ETHNOPHARMACOLOGICAL RELEVANCE:Bufei Huoxue capsule (BHC) as a classic Chinese patent medicine formula, has the efficacy of tonifying the lungs and activating the blood. It has been extensively used in China for the treatment of chronic obstructive pulmonary disease (COPD) clinically. However, its mechanism is still unclear, which hampers the applications of BHC in treating COPD.AIM OF THE STUDY:The purpose of the present study was to demonstrate the protective efficacy and mechanism of BHC on COPD model rats by integrating serum metabolomics analysis and network pharmacology study.MATERIALS AND METHODS:A COPD rat model was established by cigarette fumigation combined with lipopolysaccharide (LPS) airway drip for 90 consecutive days. After oral administration for 30 days, the rats were placed in the body tracing box of the EMKA Small Animal Noninvasive Lung Function Test System to determine lung function related indexes. Histopathological alteration was observed by H&E staining and Masson staining. The serum levels of inflammatory cytokine, matrix metalloprotein 9, and laminin were determined by ELISA kits. Oxidative stress levels were tested by biochemical methods. UHPLC-Q-TOF/MS analysis of serum metabolomics and network pharmacology were performed to reveal the bioactive metabolites, key components and pathways for BHC treating COPD. WB and ELISA kits were used to verify the effects of BHC on key pathway.RESULTS:BHC could improve lung function, immunity, lung histopathological changes and collagen deposition in COPD model rats. It also could significantly reduce inflammatory response in vivo, regulate oxidative stress level, reduce laminin content, and regulate protease-antiprotease balance. Metabolomics analysis found 46 biomarkers of COPD, of which BHC significantly improved the levels of 23 differential metabolites including arachidonic acid, leukotriene B4 and prostaglandin E2. Combined with the results of network pharmacology, the components of BHC, such as calycosin, oxypaeoniflora, (S)-bavachin and neobavaisoflavone could play therapeutic roles through the arachidonic acid pathway. In addition, the results of WB and ELISA indicated that BHC could suppress the expressions of COX2 and 5-LOX in lung tissues and inhibit the generation of AA and its metabolites in serum samples. Regulation of arachidonic acid metabolic pathway may be the crucial mechanism for BHC treating COPD.CONCLUSIONS:In summary, the studies indicated that BHC exhibited the protective effect on COPD model rats by anti-inflammatory and anti-oxidative properties through arachidonic acid metabolism pathway. This study provided beneficial support for the applications of BHC in treating COPD.

Water buffalo horn (WBH), a traditional Chinese medicine, is known for its antipyretic, anti-inflammatory and antioxidant properties. This study aims to investigate the therapeutic potential of WBH keratin (WBHK) and its derived thiol-rich peptide fractions (SHPF) for oxidative stress and inflammation. WBHK and SHPF were prepared and tested using various models including LPS-induced fever in rabbits, H2O2-induced oxidative damage in bEnd.3 cells, TNF-α-induced inflammation in bEnd.3 cells and LPS-induced inflammation in RAW 264.7 cells. Expression of key markers, such as Nrf2, Hmox-1 and NF-κB, were analyzed using qRT-PCR, ELISA and Western blotting. Label-free quantitative proteomic analysis was used to identify key differential proteins associated with the efficacy of SHPF. Our results demonstrated that treatment with WBHK significantly reduced body temperature after 0.5 h of administration in the fever rabbit model. SHPF could alleviate cellular inflammatory injury and oxidative damage by activating the key transcription factor Nrf2 and increasing the expression level of Hmox-1. SHPF could inhibit the NF-κB pathway by reducing IκB phosphorylation. It was also found that SHPF could reduce pro-inflammatory cytokine (IL-6, COX-2 and PGE2) and inhibit the expression of VCAM-1, ICAM-1, IL-6 and MCP-1. Proteomics analysis showed that SHPF could inhibit HMGB1 expression and release. The results indicated that SHPF could significantly reduce inflammation and oxidative stress by regulating the Nrf2/Hmox-1 and NF-κB pathways. These findings suggest the potential therapeutic applications of WBH components in the treatment of oxidative stress and inflammation-related diseases.

Ethnopharmacological relevanceSaiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies.Aim of the studyThe purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension.Materials and methodsThe GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension.ResultsSAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a “biomarker-target-peptide” network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system.ConclusionsFunctional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.

Due to the highly stable structure of keratin,the extraction and dissolution steps of animal medicines rich in keratin are complex,which seriously restricts the detection efficiency and flux.Therefore,this study simplified the pre-treatment steps of horn samples and optimized the detection methods of characteristic peptides to improve the efficiency of identifying the specificity of horn-de-rived animal medicines.For detection of the characteristic peptides in horn-derived animal medicines treated with/without iodoace-tamide(IAA),the ion pair conditions of the characteristic peptides were optimized,and the retention time,intensity and other data of the specific peptides were compared between the samples treated with/without IAA.Two pre-treatment methods,direct enzymatic hy-drolysis and total protein extraction followed by enzymatic hydrolysis,were used to prepare horn-derived animal medicine samples.The effects of different methods on the detection of specific peptides in the samples of Saiga antelope horn,water buffalo horn,goat horn,and yak horn were compared regarding the retention time of specific peptides and ion intensity.The results indicated that after direct enzymatic hydrolysis,the specific peptides in the samples without IAA treatment can be detected.Compared with the characteristic peptides in the samples treated with IAA,their retention time shifted back and the mass spectrometry response slightly decreased.The specific peptides of the samples without IAA treatment had good specificity and did not affect the specificity identification of horn-de-rived animal medicines.Overall,the process of direct enzymatic hydrolysis can be used to treat horn samples,omitting the steps of pro-tein extraction and dithiothreitol and IAA treatment,significantly improving the pre-treatment efficiency without affecting the specificity identification of horn-derived animal medicines.This study provides ideas for quality research and standard improvement of horn-de-rived animal medicines.

Background Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances.Methods An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH.Results SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples.Conclusion In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

Objective To enrich the thiols-rich peptide fractions（SHPF）from Shuiniujiao（Bubali Cornu, water buffalo horn）and investigate its antioxidant and anti-inflammatory activities. Methods SHPF was enriched from Bubali Cornu extract by Thiopropyl Sepharose 6B, and the content of free-SH was determined by Ellman method. The enrichment process was optimized by single factor experiment. SHPF was identified based on Nano LC-MS/MS technology. Oxidative damage of bEnd3 cells were induced by H2O2 in vitro, and cell proliferation assay kit（CCK-8）and lactate dehydrogenase（LDH）kit were used to determine the antioxidant activity of SHPF. The secretions of cytokines interleukin-6（IL-6）, IL-1β and tumor necrosis factor-α（TNF-α）were determined by qPCR after LPS induced inflammatory damage of RAW264.7. Results The optimized SHPF enrichment process was as follows: loading volume of 10 μmol free-SH, adsorption time of 1 h, and eluent containing β-mercaptoethanol（β-Me）. A total of 704 peptides were identified from the Bubali Cornu enrichment solution, among which 154 thiols-contained peptides, accounting for 21.9% of the total peptides,mainly derived from keratin and keratin-related proteins. SHPF can improve the survival rate of oxidatively damaged bEnd3 cells,reduce the leakage of LDH, and reduce the secretion of inflammatory factors IL-6, IL-1β and TNF-α in RAW264.7 cells. Conclusion The optimized enrichment process can significantly improve the enrichment efficiency of SHPF, and SHPF has good antioxidant and anti-inflammatory activities, which provides a research idea and direction for the study of the material basis of Bubali Cornu efficacy.

Saiga antelope horn and Rhinoceros horn have been used in traditional Chinese medicine for thousands of years. However, due to the protection of wildlife, the application of these rare animal horns has been restricted or prohibited. Therefore, water buffalo horn, goat horn, and yak horn have been applied as alternatives to Rhinoceros horn or Saiga antelope horn in a clinic. It is extremely difficult to distinguish normal animal horns in powdered or decocted form, especially identifying related species such as water buffalo horn, yak horn, and cattle horn. In this work, mathematics set and label-free proteomics analysis were combined for discovering keratin-derived specific peptide biomarkers. By using mathematics set analysis after nano liquid chromatography-tandem mass spectrometry-based proteomics, the selected species-specific peptides could be used to identify the authenticity of the Saiga antelope horn and goat horn. Furthermore, peptide biomarkers were selected to distinguish related species-derived horns, water buffalo horn, yak horn, and cattle horn. In total, eight peptide biomarkers were selected and applied for simultaneously distinguishing different horn samples. The present strategy provides a method for peptide biomarkers discovery and also has positive significance for ensuring the quality and efficacy of animal horn-derived traditional Chinese medicines and their products.

野生药用动物驯化养殖和珍稀濒危动物药的替代资源研究与开发是国家重大任务,回顾和分析了我国动物药资源及替代研究的历史与现状,提出了野生药用动物驯化养殖替代策略、基于中医药理论的药性与功效相似药材替代策略、基于动物种类亲缘学的同种属或近缘药材替代策略、基于药效成分组合的合成替代策略、基于生物学技术的合成替代策略等珍稀动物药替代方法,以期为珍稀动物药替代品的研究提供借鉴与指引,实现动物药资源的可持续发展与利用.

水牛角为牛科动物水牛Bubalus bubalis Linnaeus的角,具有清热凉血,解毒,定惊的功效,主要用治温病高热,神昏谵语,发斑发疹,吐血衄血,惊风,癫狂等疾病.查阅历代本草书籍和文献资料,系统整理水牛角的基原、性味功效、配伍应用、物质组成、鉴定与质量评价方法、生物效应评价、现代临床应用以及作为犀角代用资源的应用历史,为进一步阐明水牛角的功效物质基础、作用机制及质量标准提升等提供研究思路与策略.通过梳理与凝练,以期为水牛角基础与应用研究提供依据与借鉴,为完善水牛角质量与药效评价体系、推动中药资源产业的可持续发展提供科学的理论依据.

目的:对历代本草及古今方剂中有关补骨脂的药性、功效记述及其组方配伍用药特点进行系统的梳理分析,以期深入探究其临床用药规律.方法:借助南京中医药大学方剂文献数据库,收集历代本草及古今方剂中补骨脂的论述,采用频数统计分析、Apriori算法对补骨脂方剂进行分析处理、关联规则等数据挖掘.结果:补骨脂为古波斯国外来药材,后引种于我国并归化为传统中药;补骨脂药用始载于《雷公炮炙论》,言其"性本大燥、毒",后世本草多提示补骨脂性燥,需经炒、盐炙或酒炙等炮制后使用;历代本草对其药性记载相似,为辛、苦、温,功效为温肾助阳,纳气平喘,温脾止泻.同时提示,补骨脂恶甘草,忌铁、芸苔及诸血;阴虚火旺、湿热等患者不宜使用等.经数据挖掘发现补骨脂常与当归、杜仲等补虚药组方,以提高补益气血之功效;与肉桂、附子、小茴香等温里药配伍,以增强温补肾阳的功用;与胡桃肉配伍,得以水火相济,以图延年益气,补添筋骨之目的.结论:基于上述古今知识挖掘分析,阐明了补骨脂的产地出处、饮片炮制、合理伍用、禁忌警示等,为中药补骨脂的临床合理用药提供了有益的借鉴和指引.

目的 基于脂多糖(LPS)诱导发热大鼠模型评价牦牛角解热活性并探讨其作用机制,以期为牦牛角新资源药材与开发利用提供科学依据.方法 以大鼠肛温变化值及体温反应指数评价牦牛角解热活性;采用ELISA试剂盒测定下丘脑中PGE2、cAMP的含量及血清中TNF-α与IL-1β的含量,并结合超高压液相色谱飞行时间质谱法(UHPLC-Q-TOF-MS)检测发热大鼠血浆中内源性标志物,探索牦牛角解热机制.结果 牦牛角给药后1、2、3 h大鼠体温明显下降(P<0.05),低剂量组TNF-α及cAMP水平均显著降低(P<0.01),高剂量组cAMP水平显著降低(P<0.01),牦牛角给药组均能抑制IL-1β与PGE2水平.从空白组与模型组血浆样本中共鉴定出15个潜在差异代谢物,牦牛角高剂量给药后可显著回调其中11个代谢物,主要包括磷脂酰乙醇胺、鞘磷脂、腺嘌呤、琥珀酸、L-苏氨酸、4-羟脯氨酸、磷脂酰胆碱、溶血性磷脂酰乙醇胺等,主要涉及甘油磷脂代谢通路.结论 牦牛角解热活性确切,其作用机制可能与抑制内源性致热源与中枢体温正性调节介质释放、调节脂质代谢密切相关.

山羊角为牛科动物山羊Capra hirus的角,具有清热、镇惊、明目、解毒之功,主要用于治疗小儿惊厥、高热神昏、青盲等疾病.系统梳理总结山羊角的本草记载与历史沿革、物质组成、药理活性、鉴定与质量评价方法、现代临床应用,深入挖掘了山羊角的药用资源价值,并进一步提出以类效替代原则开发珍稀动物药新资源药材的思路与建议,为实现珍稀濒危角类药材资源的补偿与供给、引导山羊产业加工过程巨量副产物的资源化利用、服务于中药资源产业的可持续发展及畜牧产业的提质增效提供科学依据.

动物药资源是祖国医药学宝库的重要组成部分,特别是珍稀动物药资源为中华民族生存繁衍和人口健康做出了重要贡献.基于药用动物资源来源渠道多样、基原种类丰富,动物药功效物质类型复杂、适宜的活性评价方法较为薄弱等因素,我国动物药现代科学研究相较于植物药的研究进展尚显滞后,特别是符合动物药研究特色的系统方法体系亟待加强和完善.基于生物化学、天然产物化学、中药资源化学、系统生物学、生物工程、生物信息学等多学科现代科学技术进展,结合动物药的品质形成、功效物质基础、药材生产与质量评价、多途径替代策略等层面,较为系统地回顾分析了近年来我国动物药研究的方法学进展.从基于多组学、生物信息学、生物工程等技术方法的动物药功效物质纯化、鉴定与制备研究,动物药生物效应评价与机制研究,基于专属肽类定性/定量分析的动物药精准质控研究,动物药现代研究方法学的展望等方面进行了梳理和凝练,以期为推动药用动物资源及动物药研究和产业化提供方法学借鉴,为进一步丰富完善适宜于动物药研究的系统方法学提供参考,为促进我国动物药资源与特色经济产业可持续发展做出应有的贡献.

本草记载牦牛角具清热解毒、凉血熄风之功.现代研究表明,牦牛角中主要含有蛋白质及巯基多肽类、氨基酸类、核苷类、宏微量元素类等成分,具有解热、镇静、镇痛等生物活性.对牦牛角化学成分组成、生物活性评价、药用价值体现、资源化利用等方面的研究进展进行了较为系统的回顾性分析和整理,提出在牦牛资源产业链中应重视和珍惜牦牛角药用价值的深度挖掘、重视和加强牦牛角在医药领域的基础性研究、重视和开展牦牛角药材标准的研究,以期为牦牛角这一宝贵的民族动物药资源的多元化、高值化利用提供参考.

牦牛角药用记载于公元8世纪《四部医典》与明代《本草纲目》.随着其资源的丰富及现代研究的深入,牦牛角的资源价值越来越受到关注.从资源现状、传统本草记载及临床应用等方面对牦牛角这一独特的民族药用动物药材进行较为系统地梳理和分析,以期深入挖掘其药用资源价值,提升资源利用效率,为牦牛角资源产业链的延伸提供参考.

The rhizome of Polygonatum cyrtonema (Polygonati Rhizoma) is widely consumed as medicine-homologyfood in Asia for its tonic effect, which can be enhanced by traditional steam-sun drying for nine cycles. However, the multi-constituents variation in this process was unclear, and the necessity of nine cycles should be further discussed. In this study, the multiple constituents, including saccharides, amino acids, nucleosides and bases, lipids, saponins, homoisoflavones and cinnamamides, in P. cyrtonema treated with sun drying, heated air drying, each cycle of steam-heated air drying, infrared drying and microwave drying were compared. The results showed that the content of total saccharides increased in samples from one to four cycles of steam-heated air drying (365.0-945.6 mg/g) and decreased from four to nine (945.6-288.0 mg/g). The content of fructose increased in samples from one to six cycles (29.9-234.7 mg/g) and decreased from six to nine (234.7-177.7 mg/g). The abundance of most phospholipids and free fatty acids increased continuously from one to nine cycles while most of the amino acids, nucleosides and bases showed continuous declining trend. Principal component analysis showed that the samples treated with one to four cycles were wider in distance than four to nine, indicating the chemical composition tending to be stable after fourth steaming. If taking total saccharides, fructose, and phospholipids as the major quality indicator, four cycles of steam-heated air drying processing should be the ideal postharvest processing method to obtain better taste, flavor and functionality. Samples treated with heated-air drying and infrared drying were far in distance from steaming ones by hierarchical cluster analysis, which means these processing methods were not suitable to replace the traditional steam-sun drying process. Collectively, the above results will not only provide novel processing methods that will obtain the high active ingredients for P. cyrtonema, but also shed light on the optimization of processing technology for the industrial production of medicinal crops which need nine cycles of steam-sun drying processing. (c) 2021 Elsevier B.V. All rights reserved.

目的 基于网络药理学方法和斑马鱼模型探讨瓜蒌薤白半夏汤干预慢性阻塞性肺疾病(chronic obstructive pulmoriary disease,COPD)的潜在作用机制.方法 运用中药系统药理学数据库与分析平台(TCMSP)、中医药百科全书数据库(ETCM)、中医药综合数据库(TCMID)以及国内外相关文献检索瓜蒌薤白半夏汤的主要活性成分,通过TCMSP和SwissTargetPrediction数据库预测靶点;通过GeneCards数据库、在线人类孟德尔遗传数据库(OMIM)和TCMSP数据库获取COPD相关靶点,并采用交集法筛选出与瓜蒌薤白半夏汤活性成分作用的共同靶点.运用Cytoscape 3.7.1软件构建"中药-活性成分-靶点"网络,通过String数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络;通过DAVID数据库对共有基因进行基因本体(gene ontology,GO)功能富集分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;借助斑马鱼炎症模型对筛选的靶点进行实验验证.结果 瓜蒌薤白半夏汤共筛选出成分955个,潜在活性成分106个,核心活性成分如芹菜素、茴香酸、美迪紫檀素、金圣草黄素、香叶木素等74个,对应靶点1134个;PPI网络分析获得瓜蒌薤白半夏汤干预COPD的关键作用靶点408个,包括碳酸酐酶9(carbonic anhydrase 9,CA9)、前列腺素内过氧化物合酶1 (prostaglandin-endoperoxide synthase 1,PTGS1)、胰岛素(insulin,INS)、白细胞介素-6(interleukin-6,IL-6)、丝氨酸/苏氨酸蛋白激酶1(serine/threonine protein kinase 1,AKT1)、肿瘤坏死因子(tumor necrosis factor,TNF)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、MAPK3、血管内皮生长因子A(vascular endothelial growth factorA,VEGFA)、表皮生长因子受体(epidermal growth factor receptor,EGFR)等;GO功能及KEGG通路富集分析得出与瓜蒌半夏薤白汤干预COPD作用相关的生物过程1096个,如炎症反应、细胞溶质、酶结合等;相关信号通路125条,如癌症通路、TNF信号通路、前列腺癌、缺氧诱导因子1信号通路、神经活性配体-受体相互作用等.斑马鱼炎症模型实验结果显示,瓜蒌薤白半夏汤显著降低IL-6、B淋巴细胞2(B-cell lymphoma 2,BCL2)和EGFR mRNA表达水平(P＜0.05),降低半胱氨酸蛋白酶8(Caspases 8,CASP8)mRNA表达水平.结论 瓜蒌薤白半夏汤可能通过作用于EGFR、IL-6、BCL2、CASP8等靶点,调节多条信号通路,从而发挥对COPD的治疗作用.

本研究基于免疫应激大鼠模型,研究补骨脂与赤芍配伍前后对其特异质肝损伤作用的影响及其代谢网络调控机制.采用低剂量脂多糖(lipopolysaccharide,LPS)注射致免疫应激SD大鼠模型,分别比较补骨脂单用及补骨脂-赤芍配伍给药后,模型动物肝脏谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)的活性及肝脏病理变化;通过UHPLC-QTOF/MS分析不同组别大鼠血清代谢轮廓特征,结合主成分分析法(principal component analysis,PCA)、偏最小二乘判别分析法(orthogonal partial least squares discriminant analysis,OPLS-DA),研究补骨脂与赤芍配伍后对特异质肝损伤大鼠血清中内源性代谢产物的影响,并应用HMDB数据库及MetaboAnalyst在线通路富集工具进行生物标志物的鉴定和代谢通路富集分析.结果显示,对于LPS致免疫应激大鼠模型,补骨脂组AST、ALT均显著升高(P＜0.01),肝脏切片可见明显的病理损伤,而其配伍赤芍后肝损伤作用显著降低.代谢组学分析显示赤芍主要通过调节花生四烯酸代谢和甘油磷脂代谢等信号通路改善补骨脂致肝毒性大鼠体内的血清代谢异常.

Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs (PPL@MNPs), and then the PPL@MNPs were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 μM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.

目的 探索补肺活血胶囊用于新型冠状病毒肺炎(COVID-19)恢复期治疗的潜在作用机制,为其临床用药提供理论指导.方法 通过中药系统药理学分析平台(TCMSP)、BATMAN-TCM、中国知网(CNKI)和Pubmed数据库获得补肺活血胶囊的活性成分及作用靶点;通过GeneCards数据库获取COVID-19相关靶点,并采用交集法筛选出与补肺活血胶囊活性组分作用的共同靶点,运用Cytoscape 3.7.2构建“中药-化合物-靶点”网络,并通过String数据库构建蛋白-蛋白相互作用(PPI)网络;通过DAVID数据库进行KEGG通路和GO功能富集分析,并运用R version 3.6.3软件将结果进行可视化;采用AutoDock Tools 1.5.6、AutoDock vina 1.1.2进行分子对接研究.结果 从补肺活血胶囊中共筛选出潜在活性成分32个,对应靶点203个,核心化合物11个,核心靶点52个;PPI网络分析获得补肺活血胶囊干预COVID-19关键作用靶点25个;GO及KEGG富集分析得出与补肺活血胶囊治疗COVID-19作用相关的生物过程251个(P＜0.05),相关信号通路93条(P＜0.05);分子对接结果显示补肺活血胶囊核心化合物与新型冠状病毒(SARS-CoV-2) 3CL水解酶和血管紧张素转化酶Ⅱ(ACE2)具有较好的亲和.结论 补肺活血胶囊含有的核心化合物可作用于IL6、MAPK8、PTGS2、PTGS1、NCOA2等靶点,调节多条信号通路,从而发挥对COVID-19恢复期的治疗作用.