Momordica charantia silver nanoparticles modulate SOCS/JAK/STAT and P13K/Akt/PTEN signalling pathways in the kidney of streptozotocin-induced diabetic rats.

OBJECTIVES: Diabetes nephropathy (DN) is one of the complications of diabetes mellitus (DM) marked by gradual progressive loss of renal function. SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways are among the chain of interactions implicated in the onset, progression and pathology of DN. Momordica charantia (bitter melon) is often used in folk medicine as therapy for DM due to its hypoglycemic properties. This study was designed to evaluate M. charantia silver nanoparticles' therapeutic effect on DN-induced by streptozotocin (STZ) in Wistar rats. METHODS: The M. charantia nanoparticles used was synthesized using the filtrate from the plant methanolic extract added to 1 mM concentration of aqueous silver nitrate. DM was induced in Wistar rats by intraperitoneal injection of STZ (65 mg/kg). The animals' treatment groups were divided into; Diabetic control (65 mg/kg STZ), Control, and groups treated with silver nitrate (10 mg/kg), M. charantia nanoparticles (50 mg/kg), metformin (100 mg/kg), and plant extract (100 mg/kg). Treatment was terminated after 11 days. RT-PCR determined renal mRNA expression of Akt, PI3k, PTEN, TGF-ß, JAK2, STAT3, STAT5, SOCS3, SOCS4 and glucokinase (GCK). Consequently, characterized compounds from M. charantia identified from literatures were docked with PI3K, JAK2 and TGF-ß and STAT3 to retrieve potential hits. RESULTS: Oral administration of M. charantia nanoparticles (50 mg/kg) to STZ-induced diabetic untreated rats significantly ((p < 0.05) down-regulated the mRNA expression of Akt, PI3k, TGF-ß, JAK2, STAT3 and upregulated the mRNA expression of PTEN, SOCS3 and SOCS4, thus establishing the role of M. charantia nanoparticles in alleviating DN in diabetic rats. Additionally, there was a significant up-regulation of glucose metabolizing gene (glucokinase) upon administering M. charantia nanoparticles. Molecular docking results showed 12 compounds from bitter melon with docking score ranging from -6.114 kcal/mol to -8.221 kcal/mol that are likely to exert anti-diabetic properties. CONCLUSION: Observation drawn from this study suggests that M. charantia nanoparticles ameliorate DN through regulation of SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways.

Involvement of fat mass and obesity gene (FTO) in the anti-obesity action of Annona muricata Annonaceae: in silico and in vivo studies.

Background: Annona muricata (Annonaceae) known as soursop is a common tropical plant species known for its numerous medicinal properties including obesity. The underlying mechanism of anti-obesity effect of A. muricata was investigated. The fat mass and obesity associated protein (FTO) is a validated potential target for anti-obesity drugs. Methods: The interaction of compounds previously characterized from A. muricata was investigated against FTO using Autodock Vina. Also, modulation of FTO and STAT-3 mRNA expression by A. muricata was investigated in high fat diet induced obese rats (HFDR) using RT-PCR. Results: A significant up-regulation of FTO gene was observed in HFDR when compared to control rats, while administration of A. muricata (200 mg/kg) significantly (p < 0.05) down-regulated FTO gene expression when compared to HFDR group. The effect of obesity on STAT-3 gene expression was also reversed by A. muricata (200 mg/kg). In silico study revealed annonaine and annonioside (-9.2 kcal/mol) exhibited the highest binding affinity with FTO, followed by anonaine and isolaureline (-8.6 kcal/mol). Arg-96 is a critical amino acid enhancing anonaine, isolaureline-FTO binding. Conclusion: This study suggests the possible anti-obesity mechanism of A. muricata is via down-regulation of FTO with concomitant up-regulation of STAT-3 genes. This study confirmed the use of this plant in the management of obesity and the probable compounds responsible for its antiobesity effect are annonaine and annonioside.

Saponins as adipokines modulator: A possible therapeutic intervention for type 2 diabetes.

Development of type 2 diabetes has been linked to ß-cell failure coupled with insulin resistance and obesity. Adipose tissue, known as the fat store, secretes a number of hormones and proteins collectively termed adipokines some of which regulate insulin sensitivity. Dysregulation in the secretion of adipokines has been linked to insulin resistance and type 2 diabetes. In this review, we summarized evidence of the role of adipokines with focus on leptin, adiponectin, adipsin, visfatin and apelin in the pathogenesis of type 2 diabetes and discussed the potential of saponins to modify the ill-regulated adipokines secretions, which could promote the use of this class of phytochemicals as potential antidiabetics agents.

Tithonia diversifolia saponin-blood lipid interaction and its influence on immune system of normal wistar rats.

This study investigated the effect of saponins (20-100mg/kg) from Tithonia diversifolia leaf (STD) on the liver, kidney, heart, lipid profile and hematological parameters of normal rats. The results showed that STD (20-100mg/kg) though caused a slight increase in the liver, heart and kidney activity of ALT, AST, ALP and GGT (p<0.05), did not result in corresponding increase in the serum level of these enzymes. A significant reduction in the level of triglycerides, LDL and cholesterol, creatinine, urea, LDH, PCV and hemoglobin were observed with a concomitant increase in HDL, white blood cell and lymphocyte. These study demonstrated the role of STD in enhancing immune response and in reducing cholesterol and triglycerides in normal rats at studied dosages.

Saponin as regulator of biofuel: implication for ethnobotanical management of diabetes

There has been a sharp rise in the global prevalence of diabetes, obesity, and their comorbid conditions within the last decade prompting significant research into possible causes and cure via therapeutic intervention and lifestyle adjustments. Here, the molecular bases of antidiabetic plants used in the prehistorical treatment of diabetes and obesity are reviewed with particular focus on saponin as the phytotherapeutic principle. Until recently, the phytotherapeutic potentials of saponins have been masked in the heterogeneity of phytochemicals co-extractable during traditional preparations. With improved technique of purification and cutting edge biological assay methods, saponins have emerged as a regulator of primary biofuel availability through direct interaction with energy metabolism, cell signaling, and gene expression. Specific cases of lipoprotein lipase/peroxisome proliferator-activated receptor (PPAR)-gamma/phosphatidylinositide 3-kinase (PI-3-K)/protein kinase B (Akt) activation, adiponectin gene upregulation, fatty acid binding protein 4 repression (FABP4), and glucose transporter type 4 (Glut4) membrane exocytosis have been documented which provide molecular basis for hypocholesterolemic, hypoglycemic, and anti-obesity manifestations observed in experimental animals following saponin treatment. Although intensified research is required to characterize the pharmacophoric features in saponins exhibiting these interactions, however, this preliminary lead is valuable if the world will be free of diabetes, obesity, hypertension, hyperlipidemia, and atherosclerosis in no distant future

Saponin as regulator of biofuel: implication for ethnobotanical management of diabetes.

There has been a sharp rise in the global prevalence of diabetes, obesity, and their comorbid conditions within the last decade prompting significant research into possible causes and cure via therapeutic intervention and lifestyle adjustments. Here, the molecular bases of antidiabetic plants used in the prehistorical treatment of diabetes and obesity are reviewed with particular focus on saponin as the phytotherapeutic principle. Until recently, the phytotherapeutic potentials of saponins have been masked in the heterogeneity of phytochemicals co-extractable during traditional preparations. With improved technique of purification and cutting edge biological assay methods, saponins have emerged as a regulator of primary biofuel availability through direct interaction with energy metabolism, cell signaling, and gene expression. Specific cases of lipoprotein lipase/peroxisome proliferator-activated receptor (PPAR)-gamma/phosphatidylinositide 3-kinase (PI-3-K)/protein kinase B (Akt) activation, adiponectin gene upregulation, fatty acid binding protein 4 repression (FABP4), and glucose transporter type 4 (Glut4) membrane exocytosis have been documented which provide molecular basis for hypocholesterolemic, hypoglycemic, and anti-obesity manifestations observed in experimental animals following saponin treatment. Although intensified research is required to characterize the pharmacophoric features in saponins exhibiting these interactions, however, this preliminary lead is valuable if the world will be free of diabetes, obesity, hypertension, hyperlipidemia, and atherosclerosis in no distant future.