Integration of network pharmacology, bioinformatics and experimental verification strategy to discover the pharmacological mechanisms of mogroside acts against pharyngitis

Article

作者: Huaxue, Huang ; Yizhun, Zhu ; Shuang, Zhan ; Wei, Wang ; Zhi, Peng ; Guangyu, Chen ; Jianan, Mao ; Juanjiang, Wu ; Xing, Tian

ETHNOPHARMACOLOGICAL RELEVANCESiraitia grosvenorii (Swingle) C. Jeffrey ex Lu & Zhang, a popular herb in traditional Chinese materials, has been broadly employed in food and medicine homology. According to TCM, S. grosvenorii is an essential medicine for clearing the throat and relieving the lungs (Qingyanlifei). However, the bioactive effects of S. grosvenorii on pharyngitis targets remain unclear.AIMTo determine the active compounds, prospective targets, and the associated molecular mechanisms of S. grosvenorii acts healing pharyngitis. The present study integrated network pharmacology, bioinformatics, molecular docking strategies, and in vitro verification for analysis.METHODSThe active components and potential targets of S. grosvenorii and pharyngitis-related disease targets were sourced from open databases available to the public using network pharmacology approach. The key active components, anti-pharyngitis core targets and pathways were predicted to be obtained by PPI network, GO and KEGG pathway enrichment and bioinformatics analysis. Afterward, molecular docking was executed to estimate the binding interactions of the active constituents with the primary targets. Finally, the key targets predicted via network pharmacology were retrieved from the HPA database, WGCNA, and in vitro trials were performed to further substantiate the outcomes.RESULTSA total of 23 bioactive components in S. grosvenorii and 568 herb targets were screened, producing 82 mutual targets in combination with 756 disease targets. GO enrichment analysis incorporated 1708 BP, 49 CC, and 91 MF. KEGG enrichment analysis indicated that the anti-inflammatory effect of mogroside where possessed through a variety of different pathways, including PI3K/AKT and TLR4/NFκB/MyD88 signaling pathway. Probably, the PI3K/AKT signaling pathway has a key impact in S. grosvenorii against pharyngitis. Cell experiments demonstrated that mogroside, the most crucial ingredients on S. grosvenorii, regulated the release of inflammatory cytokines, as well as PI3K/AKT and TLR4/NFκB/MyD88 signaling pathway in LPS-activated RAW264.7 cells, this evidence reinforced the predictions suggested by network pharmacology and molecular docking.CONCLUSIONThe study extensively identified the biological activities, potential targets and molecular mechanisms of S. grosvenorii in combating pharyngitis through the application of network pharmacology and in vitro assessment. A perspective strategy is provided to offer the scientific foundations and healing mechanism of TCM for pharyngitis treatment.

2024-12-01·Applied Microbiology and Biotechnology

Unraveling endophytic diversity in dioecious Siraitia grosvenorii: implications for mogroside production

Article

作者: Swarnkar, Mohit ; Shivani ; Thakur, Ankita ; Kaur, Amanpreet ; Hallan, Vipin ; Thakur, Babit Kumar ; Tamang, Anish ; Pal, Probir K ; Thakur, Deepali ; Pandey, Shiv Shanker

AbstractHost and tissue-specificity of endophytes are important attributes that limit the endophyte application on multiple crops. Therefore, understanding the endophytic composition of the targeted crop is essential, especially for the dioecious plants where the male and female plants are different. Here, efforts were made to understand the endophytic bacterial composition of the dioecious Siraitia grosvenorii plant using 16S rRNA amplicon sequencing. The present study revealed the association of distinct endophytic bacterial communities with different parts of male and female plants. Roots of male and female plants had a higher bacterial diversity than other parts of plants, and the roots of male plants had more bacterial diversity than the roots of female plants. Endophytes belonging to the phylum Proteobacteria were abundant in all parts of male and female plants except male stems and fruit pulp, where the Firmicutes were most abundant. Class Gammaproteobacteria predominated in both male and female plants, with the genus Acinetobacter as the most dominant and part of the core microbiome of the plant (present in all parts of both, male and female plants). The presence of distinct taxa specific to male and female plants was also identified. Macrococcus, Facklamia, and Propionibacterium were the distinct genera found only in fruit pulp, the edible part of S. grosvenorii. Predictive functional analysis revealed the abundance of enzymes of secondary metabolite (especially mogroside) biosynthesis in the associated endophytic community with predominance in roots. The present study revealed bacterial endophytic communities of male and female S. grosvenorii plants that can be further explored for monk fruit cultivation, mogroside production, and early-stage identification of male and female plants.Key points• Male and female Siraitia grosvenorii plants had distinct endophytic communities• The diversity of endophytic communities was specific to different parts of plants• S. grosvenorii-associated endophytes may be valuable for mogroside biosynthesis and monk fruit cultivation

2024-08-01·Neuroscience Research

Neuronal activity in the anterior paraventricular nucleus of thalamus positively correlated with sweetener consumption in mice

Article

作者: Zhu, Yingjie ; Song, Bo ; Chen, Gaowei ; Sun, Jing ; Shen, Shuifa ; Jiang, Shaolei ; Qian, Weiliang ; Liu, Zhongdong

Although the brain can discriminate between various sweet substances, the underlying neural mechanisms of this complex behavior remain elusive. This study examines the role of the anterior paraventricular nucleus of the thalamus (aPVT) in governing sweet preference in mice. We fed the mice six different diets with equal sweetness for six weeks: control diet (CD), high sucrose diet (HSD), high stevioside diet (HSSD), high xylitol diet (HXD), high glycyrrhizin diet (HGD), and high mogroside diet (HMD). The mice exhibited a marked preference specifically for the HSD and HSSD. Following consumption of these diets, c-Fos expression levels in the aPVT were significantly higher in these two groups compared to the others. Utilizing fiber photometry calcium imaging, we observed rapid activation of aPVT neurons in response to sucrose and stevioside intake, but not to xylitol or water. Our findings suggest that aPVT activity aligns with sweet preference in mice, and notably, stevioside is the sole plant-based sweetener that elicits an aPVT response comparable to that of sucrose.

项与罗汉果苷相关的新闻（医药）

2021-04-04

·医学新视点

代糖就能“心安理得”享受甜蜜？这些研究告诉你健康真相

▎药明康德内容团队编辑早在1879年，科学家就发现了第一种人造甜味剂（糖精）。当时糖短缺，而糖精又很便宜，所以非常受欢迎。随着人们对饮食营养的重视，糖对健康的危害不断被强调，于是减糖和戒糖的概念频频出现在大众视野，各种代糖也在咱们的饮食中也越来越火，代糖食品、零卡饮料、零糖调味料…… 代糖的出现，似乎满足了人们“尽情享受甜蜜又不用担心健康”的愿望，但真的有这么好的事情吗？吃代糖就不用担心“甜味”对健康造成的影响了吗？我们通过对近些年研究的总结，一起来探讨背后的潜在健康误区吧。图片来源：123RF 什么是代糖？代糖，即甜味剂。目前市面上的代糖种类很多，根据是否产生热量，可以分为：营养性甜味剂（有热量）和非营养性甜味剂（无热量）。按照代糖的来源，又可以分为3大类：天然植物来源：比如从罗汉果中提取的罗汉果苷、甜叶菊中提取的甜菊糖苷、甘草、索马甜等。糖醇：结构和糖相似，算是半天然的糖，如山梨糖醇、木糖醇、甘露糖醇、赤藓糖醇和麦芽酚等。人工和合成：比如糖精、阿斯巴甜、安赛蜜、三氯蔗糖、纽甜等这些自然界原本不存在的物质。人工和合成的甜味剂甜度最高，甜度至少是蔗糖的200倍；糖醇的甜度最低，味道和蔗糖相近，甜度是蔗糖的0.7~1.2倍。中国有相关的标准法规，对允许使用的代糖品种、使用范围、最高用量都有规定。欧美监管机构对所批准的人造甜味剂也都经过了安全性评估。一般咱们在正规渠道能买到的代糖食品、饮料，可以说不用太担心安全性。那么，是不是这就意味着我们可以放心敞开吃代糖食品了呢？图片来源：123RF 代糖对血糖有影响吗？人造甜味剂由于性质不同，在人体内的代谢情况也各异。迄今为止，进行的大多数临床研究均未报告人造甜味剂对血糖控制有显著影响或有益作用。但是有研究表明，吃代糖可能会增加糖尿病风险。2019年，一项由哈佛大学领导，复旦大学和华中科技大学研究人员共同参与的重磅研究发表，对近20万人追踪26年的数据显示：无论胖瘦，喝甜饮料都会增加糖尿病风险，而且果汁、代糖都不是理想的解决之道，多喝人造甜味剂饮料的危害似乎最大，风险增加18%。代糖能帮助减肥吗？先前有大量的数据表明，高糖饮食对健康有害，尤其是会导致体重增加。那如果吃甜味剂可以减少热量的摄入，这是不是意味着吃代糖可以减少体重增加的风险？目前，许多研究调查了代糖是否会减重，总的来说，代糖对减肥的影响并不明确，可能有积极作用、也可能没用，在某些情况下还可能会增加体重。一项由世界卫生组织委托、发表在《英国医学杂志》（BMJ）的研究，对56项不同研究进行荟萃分析表明：在大多数情况下，使用人工甜味剂的人群并没有比使用糖的人群体重下降；而且对于超重或肥胖人群，没有发现任何使用无糖甜味剂有效的证据。代糖对体重影响不明确的原因有：甜味剂的种类有很多，每种甜味剂对减肥的影响可能不同。除了改用甜味剂外，食物选择上也有可能会改变。来自悉尼大学的生物化学家Kieron Rooney博士说：“整体饮食是很重要的，因为代糖与其他食物一起食用可能会产生相互作用，从而改变能量的吸收”。甜味剂对减肥的影响很可能取决于个人的原始体重和饮食习惯。图片来源：123RF 代糖能让心情更愉悦吗？吃甜食让人愉悦。但如果吃甜味剂来改善心情，可能是吃了个“寂寞”。一项队列研究证明，吃甜味剂的人群抑郁风险增加14%。另外，代糖可能并没有让大脑真正“满足”，还有可能会让你更想吃“真的糖”。营养学博士Cornelie Nienaber-Rousseau解释说：“甜味剂对食物奖励系统的影响，可能会导致食欲增加，增加寻求食物的行为，并刺激对糖的渴望。而且非营养性甜味剂似乎会改变肠道微生物组。” 代糖能抗癌吗？对照试验的Meta分析和观察性研究显示，吃无糖甜味剂的人群，除了卵巢癌和胰腺癌风险略低，其他癌症的风险都没有差异。此外，所有经欧美监管机构批准的人造甜味剂都已经在动物实验和人类数据中进行了测试，没有一种甜味剂与癌症有任何关系。图片来源：123RF 代糖对心血管有好处吗？《美国心脏病学会杂志》（JACC）发表的一项大型研究表明，平均每天喝少量含糖饮料和人造甜味剂饮料，就与心血管疾病（CVD）风险升高有关，这意味着代糖饮料并不是一个健康的替代选择。统计发现：相较于不喝含糖饮料的人群，喝含糖饮料最多（中位数为每天185 ml）的人群更容易发生CVD事件，风险升高20%。相似地，相较于不喝人工甜味剂饮料的人群，喝人工甜味剂饮料最多（中位数为每天176.7 ml）的人群，CVD事件风险升高32%。值得注意的是，与风险升高相关的这个摄入量水平，每天一杯饮料就能达到。总结来看，根据现有证据，使用甜味剂替代糖分，特别是代糖饮料，对体重和糖尿病的风险降低的好处均没有令人信服的证据，也还没有足够的证据可以证明甜味剂对健康有益。而且，近年来也有越来越多的研究开始提示甜味剂的潜在健康危害。食用甜味剂的安全性和健康益处，仍然是科学界和整个社会争论的话题，需要更多长期研究来确定代糖的健康影响。流行病学家Gideon Meyerowitz-Katz总结说：“这是一个未解决的问题，与糖相比，所有迹象都表明人造甜味剂可能更好；但甜味剂可能比喝水更糟。” 来自哈佛大学公共卫生学院的Vasanti Malik博士也赞同：“最终目标是转向喝水或其他健康饮料”。推荐阅读哈佛20万人研究：长期喝甜饮料、代糖饮料，糖尿病风险有多高？ JACC超10万人数据：为了心血管，代糖并不是含糖饮料的健康替代 BMJ：零热量代糖对减肥无效，无益健康！这项研究可能震动世界卫生组织 45万人跨国研究：甜饮料又亮红灯！每天喝一杯，多种疾病来“要命” 参考资料： [1] Jean-Philippe Drouin-Chartier, et al., (2019). Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and Subsequent Risk of Type 2 Diabetes: Results From Three Large Prospective U.S. Cohorts of Women and Men. Diabetes Care, 10.2337/dc19-0734 [2] No compelling evidence for health benefits of non-sugar sweeteners. Retrieved Jan 4, 2019, from https://www.eurekalert.org/pub_releases/2019-01/b-nc010219.php [3] Pearlman, M., Obert, J., & Casey, L. (2017). The association between artificial sweeteners and obesity. Current gastroenterology reports, 19(12), 64. [4] Ahmad, S. Y., Friel, J. K., & MacKay, D. S. (2020). The effect of the artificial sweeteners on glucose metabolism in healthy adults: A randomized, double-blinded, crossover clinical trial. Applied Physiology, Nutrition, and Metabolism, 45(6), 606-612. [5] Are Artificial Sweeteners Healthier Than Sugar or No? Here's What Experts Think. Retrieved 28 MARCH 2021, from https://www.sciencealert.com/are-artificial-sweeteners-are-better-for-you-than-sugar-scientists-weigh-in [6] Pang, M. D., Goossens, G. H., & Blaak, E. E. (2020). The impact of artificial sweeteners on body weight control and glucose homeostasis. Frontiers in Nutrition, 7. 注：本文旨在介绍医药健康研究进展，不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德微信团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号后台回复“转载”，获取转载须知。本文来自药明康德微信团队，版权说明：本文来自药明康德微信团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号后台回复“转载”，获取转载须知。如有其他合作需求，请联系wuxi_media@wuxiapptec.com 点“在看”，分享医学新知