Allicin

关注并星标CPHI制药在线 呼吸道病毒是以呼吸道为侵入门户，在呼吸道黏膜上皮细胞中增殖，引起呼吸道局部感染或呼吸道以外组织器官病变的一类病毒，主要包括正黏病毒科（流感病毒）、副黏病毒科（副流感病毒、呼吸道合胞病毒、麻疹病毒、腮腺炎病毒、亨德拉病毒、尼帕病毒、人偏肺病毒）、冠状病毒科（SARS-CoV、MERS-CoV、2019-nCoV冠状病毒）、披膜病毒科（风疹病毒）、小RNA病毒科（鼻病毒）等不同病毒科的多种病毒。呼吸道病毒感染是全球范围内人类发病和死亡的主要原因之一，多数急性呼吸道感染是由病毒引起的。天然药物主要通过直接和间接途径发挥抗呼吸道病毒感染类疾病，直接作用是指抑制病毒的吸附和阻止病毒释放，从而保护机体细胞不受损害，间接作用则是通过免疫调节作用起到抗病毒效果。 1、抑制病毒的吸附和阻止病毒释放 血管紧张素转化酶2 (angio‐tensin-converting enzyme 2，ACE2) 是存在于宿主细胞上的一种受体，新型冠状病毒表面的刺突蛋白可以协助病毒找到宿主细胞上的 ACE2 受体并诱导病毒与受体细胞相结合，吸附宿主细胞，在酶的反应下病毒的包膜与宿主细胞融合进而入侵宿主细胞。研究发现青蒿素及其衍生物可以缠绕新冠病毒刺突蛋白的Lys353和Lys31 结合位点，从而影响其与人体ACE2受体蛋白的融合，从而阻止病毒吸附宿主细胞。高分辨质谱和ACE2生物色谱法筛选确定连花清瘟中的大黄酸、连翘苷A、连翘苷I、新绿原酸及其异构体对ACE2具有高度抑制作用。姜黄素、醉茄素A、胡椒碱、芒果苷、蒂 巴 因、小檗碱、穿心莲内酯和印楝素对SARS-CoV-2 的刺突蛋白和ACE2 受体均具有显著的结合亲和力，可以阻断刺突蛋白与ACE2 受体的结合从而抑制病毒吸附宿主细胞。中药丹参水溶性单体成分丹酚酸可通过阻止刺突蛋白六螺旋束结构形成，有效抑制新型冠状病毒的吸附。 血凝素（HA）和神经氨酸酶（NA）是流感病毒包膜上的2种糖蛋白，在流感病毒入侵宿主细胞及传播的过程中扮演着重要的角色。HA可识别并结合宿主细胞表面的唾液酸受体，使病毒粘附于宿主细胞表面、介导病毒包膜与胞内体膜融合；NA能够水解宿主细胞表面的唾液酸释放新病毒。研究发现，槲皮素可通过与流感病毒血凝素蛋白结合，竞争性抑制流感病毒血凝素与宿主细胞的唾液酸结合，抑制病毒包膜与宿主细胞膜融合，抑制病毒以胞吞形式入侵宿主细胞。发酵人参提取物可通过抑制HA、NA活性对H1N1、H3N2、H5N1、H7N9病毒起到治疗作用。穿心莲内酯磺化物可通过抑制HA活性实现抗H1N1、H3N2、乙型流感病毒（IBV）的作用。大蒜素可以用作H1N1的NA、HA、M2蛋白通道的有效多靶点抑制剂，黄芩苷可通过抑制病毒的血凝素HA2亚基活性而抑制H5N1禽流感病毒的进入。安石榴苷能抑制流感病毒的神经氨酸酶，阻止唾液酸的分解，阻断病毒释放。诃子酸和诃子林鞣酸可以抑制病毒NA蛋白的活性，破坏病毒与宿主细胞上唾液酸的结合，在感染的细胞中阻止病毒释放。 人呼吸道合胞病毒 (human respiratory syncytial virus，HRSV) 含有三种膜结合蛋白：附着蛋白(G)、融合蛋白(F)、病毒孔蛋白 (SH)。蛋白G可与宿主细胞结合，蛋白F可以融合病毒和细胞膜，使病毒核糖核蛋白能够到达细胞质。三种糖蛋白相互作用使病毒入侵宿主细胞。甘草可通过抑制病毒附着、内化减少HRSV感染，18β-甘草次酸是影响甘草抗HRSV 活性的活性成分之一。穿心莲内酯衍生物可有效抑制HRSV包膜表面糖基蛋白荧光肽的裂解，阻止病毒入侵细胞。车前草醇提液可通过与HRSV竞争结合Hep-2细胞表面的特异性受体抑制HRSV的吸附过程，同时可直接杀死病毒，发挥抗RSV作用。  2、抑制病毒的增殖 病毒感染特定的活细胞后，可以在病毒核酸的控制下，利用宿主细胞的能量系统、核糖体等合成病毒核酸和蛋白质，最后组装成结构完整、具有感染力的成熟病毒颗粒。冠状病毒3C 样蛋白酶(3C-like protease，3CLpro) 与木瓜蛋白酶样蛋白酶(papain-like protease，PLpro) 在病毒增殖过程能够将多肽链切割分解成病毒复制需要的片段。通过研究发现，木犀草素、β-谷甾醇、芒柄花黄素、紫檀素、蒙花苷、金丝桃苷等通过与3CLpro特异性结合，阻止3CLpro发挥作用。萝卜硫素 (SFN) 是一种缓慢结合的抑制剂，SFN与3CLpro能够发生共价反应， 形成了SFN-3CLpro复合物，从而阻断3CLpro的作用。杨梅素可以与3CLpro共价结合，阻止3CLpro发挥作用，从而抑制病毒的增殖。冬凌草甲素不仅能够抑制3CLpro 的活性，而且在高浓度下可以阻止PLpro主导的反应活动，从而阻止病毒的增殖。新橙皮苷、蛇床子素等与PLpro结合，阻止PLpro发挥作用，从而抑制病毒增殖。西北甘草异黄酮和甘草异黄酮 A可以与RNA依赖的RNA聚合酶 (RNA-dependent RNA polymerase，RdRp) 结合形成复合物，阻止RdRp发挥作用，从而抑制病毒的增殖。 核因子-κB (nuclear factor-κB，NF-κB) 信号通路可以调节流感病毒RNA合成，在病毒的复制过程中发挥重要作用。葡萄红素B能够抑制H1N1病毒在MDCK和A549细胞中的复制，并通过IκB激酶 (IκB kinase，IKK) 去磷 酸化抑制NF-κB 转入细胞核，从而降低了病毒诱导的活性氧 (reactive oxygen species，ROS)的生成。细胞周期蛋白依赖性激酶抑制剂p21可以直接与病毒聚合酶酸性蛋白结合，并通过破坏核糖核蛋白复合物的形成来限制IAV聚合酶活性，从而阻止病毒增殖。 免疫调节        病毒感染机体时，巨噬细胞是防御系统的第一道屏障，产生各种抗病毒因子如白细胞介素IL-1、IL-6、肿瘤坏死因子TNF⁃α等，介导机体发挥抗病毒免疫应答，进而抑制和清除体内病毒细胞。人参多糖治疗H9N2感染的鸡发现，其胚胎成纤维细胞CEF中MHC Ⅱ基因表达及细胞因子IL-2、IL-4、IL-10水平升高，表明人参多糖可通过增强体液免疫应答促进机体抗病毒活性。儿茶提取物可增强流感病毒感染小鼠的细胞免疫，还能促进特异性中和抗体产生。干扰素是细胞相互交流以预防和根除病毒感染的一种手段，分为Ⅰ型、Ⅱ型、Ⅲ型。先天性免疫细胞分泌的以IFN⁃α 与IFN⁃β 为主的Ⅰ型干扰素（IFN）介导的天然免疫机制是宿主细胞抵抗冠状病毒最重要的方式之一。研究报道，黄檗水提物通过诱导Ⅰ型干扰素（IFN⁃β）或促炎性细胞因子（IL-6、TNF⁃α）和随后刺激在宿主细胞中的抗病毒状态， 从而抑制病毒复制， 提高小鼠对甲型流感病毒H1N1、H5N2、H7N3、H9N2的感染存活率。IFN⁃γ 属于Ⅲ型干扰素，主要由Ⅰ型辅助性T细胞（Th1细胞）及自然杀伤细胞产生。研究表明，红参水提物可通过抑制HRSV诱导的小鼠树突状和巨噬细胞样细胞中炎性因子TNF⁃α、IL-6、IL-8表达和人肺上皮细培养液中活性氧的形成，降低肺病毒载量，增强干扰素IFN⁃γ分泌以及增加小鼠 HRSV感染后CD8+T细胞和CD11c+树突状细胞的数量等多种机制发挥抗HRSV作用。此外，红参水提取物可诱导甲型流感病毒H5N1感染的小鼠肺组织IFN⁃α、IFN⁃γ 产生，增强免疫从而减轻H5N1流感病毒的感染。 视黄酸诱导基因1样受体（RLRs）信号通路在抗病毒免疫的过程中发挥着重要作用。当16HBE细胞被H1N1 病毒感染后，炎症因子IL-4、IFN⁃γ、RLRs通路相关因子RIG-Ⅰ、IFN⁃β 启动子刺激物⁃1（IPS-1）、IRF-7、IRF-3、NF⁃κB水平均升高，穿心莲内酯干预后上述因子水平均降低，提示穿心莲内酯可通过降低其信号因子来影响RLRs信号通路。研究发现，连翘酯苷A可通过降低小鼠肺部免疫细胞的RLRs信号通路相关蛋白RIG-Ⅰ、MAVS、NF?κBp65表达，降低Th 1/Th 2和Th 17/Treg比例，从而减轻甲型流感病毒FM1株在小鼠肺部引起的炎症反应。 Toll样受体（TLRs）信号通路也是和呼吸道病毒相关的天然免疫主要信号通路之一， TLRs可以激活 NF⁃κB等转录因子，促进多种与免疫有关的细胞因子及趋化因子的分泌从而引起炎症反应。玉叶金花水提物能抑制感染流感病毒A/FM1/47（H1N1）小鼠血清TNF⁃α、IL⁃6、 IL-1β过表达及肺组织中TLR7、MyD88、NF⁃Κb mRNA及蛋白表达，提示玉叶金花可通过降低TLR7介导的MyD88依赖的信号转导通路活化抑制 NF⁃κB活性，从而减轻炎症风暴， 发挥抗流感病毒作用。研究发现，栀子苷通过影响TLR3/TRIF信号通路，降低炎性细胞因子IL-6、TNF⁃α 表达，促进抗病毒因子IFN⁃β 合成，保护A/FM/1/4（H1N1）建立的流感病毒性肺炎小鼠引起的病毒性肺损伤。黄芩苷可通过抑制TLR4/NF⁃κB信号转导途径，降低下游细胞因子IL-6 水平来发挥抑制 HRSV 感染的作用。 参考文献：       [1]王剑,张萍萍,于健,等.天然药物抗呼吸道病毒活性成分及其作用机制研究进展[J].药学学报,2024,59(04):853-865. [2]杜正彩,郝二伟,韦棪婷,等.中国-东盟传统药用植物抗呼吸道常见病毒研究进展[J].中成药,2022,44(11):3579-3587. 作者简介： 小米虫，药品质量研究工作者，长期致力于药品质量研究及药品分析方法验证工作，现就职于国内某大型药物研发公司，从事药品检验分析及分析方法验证。 END 【智药研习社直播预告】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

New clinical study indicates ABG10+® supports drug therapy to maintain blood pressure levels in a normal range. MADRID, Oct. 9, 2023 /PRNewswire/ -- Results of a new clinical study have confirmed the blood pressure balancing effect of Pharmactive Biotech Products, SLU's ABG10+®. Aged Black Garlic (ABG10+®) has demonstrated the positive effect in blood pressure in patients exhibiting Grade-1 hypertension receiving prescribed drug treatment. Continue Reading Pharmactive’s Aged Black Garlic Extract May Improve High blood Pressure Levels in New Study Aged Black Garlic is a whole raw garlic bulb (Allium sativum L) that has been aged under controlled temperatures for a certain period of time. Pharmactive's proprietary ageing process potentiates the accumulation of garlic's bioactive complex of antioxidant compounds, including polyphenols, flavonoids, and melanoidins—particularly S-allyl cysteine (SAC). The study, published in the research journal Nutrients, was a randomized, triple-blind controlled trial conducted at the Hospital Universitari Arnau de Vilanova (Lleida, Spain), and in collaboration with the Atherothrombotic Disease Detection and Treatment Unit (UDETMA). Led by Dr. José Carlos Serrano, Ph.D., the study involved 81 volunteers suffering from Stage 1 hypertension and who were already on blood pressure-reducing medication. Over a period of 12 weeks, the subjects received 250mg of ABG10+ daily, which provided 0.25mg of SAC, or a placebo. No changes were made to diet or lifestyle and the subjects were instructed to continue taking their blood pressure medication. Blood pressure measurements were recorded daily at home by the participants as well as at baseline and at the end of the study by specialists. The addition of ABG+ supplementation helped better control blood pressure levels, with reductions observed in both systolic and diastolic blood pressure of 1.8 mmHg and 1.5 mmHg, respectively. Moreover, it was observed via blood serum tests that ABG10+ supplementation may boost the release of nitric oxide and increase the body's antioxidant capacity. ACE (angiotensin converting enzyme) activity seemed to be reduced, and lower blood uric acid levels also were observed. "These secondary parameters help us gain an understanding of the likely mechanism behind ABG10+'s effect on blood pressure," explains Alberto Espinel, Open Innovation Director of Pharmactive. "Nitric oxide is a natural vasorelaxant produced in the body to maintain cardiovascular function, improving blood pressure, and increasing blood flow. Nitric oxide also is a cellular antioxidant and thus helps mitigate oxidative stress and its associated negative effects on blood vessels and the cardiovascular system. Reducing the angiotensin converting enzyme activity is a key strategy to decrease blood pressure in hypertensive patients." The majority of the volunteers enrolled in the study had a medical history of high blood pressure spanning 15 years on average. Despite adhering to their prescribed pharmacological routine, they were still unable to maintain blood pressure levels within a normal range. "This study suggests that incorporating food bioactives such as aged black garlic extract into the treatment regimen could serve as a valuable complement to conventional drug therapy, and could contribute to reduced cardiovascular risk," Espinel adds. "Such intervention could be especially beneficial for the management of arterial high blood pressure in persons experiencing resistance to drug therapy—all without inducing side effects." Hypertension is a leading risk factor for cardiovascular disease, including stroke and heart failure. Research has demonstrated that even modest reductions in blood pressure can lead to meaningful gains in the prevention of such incidents. For example, a reduction of 2mm Hg in systolic blood pressure can reduce the risk of stroke by 10% in middle age. The new study followed favorable outcomes of a 2022 clinical trial involving ABG+, where participants with moderately elevated cholesterol levels achieved significant reduction in diastolic blood pressure (5.85 mmHg on average) compared to placebo. "As garlic ages, its fresh compounds like allicin and sulphur undergo chemical changes, forming new compounds, including SAC and melanoidins," explains Carlos Rodríguez, Communication Manager. "These compounds create the special flavor, aroma, and color of aged black garlic which is why it is a culinary favorite of chefs. Yet these same bioactive compounds are believed to possess powerful antioxidant and support cardio health." Pharmactive's ABG10+ extract is derived from garlic grown and cultivated in Castilla la Mancha, two hours away from the company's facility in Madrid, and gently processed using green technology, without the use of solvents, or chemicals. The ingredient can readily be incorporated into supplements as well as functional foods. About Pharmactive Pharmactive Biotech Products, SLU, is a Madrid-based pioneering biotechnology company that develops and manufactures differentiated natural ingredients supported by science, such as damiana extract, pure saffron extract, and aged black garlic. The company's mission is to make a daily positive and significant impact on people's health and well-being through premium botanical ingredients backed by scientific studies and approved by ethics committees. Be sure to visit Pharmactive at Supply Side West, 25-26 Oct (Booth #2965). For more information, contact: Photo - SOURCE Pharmactive Biotech Products, S.L.