Evaluation of terpenes rich Hura crepitans extract on glucose regulation and diabetic complications in STZ-induced diabetic rats

Halimat Yusuf Lukman; Yucheng Kuo; Mayowa Solomon Owolabi; Bashir Lawal; Lung-Ching Chen; Olabode T. Ajenifujah; Adewale O. Fadaka; Femi Olawale; Sunday A. Onikanni; Saidu Sani; Michel De Waard; Dalia Fouad; Gaber El-Saber Batiha; Saheed Sabiu; Alexander T.H. Wu; Hsu-Shan Huang

Biomedicine & Pharmacotherapy (Oct 2024)

Evaluation of terpenes rich Hura crepitans extract on glucose regulation and diabetic complications in STZ-induced diabetic rats

Halimat Yusuf Lukman,
Yucheng Kuo,
Mayowa Solomon Owolabi,
Bashir Lawal,
Lung-Ching Chen,
Olabode T. Ajenifujah,
Adewale O. Fadaka,
Femi Olawale,
Sunday A. Onikanni,
Saidu Sani,
Michel De Waard,
Dalia Fouad,
Gaber El-Saber Batiha,
Saheed Sabiu,
Alexander T.H. Wu,
Hsu-Shan Huang

Affiliations

Halimat Yusuf Lukman: Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa
Yucheng Kuo: Department of Pharmacology, College of Medicine, Taipei Medical University, Taiwan; School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40604, Taiwan
Mayowa Solomon Owolabi: Department of Breast Cancer, Baylor College of Medicine, USA
Bashir Lawal: UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
Lung-Ching Chen: Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan
Olabode T. Ajenifujah: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
Adewale O. Fadaka: Department of Biotechnology, University of The Western Cape, Belleville, South Africa
Femi Olawale: Nano Gene and Drug Delivery Group, University of KwaZulu-Natal, South Africa
Sunday A. Onikanni: Centro de Ciências da Saúde, Instituto de Ciências Biomédicas, Laboratório de Endocrinologia Experimental-LEEx, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-617, Brazil; Department of Chemical Sciences, Biochemistry Unit, Afe-Babalola University, Ado-Ekiti, Ekiti State, Nigeria
Saidu Sani: Alex Ekwueme-Federal University Ndufu-Alike, Ikwo, Nigeria
Michel De Waard: Smartox Biotechnology, 6 rue des Platanes, F-38120 Saint-Egrève, France; L’institut du thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France; LabEx Ion Channels, Science & Therapeutics, Université de Nice Sophia-Antipolis, F-06560 Valbonne, France
Dalia Fouad: Department of Zoology, College of Science, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
Gaber El-Saber Batiha: Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira 22511, Egypt
Saheed Sabiu: Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa
Alexander T.H. Wu: TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan; The Ph.D. Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Corresponding author at: The Ph.D. Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Hsu-Shan Huang: PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan; PhD Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; Corresponding author at: PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.

Journal volume & issue: Vol. 179
p. 117308

Abstract

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The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of −12.4, −10.9, −10.3, and −9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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