Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

天麻素生物合成的研究进展

天麻素是我国名贵中药材天麻中的一种主要活性成分，具有降血压、抗癫痫、抑制肿瘤、保护神经等多方面的药理活性。随着市场对天麻素需求的不断增长以及传统获取方法固有的问题，导致急需新的方法来解决天麻素生产实际中面临的各项困难。生物合成法是一种有别于传统获取法的新方法，已在天麻素获取上取得了较大进展和成果，故现阶段有必要从天麻素生物合成途径、植物转化法和微生物转化法3个方面，对天麻素生物合成进行系统地阐述，从而为进一步改进和完善天麻素生产方法，以满足人们对其不断增长的需求提供有价值的参考。     

Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials

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Sequential divergence and the multiplicative origin of community diversity

Phenotypic and genetic variation in one species can influence the composition of interacting organisms within communities and across ecosystems. As a result, the divergence of one species may not be an isolated process, as the origin of one taxon could create new niche opportunities for other species to exploit, leading to the genesis of many new taxa in a process termed “sequential divergence.” Here, we test for such a multiplicative effect of sequential divergence in a community of host-specific parasitoid wasps, Diachasma alloeum, Utetes canaliculatus, and Diachasmimorpha mellea (Hymenoptera: Braconidae), that attack Rhagoletis pomonella fruit flies (Diptera: Tephritidae). Flies in the R. pomonella species complex radiated by sympatrically shifting and ecologically adapting to new host plants, the most recent example being the apple-infesting host race of R. pomonella formed via a host plant shift from hawthorn-infesting flies within the last 160 y. Using population genetics, field-based behavioral observations, host fruit odor discrimination assays, and analyses of life history timing, we show that the same host-related ecological selection pressures that differentially adapt and reproductively isolate Rhagoletis to their respective host plants (host-associated differences in the timing of adult eclosion, host fruit odor preference and avoidance behaviors, and mating site fidelity) cascade through the ecosystem and induce host-associated genetic divergence for each of the three members of the parasitoid community. Thus, divergent selection at lower trophic levels can potentially multiplicatively and rapidly amplify biodiversity at higher levels on an ecological time scale, which may sequentially contribute to the rich diversity of life.Population divergence is a fundamental evolutionary process contributing to the diversity of life (1). Studies of how new life forms originate typically focus on how barriers to gene flow evolve in specific lineages, resulting in their divergence into descendent daughter taxa. As a result, evolutionary biologists now have a good understanding of how variation within a population is transformed by selection into differences between taxa (1–3). What is less well understood is whether the divergence of one population has consequences that ripple through the trophic levels of an ecosystem and affect entire communities of interacting organisms. Studies in paleontology (4–6), community ecology (7, 8), systematics (8, 9), and ecosystem genetics (10, 11) suggest that evolutionary change in one lineage can influence entire communities of organisms. For example, when the genotype/phenotype of a “foundation” species influences the relative fitness of other species, evolutionary change(s) in this genotype/phenotype may affect organisms in adjacent trophic levels (10, 11). If these evolutionary changes are linked to ecological adaptation and reproductive isolation (RI), associated organisms may diverge in parallel, potentially creating entire coevolved communities distinct from one another (12–15). Therefore, population divergence may not always be an isolated process, as the differentiation of one taxon could beget the divergence of many others.Such “sequential” or “cascading” divergence events may be particularly relevant to understanding why some groups of organisms, like plants, the insects that feed on them, and the parasitoids that attack the insects, are more diverse and species-rich than other groups (8, 9, 12–15). Specifically, when phytophagous insects diversify by adapting to new host plants, they create a new habitat for their parasitoids to exploit (Fig. 1). If a parasitoid shifts to the new habitat, it can encounter the same divergent ecological selection pressures as its insect host, which could result in the parallel divergence of insect host and parasitoid (12–15) (Fig. 1A). Moreover, sequential divergence may have multiplicative effects in generating biodiversity, as the shift of an insect to a new plant may open a new niche opportunity for not just one but the entire community of parasitoids attacking the insect host (12, 13) (Fig. 1B). However, few convincing examples of sequential divergence exist (12–15), and in no study is there both genetic and ecological evidence for sequential divergence multiplicatively amplifying biodiversity.Open in a separate windowFig. 1.Three scenarios of codivergence in a host−parasitoid system. (A) A single sequential divergence event, (B) sequential divergence with multiplicative amplification of biodiversity, and (C) cospeciation in allopatry. In A, codivergence is driven by the cascade of divergent ecological selection pressures across trophic levels in sympatry. Here, a degree of divergent ecological adaptation must accompany the host shift such that parasitoids are not merely moving between geographically separated hosts. In B, the multiplicative effects of sequential divergence can be seen as several members of the parasitoid community diverge in parallel with their host. In C, codivergence (cospeciation) occurs after host plant, fly, and parasitoid populations become jointly geographically isolated (black bar), resulting in parallel allopatric speciation. Here, little differentiation need accompany the initial host shift of fly or parasitoid. Cospeciation is not necessarily driven by the creation and adaptation to new niches but by the concordant geographic and reproductive separation of hosts and parasitoids.Here, we test for the multiplicative effects of sequential divergence in the community of parasitoid wasps (Hymenoptera: Braconidae) that attack fruit flies in the Rhagoletis pomonella sibling species complex (Diptera: Tephritidae) (Fig. 2). Several features of the biology and biogeography of the Rhagoletis−parasitoid system make it ideal for investigating the multiplicative divergence hypothesis and allow us to directly test multiple criteria supporting sympatric host race formation (16) and sequential divergence (12, 13), summarized in 1–3, 17–19), the hypothesized initial stage of ecological speciation (16, 17). The short time frame and sympatric spatial context of R. pomonella’s shift to apple exclude passive codivergence or speciation (Fig. 1C) as an explanation for differentiation. Specifically, fly and wasp populations could not have diverged in concert, because they became jointly geographically separated in the past (Fig. 1C). Rather, if flies and wasps display concordant adaptations, it is likely due to the direct effects of divergent ecological selection resulting from host shifts cascading from host plants to flies to parasitoids (Fig. 1 A and B).Open in a separate windowFig. 2.The community of host-specific parasitoids that attack members of the (A) Rhagoletis pomonella sibling species complex: (B) D. alloeum, (C) D. mellea, and (D) U. canaliculatus that (E) emerge from the fly pupal case as adults following overwintering. (Scale bar, 1 mm.)

Table 1.

Summary of conditions (criteria) conducive to and supporting hypotheses of sympatric host race formation (modified from ref. 16) and sequential divergence (modified from refs. 12 and 13)

药食心葆汤对心血瘀阻证冠心病患者血清同型半胱氨酸及凝血功能的影响

目的:观察药食心葆汤联合西药治疗冠心病的临床疗效及其对血清同型半胱氨酸(homocysteine,HCY)水平凝血功能的影响,并探讨其作用机制。方法:选取2015年1月至2016年1月于郑州市中医院心内科入院治疗并确诊为心血瘀阻证的冠心病患者200例,按照随机数字表法分为对照组和观察组,对照组102例,观察组98例,对照组患者采用常规西药治疗,观察组在此基础上联合药食心葆汤治疗,药物干预治疗8周,比较两组患者血清同型半胱氨酸(HCY),凝血功能[凝血酶原时间(prothrombin time,PT),部分凝血活酶时间(activated partial thromboplastin time,APTT),纤维蛋白原(fibrinogen,FIB)]等指标。结果:治疗后观察组患者凝血功能、血清HCY水平改善程度优于对照组(P0.05);观察组可明显降低CHD患者血清HCY水平(P0.05),调节患者的凝血功能(P0.05),组间比较显示两组有明显差别,特别是在改善凝血功能方面,观察组明显优于对照组(P0.05),对照组治疗前后各项指标没有统计学差异。结论:药食心葆汤联合西药治疗冠心病的临床疗效确切,能有效降低CHD患者HCY水平、调节凝血功能,值得临床推广使用。     

植物外泌体样纳米囊泡的研究进展

植物外泌体样纳米囊泡(plantexocrine-likenano-vesicles,PELNs)是一种新兴的纳米治疗剂及传递平台,不但具有疾病治疗潜力,而且可以作为药物的载体靶向疾病位点,起到治疗递送双重作用,更重要的是PELNs具有绿色天然和低免疫原性等特点。本综述系统介绍了PELNs的外囊阳性细胞器、多囊泡体、液泡和自噬小体几种分泌机制;脂质、蛋白质和核酸3种组成成分;离心法、超滤法、尺寸排阻色谱法、流场-流分馏法、免疫磁珠法、聚合物沉淀法等分离方法及其抗炎、抗肿瘤、保护再生、抗病毒、保肝等生物学功能,整理了PELNs作为治疗剂及分子传递平台目前已发现的潜在机制,提出了PELNs研究过程中存在的产量化、机制研究及临床试验少等问题,并展望了其未来的发展潜力。     

青龙藤提取物对糖尿病模型大鼠的降血糖作用

目的：探讨青龙藤提取物(BH)降低糖尿病模型大鼠的血糖作用。方法：将32只雄性Wistar大鼠随机均分成4组,正常对照组,其他3组以链脲佐菌素（STZ）制成接近于人1型糖尿病的大鼠糖尿病模型。3 d后经血糖测试仪检测,血糖含量>16.65 mmol•L^-1为制模成功。1组作为糖尿病模型对照组,另外2组7d后每天分别灌胃给予BH(465 mg•kg^-1)和消渴丸（XKW,625 mg•kg^-1）,连续5周给药。每周1次测定给药过程中各组大鼠血糖变化。注射STZ 3 d和实验结束后,采用放射免疫分析方法分别测定各组大鼠血清中胰岛素含量。实验结束后观察各组大鼠胰岛β细胞的形态变化。结果：给予BH和消渴丸5周后,糖尿病BH给药组大鼠血糖由(18.3±1.8)mmol•L^-1下降到(5.3±1.2) mmol• L^-1,消渴丸对照组血糖由（18.4±1.9）mmol•L^-1下降到(5.2±0.8) mmol•L^-１,两组与糖尿病模型对照组［(19.9±1.9) mmol•L^-1］比较差异均有显著性(P<0.001)。糖尿病BH给药组大鼠血清胰岛素含量由(18.8±2.3)mU• L^-1升高到（42.2±3.5）mU•L^-1, 消渴丸组大鼠血清胰岛素含量由(18.1±3.3)mU•L^-1升高到（40.9±3.7）mU•L^-1,两组与糖尿病模型对照组［(18.7±3.1) mU •L^-1］ 比较差异均有显著性（Ｐ<0.01）,且基本接近正常对照组。糖尿病模型组大鼠的胰岛变小,细胞萎缩,胞核固缩、消失,分泌颗粒减少。应用BH和消渴丸5周后,上述异常变化消失且胰岛细胞形态趋向正常。结论：BH对糖尿病大鼠有降低血糖、升高血清胰岛素、恢复和保护胰岛β细胞的作用。