Bioprospection of Hura crepitans metabolites against oxidative stress and inflammation: An in vitro and in silico exploration

Yu-Cheng Kuo; Bashir Lawal; Halimat Yusuf Lukman; Lung-Ching Chen; Sheng-Liang Huang; Yi-Fong Chen; Adewale O Fadaka; Femi Olawale; Ayo Olasupo; Olabode T Ajenifujah; Dalia Fouad; Marios Papadakis; Gaber El-Saber Batiha; Saheed Sabiu; Alexander T H Wu; Hsu-Shan Huang

doi:10.7150/ijms.109116

Bioprospection of Hura crepitans metabolites against oxidative stress and inflammation: An in vitro and in silico exploration

Int J Med Sci. 2025 Mar 12;22(8):1837-1851. doi: 10.7150/ijms.109116. eCollection 2025.

Authors

Yu-Cheng Kuo^{1

2}, Bashir Lawal³, Halimat Yusuf Lukman⁴, Lung-Ching Chen^{5

6}, Sheng-Liang Huang⁷, Yi-Fong Chen⁸, Adewale O Fadaka⁹, Femi Olawale¹⁰, Ayo Olasupo¹¹, Olabode T Ajenifujah¹², Dalia Fouad¹³, Marios Papadakis¹⁴, Gaber El-Saber Batiha¹⁵, Saheed Sabiu⁴, Alexander T H Wu^{16

17

18

19}, Hsu-Shan Huang^{8

20

21}

Affiliations

¹ Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
³ UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁴ Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P. O. Box 1334, Durban 4000, South Africa.
⁵ Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.
⁶ School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan.
⁷ Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Centre, Taipei 11490, Taiwan.
⁸ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
⁹ Department of Biotechnology, University of The Western Cape, Belleville, South Africa.
¹⁰ Nano Gene and Drug Delivery Group, University of Kwazulu Natal, South Africa.
¹¹ Wonderful Institute for Sustainable Engineering, Chemical and Petroleum Engineering. University of Kansas.
¹² Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh PA, USA 15213.
¹³ Department of Zoology, College of Science, King Saud University, PO Box 22452, Riyadh 11495, Saudi Arabia.
¹⁴ Department of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, Germany.
¹⁵ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt.
¹⁶ The Ph.D. Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
¹⁷ Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan.
¹⁸ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
¹⁹ Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan.
²⁰ School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan.
²¹ Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.

Abstract

Background: Despite the recognized therapeutic potential of Hura crepitans, its mechanistic antioxidant and anti-inflammatory actions remain underexplored. Methods: This study investigates the inhibitory effects, binding stability, and interactions of metabolites from H. crepitans on oxidative and inflammatory biomarkers/targets using in vitro analyses and molecular dynamics (MD) simulations. Results: In vitro experiments revealed significant dose-dependent antioxidant and anti-inflammatory activities. The crude methanolic extract (CMEHC) showed notable half-maximal inhibitory concentration (IC₅₀) values for antioxidant assays, such as diphenyl picrylhydrazine (45.51 µg/mL) and ferric-reducing power (10.86 µg/mL), with comparable performance to standard ascorbic acid. Anti-inflammatory activities, including protein denaturation, proteinase inhibition, and membrane stabilization, demonstrated IC₅₀ values between 77.29-171.30 µg/mL. Liquid chromatography-mass spectrophotometry identified five primary compounds, predominantly phenolics, with rutin as the most abundant. Computational analyses confirmed these compounds' safety profiles, robust binding interactions, and stability against oxidative and inflammatory targets, with rutin forming the most stable interactions. Conclusion: These findings highlight the potential of H. crepitans phenolics as alternative therapies for oxidative stress and inflammation, warranting further drug development studies.

Keywords: Hura crepitans; anti-inflammatory; antioxidant; in silico; in vitro; phenolic compounds.

MeSH terms

Anti-Inflammatory Agents* / chemistry
Anti-Inflammatory Agents* / pharmacology
Antioxidants* / chemistry
Antioxidants* / pharmacology
Humans
Inflammation* / drug therapy
Molecular Docking Simulation
Molecular Dynamics Simulation
Oxidative Stress* / drug effects
Plant Extracts* / chemistry
Plant Extracts* / pharmacology

Substances

Antioxidants
Plant Extracts
Anti-Inflammatory Agents