Pharmacological Activities and Pharmacokinetic Study of Hyperoside: a Short Review
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Raza et al Tropical Journal of Pharmaceutical Research February 2017; 16 (2): 483-489 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v16i2.30 Review Article Pharmacological activities and pharmacokinetic study of hyperoside: A short review Aun Raza, Xiuquan Xu, Huifang Sun, Jian Tang* and Zhen Ouyang School of Pharmacy, Jiangsu University, Zhenjiang 212013, China *For correspondence: Email: [email protected]; Tel/Fax: +86-511-85038201 Received: 1 March 2016 Revised accepted: 13 September 2016 Abstract Hyperoside (quercetin-3-O-D-galactoside) is a flavonol glycoside which has been isolated from different plants. It has different pharmacological actions such as anti-inflammatory, anti-depressant, neuro- protective, cardio-protective, anti-diabetic, anti-cancer, anti-fungal, radio-protective, gastro-protective, and antioxidant activities. Studies on its pharmacokinetic (PK) properties revealed that it is a stable compound with no significant gender variation in its activities. Other significant details on its pharmacological properties and information for future investigations on its components are provided. Keywords: Hyperoside; Anti-inflammatory, Antidepressant, Neuroprotective, Antidiabetic, Anticancer, Antioxidant, Cytochrome P450 Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus, International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts INTRODUCTION plants such as Hypericum perforatum[5], Ligularia fischeri [6], Crataegus davisii [7], Natural products have recently attracted much Divaricate saposhnikovia [8] and Hypericum attention in drug discovery and food supplement mysorense [9]. Hyperoside is associated with research because they are frequently used due several potent pharmacological activities which to their chemical diversity and potent include anti-inflammatory, anti-thrombotic, anti- bioactivities. Flavonoids are plant polyphenols diabetic, anti-viral, anti-fungal, hepato-protective, found in herbs, vegetables and fruits. They are and antioxidant protective effects [10-14] (Table well known for their hepatoprotective, 1). cardioprotective, antipyretic, analgesic, and anti- inflammatory activities [1]. Flavonoids comprise a large group of polyphenolic with a benzo-γ- pyrone structure. They are synthesized by the phenylpropanoid pathway. Available reports show that secondary phenolic metabolites including flavonoids are responsible for a variety of pharmacological activities [2]. Hyperoside (Figure 1), also known as quercetin- 3-O-D-galactoside, is a flavonol glycoside present in a variety of vegetables and fruits [3,4]. Figure 1: Chemical structures of hyperoside(1) and quercetin (2) It has been isolated from various medicinal Trop J Pharm Res, February 2017; 16(2): 483 Raza et al Table 1: Pharmacological activities of hyperoside Activities References Anti-inflammatory activity [13], [14], [15], [16], [17] Anti-nociceptive activity [18], [14] Anti-depressant activity [19], [20], [21] Neuro-protective effects [22], [23], [24], [25], [26] Protective activity on brain [27], [28], [29], [30], [31], [26] Cardio-protective activity [32], [33], [34], [35] ,[11] Anti-diabetic activity [36], [37], [38], [16], [10], [39] Anti-cancer activity [40], [41], [42] Anti-viral activity [2], [43], [44] Hepato-protective activity [45] Antioxidant activity [46], [12], [1], [47], [48], [49] Immuno-modulatory activity [50], [43] Cytochrome P450 isoform inhibitory activity [51] Other activities [9], [52], [53], [54], [55], [56] PHARMACOLOGICAL APPLICATIONS OF intracellular Ca2+ induced by corticosteroid (10 HYPEROSIDE μM). Its ability to boost brain-derived neurotrophic factor (BDNF) and cAMP response Anti-inflammatory Activity element binding protein (CREB) has also been reported [21]. In mice orally administered Hyperoside exhibited anti-inflammatory activity in hyperoside at doses of 10-30 mg/kg for 10 days, mouse ear edema, with inhibition of arachidonic antidepressant-like activity was noticed in acid-induced edema by more than 15 %, and suspension test (TST) and forced swimming test crotonoil-induced edema by 19-25 % [15]. When (FST) that may be affected in their interaction mixed with isoquercitrin it produced anti- with serotonergic (5-HT2A and 5-HT2) systems inflammatory activity against carrageen-induced [20,22]. Antidepressant-like effects of hyperoside hind paw edema in albino mice, with 30 % have also been observed in forced swimming inhibition for 6 h [16]. This phytochemical tests in rats. The antidepressant effect in rats isolated from the leaves of Tripodanthus was prevented by the administration of sulpiride acutifolius has been reported to produce its anti- (D2-antagonist). Evidence indicates that the inflammatory effect by inhibiting cyclooxygenase- antidepressant effect of hyperoside is mediated 2 (COX-2) and hyaluronidase [17]. Hyperoside through the dopaminergic system [21,23]. suppressed vascular inflammatory processes caused by high glucose level in the human Neuroprotective activity umbilical vein endothelilal cells (HUVECs) and in mice [18]. It suppresses the production of In vitro studies have shown that pretreatment interleukin-6 (IL-6), tumor necrosis factor (TNF) with hyperoside (0.01-1 µmol/L) for 4 h and nitric oxide (NO) in lipopolysaccharide (LPS) decreased apoptosis in PC12 cells induced by -stimulated mouse peritoneal macrophages sodium azide (20 µM).This neuro-protective [17,19]. action has been attributed to inhibition of ROS production [22,24]. At 5-20 µM, hyperoside Anti-nociceptive activity protected primary rat cortical neuron from neurotoxcity of β-amyloid protein (Aβ) induced by Studies have shown that hyperoside exhibits sodium azide at 20 µM for 24 h. Thus, analgesic activity by down regulating calcium hyperosdie could be a useful therapeutic remedy (Ca2+) concentrations in afferent nerve endings for Alzheimer’s disease (AD) and other [18,20]. It has anti-nociceptive activity in p- neurodegenerative diseases [23,25]. benzoquinone-induced abdominal constriction in Furthermore, in in vitro ischemic models of mice with inhibition of 25 % [16]. oxygen–glucose deprivation followed by reperfusion (OGD-R), it was observed that Anti-depressant effect hyperoside offered protection from ischemic neuron damage by nitric oxide signaling process Hyperoside isolated from Apocynum venetum [26]. It has also been reported that hyperoside leaves has been shown to exhibit excellent anti- attenuates neuronal apoptosis triggered by L- depressant activity. In vitro study confirmed that glutamate through inhibition of NR2B-containing 2.5-10 μg/ml of the compound shielded PC12 N-methyl-D-aspartate (NMDA) subtype of cells from the lesions and high influx of glutamate receptors [27]. At 16 µM it has been Trop J Pharm Res, February 2017; 16(2): 484 Raza et al shown to effectively reduce elevated levels of NO excellent α-glucosidase inhibitory action [40]. In a and Ca2+ from 34.4 µM and 640 nM to 25.0 µM molecular docking studies, it was shown that and 331 nM in brain cells, respectively. hyperoside could be an effective docking agent Hyperoside also reduces the level of neuronal with targets of Type Ⅱdiabetes mellitus [12,41]. damage caused by anoxia as a result of 2+ increased concentration of NO and Ca in brain Anticancer activity cells [28]. In an in vitro study on osteosarcoma cells, Protective activity on brain hyperoside was reported to restrain the growth of U2OS osteosarcoma cell lines (IC value 223.5 Hyperoside at 1~10 µM reduced the degree of 50 ± 9.5 µg/ml for 72 h) and MG63 ( IC value 239 cerebral injury induced by oxygen-glucose 50 ± 22.4 µg/ml for 72 h) by revitalizing the G /G deprivation followed by reperfusion [29].This 0 1 arrest in cell cycle [42]. In addition, hyperoside in provided protective effect on focal brain ischemia-reperfusion injury and restrained brain combination with Quercetin produced anti-cancer edema in rats [30].Moreover, it was observed effects in 786-O renal cancer cells (IC50 value that hyperoside has protective effect on focal 18.2, 18.7,11.8µg/ml at 48, 72 and 96 h) [43]. brain ischemia and reperfusion injury induced by oxidative damage in rats [31]. Furthermore, it Antiviral activity was observed that brain tissues treated with this compound had lower water content [32]. Another Hyperoside from Abelmoschus manihot (L) study revealed that it shields rats from brain medik inhibited the production of HBeAg and ischemia-reperfusion injury and protects them HBsAg by hepatitis B virus (HBV)-producing from cognitive disability [33]. 2.2.15 cells, and inhibited the duck hepatitis B virus (DHBV)-DNA levels in HBV- infected duck Cardiovascular protective activity models [2]. Its antiviral activity was investigated in covalently-closed circular DNA (cccDNA) of Hyperoside at 25 and 50 mg/kg protected rats duck hepatitis B virus [44]. Yinqiaosan powder from cardiomyocyte apoptosis caused by which contains hyperoside is known to possess ischemia and perfusion, and at 0.50 μmol/L antiviral action against influenza virus [45]. protected cultured rat neonatal cardiomyocyte from apoptosis [34]. It was also reported that Hepatoprotective