Mumefural Improves Blood Flow in a Rat Model of FeCl3-Induced Arterial Thrombosis

Abstract

Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague–Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.

Mumefural prevents insulin resistance and amyloid-beta accumulation in the brain by improving lowered interstitial fluid pH in type 2 diabetes mellitus

“…This means that foods containing 0.05% mumefural provided mumefural of 22.5 mg (45 g × 0.05%)/kg body weight/day. Thus, the amount of mumefural applied in the present study would be reasonable compared with the amount of mumefural applied in previous studies (Nishimura et al 2017;Bang et al 2019;Bang and Jeon 2020;Mahboubi 2021). Blood has strong pH buffers such as hemoglobin and albumin, thus arterial blood pH is strictly maintained at pH of 7.35-7.45 under normal conditions (Marunaka 2021), while metabolic disorders cause acidosis, which is one of typical symptoms of severe T2DM (Souto et al 2011).…”

“…OLETF rats lacking CCK1 receptors have been established as an animal model of human T2DM (Kawano et al 1992;Funakoshi et al 1995) and LETO rats have been used as control non-T2DM rats for OLETF rats (El-Mahmoudy et al 2005;Ohno et al 2017;Oshima et al 2019;Kuno et al 2020). Mumefural of 10 mg/kg body weight for Sprague-Dawley rats has been applied via one shot intraperitoneal injection (Bang and Jeon 2020). Another study (Bang et al 2019) has orally applied 80 mg/ kg body weight/day for Wister rats for 42 days.…”

“…Plum extract contains 1-[5-(2-formylfuryl) methyl] dihydrogen 2-hydroxypropane-1,2,3,-tricarboxylate, mumefural (Kim et al 2020), and a related compound, 5-hydroxymethyl-2-furfural (HMF) (Chuda et al 1999). Mumefural is reported to improve human blood fluidity and thereby ameliorate cardiovascular diseases such as hypertension and/or atherosclerosis frequently observed in T2DM (Bang and Jeon 2020). Further, the safety for oral mumefural intake has been studied (Kim et al 2020).…”

Role of Neutrophils and NETs in Animal Models of Thrombosis

“…As shown in Table 1, the main species used to study thrombosis are zebrafish [25][26][27], mice [8,[28][29][30][31][32][33], rats [34,35], rabbit [36][37][38] hamsters [39,40], guinea pigs [41,42], pigs [43][44][45], dogs [46][47][48], and baboons [9,49,50]. Of course, the mouse remains the reference animal model in the study of cardiovascular disease for several reasons: (1) it is a mammalian species with many physiological similarities to humans, (2) it is economical to house, (3) it is easy to manipulate, and (4) its genome is easily modifiable, allowing the creation of numerous transgenic lines [25].…”

“…Many pathologies are associated with it, which is why it has been studied in many vascular areas. Among the best charac-terized veins, we found the inferior vena cava [8,9,43], jugular vein [38,46], and femoral vein [8,35,41]. For arterial thrombosis, the most studied vessel is the carotid artery [29,32], although the mesenteric [28,31] and cremasteric [28] arterioles are sometimes used.…”