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.

Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers.

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N'-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe2+-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7's (N'-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (-7.1 kcal/mol) and ENTPDase (-7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO4 by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase.

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.

Analysis of COI gene, prevalence, and intensity of the bat fly Cyclopodia greeffi on roosting straw-coloured fruit bat Eidolon helvum in Southwest Nigeria.

We investigated ectoparasite diversity, interspecific infestation rates and host preference in roosting fruit bats, Eidolon helvum, from Bowen University, Southwest Nigeria. Fur of captured E. helvum were sampled monthly for ectoparasites from January 2021 to June 2022. We examined a total of 231 E. helvum and observed a significant female to male adult sex ratio (0.22:1); with 53.9% ectoparasitic infestation rate. We identified and enumerated the ectoparasite; and subjected its Cytochrome c oxidase subunit I (COI) gene to phylogenetic analysis with other nycteribiids. COI gene sequences obtained formed a distinct clade with other C. greeffi sequences. We recovered a total of 319 (149 female and 170 male) ectoparasites and observed a balanced C. greeffi female to male adult sex ratio of 0.88:1. Ectoparasitic sex distribution had no association with host sex and season. Prevalence was significantly higher during the wet season, but not between sexes of E. helvum. The intensity of infestation, 3.7 ± 0.4 individuals per fruit bat, was significantly higher during the wet season with a bimodal seasonal distribution. The strongly male-biased host adult sex ratio had no significant influence on C. greeffi metapopulation adult sex ratio.

Annona muricata L. peel extract inhibits carbohydrate metabolizing enzymes and reduces pancreatic ß-cells, inflammation, and apoptosis via upregulation of PI3K/AKT genes.

BACKGROUND AND OBJECTIVE: Annona muricata L. peel has been recognized for many ethnobotanical uses, including diabetes management. However, limited detailed scientific information about its mechanism of antidiabetic activity exists. The objective of this study was to evaluate the anti-diabetic properties of an aqueous extract of A. muricata peel (AEAMP) and its mechanism of action on alloxan-induced diabetic rats. METHODS: In vitro antidiabetic assays, such as α-amylase and α-glucosidase were analyzed on AEAMP. Alloxan monohydrate (150 mg/kg b.w) was used to induce diabetes in the rats. 150 mg/kg b.w positive control group doses of 6.67, 13.53, and 27.06 mg/kg were administered to 3 groups for twenty-one days. The positive control group was administered 30 mg/kg of metformin. The negative and normal control groups were administered distilled water. The fasting blood glucose, serum insulin, lipid profile, inflammatory cytokines, antioxidant markers, carbohydrate metabolizing enzymes, and liver glycogen were analyzed as well as PI3K/AKT and apoptotic markers PCNA and Bcl2 by RT-PCR. RESULTS: AEAMP inhibited α-amylase and α-glucosidase enzymes more effectively than acarbose. AEAMP reduced FBG levels, HOMA-IR, G6P, F-1,6-BP, MDA, TG, TC, AI, CRI, IL-6, TNF-α, and NF-κB in diabetic rats. Furthermore, in diabetic rats, AEAMP improved serum insulin levels, HOMA-ß, hexokinase, CAT, GST, and HDL-c. Liver PI3K, liver PCNA and pancreas PCNA were not significantly different in untreated diabetic rats when compared to normal rats suggesting alloxan induction of diabetes did not downregulate the mRNA expression of these genes. AEAMP significantly up-regulated expression of AKT and Bcl2 in the liver and pancreatic tissue. It is interesting that luteolin and resorcinol were among the constituents of AEAMP. CONCLUSIONS: AEAMP can improve ß-cell dysfunction by upregulating liver AKT and pancreatic PI3K and AKT genes, inhibiting carbohydrate metabolizing enzymes and preventing apoptosis by upregulating liver and pancreatic Bcl2. However, the potential limitation of this study is the unavailability of equipment and techniques for collecting more data for the study.