PMID- 37100261 OWN - NLM STAT- MEDLINE DCOM- 20230508 LR - 20230508 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 312 DP - 2023 Aug 10 TI - Inhibitory and in silico molecular docking of Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa phytochemical compounds on human alpha-glucosidases. PG - 116501 LID - S0378-8741(23)00369-0 [pii] LID - 10.1016/j.jep.2023.116501 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herbal traditional medicine is used by millions of people in Africa for treatment of ailments such as diabetes mellitus, stomach disorders and respiratory diseases. Xeroderris stuhlmannii (Taub.) Mendonca & E.P. Sousa (X. stuhlmannii (Taub.)) is a medicinal plant used traditionally in Zimbabwe to treat type 2 diabetes mellitus (T2DM) and its complications. However, there is no scientific evidence to support its inhibitory effect against digestive enzymes (alpha-glucosidases) that are linked to high blood sugar in humans. AIM OF THE STUDY: This work aims to investigate whether bioactive phytochemicals of crude X. stuhlmannii (Taub.) can scavenge free radicals and inhibit alpha-glucosidases in order to reduce blood sugar in humans. MATERIALS AND METHODS: Here we examined the free radical scavenging potential of crude aqueous, ethyl acetate and methanolic extracts of X. stuhlmannii (Taub.) using the diphenyl-2-picrylhydrazyl assay in vitro. Furthermore, we carried out in vitro inhibition of alpha-glucosidases (alpha-amylase and alpha-glucosidase) by the crude extracts using chromogenic 3,5-dinitrosalicylic acid and p-nitrophenyl-alpha-D-glucopyranoside substrates. We also used molecular docking approaches (Autodock Vina) to screen for bioactive phytochemical compounds targeting the digestive enzymes. RESULTS: Our results showed that phytochemicals in X. stuhlmannii (Taub.) aqueous, ethyl acetate and methanolic extracts scavenged free radicals with IC(50) values ranging from 0.002 to 0.013 mug/mL. Furthermore, crude aqueous, ethyl acetate and methanolic extracts significantly inhibited alpha-amylase and alpha-glucosidase with IC(50) values of 10.5-29.5 mug/mL (versus 54.1 +/- 0.7 mug/mL for acarbose) and 8.8-49.5 mug/mL (versus 161.4 +/- 1.8 mug/mL for acarbose), respectively. In silico molecular docking findings and pharmacokinetic predictions showed that myricetin is likely a novel plant-derived alpha-glucosidase inhibitor. CONCLUSION: Collectively, our findings suggest pharmacological targeting of digestive enzymes by X. stuhlmannii (Taub.) crude extracts may reduce blood sugar in humans with T2DM via inhibition of alpha-glucosidases. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Nyathi, Brilliant AU - Nyathi B AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Bvunzawabaya, Jonathan Tatenda AU - Bvunzawabaya JT AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe; Department of Chemical Sciences, Faculty of Science and Technology Midlands State University, Private Bag 9055 Senga Road, Gweru, 263, Zimbabwe. FAU - Venissa P Mudawarima, Chido AU - Venissa P Mudawarima C AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Manzombe, Emily AU - Manzombe E AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Tsotsoro, Kudakwashe AU - Tsotsoro K AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Selemani, Major Allen AU - Selemani MA AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Munyuki, Gadzikano AU - Munyuki G AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe. FAU - Rwere, Freeborn AU - Rwere F AD - Department of Chemistry, School of Natural Sciences and Mathematics, Chinhoyi University of Technology, Chinhoyi, Zimbabwe; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address: frwere@stanford.edu. LA - eng PT - Journal Article DEP - 20230424 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 76845O8NMZ (ethyl acetate) RN - EC 3.2.1.20 (alpha-Glucosidases) RN - 0 (Plant Extracts) RN - 0 (Blood Glucose) RN - T58MSI464G (Acarbose) RN - 0 (Glycoside Hydrolase Inhibitors) RN - Y4S76JWI15 (Methanol) RN - 0 (Phytochemicals) RN - EC 3.2.1.1 (alpha-Amylases) RN - 0 (Antioxidants) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2 MH - alpha-Glucosidases/chemistry MH - Molecular Docking Simulation MH - Plant Extracts/pharmacology/therapeutic use/chemistry MH - Blood Glucose MH - Acarbose MH - Glycoside Hydrolase Inhibitors/pharmacology/chemistry MH - *Plants, Medicinal/chemistry MH - Methanol MH - Phytochemicals/pharmacology/therapeutic use MH - alpha-Amylases/chemistry MH - Antioxidants/pharmacology OTO - NOTNLM OT - Antioxidant OT - Diabetes mellitus OT - Docking OT - Flavonoids OT - Inhibition OT - Phytochemicals OT - Polyphenols COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/27 00:42 MHDA- 2023/05/08 06:41 CRDT- 2023/04/26 19:28 PHST- 2023/02/05 00:00 [received] PHST- 2023/03/19 00:00 [revised] PHST- 2023/04/13 00:00 [accepted] PHST- 2023/05/08 06:41 [medline] PHST- 2023/04/27 00:42 [pubmed] PHST- 2023/04/26 19:28 [entrez] AID - S0378-8741(23)00369-0 [pii] AID - 10.1016/j.jep.2023.116501 [doi] PST - ppublish SO - J Ethnopharmacol. 2023 Aug 10;312:116501. doi: 10.1016/j.jep.2023.116501. Epub 2023 Apr 24.