Pinoresinol-4-O-β-D-glucopyranoside: a lignan from prunes (Prunus domestica) attenuates oxidative stress, hyperglycaemia and hepatic toxicity in vitro and in vivo Fadia S. Youssef a , Mohamed L. Ashour a,b , Hesham A. El-Beshbishy c,d , Alaaeldin Ahmed Hamza e , Abdel Nasser B. Singab a and Michael Wink f a Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt, b Batterjee Medical College, Jeddah, c Medical Laboratory Sciences Department, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia, d Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt, e Hormone Evaluation Department, National Organization for Drug Control and Research (NODCAR), Giza, Egypt and f Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany Keywords antihyperglycaemic activity; hepatoprotective; molecular modelling; pinoresinol-4-O-β-D-glucopyranoside; Prunus domestica; streptozotocin Correspondence Michael Wink, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, Heidelberg D-69120, Germany. E-mail: wink@uni-heidelberg.de Abdel Nasser B. Singab, Faculty of Pharmacy, Ain Shams University, AfricanUnion Organization Street, Cairo 11566, Egypt. E-mail: dean@pharma.asu.edu.eg Received June 25, 2020 Accepted July 25, 2020 doi: 10.1111/jphp.13358 Abstract Objectives This study aimed to explore the pharmacological properties of pinor- esinol-4-O-β-D-glucopyranoside (PG), isolated from prunes. Methods In-vitro antioxidant activity was assessed using ferric reducing antioxi- dant power (FRAP) and 2,2’-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid]- diammonium salt (ABTS) assays. In-vivo hepatoprotective activity was evaluated using CCl 4 -induced hepatotoxicity mouse model. The antihyperglycaemic activ- ity was determined in vitro using α-glucosidase and α-amylase inhibiting activity and in vivo using streptozotocin-treated model. Molecular modelling was done on α-amylase, α-glucosidase, aldose reductase and peroxisome proliferator-acti- vated receptor gamma. Key findings Pinoresinol-4-O-β-D-glucopyranoside showed promising antioxi- dant activity in FRAP and ABTS assays with total antioxidant capacity equal 418.47 and 1091.3 μmol/g in terms of ascorbic acid, respectively. PG (50 mg/kg b.w.) exhibited a hepatoprotective activity in vivo as it lowered AST and ALT levels. PG showed a potent in-vitro antihyperglycaemic activity as it inhibited α- glucosidase with an IC 50 value of 48.13 μg/ml. PG caused a prominent decline in serum glucose level by 37.83% in streptozotocin-treated mice with promising ele- vation in insulin level of 25.37%. Oxidative stress markers were reduced by PG, and it showed a high fitting on α-amylase and α-glucosidase active sites. Conclusions Pinoresinol-4-O-β-D-glucopyranoside is a natural entity combating oxidative stress, hepatic damage and diabetes. Introduction Overproduction of reactive oxygen species will ultimately lead to oxidative stress in cells and can eventually mediate several health conditions such as hepatic diseases as well as multiple metabolic disorders such as diabetes. [1] Nowadays, diabetes mellitus is considered among the commonly spread metabolic dysfunctions with an explicit influence on morbidity and mortality. Diabetes mellitus may be due to the development of resistance to insulin receptors or to the insufficient synthesis of insulin. Conse- quently, glucose levels in the blood become imbalanced. Thus, hyperglycaemia is often the cause of several compli- cations such as nephropathy, retinopathy and neuropathy in addition to various ulceration and cardiovascular com- plications. [2,3] However, liver disorders such as hepatocellular carci- noma, liver cirrhosis and fibrosis as well as hepatitis are commonly caused by oxidative stress enhanced by hepato- toxins and xenobiotics which mediate hepatic inflamma- tion with an ultimate loss of liver integrity and function. The treatment of both diabetes and hepatic ailments still constitutes a massive challenge facing the healthcare system owing to the pronounced side effects triggered by synthetic © 2020 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 72 (2020), pp. 1830–1839 1830 Research Paper Downloaded from https://academic.oup.com/jpp/article/72/12/1830/6132669 by guest on 28 January 2024