Catharanthus roseus Combined with Ursolic Acid Attenuates Streptozotocin-Induced Diabetes through Insulin Secretion and Glycogen Storage

Abstract

Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50 mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50 mg/kg p.o., Group 4 as a STZ+UA group orally at 50 mg/kg, Group 5 as a STZ+CREE (25 mg/kg p.o.)+UA (25 mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1 mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P<0.001) reduced to 98.35±2.45 mg/dl in comparison with that in Group 2 (321.75±5.46 mg/dl). The level of plasma insulin in Group 5 increased (13.65±0.10 μU/ml) significantly (P<0.01) as compared with that in Group 2 (05.93±0.31 μU/ml). In Group 5, the level of glycogen in liver was significantly (P<0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P<0.01; P<0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.

Botanical Interventions to Improve Glucose Control and Options for Diabetes Therapy

“…In Wistar rats exposed to STZ (50 mg/kg, single injection), 28 days of ursolic acid treatment (50 mg/kg/day, oral gavage) reduced blood glucose with similar efficacy as glimepiride. Although ursolic acid treatment significantly elevated plasma insulin levels compared to diabetic control animals, circulating levels were not completely restored to non-diabetic control values as observed with glimepiride [186]. Similarly, in diabetic Wistar rats (STZ 30 mg/kg, 2 injections), 14 days of ursolic acid treatment (200 mg/kg/ day, i.p.…”

“…To our knowledge, ursolic acid has not been studied in genetic rodent models of T1DM and T2DM. However, in models of induced hyperglycemia (STZ) and glucose intolerance (HFD), ursolic acid has been shown to exert positive effects on circulating levels of insulin and glucose [185][186][187][188]. Furthermore, studies in patients with metabolic syndrome have also shown anti-diabetic effects [189].…”

The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease

“…In addition to its anti-inflammatory effects, recent studies showed that UA improves insulin resistance and hyperinsulinemia in diet-induced obesity rats [249][250][251]. Indeed, UA administration decreased body weights and blood glucose via angiotensin II type 1 receptor (AT1R)-associated protein 1 (ARAP1)/AT1R pathway in db/db mice [252].…”

Anti-diabetic properties of sadabahar plant

“…When compared to dichloromethane and methanol extracts, which dropped blood glucose levels by 49-58 percent in diabetic rats, the aqueous extract was found to lower blood glucose by roughly 20%. The enhanced glucose consumption in the liver has resulted in the hypoglycemic impact.In a mouse insulinoma cell line, vindoline was discovered to raise insulin levels (MIN6) (Alkreathy HM and Ahmad A, 2020) [2] . Pharmacological studies of alkaloids obtained from C. roseus have been conducted, and a medicine developed from the plant has been sold as a diabetes cure under the brand name Vinculin (Jai Narayan Mishra et al, 2017) [18] .…”