Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate

Abstract

Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2–PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.

Pharmacological Prospects of Morin Conjugated Selenium Nanoparticles—Evaluation of Antimicrobial, Antioxidant, Thrombolytic, and Anticancer Activities

“…Phytoconstituents like alkaloid, glycosides, saponins, tannins, and flavonoids are also identified to exhibit thrombolysis activity [ 52 , 53 ]. Specifically, Morin hydrate was found to increase the occlusion time of thrombotic platelet plug formation that can be established as a novel therapeutic agent for treating thromboembolic disorders [ 54 ]. Hence, in this study, the thrombolytic activity of Ba-SeNp-Mo was quantified that supports the applications of nanomaterials as thrombolytic agents or carriers of thrombolytic drugs.…”

Regulation of Key Antiplatelet Pathways by Bioactive Compounds with Minimal Bleeding Risk

“…Other studies have shown that xanthohumol prevents both venous and arterial thrombosis without incurring a bleeding risk. Xanthohumol is a prenylated flavonoid that is present in several flowers, e.g., Hops (Humuluslupulus L.) used for beer preparation, and it is present in the the prenyl group bounded to ring A [74,75]. Xanthohumol has been reported to exert protective effects in metabolic syndrome and related diseases [74].…”

The anticarcinogenic and anticancer effects of the dietary flavonoid, morin: Current status, challenges, and future perspectives

“…(Kapoor & Kakkar, 2012), leaves of the guave plant ( Psidium guajava L.) (Rattanachaikunsopon & Phumkhachorn, 2010), old fustic ( Maclura tinctoria [L.] D.Don ex Steud .) (Hsia et al, 2018), tea, coffee (El‐Haddad, Sheta, & Boshra, 2018), acridocarpus orientalis A.Juss . (Hussain et al, 2014), onion ( Allium cepa L.), and apple ( Malus spec .)…”

“…This dietary flavonol is considered as a promising bioactive compound with beneficial effects on the prevention and treatment of chronic disorders related to oxidative stress and inflammation process (Caselli et al, 2016; Solairaja, Andrabi, Dunna, & Venkatabalasubramanian, 2021). Morin has been found to have antioxidant (Yong & Ahn, 2018), anti‐inflammatory (Khamchai et al, 2020; Qu, Wang, Liu, Gao, & Liu, 2018), neuroprotective (Lee, Lee, et al, 2016; Zhang et al, 2010), antihyperlipidemic (Vishnukumar, Stephan, & Chandra, 2012), antihypertensive (Prahalathan, Kumar, & Raja, 2012), antidiabetic (Paoli et al, 2013; Razavi, Kouhsari, & Abnous, 2019; Vanitha et al, 2014), antihyperuricemic (Li, Yang, Lu, Ma, & Zhang, 2018; Wang et al, 2010), antithrombotic (Hsia et al, 2018), antiviral (Gupta et al, 2021; Hong et al, 2020), antibacterial (Amin, Khurram, Khattak, & Khan, 2015; Nag, Dastidar, & Chakrabarti, 2021), antiallergic (Kandhare, Liu, Mukherjee, & Bodhankar, 2019), and anticancer effects (Lee et al, 2019; Nie et al, 2019; Nowak, Sypniewski, & Bednarek, 2020). Studies indicate that morin possesses significant protective activities against toxicity and side effects of several drugs, without affecting their functions (Al Numair, Chandramohan, Alsaif, & Baskar, 2012; Kuzu et al, 2019; Merwid‐Ląd et al, 2014; Özdemir, Kucukler, Çomaklı, & Kandemir, 2020).…”