Myricetin as a Promising Molecule for the Treatment of Post-Ischemic Brain Neurodegeneration

The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding the benefits of myricetin in post-ischemic neurodegeneration. The data in this article contribute to a better understanding of the potential benefits of myricetin in the treatment of post-ischemic brain neurodegeneration, and inform physicians, scientists and patients, as well as their caregivers, about treatment options. Due to the pleiotropic properties of myricetin, including anti-amyloid, anti-phosphorylation of tau protein, anti-inflammatory, anti-oxidant and autophagous, as well as increasing acetylcholine, myricetin is a promising candidate for treatment after ischemia brain neurodegeneration with full-blown dementia. In this way, it may gain interest as a potential substance for the prophylaxis of the development of post-ischemic brain neurodegeneration. It is a safe substance, commercially available, inexpensive and registered as a pro-health product in the US and Europe. Taken together, the evidence available in the review on the therapeutic potential of myricetin provides helpful insight into the potential clinical utility of myricetin in treating neurodegenerative disorders with full-blown dementia. Therefore, myricetin may be a promising complementary agent in the future against the development of post-ischemic brain neurodegeneration. Indeed, there is a scientific rationale for the use of myricetin in the prevention and treatment of brain neurodegeneration caused by ischemia.     

A New Asymmetric ent-Kauranoid Dimer from Rabdosia rubescens

Objective To study the ent-kaurane diterpenoids from Rabdosia rubescens. Methods The compounds were isolated by chromatographies and their structures were identified by spectral analyses. Results Four compounds were isolated, and they were identified as bisrubescensin E (1), 2α,3α,24-trihydroxyurs-12-en-28-oic acid (2), 2α,3α,24-trihydroxyurs-12,20-(30)-dien-28-oic acid (3), and 6,7-dihydroxycoumarin (4). Conclusion Compound 1 is a new asymmetric ent-kauranoid dimer. Compound 2 is isolated from the plant for the first time. Compounds 3 and 4 are isolated from the plants of Rabdosia (Bl.) Hassk for the first time.     

Flavonoids inhibit both rice and sheep serotonin N‐acetyltransferases and reduce melatonin levels in plants

The plant melatonin biosynthetic pathway has been well characterized, but inhibitors of melatonin synthesis have not been well studied. Here, we found that flavonoids potently inhibited plant melatonin synthesis. For example, flavonoids including morin and myricetin significantly inhibited purified, recombinant sheep serotonin N‐acetyltransferase (SNAT). Flavonoids also dose‐dependently and potently inhibited purified rice SNAT1 and SNAT2. Thus, myricetin (100 μmol/L) reduced rice SNAT1 and SNAT2 activity 7‐ and 10‐fold, respectively, and also strongly inhibited the N‐acetylserotonin methyltransferase activity of purified, recombinant rice caffeic acid O‐methyltransferase. To explore the in vivo effects, rice leaves were treated with flavonoids and then cadmium. Flavonoid‐treated leaves had lower melatonin levels than the untreated control. To explore the direct roles of flavonoids in melatonin biosynthesis, we first functionally characterized a putative rice flavonol synthase (FLS) in vitro and generated flavonoid‐rich transgenic rice plants that overexpressed FLS. Such plants produced more flavonoids but less melatonin than the wild‐type, which suggests that flavonoids indeed inhibit plant melatonin biosynthesis.     

藤茶中杨梅素、二氢杨梅素及其乙酰化衍生物在SD大鼠体内药动学研究

目的：建立LC-MS/MS法测定SD大鼠血浆中杨梅素（myricetin,MY）和二氢杨梅素（dihydromyricetin,DMY）的浓度,将其运用到药动学研究,并评价DMY乙酰化衍生物是否改善生物利用度。方法：SD大鼠随机分为4组,分别灌胃DMY （100 mg·kg^-1,相当于9 375.0 μmo·L^-1）的0.5%羧甲基纤维素钠生理盐水溶液,以及等摩尔剂量的DMY-1、DMY-2、MY。于给药前0.0 h和给药后0.08,0.17,0.25,0.33,0.50,0.75,1.0,2.0,4.0,6.0,8.0,12.0 h尾静脉断尾采血200 μL,血浆样品经0.1%甲酸-乙腈沉淀蛋白,内标法定量,DAS3.0和SPSS统计分析得到药动学参数和曲线。结果：低、中、高的质控样品日内、日间精密度RSD均小于10.2%;DMY和MY的基质效应分别为98.3%~105.5%、98.0%~108.1%;萃取回收率分别为99.4%~103.0%、95.0%~99.7%,均符合生物样品分析检测的要求;DMY-2和DMY-1组相比于DMY组,相对生物利用度分别为47.22%,10.70%,表明口服灌胃给药DMY相对生物利用度要高出乙酰化衍生物组。结论：本研究建立测定大鼠血浆中DMY和MY的LC-MS/MS法,具有灵敏度高、准确性高、重复性好等优点,能够满足生物样品分析检测的要求,可应用于MY、DMY及其衍生物的药动学研究,也可为DMY结构修饰和新药开发提供参考依据。     

聚酰胺柱色谱法分离黄酮醇与二氢黄酮醇类化合物

目的 采用聚酰胺柱色谱分离黄酮醇与二氢黄酮醇类化合物.方法 采用聚酰胺柱色谱作为分离手段,结合紫外、红外吸收光谱进行检测.结果 运用聚酰胺柱色谱法一次分离得高纯度黄酮醇与二氢黄酮醇.结论 本实验为分离2,3位饱和度不同黄酮醇类化合物提供了较稳定的、简便的分离方法 .     

Enzymatic synthesis of myricetin 3-O-galactoside through a whole-cell biocatalyst

Objective: Myricetin 3-O-galactoside is an active compound with pharmaceutical potential. The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-O-galactoside. Thus, it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering. Methods: Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3) to reconstruct a UDP-D-galactose (UDP-Gal) biosynthetic pathway in Escherichia coli. The resultant chassis strain was able to produce UDP-Gal. Subsequently, a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal. An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E. coli. Results: The obtained engineered strain was demonstrated to be capable of producing myricetin 3-O-galactoside, reaching 29.7 mg/L. Conclusion: Biosynthesis of myricetin 3-O-galactoside through engineered E. coli could be achieved. This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.     

Cardioprotective potential of myricetin in isoproterenol‐induced myocardial infarction in wistar rats

The study aimed to evaluate the protective role of myricetin obtained from Vitis vinifera (Vitaceae) on heart rate, electrocardiographic (ECG) patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphological and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate and ST elevation in ECG, and a significant increase in the levels of cardiac marker enzymes – lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum. Isoproterenol significantly reduced superoxide dismutase (SOD) and catalase (CAT) activity and increased vascular reactivity to various catecholamines. Pretreatment with myricetin (100 mg/kg, p.o. and 300 mg/kg, p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, levels of LDH, CK, AST, SOD, CAT, vascular reactivity changes and ECG patterns. Treatment with myricetin (100 mg/kg and 300 mg/kg) alone did not alter any of the parameters compared with vehicle treated Wistar rats. Myricetin treated animals showed a lesser degree of cellular infiltration in histopathological studies. Thus, myricetin (100 mg/kg and 300 mg/kg) ameliorates the cardiotoxic effects of isoproterenol and may be of value in the treatment of MI. Copyright © 2009 John Wiley & Sons, Ltd.     

杨梅树皮的化学成分研究

目的 对杨梅（Myrica ruba）树皮的化学成分进行研究。方法用色谱法分离，并用波谱法对化合物的结构进行鉴定。结果从杨梅树皮中分离鉴定了6个化合物，其结构分别为杨梅素（myricetin，1）、杨梅苷（myricitrin，2）、taraxerol（3）、myricadoil（4）、myricanol（5）和myricanone（6）。结论首次报道湖南杨梅树皮的化学成分；1为湖南杨梅树皮的主要化学成分，该植物可作为杨梅素的资源植物加以开发利用。     

藤茶素胶囊中2种主要活性成分的RP—HPLC定量分析方法研究

目的:建立藤茶素胶囊中2种主要活性成分即双氢杨梅树皮素(dihydrowyricetin)及杨梅树皮素(myricetin)的RP-HPLC定量分析方法,以控制其质量。方法:采用反相高效液相色谱法。以ODS柱分析,流动相为甲醇-水-冰醋酸(50:50:1),流速1.0mL·min~(-1),检测波长275nm。结果:双氢杨梅树皮素和杨梅树皮素在0.096～0.960μg范围内线性良好,其高、中、低3个量的平均回收率分别为99.66％,100.3％,99.92％和99.67％,99.71％,100.2％,RSD分别为0.44％,0.30％,0.25％和0.59％,0.38％,0.23％(n=3)。结论:本法简便,快速,重复性好,可作为藤茶素胶囊的质量控制方法。