RESUMO
BACKGROUND AND OBJECTIVE: Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway. METHODS: Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined. RESULTS: We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine). CONCLUSION: Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Ratos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/metabolismo , Estreptozocina/farmacologia , Rim/patologia , Ácido Úrico/metabolismo , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Diabetes Mellitus/patologiaRESUMO
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.
RESUMO
White Butterfly (Clerodendrum volubile) leaf is commonly used in traditional medicine for the management of various diseases including diabetes without the full understanding of the scientific basis for its use. This study sought to evaluate the antihyperglycemic, antihyperlipidemic and antioxidant effect of C. volubile leaves in streptozotocin (STZ)-induced diabetic rats. Aqueous extract of C. volubile was prepared and its effect assessed on relevant enzymes associated with diabetes. Fifty male Wistar rats were randomly separated into 10 groups each containing five rats. The induction of diabetes in rats was by a single intraperitoneal injection of STZ (65 mg/kg body weight) while C. volubile extract was administered orally to diabetic and non-diabetic animals, at the doses of 50, 100 and 200 mg/kg body weight for 14 days. Metformin (100 mg/kg body weight) served as positive control. Clerodendrum volubile extract inhibited α-glucosidase (IC50 = 0.20 mg/ml) and α-amylase (IC50 = 0.58 mg/ml). Furthermore, administration of C. volubile extract significantly reduced the elevated plasma glucose level and body weight, improved kidney functions, attenuated oxidative stress by decreasing MDA levels, enhancing superoxide dismutase, catalase and glutathione peroxidase activities, reinstated the lipid profile to nearly normal level and restored pancreatic histological integrity in diabetic rats. The results reveal that C. volubile represents a source of phytochemicals that exerts their antidiabetic effects through the modulation of glycemic and atherogenic indices as well as mitigation of free-radical-mediated damage.