Deciphering the potential mechanism of Siwu decoction for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Siwu decoction(SWD)is a traditional Chinese herbal decoction commonly used for treating various symptoms of blood deficiency and blood stasis,including cancer-related anemia(CRA).However,due to its complex composition,the key active ingredients and underlying mechanisms of its therapeutic effects often remain unknown.This research aims to use network pharmacology and molecular docking technology to systematically elucidate the potential mechanisms underlying the efficacy of SWD in treating cancer-related anemia.Methods:The key constituents of SWD were procured from the TCMSP database.Leveraging the Swiss ADME and Swiss Target Prediction databases,potential targets were recognized.Disease-related targets were assembled via the GeneCards and DrugBank databases.Constructing the PPI network involved the utilization of the STRING database,followed by visualization through Cytoscape 3.9.1 software.Subsequently,GO and KEGG enrichment analysis was conducted utilizing the DAVID database,with visual analysis performed on the macrobiotic platform.For molecular docking,the Autodock software was employed,and the molecular docking outcomes were visualized using the PyMOL software.Results:In this investigation,a comprehensive revelation of 18 primary active compounds and 511 associated targets linked to CRA was accomplished.The outcomes of protein-protein interaction(PPI)analysis unequivocally identified AKT1,EGFR,SRC,VEGFA,HRAS,MAPK3,and STAT3 as pivotal proteins within the SWD’s framework for effective CRA intervention.Notably,signaling pathways such as the HIF-1,JAK-STAT,TNF-α,and PI3K-Akt pathways,intricately involved in hematopoietic stem cell proliferation,differentiation,and inflammatory response,emerged as closely intertwined with the therapeutic application of SWD for CRA treatment.The congruence between these potential targets and SWD’s primary therapeutic constituents for CRA treatment was substantiated by the outcomes of molecular docking analysis.Conclusion:This work provided a reference for further fundamental research by outlining the primary active ingredients and putative molecular mechanisms of SWD in the treatment of CRA.

Deciphering the potential mechanism of Radix Rehmanniae Praeparata for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Rehmanniae Radix Praeparata(RRP,Shu Dihuang in Cinese)is a traditional Chinese herb with multiple pharmacological effects and is commonly used to treat blood deficiency syndrome,such as cancer-related anemia(CRA),alone or in combination with other herbs.However,its main active ingredients and mechanisms of action in treating CRA remain unknown.This study aims to elucidate RRP’s potential mechanism and main active components in treating CRA by using network pharmacology and molecular docking technology system.Methods:The main components of RRP were obtained by the TCMSP database and literature search,and active components and potential targets were obtained by the SwissADME and SwissTargetPridiction databases.CRA targets were collected through GeneCards,DisGeNET,and DrugBank databases.Protein-protein interaction networks of potential targets were constructed via STRING 11.5 and analyzed visually with Cytoscape 3.9.1.The Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,which were subsequently visualized with Cytoscape 3.9.1 or SangerBox platform.Moreover,Autodock Vina was used for the molecular docking of potential targets and main active ingredients that were visualized with PyMOL software.Results:In this study,31 main active ingredients of PPR were screened,and 155 related targets related to CRA were unearthed.Protein-protein interaction results showed that PPR’s core proteins for CRA intervention correlate to STAT3,SRC,MAPK3,MAPK1,PIK3R1,PIK3CA,and AKT.Multiple signaling pathways were closely related to the treatment of CRA intervened by PPR,including the PI3K-Akt signaling pathway,HIF-1 signaling pathway,JAK-STAT3 signaling pathway,TNF-αsignaling,cytokine signaling pathway and NF-kappB signaling pathway,which are closely involved in the proliferation and differentiation of hematopoietic stem cell and inflammatory response.Molecular docking results showed that these potential targets had good conformation with the core active components of RRP for treating CRA.Conclusion:This study revealed RRP’s main active components and potential molecular mechanisms in treating CRA,providing a reference for subsequent basic research.

Natural products as a crucial source of anti-inflammatory drugs: recent trends and advancements

Natural active molecules are key sources of modern innovative drugs. Particularly, a great amount of natural active molecules have been reported to possess promising therapeutic effects on inflammatory diseases, including asthma, rheumatoid arthritis, hepatitis, enteritis, metabolic disorders and neurodegenerative diseases. However, these natural active molecules with various molecular structures usually exert anti-inflammatory effects through diversiform pharmacological mechanisms, which is necessary to be summarized systematically. In this review, we introduced the current major anti-inflammatory natural active molecules based on their chemical structures, and discussed their pharmacological mechanisms including anti-inflammatory molecular signaling pathways and potential target proteins, which providing a referential significance on the development of novel anti-inflammatory drugs, and also revealing new therapeutic strategies for inflammatory diseases.

Annual advances of integrative pharmacology in 2019

Representative studies concerning the pharmacology of traditional medicine and active herbal products have been summarized over the past 12 months.This annual integrative pharmacology review encompasses research articles published during 2019 on the bioactive compounds and extracts used in traditional medicine.Reports highlighting the pharmacology progress of traditional medicine were specifically introduced,including artemisinin for cancer cell sensibility and induction to ferroptosis,rutin for neuroinflammation suppression,Ginseng Radix et Rhizoma for gut microbiota regulation against obesity,green tea and Pu-erh tea for metabolic syndrome,and marine-derived oligosaccharide(GV-971)from brown algae for anti-dementia.Moreover,novel TCM molecular targets and pharmacological mechanisms were trialed against different human diseases,including cancers,cardiovascular,cerebrovascular diseases,diabetes,and metabolic diseases.Notably,herb-derived bioactive products have become important treatment alternatives for cancer research in 2019.Cardiovascular and cerebrovascular diseases,together with diabetes and metabolic diseases,are ongoing research areas for traditional medicine.Moreover,inflammation and infectious disease are also attracting more attention by researchers,which might have been influenced by seasonal influenza or HIV/Ebola viral infections.Further traditional medicine investigations are required in neurodegenerative diseases,depression,and mental diseases.Taken together,the findings of the integrative pharmacology review in 2019 provide a vast number of novel lead compounds or drug candidates for future clinical agent development and also details a novel series of attractive therapeutic targets and molecular mechanisms for human diseases.

Neuroprotective Effect of Bu-Shen-Huo-Xue Extract against High Glucose-induced Apoptosis in PC12 Cells

目的：研究补肾活血方对高糖诱导PC12细胞凋亡的神经保护作用.方法：用高糖（75mM）诱导PC12细胞凋亡,将补肾活血方低剂量（20mg/L）、中剂量（50mg/L）和高剂量（100mg/L）作为药物治疗组.通过MTT法以及LDH试剂盒检测各组PC12细胞的存活率;通过Hoechst33258染色,AO/EB染色观察各组细胞的凋亡情况,通过JC-1染色观察各组细胞的线粒体膜电位变化情况;通过CM3-H2CFDA标记PC12细胞,然后用流式细胞术检测细胞内ROS的含量;通过Westernblot技术检测与线粒体介导的caspase信号通路以及MAPKs信号通路相关蛋白的表达.结果：在高糖诱导的PC12细胞凋亡中,补肾活血方能剂量依赖地提高细胞存活率以及抑制LDH的释放.而且,补肾活血方能明显抑制细胞内ROS的生成,维持线粒体膜电位,调节Bax和Bcl-2蛋白的表达,抑制细胞色素c释放到细胞质中.此外,补肾活血方能显著抑制caspase-3和PARP的激活,以及抑制JNK和p38MAPKs的磷酸化.结论：在高糖诱导的PC12细胞凋亡中,补肾活血方具有明显的神经保护作用.这种保护作用可能与抑制细胞内源性ROS的产生,以及调节线粒体介导的caspase信号通路和JNK/p38MAPK信号通路有关.

Annual advances of integrative pharmacology in 2018

A number of researches concerning pharmacology of traditional medicine and active natural products over the past 12 months have outlined the importance of reviewing the progress.This annual integrative pharmacology review evaluates researches published during 2018 in different diseases including cardiovascular and cerebrovascular diseases,cancers,diabetes and metabolic diseases,and so on.The emphasis is on bioactive compounds and extracts from traditional herbs,as well as the novel molecular targets and mechanisms.Moreover,some traditional prescriptions in China and other geographical locations have also been included.

The role of natural products in regulating pyroptosis

In recent years,large numbers of novel cell death types have been reported such as autophagic death,paraptosis,mitosis,oncosis and pyroptosis.As a new type of proinflammatory programmed cell death,pyroptosis has attracted increasing attentions gradually,and its morphological characteristics and molecular mechanisms are significantly different from other cell death types such as necrosis and apoptosis.Many research groups have demonstrated the association between pyroptosis and various human diseases including immunological disease,cancer,atherosclerosis,infectious disease,and cardiovascular and cerebrovascular disease.Natural products are small molecules synthetized in organisms including primary and secondary metabolites.Natural products are important sources of modern innovative drugs discovery and can be used as key tools to explore the molecular mechanism of cell fate.The aim of this study is to review the molecular mechanisms and pathways of pyroptosis,and to categorize and conclude research results on the correlation between different natural products and pyroptosis in recent years.In this study,a total of 39 papers were enrolled in analyses.The molecular pathways and mechanisms of pyroptosis were clearly described.Fourteen types of natural products,their sources,effects,mechanisms and therapeutic potentials are categorized and illuminated.It is showed that a variety of natural products and pyroptosis have close correlations.They negatively or positively affect or act on different positions of pyroptosis inflammatory pathways,indicating that they may have certain potential therapeutic effects on pyroptosis-related diseases.Pyroptosis,a relatively new way of cell death,is closely associated with a variety of diseases.Natural products can have obvious effects on the process of pyroptosis as potential sources of new drugs.In-depth studies using natural products to investigate pyroptosis will help to enhance our understandings of human diseases and establish effective prevention and treatment strategies.

Traditional Chinese medicine target identification based on ＂Target Fishing＂ strategy

OBJECTIVE Our group mainly focuses on the target identification and pharmacological mechanism study of TCM.We deeply identified the direct targets of the active ingredients in TCM using molecule probe-'Target Fishing' technology in chemical biology,and explored the related signaling pathways to explain the traditional efficiency of TCM.METHODS We synthesized biotin-tagged mole.cule probe by connecting biotin tag to TCM active molecule using PGE as a linker.Then,the biotintagged molecule probe was bound to the surface of solid beads by strong biotin-avidin interaction.Thus,the molecule probe-bound beads were mixed with cell lysates to capture the potential targets and identified by MS.RESULTS Our study found that SA which was an anti-inflammatory compound.could selectively bind to IMPDH2 in microglial cells,and SA showed weaker anti-inflammatory effect on IMPDH2-knock down microglial cells,suggesting IMPDH2 as a key anti-inflammatory target for SA.Ad.ditionally,handelin was a key anti-inflammatory compound.We identified the target protein of handelin as Hsp70 from microglial cells using target pull-down technology.Moreover,handelin showed weaker anti-inflammatory effect on Hsp70-knock down microglial cells,revealing that Hsp70 was the direct antiinflammatory target of handelin.CONCLUSION Our study provided methodology references for TCM target identification in the future,and also showed a new insight for exploring the pharmacological mechanism of TCM active ingredients.More importantly,we can perform scientific annotation for TCM efficiency by clarifying the biological functions of each target protein,showing important significance on modernization and internationalization of TCM.

Annual advances of integrative pharmacology in 2020

Major studies on the pharmacology of traditional herbs as well as active compounds have been introduced in this review over the previous 12 months.This annual integrative pharmacology review includes the reports published in 2020 on bioactive herbal extracts and novel compounds in traditional medicine.Pharmacological reports on traditional herbs as well as their active compounds for anticancer,inflammation,and metabolic diseases occupy dominant positions.Traditional medicines are still widely reported as a crucial treatment to exhibit anticancer efficacy in numerous human cancer cells.Moreover,the focus on the discovery of bioactive compounds from traditional medicines against mental disorders and neurodegenerative diseases seems to increase.The reports on bone loss and organ fibrosis treatments have notably gradually increased.Furthermore,studies of traditional herbs on cardiovascular and cerebrovascular diseases show a declining trend.These pharmacological reports in 2020 collectively show several crucial therapeutic targets and promising candidate compounds from traditional medicines for human diseases.

Advances in anti-inflammatory and immunoregulatory mechanisms of sinomenine

Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.

Marine natural products with anti-inflammation effects

The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.

Targeting SARS-CoV-2 main protease for drug discovery

The unprecedented pandemic of Coronavirus Disease 2019(COVID-19)was first emerged in Wuhan,China and has spread globally due to its high transmissibility and infectivity,which seriously threaten global health.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a specific virus that can cause COVID-19.Currently,more than 45 million cases have been confirmed according to data supplied by Johns Hopkins University,and at least 1.1 million people have died from SARS-CoV-2.Unfortunately,the number of infected cases continues to grow,while no specific drugs or vaccines are available for the treatment of COVID-19.Therefore,specific drugs against SARS-CoV-2 infection,offering efficacy and safety,are urgently needed.

Infectious Diseases Research:a new branch of Traditional Medical Resaerch journal family covering the researches on infectious diseases

Infectious diseases are caused by pathogenic microorganisms,including bacteria,viruses,parasites or fungi.Nowadays,superbug,drug resistant malaria,severe acute respiratory syndrome,Ebola virus,middle east respiratory syndrome and COVID-19 coronavirus have been major threat worldwide,and have great impacts on public health and the world economy.Therefore,highly potent anti-infectious agents and effective treatment strategies are urgently needed.

中药作用靶点方法学研究进展

靶点(drug target)是药物作用的源头,是药物治疗疾病最直接、最重要、最初始的生物学基础.长期以来,中药由于其自身成分复杂的特点,关于作用靶点的揭示与阐明,以及分子药理机制等相关研究一直未能获得突破性进展,因此严重制约了中药的现代化和国际化进程.但是近年来,随着分子生物学、化学生物学以及生物物理学等前沿学科的发展,人们不断摸索和建立了一系列药物靶点的鉴定和识别方法,并尝试将这些方法应用于中药活性成分以及中药复方的作用靶点研究中,且取得了不少原创性成果,极大地推动了中医药的前进步伐.本文总结了近年来在中药靶点研究中出现的新方法与新策略,希望能够对从事中药现代化研究的人们提供全新思路,并拓展新的研究方向,最终促进中医药现代科学研究取得更大的突破.

Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity

Mitochondrial fusion/hission dynamics plays a fundamental role in neuroprotection;however,there is till a severe lack oftherapeutic targets for this biological process.Here,we found that the naturally derived small molecule echinacoside(ECH)signifhcantly promotes mitochondrial fusion progression.ECH selectively binds to the previously uncharacterized casein kinase 2(CK2)α'subunit(CK2a)as a direct cellular target,and genetic knockdown of CK2α'abolishes ECH-mediated mitochondrial fusion.Mechanistically,ECH allosterically regulates CK2α'conformation to recruit basic transcription factor 3(BTF 3)to form a binary proteincomplex.Then,the CK2α'/BTF3 complex facilitatesβ-catenin nuclear translocation to activate TCF/AEF transcription factors andstimulate transcription of the mitochondrial fusion gene Mfn2.trikingly,in a mouse middle cerebral artery occlusion(MCAO)model,ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2expression in wild-type but not CK2α'^(+/-)mice.Taken together,our findings reveal,for the first time,that CK2 is essential forpromoting mitochondrial fusion in a Wnt/B-catenin-dependent manner and suggest that pharmacologically targeting CK2 is apromising therapeutic strategy for ischemic stroke.

Three new phenanthrenes from Cremastra appendiculata (D.Don) Makino

Three new phenanthrenes,along with one known phenanthrene,were isolated from the ethanolic extract of the tubers of Cremastra appendiculata（D.Don） Makino.Their structures were elucidated on the basis of extensive spectroscopic analysis.Compounds 1-4 were tested for in vitro cytotoxic activities against human lung（A549）,colon（HCT-116）,liver（HepG2）,and breast（MCF-7 and MDA-MB-231） cancer cell lines.

Three new eudesmane sesquiterpenes from Artemisia vestita

Three eudesmane sesquiterpene lactones, namely artemivestinolides A-C （1-3）, along with three known 11-epimeric lactones （4-6）, were isolated from the aerial parts ofArtemisia vestim. Their structures were elucidated on the basis of extensive spectroscopic analyses （IR, HR-ESIMS, 1D NMR and 2D NMR）, and the absolute configurations were determined by single-crystal X-ray diffraction （with copper radiation）. Furthermore, in an in vitro assay, the three new compounds exhibited a moderate inhibition of the lipopolysaccharide （LPS）-induced nitric： oxide （NO） production in BV-2 microglial cells.

Correction: Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity

In the process of collating the published data,the editors noticed one inadvertent mistake occurred during the production process in Fig.6 that needs to be corrected.1 The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.