Apigetrin-enriched Pulmeria alba extract prevents assault of STZ on pancreatic β-cells and neuronal oxidative stress with concomitant attenuation of tissue damage and suppression of inflammation in the brain of diabetic rats

Tawakaltu Abdulrasheed-Adeleke; Bashir Lawal; Eyuwa Ignatius Agwupuye; Yucheng Kuo; Amarachi Mary Eni; Okwukwe Faith Ekoh; Halimat Yusuf Lukman; Amos S Onikanni; Femi Olawale; Sani Saidu; Yunusa O Ibrahim; Maliha Abdullah Saleh Al Ghamdi; Sarah S Aggad; Abdulrahman A Alsayegh; Nada H Aljarba; Gaber El-Saber Batiha; Alexander T H Wu; Hsu-Shan Huang

doi:10.1016/j.biopha.2023.114582

Apigetrin-enriched Pulmeria alba extract prevents assault of STZ on pancreatic β-cells and neuronal oxidative stress with concomitant attenuation of tissue damage and suppression of inflammation in the brain of diabetic rats

Biomed Pharmacother. 2023 Jun:162:114582. doi: 10.1016/j.biopha.2023.114582. Epub 2023 Mar 28.

Authors

Tawakaltu Abdulrasheed-Adeleke¹, Bashir Lawal², Eyuwa Ignatius Agwupuye³, Yucheng Kuo⁴, Amarachi Mary Eni⁵, Okwukwe Faith Ekoh⁵, Halimat Yusuf Lukman⁶, Amos S Onikanni⁷, Femi Olawale⁸, Sani Saidu⁵, Yunusa O Ibrahim¹, Maliha Abdullah Saleh Al Ghamdi⁹, Sarah S Aggad¹⁰, Abdulrahman A Alsayegh¹¹, Nada H Aljarba¹², Gaber El-Saber Batiha¹³, Alexander T H Wu¹⁴, Hsu-Shan Huang¹⁵

Affiliations

¹ Department of Biochemistry, Federal University of Technology P.M.B. 65, Minna 920001, Niger State, Nigeria.
² Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Department of Medical Laboratory Science, Faculty of Medical and Health Sciences, Newgate University Minna, Nigeria. Electronic address: bashirlawal12@gmail.com.
³ Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Nigeria.
⁴ Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan; School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
⁵ Department of Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, P.M.B. 1010, Abakaliki, Ebonyi State, Nigeria.
⁶ Department of Chemical Sciences, Biochemistry Unit, College of Natural and Applied Sciences, Summit University, Offa, PMB 4412, Nigeria.
⁷ Department of Chemical Sciences, Biochemistry Unit, Afe-Babalola University, Ado-Ekiti, Ekiti State, Nigeria; College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taiwan.
⁸ Nano gene and Drug Delivery Group, University of Kwazulu Natal, South Africa.
⁹ Consultant Adult Endocrinology and metabolism, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia.
¹⁰ Department of Food and Nutrition, Faculty of Human Sciences and Design, King Abdulaziz University, Jeddah 21589 Saudi Arabia.
¹¹ Clinical Nutrition Department, Applied Medical Sciences College Jazan University, Jazan 82817, Saudi Arabia.
¹² Department of Biology,College of science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
¹³ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt.
¹⁴ 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; Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Cardiovascular Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address: chaw1211@tmu.edu.tw.
¹⁵ Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 11490, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan; PhD Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: huanghs99@tmu.edu.tw.

PMID: 36989727
DOI: 10.1016/j.biopha.2023.114582

Abstract

In the present study, in vitro, in vivo, and in silico models were used to evaluate the therapeutic potential of Pulmeria alba methanolic (PAm) extract, and we identified the major phytocompound, apigetrin. Our in vitro studies revealed dose-dependent increased glucose uptake and inhibition of α-amylase (50% inhibitory concentration (IC₅₀)= 217.19 µg/mL), antioxidant (DPPH, ferric-reducing activity of plasma (FRAP), and lipid peroxidation (LPO) [IC₅₀ = 103.23, 58.72, and 114.16 µg/mL respectively]), and anti-inflammatory potential (stabilizes human red blood cell (HRBC) membranes, and inhibits proteinase and protein denaturation [IC₅₀ = 143.73, 131.63, and 198.57 µg/mL]) by the PAm extract. In an in vivo model, PAm treatment reversed hyperglycemia and attenuated insulin deficiency in rats with streptozotocin (STZ)-induced diabetes. A post-treatment tissue analysis revealed that PAm attenuated neuronal oxidative stress, neuronal inflammation, and neuro-cognitive deficiencies. This was evidenced by increased levels of antioxidants enzymes (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), and decreased malondialdehyde (MDA), proinflammatory markers (cyclooxygenase 2 (COX2), nuclear factor (NF)-κB and nitric oxide (NOx)), and acetylcholinesterase (AChE) activities in the brain of PAm-treated rats compared to the STZ-induced diabetic controls. However, no treatment-related changes were observed in levels of neurotransmitters, including serotonin and dopamine. Furthermore, STZ-induced dyslipidemia and alterations in serum biochemical markers of hepatorenal dysfunction were also reversed by PAm treatment. Extract characterization identified apigetrin (retention time: 21,227 s, 30.48%, m/z: 433.15) as the major bioactive compound in the PAm extract. Consequently, we provide in silico insights into the potential of apigetrin to target AChE/COX-2/NOX/NF-κB Altogether the present study provides preclinical evidence of the therapeutic potential of the apigetrin-enriched PAm extract for treating oxidative stress and neuro-inflammation associated with diabetes.

Keywords: Attenuation; Dyslipidemia; Phytoconstituent; Pulmeria alba methanolic extract; Streptozotocin.

MeSH terms

Acetylcholinesterase / metabolism
Animals
Antioxidants / pharmacology
Blood Glucose / metabolism
Brain / metabolism
Diabetes Mellitus, Experimental* / drug therapy
Humans
Inflammation / drug therapy
Oxidative Stress
Plant Extracts / pharmacology
Rats
Rats, Wistar
Streptozocin / therapeutic use

Substances

apigetrin
Acetylcholinesterase
Blood Glucose
Antioxidants
Streptozocin
Plant Extracts