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.     

Medicinal nicotine in COVID-19 acute respiratory distress syndrome,the new corticosteroid

The cholinergic anti-inflammatory pathway (CAP) refers to the anti-inflammatory effects mediated by the parasympathetic nervous system. Existence of this pathway was first demonstrated when acetylcholinesterase inhibitors showed benefits in animal models of sepsis. CAP functions via the vagus nerve. The systemic anti-inflammatory effects of CAP converges on the α7 nicotinic acetylcholine receptor on splenic macrophages, leading to suppression of pro-inflammatory cytokines and simultaneous stimulation of anti-inflammatory cytokines, including interleukin 10. CAP offers a novel mechanism to mitigate inflammation. Electrical vagal nerve stimulation has shown benefits in patients suffering from rheumatoid arthritis. Direct agonists like nicotine and GTS-1 have also demonstrated anti-inflammatory properties in models of sepsis and acute respiratory distress syndrome, as have acetylcholinesterase inhibitors like Galantamine and Physostigmine. Experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome indicates that immunomodulators have a protective role in patient outcomes. Dexamethasone is the only medication currently in use that has shown to improve clinical outcomes. This is likely due to the suppression of what is referred to as a cytokine storm, which is implicated in the lethality of viral pneumonia. Nicotine transdermal patch activates CAP and harvests its anti-inflammatory potential by means of an easily administered depot delivery mechanism. It could prove to be a promising, safe and inexpensive additional tool in the currently limited armamentarium at our disposal for management of COVID-19 induced acute hypoxic respiratory failure.     

肝移植术后移植物抗宿主病的诊治进展

肝移植术后移植物抗宿主病(GVHD)发生率低，但病死率极高，典型症状包括不明原因发热、皮疹、腹泻和骨髓抑制。其发病机制目前尚未完全阐明，诊断缺乏统一标准，治疗缺乏特异性手段。近年来，针对GVHD免疫反应进程中的病理生理学研究，为开辟新的诊断方法和治疗手段提供可能。目前，大剂量糖皮质激素联合静脉注射免疫球蛋白冲击、免疫抑制剂减少或停用可能是较为有效的治疗方案。而对于糖皮质激素难治性GVHD，应用多种不同的分子靶向药物可能对改善受者预后起到积极作用。     

Piperazine derivatives with central pharmacological activity used as therapeutic tools

Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant and anxiolytic applications. Benzylpiperazine is the prototype of piperazine derivatives; this substance is the main component of recreational drugs, partly due to its stimulant and euphoric effects. This paper describes some piperazine derivatives used therapeutically as antipsychotic (clozapine), antidepressant (vortioxetine) and anxiolytic (buspirone) drugs.     

基于高通量测序技术研究药食两用薏苡仁中污染真菌多样性

目的:调查药食两用薏苡仁中污染真菌多样性,为其安全使用提供参考依据。方法:收集薏苡仁样品18批,提取真菌DNA并扩增ITS2序列,基于Illumina MiSeq PE250平台进行高通量测序。结果:共检测到4门18纲44目99科149属的真菌,子囊菌门Ascomycota是最优势菌门,镰刀菌属Fusarium(3.05%~60.32%)是属水平最优势属,其次是曲霉属Aspergillus(2.20%~45.44%)、白僵菌属Beauveria(0.07%~63.21%)、链格孢属Alternaria(0.80%~11.92%)、Arachnomyces(0.03%~39.36%)和青霉属Penicillium(0.24%~8.03%)。此外,共检测到5种潜在产毒真菌,分别是烟曲霉A.fumigatus、土曲霉A.terreus、梨孢镰刀菌F.poae、囊状青霉P.capsulatum和展青霉P.paxilli。结论:高通量测序技术可以快速有效地检测薏苡仁中污染真菌种类,为薏苡仁污染真菌毒素提供风险预警。     

至阳八阵穴隔附子饼灸治疗糖尿病胃轻瘫临床研究

目的观察至阳八阵穴隔附子饼灸治疗脾胃气虚型糖尿病胃轻瘫的疗效及对胃泌素(GAS)、胃动素(MTL)和血管活性肠肽(VIP)水平的影响。方法86例脾胃气虚型糖尿病胃轻瘫患者随机分为对照组和治疗组,每组43例。治疗组给予至阳八阵穴隔附子饼灸;对照组口服枸橼酸莫沙必利片。治疗12周后观察胃轻瘫主要症状指数量表症状积分改善情况、胃排空率及血清GAS、MTL、VIP水平。结果治疗组治疗后在胃轻瘫主要症状指数量表症状积分及胃排空率方面明显高于对照组,差异均有统计学意义(P<0.05)。治疗组治疗后血清GAS、MTL水平明显高于对照组,血清VIP水平明显低于对照组,差异均有统计学意义(P<0.05)。治疗组总有效率为90.7%,明显高于对照组的72.1%(P<0.05)。结论采用至阳八阵穴隔附子饼灸能快速促进糖尿病胃轻瘫患者胃功能的恢复,改善症状和体征,其作用机制可能与升高患者血清GAS和MTL水平,降低VIP水平有关。     

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

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隔药灸崔氏四花穴治疗小儿咳嗽变异性哮喘疗效观察及对机体免疫功能的影响

目的观察隔药灸崔氏四花穴治疗小儿咳嗽变异性哮喘的疗效及对机体免疫功能的影响。方法选择小儿咳嗽变异性哮喘患者90例,随机分为观察组和对照组,每组45例。观察组给予隔药灸崔氏四花穴治疗,对照组给予口服孟鲁斯特钠咀嚼片治疗,治疗6周后观察咳嗽症状评分、肺气道功能指标、血清嗜酸性粒细胞、嗜酸性粒细胞阳离子蛋白、免疫球蛋白E及CD^3﹢、CD^4﹢、CD^8﹢、CD^4﹢/CD^8﹢的变化,并统计临床疗效。结果观察组治疗后咳嗽症状评分,血清EOS、ECP及IgE水平,CD^4﹢、CD^8﹢、CD^4﹢/CD^8﹢水平均明显低于对照组(P<0.05);血清CD8﹢水平明显高于对照组(P<0.05)。观察组治疗后在肺气道功能指标(MEF75%,MEF50%,MEF25%)方面明显高于对照组(P<0.05)。观察组、对照组临床疗效总有效率分别为91.1%、75.6%,差异有统计学意义(P<0.05)。结论隔药灸崔氏四花穴可以有效改善小儿咳嗽变异性哮喘患者的咳嗽症状,提高小儿咳嗽变异性哮喘患者的免疫功能。