Diabetes mellitus, a major cause of mortality around the globe, can result in several secondary complications, including diabetic foot syndrome, which is brought on by diabetic neuropathy and ischemia. Approximately 15% of diabetic patients suffer from diabetic foot complications, and among them 25% are at risk of lower limb amputations. Diabetic foot ulcers are characterized as skin lesions, gangrene, or necrosis, and may develop due to several reasons, including hyperglycemia and slower wound healing in diabetic patients. A management protocol involving wound cleaning, oral antibiotics, skin ointments, and removing dead tissue is currently followed to treat diabetic foot ulcers. In severe cases, amputation is performed to prevent the infection from spreading further. The existing therapy can be costly and present adverse side effects. Combined with a lack of vascular surgeons, this ultimately results in disability, especially in developing nations. There is a growing interest in the use of alternative therapies, such as medicinal plants, to discover more efficient and affordable treatments for diabetic foot syndrome. It has been observed that treatment with numerous plants, including Carica papaya, Annona squamosa, Catharanthus roseus, and Centella asiatica, promotes wound healing, reduces inflammation, and may decrease the number of amputations. However, little information is currently available on the prevention and management of diabetic foot ulcers, and additional research is necessary to completely understand the role of alternative therapies in the treatment of diabetic foot complications.

Background: Artocarpus heterophyllus, familiar as jackfruit, is a tropical fruit highly valued not only for its nutritional content but also for its medicinal properties, including potential antidiabetic effects. Objectives: This study aimed to evaluate the insulinotropic, β-cell proliferative and anti-hyperlipidaemic properties of the ethanol extract of unripe Artocarpus heterophyllus (EEAH) in high-fat-fed (HFF) diet-induced obese mice. Method: We evaluated acute insulin secretion and β-cell proliferation in BRIN-BD11 cells, and assessed in vitro glucose diffusion and starch digestion. In vivo, acute and chronic studies in HFF induced obese mice measured glucose tolerance, body weight, food and fluid intake, and lipid profiles. A preliminary phytochemical screening was also performed. Results: In this study, EEAH exhibited significant antidiabetic activity through multiple mechanisms. EEAH enhanced glucose-stimulated insulin secretion in BRIN-BD11 β-cells via K_ATP channel modulation and cAMP-mediated pathways, with partial dependence on extracellular calcium, and it also promoted β-cell proliferation. In vitro assays revealed its ability to inhibit starch digestion and glucose diffusion, indicating delayed carbohydrate digestion and absorption. In high-fat-fed (HFF) obese mice, the acute and chronic oral administration of EEAH improved oral glucose tolerance, reduced fasting blood glucose, decreased body weight, and normalized food and fluid intake. Lipid profile analysis showed increased HDL and reduced total cholesterol, LDL, and triglycerides, while higher doses of EEAH also enhanced gut motility. Phytochemical screening revealed the presence of bioactive compounds such as alkaloids, tannins, flavonoids, saponins, steroids, and terpenoids, which are likely responsible for these therapeutic effects. Conclusion: These findings highlight EEAH as a promising natural candidate for adjunctive therapy in managing type 2 diabetes and associated metabolic disorders and emphasize the importance of future multi-omics studies to elucidate its molecular targets and pathways.

Artocarpus heterophyllus, familiar as jackfruit, is a tropical fruit highly valued not only for its nutritional content but also for its medicinal properties, including potential antidiabetic effects. In this study, ethanolic extract of unripe Artocarpus heterophyllus (EEAH) exhibited significant antidiabetic activity through multiple mechanisms. EEAH enhanced glucose-stimulated insulin secretion in BRIN-BD11 β-cells via KATP channel modulation and cAMP-mediated pathways, with partial dependence on extracellular calcium, and it also promoted β-cell proliferation. In vitro assays revealed its ability to inhibit starch digestion and glucose diffusion, indicating delayed carbohydrate digestion and absorption. In high-fat-fed (HFF) obese mice, Acute and chronic oral administration of EEAH improved oral glucose tolerance, reduced fasting blood glucose, decreased body weight, and normalized food and fluid intake. Lipid profile analysis showed increased HDL and reduced total cholesterol, LDL, and triglycerides, while higher doses of EEAH also enhanced gut motility. Phytochemical screening revealed the presence of bioactive compounds such as alkaloids, tannins, flavonoids, saponins, steroids and, terpenoids, which are likely responsible for these therapeutic effects. These findings highlight EEAH as a promising natural candidate for adjunctive therapy in managing type 2 diabetes and associated metabolic disorders and emphasize the importance of future multi-omics studies to elucidate its molecular targets and pathways.