Although trace elements are essential for life, environmental contamination due to metal accumulation and overuse in various sectors, such as healthcare, agriculture, industry, and cosmetics, poses significant health concerns. Exposure of plants to heavy metals leads to the overproduction of reactive oxygen species (ROS) due to their ability to change mitochondrial membrane permeability and restrict the action of ROS clearance enzymes in the cellular antioxidant system. The interaction of ROS with cellular membranes, heavy-metal-induced interactions directly or indirectly with different macromolecules, and signaling pathways leads to the accumulation of environmental pollutants and oxidative stress in exposed organisms. The heavy metal–ROS–cell signaling axis affects various pathological processes such as ATP depletion, excess ROS production, mitochondrial respiratory chain damage, decoupling of oxidative phosphorylation, and mitochondrial death. This review focuses on discussing the toxic effects of different heavy metals on plants, with particular emphasis on oxidative stress, its consequences, and mitigation strategies.

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancreatic beta-cell function, as well as on glucose tolerance and appetite. The insulin secretory effects of GLP-1 and GLP-2 (10⁻¹²–10⁻⁶ M) were investigated in BRIN-BD11 beta-cells as well as isolated mouse islets, with the impact of test peptides (10 nM) on real-time cytosolic cAMP levels further evaluated in mouse islets. The impact of both peptides (10⁻⁸–10⁻⁶ M) on beta-cell growth and survival was also studied in BRIN BD11 cells. Acute in vivo (peptides administered at 25 nmol/kg) glucose homeostatic and appetite suppressive actions were then examined in healthy mice. GLP-1, but not GLP-2, concentration dependently augmented insulin secretion from BRIN-BD11 cells, with similar observations made in isolated murine islets. In addition, GLP-1 substantially increased [cAMP]_cyt in islet cells and was significantly more prominent than GLP-2 in this regard. Both GLP-1 and GLP-2 promoted beta-cell proliferation and protected against cytokine-induced apoptosis. In overnight fasted healthy mice, as well as mice trained to eat for 3 h per day, the administration of GLP-1 or GLP-2 suppressed appetite. When injected conjointly with glucose, both peptides improved glucose disposal, which was associated with enhanced glucose-stimulated insulin secretion by GLP-1, but not GLP-2. To conclude, the impact of GLP-1 and GLP-2 on insulin secretion is divergent, but the effects of beta-cell signaling and overall health are similar. Moreover, the peripheral administration of either hormone in rodents results in comparable positive effects on blood glucose levels and appetite.

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.

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.

Pomegranate (Punica granatum), a shrub belonging to the Lythraceae family, has long been recognized for its diverse pharmacological benefits, including potential roles in managing inflammation and diabetes. The present study explored the insulin-secretory and β-cell proliferative properties of the ethanol extract of P. granatum fruit peel (EEPG) and assessed its influence on glucose regulation in high-fat-fed diet-induced obese mice (HFDi-OM) through in vivo and in silico studies. In vitro, EEPG was found to activate cAMP-dependent pathways and regulate K_ATP channels, thereby enhancing glucose-stimulated insulin secretion from BRIN-BD11 β-cells, with partial reliance on extracellular calcium. EEPG promoted β-cell proliferation, as indicated by an increase in Ki-67 positive cells, and displayed inhibitory effects on glucose diffusion and starch hydrolysis, suggesting a capacity to delay carbohydrate digestion and absorption. Furthermore, EEPG demonstrated antioxidant activity by neutralizing free radicals. In an acute test, EEPG (at doses of 150 and 250 mg/5 mL/kg) improved oral glucose tolerance and elevated plasma insulin levels. Long-term oral treatment for 21 days to HFDi-OM led to a significant reduction in fasting blood glucose, body weight, and food and fluid intake. It also enhanced gastrointestinal motility and improved lipid profiles by increasing HDL and lowering total cholesterol, LDL, and triglycerides. The therapeutic properties of EEPG are likely attributed to its rich bioactive components, including flavonoids (quercetin, kaempferol, catechin, and epicatechin) and phenolic acids (ellagic acid), which exhibited strong multi-target binding affinities in in silico molecular docking studies toward SUR1, PDE4, PI3K, and α-amylase, thereby supporting enhanced insulin secretion, β-cell function and glucose homeostasis.