Bambusa vulgaris leaves reverse mitochondria dysfunction in diabetic rats through modulation of mitochondria biogenic genes.

OBJECTIVES: There is evidence that mitochondrial dysfunction mediated by hyperglycemia increases the incidence of diabetes and age-related insulin resistance. Thus, maintaining mitochondrial integrity may provide alternative therapeutic approach in diabetes treatment. This study aimed to evaluate the effect of Bambusa vulgaris leaf extract on mitochondrial biogenesis in the pancreas of diabetic rats. METHODS: 11 weeks old male rats (n=30) were purchased, and sorted into the following groups: control, diabetic control, diabetes + metformin (100 mg/kg), diabetes + Aq. B. vulgaris (100 mg/kg), diabetes + Aq. B. vulgaris (200 mg/kg), and diabetes + Aq. B. vulgaris (300 mg/kg). Diabetes was induced in the rats by a single dose of 65 mg/kg streptozotocin (STZ). The mRNA expression of genes related to mitochondria biogenesis (pgc-1α, Nrf2, GSK3ß, AMPK and SIRT2) and genes of Nrf2-Keap1-ARE signaling pathway were determined by reverse transcriptase polymerase chain reaction. Molecular docking studies including lock and key docking and prime MM-GBSA were incorporated to identify the lead chemical compounds in Bambusa vulgari. RESULTS: The results showed that B. vulgaris leaf extract promotes mitochondrial biogenesis via altering the mRNA expression of mitochondrial master regulator pgc-1α, other upstream genes, and the Nrf2-Keap1-ARE antioxidant pathway. Through molecular docking results, cryptochlorogenic acid, hesperidin, orientin, vitexin, scopolin, and neochlorogenic were found as the crucial chemicals in B. vulgaris with the most modulating effect on PGC-1α, AMPK, and GSK3. CONCLUSIONS: This study thus suggests that B. vulgaris leaf extract restores the integrity of mitochondria in diabetic rats.

Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: In silico and in vivo studies.

Momordica charantia (bitter lemon) belongs to the cucurbitaceae family which has been extensively used in traditional medicines for the cure of various ailments such as cancer and diabetes. The underlying mechanism of M. charantia to maintain glycemic control was investigated. GLP-1 and DPP-4 gene modulation by M. charantia (5-20% inclusion in rats diet) was investigated in vivo by RT-PCR and possible compounds responsible for diabetic action predicted through in silico approach. Phytochemicalss previously characterized from M. charantia were docked into glucacon like peptide-1 receptor (GLP-1r), dipeptidyl peptidase (DPP4) and Takeda-G-protein-receptor-5 (TGR5) predicted using Autodock Vina. The results of the in silico suggests momordicosides D (ligand for TGR5), cucurbitacin (ligand for GLP-1r) and charantin (ligand for DPP-4) as the major antidiabetic compounds in bitter lemon leaf. M. charantia increased the expression of GLP-1 by about 295.7% with concomitant decreased in expression of DPP-4 by 87.2% with 20% inclusion in rat's diet. This study suggests that the mechanism underlying the action of these compounds is through activation of TGR5 and GLP-1 receptor with concurrent inhibition of DPP4. This study confirmed the use of this plant in diabetes management and the possible bioactive compounds responsible for its antidiabetic property are charantin, cucurbitacin and momordicoside D and all belong to the class of saponins.

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 from the fruit of Solanum anguivi protects against oxidative damage mediated by Fe2+ and sodium nitroprusside in rat brain synaptosome P2 fraction.

Solanum anguivi fruit saponin has antidiabetic property via interference with cellular energy metabolism and inhibition of reactive oxygen species (ROS) generation. In the current study, brain specific in vitro anti-oxidant role of S. anguivi saponin was investigated in the P2 synaptosomal fraction of rat brain. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, S. anguivi saponin concentration- dependently (10-200 µg/ml) reversed Fe2+ and sodium nitroprusside- induced decrease in mitochondrial activity via inhibition of ROS production, ROS-induced oxidation of protein and non-protein thiol-containing molecules and lipid peroxidation as measured by thiobarbituric acid reactive substances levels. Conclusively, S. anguivi fruit saponin represents a class of natural compounds with the ability to reverse synaptosomal disruption, loss of mitochondrial integrity and function often associated with the progression of Huntington's disease, Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis diseases.

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.

African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca(2+)-induced mitochondrial swelling.

OBJECTIVE: To evaluate the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore as well as mitochondrial membrane potential (ΔΨm) isolated from rat liver. METHODS: Antioxidant activity of SAG was assayed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, iron chelation and ability to inhibit lipid peroxidation in both liver and brain homogenate of rats. Also, the effect of SAG on mitochondrial membrane potential and mitochondrial swelling were determined. Identification and quantification of bioactive polyphenolics was done by HPLC-DAD. RESULTS: SAG exhibited potent and concentration dependent free radical-scavenging activity (IC50/DPPH=275.03±7.8 µg/mL). Reductive and iron chelation abilities also increase with increase in SAG concentration. SAG also inhibited peroxidation of cerebral and hepatic lipids subjected to iron oxidative assault. SAG protected against Ca(2+) (110 µmol/L)-induced mitochondrial swelling and maintained the ΔΨm. HPLC analysis revealed the presence of gallic acid [(17.54±0.04) mg/g], chlorogenic acid (21.90±0.02 mg/g), caffeic acid (16.64±0.01 mg/g), rutin [(14.71±0.03) mg/g] and quercetin [(7.39±0.05) mg/g]. CONCLUSIONS: These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.