Spilanthes filicaulis (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy.

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.

Elemental evaluation, nutritional analysis, GC-MS analysis and ameliorative effects of Artocarpus communis J.R.Forst. & G.Forst. seeds' phytoconstituents on metabolic syndrome via in silico approach.

The nutritional as well as beneficial effects of the Artocarpus communis seed on metabolic syndrome complications have not been studied. In this research, the aim was to investigate the nutritional composition and beneficial effects of Artocarpus communis seeds' phytoconstituents on the p53 core, fat mass and obesity-associated (FTO) protein and cytochrome P450 CYP11A1 domains. The elements and phytochemicals in the seed were determined through atomic absorption spectroscopy assay and gas chromatography-mass spectrometry (GC-MS) analysis, respectively. Also, the compounds detected were docked to the p53 core, FTO protein and cytochrome P450 CYP11A1 domains protein. Artocarpus communis seed contains sodium (7.824 ± 0.0134 ppm), magnesium (10.187 ± 0.0239 ppm) and iron (1.924 ± 0.0017), while zinc and cadmium were undetected. Phenolics and flavonoids were the most abundant phytochemicals in the seed. Phytoconstituents, such as pentadecanoic acid, hexadecanoic acid and methyl ester, possessing different therapeutic effects were identified via GC-MS analysis. In A. communis seed, 3-methyl-4-nitro-5-(1-pyrazolyl) pyrazole and phenanthrene were able to bind more peculiarly and specifically to the p53 core, FTO protein and cytochrome P450 CYP11A1 domains. One of the important processes that were hypothesized for the recovery of metabolic syndrome in affected victims is shown by the molecular dynamics analysis, which shows that the binding of these chemicals to the targeted structure stabilized the proteins. Therefore, Artocarpus communis seeds could be a new strategy for the management of metabolic syndrome.Communicated by Ramaswamy H. Sarma.

GC-MS chemical profiling, antioxidant, anti-diabetic, and anti-inflammatory activities of ethyl acetate fraction of Spilanthes filicaulis (Schumach. and Thonn.) C.D. Adams leaves: experimental and computational studies.

Introduction: This study aimed to investigate the chemical profile of GC-MS, antioxidant, anti-diabetic, and anti-inflammatory activities of the ethyl acetate fraction of Spilanthes filicaulis leaves (EFSFL) via experimental and computational studies. Methods: After inducing oxidative damage with FeSO4, we treated the tissues with different concentrations of EFSFL. An in-vitro analysis of EFSFL was carried out to determine its potential for antioxidant, anti-diabetic, and anti-inflammatory activities. We also measured the levels of CAT, SOD, GSH, and MDA. Results and discussion: EFSFL exhibited anti-inflammatory properties through membrane stabilizing properties (IC50 = 572.79 µg/ml), proteinase inhibition (IC50 = 319.90 µg/ml), and inhibition of protein denaturation (IC50 = 409.88 µg/ml). Furthermore, EFSFL inhibited α-amylase (IC50 = 169.77 µg/ml), α-glucosidase (IC50 = 293.12 µg/ml) and DPP-IV (IC50 = 380.94 µg/ml) activities, respectively. Our results indicated that induction of tissue damage reduced the levels of GSH, SOD, and CAT activities, and increased MDA levels. However, EFSFL treatment restores these levels to near normal. GC-MS profiling shows that EFSFL contains 13 compounds, with piperine being the most abundant. In silico interaction of the phytoconstituents using molecular and ensembled-based docking revealed strong binding tendencies of two hit compounds to DPP IV (alpha-caryophyllene and piperine with a binding affinity of -7.8 and -7.8 Kcal/mol), α-glucosidase (alpha-caryophyllene and piperine with a binding affinity of -9.6 and -8.9 Kcal/mol), and to α-amylase (piperine and Benzocycloheptano[2,3,4-I,j]isoquinoline, 4,5,6,6a-tetrahydro-1,9-dihydroxy-2,10-dimethoxy-5-methyl with a binding affinity of -7.8 and -7.9 Kcal/mol), respectively. These compounds also presented druggable properties with favorable ADMET. Conclusively, the antioxidant, antidiabetic, and anti-inflammatory activities of EFSFL could be due to the presence of secondary metabolites.