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Background: The global epidemic of diabetes mellitus (DM) has become a severe metabolic disorder and a threat to public health. Medicinal plants as a remedy for managing diabetes is accepted worldwide due to their long-term effectiveness and fewer side effects, mainly attributed to the phytochemicals. Paris polyphylla is a valuable medicinal herb endowed with steroidal saponins of therapeutic importance. The plant is popularly used as an anticancer agent. However, the antidiabetic potential of P. polyphylla has not been explored. So, the present study was undertaken to investigate the antidiabetic potential of P. polyphylla extract enriched with diosgenin (PPED) in vitro and in vivo in streptozotocin (STZ) induced diabetic rats. Method: P. polyphylla rhizomes were used to extract diosgenin-enriched extracts. The P. polyphylla extract enriched with diosgenin (PPED) was quantified using standard diosgenin in HPLC. The in vitro antidiabetic efficacy of PPED was determined by α-glucosidase and α-amylase enzyme inhibitory activity. PPED 1 (200 mg/kg b.w) and PPED 2 (400 mg/kg b.w) was administered in normal glycemic rats to evaluate the oral glucose tolerance test (OGTT). PPED 1 and PPED 2 were orally dosed for 28 days daily in STZ-induced diabetic rats, and the fasting blood glucose level and body weight were monitored every 7 days. Furthermore, the antioxidant, serum biochemical parameters, and pancreatic histopathology were studied. Results: P. polyphylla extract enriched with diosgenin was quantified. PPED exhibited a concentration-dependent inhibition of α-amylase and α-glucosidase enzymes with IC50 275.7 ± 0.59 μg/mL and 121.9 ± 1.21 μg/mL. Daily oral dosage of PPED 1 and PPED 2 for 28 days leads to a significant decrease in fasting blood glucose level and recovery of body weight compared to the diabetic control. The liver and kidney antioxidant parameters also improved with PPED dosage. According to our study, the PPED 1 and PPED 2 treated groups showed a decrease in glycated hemoglobin (HbA1c) and hyperlipidemia, as well as an improvement in protein, liver, and kidney function parameters. Moreover, PPED administration also ameliorates the pancreatic islets' size and β-cell granularity compared to the diabetic control group. It is, therefore, possible to conclude that PPED has the potential as an antidiabetic agent. Conclusion: This is the first report of P. polyphylla extract enriched with diosgenin as a potent antidiabetic agent. The present study broadens the therapeutic horizon of P. polyphylla as an invaluable medicinal plant.

Type 2 diabetes has become one of the major health concerns of the 21st century, marked by hyperglycemia or glycosuria, and is associated with the development of several secondary health complications. Due to the fact that chemically synthesized drugs lead to several inevitable side effects, new antidiabetic medications from plants have gained substantial attention. Thus, the current study aims to evaluate the antidiabetic capacity of the Ageratina adenophora hydroalcoholic (AAHY) extract in streptozotocin–nicotinamide (STZ–NA)-induced diabetic Wistar albino rats. The rats were segregated randomly into five groups with six rats each. Group I was normal control, and the other four groups were STZ–NA-induced. Group II was designated diabetic control, and group III, IV, and V received metformin (150 mg/kg b.w.) and AAHY extract (200 and 400 mg/kg b.w.) for 28 days. Fasting blood glucose, serum biochemicals, liver and kidney antioxidant parameters, and pancreatic histopathology were observed after the experimental design. The study concludes that the AAHY extract has a significant blood glucose lowering capacity on normoglycemic (87.01 ± 0.54 to 57.21 ± 0.31), diabetic (324 ± 2.94 to 93 ± 2.04), and oral glucose-loaded (117.75 ± 3.35 to 92.75 ± 2.09) Wistar albino rats. The in vitro studies show that the AAHY extract has α-glucosidase and α-amylase inhibitory activities which can restore the altered blood glucose level, glycated hemoglobin, body weight, and serum enzymes such as serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, serum alkaline phosphatase, total protein, urea, and creatinine levels close to the normal range in the treated STZ–NA-induced diabetic rats. The evaluation of these serum biochemicals is crucial for monitoring the diabetic condition. The AAHY extract has significantly enhanced tissue antioxidant parameters, such as superoxide dismutase, glutathione, and lipid peroxidation, close to normal levels. The presence of high-quantity chlorogenic (6.47% w/w) and caffeic (3.28% w/w) acids as some of the major phytoconstituents may contribute to the improvement of insulin resistance and oxidative stress. The study provides scientific support for the utilization of A. adenophora to treat type 2 diabetes in the STZ–NA-induced diabetic rat model. Although the preventive role of the AAHY extract in treating Wistar albino rat models against type 2 diabetes mellitus is undeniable, further elaborative research is required for efficacy and safety assessment in human beings.

Paris polyphylla Sm. (Melanthiaceae) is an essential, vulnerable herb with a wide range of traditional applications ranging from fever to cancer in various communities. The use of P. polyphylla in India is limited to traditional healers. Here, we demonstrated that P. polyphylla extract (PPE) has good phenol, flavonoid, saponin, and steroidal saponin content and anti-oxidant activity with IC50 35.12 ± 6.1 μg/mL in DPPH and 19.69 ± 6.7 μg/mL in ABTS. Furthermore, PPE induces cytotoxicity in HCT-116 with IC50 8.72 ± 0.71 μg/mL without significant cytotoxicity inthe normal human colon epithelial cell line, CCD 841 CoN. PPE inhibits the metastatic property and induces apoptosis in HCT-116, as measured by Annexin V/PI, by increasing the production of reactive oxygen species (ROS) and caspase 3 activation. PPE acts synergistically with 5FU and cisplatin in HCT-116 and potentiates their therapeutic significance. Steroidal saponins with anticancer activities were detected in PPE by HR-LCMS. The present study demonstrated that PPE induces apoptosis by increasing ROS and activating caspase 3, which was attributed to steroidal saponins. PPE can be used as a potential natural remedy for colon cancer.