28 days following diabetes induction for 28 days continuously. The body weight was recorded. Urine and blood glucose levels were measured by Combur test and glucometer, respectively. The rat’s left ventricular cardiac tissue and proximal aorta were analyzed under the electron microscope.	Negeri Sembilan, Malaysia	Leaf	Aqueous		Compared to untreated diabetic rats, PS supplementation to diabetic rats caused: - Higher body weight (178 ± 10.91 g vs. 231 ± 13.52 g, p < 0.05). - Lower FBG level (31.9 ± 1.72 mmol/L vs. 23.2 ± 2.24 mmol/L, p < 0.05). - Lower urine glucose level. - Less irregular arrays of myofibrils within the cardiac sarcomere. - Less disrupted cardiac muscle fibres. - Intact cardiac mitochondria with reduced mitochondrial size and cytoplasmic spaces. - Less disruption of the elastic lamina, decreased proliferation of smooth muscle cells and presence of the endothelial cells in the proximal aorta.	PS has antidiabetic effect and restores ultrastructural integrity of the diabetic cardiovascular tissues.	Thent et al. (2012b)
In vivo animal study. Male Wistar rats (5 weeks old) were divided into five groups (n = 6–8) including nondiabetic control, untreated diabetic (induced with single intraperitoneal injection of 75 mg/kg STZ), diabetic treated with glibenclamide (5 mg/kg orally), diabetic treated with PS1 (0.125 g/kg orally) and diabetic treated with PS2 (0.250 g/kg orally). Treatments were administered for 7 days. Fasting plasma glucose level and oral glucose tolerance test (OGTT) were determined.	Bangkok, Thailand	Whole plant	Aqueous, methanol soluble fraction and methanol insoluble fraction of aqueous extract.		- Single dose of PS did not reduce the blood glucose but repeated administration of 0.125 g/kg PS for 7 days produced significant decrease in the plasma glucose of diabetic rats. - Hypoglycemic effect of the methanol soluble fraction of PS aqueous extract was more potent than the aqueous extract.	PS has hypoglycemic effect.	Peungvicha et al. (1998)

FBG, fasting blood glucose; OGTT, oral glucose tolerance test; PS, Piper sarmentosum Roxb.; SBP, systolic blood pressure; STZ, streptozotocin.