大黄素治疗代谢相关脂肪性肝病的作用机制研究进展

代谢相关脂肪性肝病既往称为非酒精性脂肪肝，与肥胖、糖尿病、高脂血症等关系密切，还明显增加心血管死亡的风险。大黄素是大黄、何首乌中主要的活性成分，具有多种生物学功能。大黄素可通过降低肝细胞脂质沉积、抑制肝脏炎症反应、抗胰岛素抵抗、抑制肝纤维化、抗氧化应激反应等多种途径对代谢相关脂肪性肝病发挥治疗作用。总结了大黄素治疗代谢相关脂肪性肝病的作用机制，为代谢相关脂肪性肝病的治疗提供参考。     

基于JAK2/STAT3信号通路探讨大黄素保护AR42J胰腺腺泡细胞损伤的作用机制

目的基于JAK2/STAT3信号通路探讨大黄素保护AR42J胰腺腺泡细胞损伤的作用机制。方法将AR42J细胞以1×10~5/mL铺于6孔板,分为对照组、雨蛙素组(雨蛙素10~(-8) mol/L)、大黄素组(终浓度0.25、0.5、1.0mg/L),通过碘-淀粉比色法淀粉酶(AMS)试剂盒测定细胞上清淀粉酶活力水平,确定雨蛙素刺激AR42J胰腺腺泡细胞损伤的收样时间;ELISA法检测TNF-α活力;Western blot法分析JAK2/STAT3通路相关蛋白的表达情况。结果①与对照组比较,雨蛙素组中的AMS、TNF-α、JAK2/STAT3通路相关蛋白表达量显著提高,差异有统计学意义(P0.05)。②与雨蛙素组比较,大黄素各干预组可显著降低雨蛙素诱导的胰腺腺泡细胞损伤的淀粉酶活力、TNF-α含量、JAK2和STAT3的mRNA相对表达量,差异有统计学意义(P0.01)。③大黄素0.5、1.0 mg/L干预组的作用优于0.25 mg/L干预组,差异有统计学意义(P0.001)。结论大黄素能够减轻雨蛙素诱导的胰腺腺泡细胞损伤,其作用机制可能与调控JAK2/STAT3信号通路有关。     

Aloe‐emodin: A review of its pharmacology,toxicity, and pharmacokinetics

Aloe‐emodin is a naturally anthraquinone derivative and an active ingredient of Chinese herbs, such as Cassia occidentalis, Rheum palmatum L., Aloe vera, and Polygonum multiflorum Thunb. Emerging evidence suggests that aloe‐emodin exhibits many pharmacological effects, including anticancer, antivirus, anti‐inflammatory, antibacterial, antiparasitic, neuroprotective, and hepatoprotective activities. These pharmacological properties lay the foundation for the treatment of various diseases, including influenza virus, inflammation, sepsis, Alzheimer's disease, glaucoma, malaria, liver fibrosis, psoriasis, Type 2 diabetes, growth disorders, and several types of cancers. However, an increasing number of published studies have reported adverse effects of aloe‐emodin. The primary toxicity among these reports is hepatotoxicity and nephrotoxicity, which are of wide concern worldwide. Pharmacokinetic studies have demonstrated that aloe‐emodin has a poor intestinal absorption, short elimination half‐life, and low bioavailability. This review aims to provide a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of aloe‐emodin reported to date with an emphasis on its biological properties and mechanisms of action.     

中药活性成分大黄素用于治疗新型冠状病毒肺炎的可能性

2019新型冠状病毒感染已严重威胁到人们的健康和生活,但目前尚无特效治疗药物对其进行有效的防控。大黄素作为蓼科植物大黄及虎杖的主要活性成分,具有广谱的抗病毒活性,对包括SARS冠状病毒(SARS-CoV)、流感病毒、HIV病毒、HBV病毒等的感染和复制具有抑制作用。因此,本文就抗SARS-CoV的中成药及中药复方、大黄素及复方制剂抗病毒的机制、含大黄及虎杖的复方制剂抗病毒的临床研究和大黄素用于治疗新型冠状病毒肺炎(COVID-19)的可能性进行综述,旨在探讨其治疗2019新型冠状病毒的临床可能性。     

利用1H-NMR技术研究大黄素染毒后大鼠内源性代谢物的改变

目的 采用¹H NMR的代谢组学技术揭示大黄素的肾毒性机制,寻找肾脏损害的早期生物标志物.方法 雄性SD大鼠20只,随机分为溶剂对照,大黄素170、500、1 500 mg/(kg·d)3个剂量组,连续给药16 d,给药结束后收集24 h尿液,血浆及肾组织,测定¹H NMR谱,并进行血浆生化指标测定和肝脏组织病理学检查.结果 1 500 mg/(kg·d)大黄素服用16 d可引起大鼠血肌酐下降,大黄素可导致肾细胞胞浆中出现明显的空泡化改变.代谢成分的改变主要表现为血液中乳酸、糖、氨基酸和脂肪酸成分下降;尿液中乳酸、糖和氨基酸成分增加;肾脏组织中醋酸盐和肌酐/肌酸明显升高,乳酸和胆碱/磷酸卵磷脂水平下降,饱和与不饱和脂肪酸及磷脂的成分比例明显改变.结论 代谢组学分析在识别药物诱导代谢成分改变方面较传统技术更灵敏;脂肪和能量代谢紊乱参与了大黄素的肾毒性,尿液中氨基酸、葡萄糖氧化三甲胺(TMAO)及肌酐可作为大黄素诱导肾组织损害的潜在生物标志物.     

Synthesis,Characterization, and Anticancer Activity of Novel Lipophilic Emodin Cationic Derivatives

Seventeen novel emodin derivatives were synthesized, and the structures were confirmed by IR, H NMR, MS, and elemental analysis. The cytotoxic activity of the derivatives was evaluated against A375, BGC‐823, HepG2, and HELF cells by MTT assay. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. The lead compound 9a induced a loss of the mitochondrial transmembrane potential (?Ψm), an increase in reactive oxygen species (ROS), release of cytochrome c and activation of caspase‐3 and caspase‐9. In addition, the confocal study showed that emodin derivative 9a (containing asymmetric hydrocarbon tails) was mainly localized in mitochondria, demonstrating a key role of the mitochondria‐mediated apoptosis pathway in cancer cells. Taken together, the results demonstrate that embodin derivative 9a preferentially regulates the ROS‐mediated apoptosis in A375 cells through the induction of cytochrome c expression and activation of caspase‐3 and caspase‐9 proteins.     

基于支持向量机的5种大黄苷元治疗脑缺血的配伍研究

目的筛选大黄中5种能够治疗脑缺血的大黄苷元(芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚)的最佳配伍。方法采用均匀设计法将大鼠分为14组,每组15只。采用线栓法制备大鼠大脑中动脉闭塞(MCAO)模型,以神经功能症状评分、脑梗死面积为指标,探讨不同配伍的大黄苷元对脑缺血大鼠的影响,同时基于支持向量机(SVM)建立大黄苷元药效预测模型。结果经SVM回归分析,得到大黄苷元最优配伍为芦荟大黄素6.653 4 mg/kg、大黄酸26.000 8 mg/kg、大黄素11.004 2 mg/kg、大黄酚3.841 4 mg/kg和大黄素甲醚3.862 0 mg/kg。结论不同配比的大黄苷元能有效改善大鼠脑缺血的各个指标,采用均匀设计结合SVM的模拟预测方法优选出了5种大黄苷元组分的最佳配比。     

多指标综合评分法优选敷胸巴布贴醇提工艺

目的:优选敷胸巴布贴的醇提工艺。方法:以大黄素、黄芩苷、桑辛素含量及浸膏得率的综合评分为指标,利用正交试验考察乙醇体积分数、溶剂用量、提取时间及提取次数对敷胸巴布贴醇提工艺的影响。采用HPLC测定大黄素及黄芩苷含量,流动相分别为甲醇-0.4%磷酸溶液(80∶20),甲醇-0.4%磷酸溶液(47∶53),检测波长分别为254,280 nm。采用紫外分光光度法测定桑辛素含量。结果:最佳醇提工艺为加6倍量75%乙醇提取2次,每次3 h。大黄素、黄芩苷、桑辛素质量分数及浸膏得率分别为0.19%,3.61%,0.51%,31.19%。结论:优选的提取工艺合理可行,有效成分提取效率高。     

大黄素对兔主动脉平滑肌细胞CatK,CatDmRNA表达的影响

目的:探讨大黄素对兔主动脉平滑肌细胞(CCC-SMC-1)组织中蛋白酶K(Cat K),组织蛋白酶D(Cat D)mRNA表达的影响。方法:以2×104/m L密度接种细胞,实验分5个实验组,大黄素0.01,0.05,0.1,0.15,0.2,0.25 mmol·L-1组,对照组为培养基空白组,培养24 h,每组设5个复孔。MTT法观察大黄素对兔主动脉平滑肌细胞增殖的抑制作用,PCR法检测大黄素对兔主动脉平滑肌细胞Cat K,Cat D mRNA的表达。结果:MTT法显示大黄素在0.05~0.25 mmol·L-1浓度对CCCSMC-1细胞增殖有抑制作用,作用24 h后的半数抑制浓度(IC50)为0.10 mmol·L-1,且IC50随作用时间的延长显著前移。PCR法显示,不同浓度的大黄素作用于兔主动脉平滑肌细胞24 h后,与正常组细胞相比,Cat K,Cat D mRNA表达上调(P0.05)。结论:大黄素能抑制CCC-SMC-1细胞的增殖,其机制可能与上调Cat K,Cat D mRNA表达有关。     

Emodin induces apoptosis of human osteosarcoma cells via mitochondria- and endoplasmic reticulum stress-related pathways

Aim: Emodin showed anti-cancer activity against multiple human malignant tumors by inducing apoptosis. However, the apoptotic inducing effect against human osteosarcoma and related mechanism are still not studied. This study was aimed to investigate them. Methods: Emodin was used to incubate human OS cell U2OS cells at serially diluted concentrations. Hoechst staining was used to evaluate apoptosis; flow cytometry was applied to assess the collapse of mitochondrial membrane potential (MMP); intracellular ROS generation was detected by DCFH-DA staining; endoplasmic reticulum stress activation was examined by western blotting. Results: Cell apoptosis of U2OS cells was induced by emodin incubation in a concentration-dependent manner; MMP collapse and ROS generation were identified at starting concentration of 80 μmol/L of emodin in a concentration-dependent manner. ER stress activation was found at beginning concentration of 40 μmol/L of emodin. The MMP collapse was inhibited while the ER stress was not inhibited by NAC administration. Conclusions: Emodin induces death of human osteosarcoma cells by initiating ROS-dependent mitochondria-induced and ROS-independent ER stress-induced apoptosis.