Hesperidin abrogates bisphenol A endocrine disruption through binding with fibroblast growth factor 21 (FGF-21), α-amylase and α-glucosidase: an in silico molecular study.

BACKGROUND: Fibroblast growth factor 21 (FGF-21), alpha-amylase, and alpha-glucosidase are key proteins implicated in metabolic dysregulations. Bisphenol A (BPA) is an environmental toxicant known to cause endocrine dysregulations. Hesperidin from citrus is an emerging flavonoid for metabolic diseases management. Through computational approach, we investigated the potentials of hesperidin in abrogating BPA interference in metabolism. The 3D crystal structure of the proteins (FGF-21, α-amylase, and α-glucosidase) and the ligands (BPA and hesperidin) were retrieved from the PDB and PubChem database respectively. Using Autodock plugin Pyrx, molecular docking of the ligands and individual proteins were performed to ascertain their binding affinities and their potentials to compete for the same binding site. Validation of the docking study was considered as the ability of the ligands to bind at the same site of each proteins. The docking poses were visualized using UCSF Chimera and Discovery Studio 2020, respectively to reveal each of the protein-ligands interactions within the binding pockets. Using SwissAdme and AdmeSar servers, we further investigated hesperidin's ADMET profile. Hesperidin used was purchased commercially. RESULTS: Hesperidin and BPA competitively bound to the same site on each protein. Interestingly, hesperidin had greater binding affinities (Kcal/mol) - 5.80, - 9.60, and - 9.60 than BPA (Kcal/mol) - 4.40, - 7.20, - 7.10 for FGF-21, α-amylase, and α-glucosidase respectively. Visualizations of the binding poses showed that hesperidin interacted with stronger bonds than BPA within the proteins' pockets. Although hesperidin violated Lipinski rule of five, this however can be optimized through structural modifications. CONCLUSIONS: Hesperidin may be an emerging natural product with promising therapeutic potentials against metabolic and endocrine derangement.

Assessment of Levels and Health Risks of Trace Metals in Soils and Food Crops Cultivated on Farmlands Near Enyigba Mining Sites, Ebonyi State, Nigeria.

ABSTRACT: In most developing countries, mining is one of the major sources of toxic heavy metals, some of which are a major health concern to the surrounding populace through soil pollution and food contamination. We investigated the levels of Ti, Mn, Ni, Cu, Zn, Pb, Rb, Sr, Se, Nb, and V in 64 soil samples, 320 samples of regularly consumed staple food crops and vegetables (Manihot esculenta [cassava] tubers, Dioscorea rotundata [white yam], Arachi hypogea [groundnut] seed, Telfariria occidentalis [fluted pumpkin leaf]), and leaves of the medical plant Zanthoxulum zanthoxyloides on farmlands near Enyigba mining sites in Ebonyi state, Nigeria. We also examined the possible health risks due to consumption of these staple foods. Energy dispersive X-ray fluorescence was used to determine the metals present in the samples. The mean levels of metals, except for Mn, Pb, and Zn, were below the threshold limits recommended by various institutions for agricultural soils. Our data also showed that food crops cultivated near these sites bioaccumulated toxic levels of these metals above the proposed values set by the World Health Organization, National Agency for Food and Drug Administration and Control, and Codex Alimentarius Commission, especially for Pb, Zn, Cu, Ni, Se, and Rb. These findings may have potential health implications for the local dwellers. The estimated daily intakes of the toxic metals through the consumption of the crop samples were below the maximum tolerable daily intakes, except for Pb and Ni, by eating groundnut, cassava, and white yam. Furthermore, the target hazard quotient, computed based on the estimated daily intake of the heavy metals, was above unity for the metals for cassava, white yam, and groundnut consumption, suggesting significant health risk. Elevated amounts of heavy metals in cassava and groundnut samples, as revealed by their metal extraction coefficient computed in this study, hint that they may be used as bioindicators of ecological and health hazards and phytoremediators of Mn, Zn, Cu, and Pb.

Anti-arthritic potential of ethanol and aqueous extracts of stem bark of Cleistopholis patens on complete Freund's adjuvant-induced rheumatoid arthritis in rats.

BACKGROUND: Traditional medicine intervention has been used in rheumatoid arthritis (RA) treatment due to limitations of conventional drugs. OBJECTIVE: This study aimed at evaluating the anti-arthritic potentials of ethanol and aqueous extracts of stem bark of Cleistopholis patens (SBCP) in complete Freund's adjuvant (CFA) induced rheumatoid arthritis in rats. MATERIALS AND METHODS: Rheumatoid arthritis was induced in groups 2 to 9 by intradermal injection of 0.1 mlkg-1 chicken type II collagen in CFA into the left hind paw of the rats. Group 1 served as normal control. Group 2 (negative control) received 5 mlkg-1 body weight normal saline while group 3 (positive control) received 10 mg/kg body weight standard drug (indomethacin). Groups 4 to 9 received varied doses of the extracts. After 10 days of RA induction, rats were treated with ethanol and aqueous extracts of SBCP orally at a dose of 400, 600 and 800 mgkg-1 for 21 days. The paw size, body weight changes, inflammatory parameters, lipid peroxidation maker and malondialdehyde (MDA) were assessed. RESULTS: Rheumatoid arthritis induction caused marked (p < 0.05) increase in paw size, inflammatory makers and MDA while significant (p < 0.05) reduction was observed in body weight relative to normal control. Treatment with extracts analogous to indomethacin markedly (p < 0.05) decreased the paw size and caused weight gain while the altered inflammatory parameters and MDA were reversed relative to negative control. CONCLUSION: The findings suggest that the extracts of SBCP have good antiarthritic potentials comparable to indomethacin and hence could be used in rheumatoid arthritis management.