Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam leaf extract prevents assault of streptozotocin on liver cells via inhibition of oxidative stress and activation of the NrF2/Keap1, PPARγ, and PTP1B signaling pathways.

BACKGROUND: Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries. PURPOSE: The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways. METHODS: A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined. RESULTS: MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats. CONCLUSION: It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM.

Exploring beetroot (Beta vulgaris L.) for diabetes mellitus and Alzheimer's disease dual therapy: in vitro and computational studies.

This study explored the flavonoid-rich extract of beetroot (Beta vulgaris L.) for type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) dual therapy by using in vitro and molecular simulation studies. Flavonoid-rich extracts of B. vulgaris fruit were evaluated for their antidiabetic and anti-alzheimic activities. Molecular docking and dynamic simulation were performed to identify potential bioactive flavonoids with dual therapeutic effects on T2D and AD. Flavonoid-rich extracts of B. vulgaris fruit (IC50 = 73.062 ± 0.480 µg mL-1) had moderate activity against α-amylase compared to the standard acarbose (IC50 = 27.104 ± 0.270 µg mL-1). Compared with acarbose, flavonoid-rich extracts of B. vulgaris fruit had appreciable activity against α-glucosidase (IC50 = 17.389 ± 0.436 µg mL-1) (IC50 = 37.564 ± 0.620 µg mL-1). For AChE inhibition, flavonoid-rich extracts of B. vulgaris fruit exhibited (p < 0.0001) inhibitory activity (IC50 = 723.260 ± 5.466 µg mL-1), albeit weaker than that of the standard control, galantamine (IC50 = 27.950 ± 0.122 µg mL-1). Similarly, flavonoid-rich extracts of B. vulgaris fruit showed considerable (p < 0.0001) inhibitory effects on BChE (IC50 = 649.112 ± 0.683 µg mL-1). In contrast, galantamine (IC50 = 23.126 ± 0.683 µg mL-1) is more potent than the extracts of B. vulgaris fruit. Monoamine oxidase (MAO) activity increased in FeSO4-induced brain damage. In contrast, flavonoid-rich extracts of B. vulgaris fruit protected against Fe2+-mediated brain damage by suppressing MAO activity in a concentration-dependent manner. HPLC-DAD profiling of the extracts identified quercetrin, apigenin, rutin, myricetin, iso-quercetrin, p-coumaric acid, ferulic acid, caffeic acid, and gallic acid. Molecular docking studies revealed quercetrin, apigenin, rutin, iso-queretrin, and myricetin were the top docked bioactive flavonoids against the five top target proteins (α-amylase, α-glucosidase AchE, BchE, and MAO). Molecular dynamic simulations revealed that the complexes formed remained stable over the course of the simulation. Collectively, the findings support the prospect of flavonoid-rich extracts of B. vulgaris root functioning as a dual therapy for T2D and AD.

Profiling the antidiabetic potential of GC-MS compounds identified from the methanolic extract of Spilanthes filicaulis: experimental and computational insight.

This study examines the nutritional composition, phytochemical profiling, and antioxidant, antidiabetic, and anti-inflammatory potential of a methanolic extract of Spilanthes filicaulis leaves (MESFL) via in vitro, ex vivo, and in silico studies. In vitro antioxidant, antidiabetic, and anti-inflammatory activities were examined. In the ex vivo study, liver tissues were subjected to FeSO4-induced oxidative damage and treated with varying concentrations of MESFL. MESFL contains a reasonable amount of nitrogen-free extract, moisture, ash content, crude protein, and fat, with a lesser amount of crude fiber. According to GC-MS analysis, MESFL contains ten compounds, the most abundant of which are 13-octadecenal and Ar-tumerone. In this study, MESFL demonstrated anti-inflammatory activities via membrane stabilizing properties, proteinase inhibition, and inhibition of protein denaturation (IC50 = 72.75 ± 11.06 µg/mL). MESFL also strongly inhibited both α-amylase (IC50 = 307.02 ± 4.25 µg/mL) and α-glucosidase (IC50 = 215.51 ± 0.47 µg/mL) activities. Our findings also showed that FeSO4-induced tissue damage decreased the levels of GSH, SOD, and CAT activities while increasing the levels of MDA. In contrast, treatment with MESFL helped to restore these parameters to near-normal levels, which signifies that MESFL has great potential to address complications from oxidative stress. Furthermore, the in silico interaction of the GCMS-identified phytochemicals with the active sites of α-amylase and α-glucosidase via molecular and ensembled-based docking displayed strong binding affinities of Ar-tumerone and 4-hydroxy-3-methylacetophenone to α-amylase and α-glucosidase, respectively. Taken together, the biological activities of MESFL might be a result of the effects of these secondary metabolites.Communicated by Ramaswamy H. Sarma.

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.