Pub Date : 2024-09-19DOI: 10.1177/1934578x241284735
Milica Aćimović, Jovana Stanković Jeremić, Marina Todosijević, Mirjana Cvetković, Biljana Lončar, Vladimir Vukić, Tamara Erceg, Lato Pezo, Valtcho D. Zheljazkov
ObjectivesImmortelle has garnered global attention for its cosmetic, medicinal, and culinary applications worldwide. Apart from neryl acetate, α-pinene and γ-curcumene as the most important components for the estimation of the essential oil quality, in recent years a group of β-diketones, known as italidiones, appear as significant quality parameters. However, it is unknown how weather conditions (temperature and precipitation) influence their accumulation in essential oil and hydrosol, nor their anti-inflammatory potential.MethodsThis study investigates the chemical composition of immortelle essential oil and hydrosol over three successive years (2019/20, 2020/21, and 2021/22), by GC-FID and GC-MS analysis. In silico molecular docking model with Vascular Adhesion Protein-1 (VAP-1) was used for the simulation of the anti-inflammatory potential of italidiones, as well as other β-diketones present in immortelle essential oil and hydrosol.ResultsDuring the three-year trial, it was established that essential oil compounds such as α-pinene, neryl acetate, and italicene were positively correlated with temperature and negatively correlated with precipitation, as well as β-diketones and total italidiones. Moreover, trans-caryophyllene, γ-curcumene, and ar-curcumene were in negative correlation with temperature, and a slight positive correlation with precipitation. On the other side, in the hydrosol the content of both total β-diketones and total italidiones was strongly negatively correlated with temperatures, and positively correlated with precipitation, which was the opposite of essential oil. Additionally, findings indicated that italidiones could bind the human VAP-1 protein in the vicinity of the topiquinone and block its function.ConclusionWeather conditions affect variations in the accumulation of volatile compounds in essential oil and hydrosol, which in some cases can affect changes in olfactory characteristics, as well as criteria prescribed by standards, and even changes in biological activities. These results indicate that italidiones, as well as other β-diketones present in immortelle, may be responsible for its anti-inflammatory activity.
{"title":"The Influence of Weather Conditions on the Immortelle Volatile Constituents from Essential oil and Hydrosol with a Focus on Italidiones and Its Molecular Docking Anti-Inflammatory Potential","authors":"Milica Aćimović, Jovana Stanković Jeremić, Marina Todosijević, Mirjana Cvetković, Biljana Lončar, Vladimir Vukić, Tamara Erceg, Lato Pezo, Valtcho D. Zheljazkov","doi":"10.1177/1934578x241284735","DOIUrl":"https://doi.org/10.1177/1934578x241284735","url":null,"abstract":"ObjectivesImmortelle has garnered global attention for its cosmetic, medicinal, and culinary applications worldwide. Apart from neryl acetate, α-pinene and γ-curcumene as the most important components for the estimation of the essential oil quality, in recent years a group of β-diketones, known as italidiones, appear as significant quality parameters. However, it is unknown how weather conditions (temperature and precipitation) influence their accumulation in essential oil and hydrosol, nor their anti-inflammatory potential.MethodsThis study investigates the chemical composition of immortelle essential oil and hydrosol over three successive years (2019/20, 2020/21, and 2021/22), by GC-FID and GC-MS analysis. In silico molecular docking model with Vascular Adhesion Protein-1 (VAP-1) was used for the simulation of the anti-inflammatory potential of italidiones, as well as other β-diketones present in immortelle essential oil and hydrosol.ResultsDuring the three-year trial, it was established that essential oil compounds such as α-pinene, neryl acetate, and italicene were positively correlated with temperature and negatively correlated with precipitation, as well as β-diketones and total italidiones. Moreover, trans-caryophyllene, γ-curcumene, and ar-curcumene were in negative correlation with temperature, and a slight positive correlation with precipitation. On the other side, in the hydrosol the content of both total β-diketones and total italidiones was strongly negatively correlated with temperatures, and positively correlated with precipitation, which was the opposite of essential oil. Additionally, findings indicated that italidiones could bind the human VAP-1 protein in the vicinity of the topiquinone and block its function.ConclusionWeather conditions affect variations in the accumulation of volatile compounds in essential oil and hydrosol, which in some cases can affect changes in olfactory characteristics, as well as criteria prescribed by standards, and even changes in biological activities. These results indicate that italidiones, as well as other β-diketones present in immortelle, may be responsible for its anti-inflammatory activity.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"49 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1177/1934578x241264621
Kunqin Ma, Xu Xu, Shengdong Wang, Chang Liu, Liping Liu
Objective: Traditional Chinese patent medicine Huoxiang Zhengqi Oral Liquid (HXZQOL) can be used topical to treat mosquito bite dermatitis (MBD). The study aimed to explore the potential mechanism of HXZQOL in treatment of MBD based on network pharmacology and experimental validation. Methods: TCMSP, SwissTargetPrediction and PubChem database were used to predict the active compounds and targets of HXZQOL and GeneCards database was utilized to predict the potential targets of MBD. Target interaction analysis was performed using Venn database, PPI and core targets were assessed using String database, and Cytoscape. Enrichment analysis on Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed using David online tool. “HXZQOL-compound-target-pathway-MBD” networks were constructed using Cytoscape. Molecular docking was carried out with Autodock vina. The inflammation model of HaCaT cells induced by TNF-a/IFN-γ was established .to validate the mechanism of HXZQOL against MBD, with the levels of inflammatory factors and protein related to IL-7 signaling pathway assessed using Elisa and Western Blot. Results: HXZQOL contained 154 active compounds and shared 88 common targets with MBD. Quercetin, apigenin, ursolic acid and luteolin were identified as potential candidate compounds, while JUN, IL-6, TNF and VEGFA were suggested as main potential targets. HXZQOL was found to act on MBD through multiple pathways including IL-17, AGE-RAGE and TNF signaling pathways. The candidate compounds demonstrated effectively binding to JUN and IL-6 targets, with binding energies below −5 kcal/mol. Western blot experiments confirmed that these compounds could down-regulate the expression of JUN protein in IL-17 signaling pathway, and significantly reduce levels of inflammatory factors TNF-α, IL-6 and NO in HaCaT cells. Conclusion: HXZQOL mainly exerts its anti MAD effect by reducing inflammation. The relevant results have laid the foundation for improving the local anti MBD effect of HXZQOL and the secondary development of HXZQOL formulations.
{"title":"Exploring the Mechanism of Huoxiang Zhengqi Oral Liquid Against Mosquito Bite Dermatitis Through Network Pharmacology and in Vitro Validation","authors":"Kunqin Ma, Xu Xu, Shengdong Wang, Chang Liu, Liping Liu","doi":"10.1177/1934578x241264621","DOIUrl":"https://doi.org/10.1177/1934578x241264621","url":null,"abstract":"Objective: Traditional Chinese patent medicine Huoxiang Zhengqi Oral Liquid (HXZQOL) can be used topical to treat mosquito bite dermatitis (MBD). The study aimed to explore the potential mechanism of HXZQOL in treatment of MBD based on network pharmacology and experimental validation. Methods: TCMSP, SwissTargetPrediction and PubChem database were used to predict the active compounds and targets of HXZQOL and GeneCards database was utilized to predict the potential targets of MBD. Target interaction analysis was performed using Venn database, PPI and core targets were assessed using String database, and Cytoscape. Enrichment analysis on Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed using David online tool. “HXZQOL-compound-target-pathway-MBD” networks were constructed using Cytoscape. Molecular docking was carried out with Autodock vina. The inflammation model of HaCaT cells induced by TNF-a/IFN-γ was established .to validate the mechanism of HXZQOL against MBD, with the levels of inflammatory factors and protein related to IL-7 signaling pathway assessed using Elisa and Western Blot. Results: HXZQOL contained 154 active compounds and shared 88 common targets with MBD. Quercetin, apigenin, ursolic acid and luteolin were identified as potential candidate compounds, while JUN, IL-6, TNF and VEGFA were suggested as main potential targets. HXZQOL was found to act on MBD through multiple pathways including IL-17, AGE-RAGE and TNF signaling pathways. The candidate compounds demonstrated effectively binding to JUN and IL-6 targets, with binding energies below −5 kcal/mol. Western blot experiments confirmed that these compounds could down-regulate the expression of JUN protein in IL-17 signaling pathway, and significantly reduce levels of inflammatory factors TNF-α, IL-6 and NO in HaCaT cells. Conclusion: HXZQOL mainly exerts its anti MAD effect by reducing inflammation. The relevant results have laid the foundation for improving the local anti MBD effect of HXZQOL and the secondary development of HXZQOL formulations.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"65 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1177/1934578x241276966
Tingjie Ye, Xiaofeng Yan, Wenhao Xiu, Changtai Qin, Yuxi Yang, Jinzu Yang, Limin Zhu, Xiaoling Wang, Wei Xu, Yanlin Lu
BackgroundTraditional Chinese Medicine Astragalus was commonly used to assist chemo-drug treatment in clinical cancer patients. However, whether Astragalus injection (AGI) reverses drug resistance remains unclear. Therefore, a meta-analysis is necessary to assess the effect of AGI on resistance reversement in cancer patients.MethodThe studies presenting tumor response rates in cancer patients receiving chemo-drugs treatment in combination with AGI were systematically searched from six common scientific databases until February 2024. The relative risks (RRs) indicating the tumor response rate, 1-year survival rate, and quality of life improvement in clinical patients among two groups were calculated in metan package. The pooled RRs with 95% confidence intervals (CIs) were used to explore the effect of AGI on enhancing drug sensitivity in terms of tumor response, 1-year survival rate and quality of life improvement in cancer patients.ResultFifty-one studies were included for meta-analysis following a thorough screening process that adhered to the inclusion and exclusion criteria. A total of 4613 patients were enrolled in all included trials. Results obtained indicated that AGI significantly enhanced the sensitivity of cancers to chemo-drugs with pooled RRs (95% CI) of 1.25 (1.18, 1.32), prolonged the 1-year survival rate of patients with pooled RRs (95% CI) of 1.34 (1.14, 1.57), improved the quality of life with pooled RRs (95% CI) of 1.61 (1.34, 1.93). Similarly, Astragalus's main component, astragaloside polysaccharides (APS), also enhances drug sensitivity in clinical cancer patients.ConclusionOur findings demonstrated that AGI had the ability to resensitize cancers to chemo-drugs and improve the quality of life of cancer patients. Therefore, AGI could potentially be used as a drug resistance reversal for resistant cancer treatment.
{"title":"Astragalus Injection Enhances the Sensitivity of Clinical Cancer Patients to Chemotherapy: A Systematic meta-Analysis","authors":"Tingjie Ye, Xiaofeng Yan, Wenhao Xiu, Changtai Qin, Yuxi Yang, Jinzu Yang, Limin Zhu, Xiaoling Wang, Wei Xu, Yanlin Lu","doi":"10.1177/1934578x241276966","DOIUrl":"https://doi.org/10.1177/1934578x241276966","url":null,"abstract":"BackgroundTraditional Chinese Medicine Astragalus was commonly used to assist chemo-drug treatment in clinical cancer patients. However, whether Astragalus injection (AGI) reverses drug resistance remains unclear. Therefore, a meta-analysis is necessary to assess the effect of AGI on resistance reversement in cancer patients.MethodThe studies presenting tumor response rates in cancer patients receiving chemo-drugs treatment in combination with AGI were systematically searched from six common scientific databases until February 2024. The relative risks (RRs) indicating the tumor response rate, 1-year survival rate, and quality of life improvement in clinical patients among two groups were calculated in metan package. The pooled RRs with 95% confidence intervals (CIs) were used to explore the effect of AGI on enhancing drug sensitivity in terms of tumor response, 1-year survival rate and quality of life improvement in cancer patients.ResultFifty-one studies were included for meta-analysis following a thorough screening process that adhered to the inclusion and exclusion criteria. A total of 4613 patients were enrolled in all included trials. Results obtained indicated that AGI significantly enhanced the sensitivity of cancers to chemo-drugs with pooled RRs (95% CI) of 1.25 (1.18, 1.32), prolonged the 1-year survival rate of patients with pooled RRs (95% CI) of 1.34 (1.14, 1.57), improved the quality of life with pooled RRs (95% CI) of 1.61 (1.34, 1.93). Similarly, Astragalus's main component, astragaloside polysaccharides (APS), also enhances drug sensitivity in clinical cancer patients.ConclusionOur findings demonstrated that AGI had the ability to resensitize cancers to chemo-drugs and improve the quality of life of cancer patients. Therefore, AGI could potentially be used as a drug resistance reversal for resistant cancer treatment.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"75 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1177/1934578x241282923
Gabriel Atampugbire, Eureka Emefa Ahadjie Adomako, Osbourne Quaye
This paper explores a diverse field of medicinal plants as potential antiviral agents, and delves into utilization of plant medicine for combating viral infections, emphasizing recent surge in research on natural products from plants as antiviral agents. Specific plant-derived compounds, like phyllanthin and iscador, have been proven to exhibit antiviral properties with great potential for pharmaceutical development. Mechanisms of antiviral action by phytochemicals that are present in medicinal plants, including direct viral inhibition, degradation of viral capsid, and immunomodulation were identified, and a combination therapy of medicinal plants with conventional antiviral drugs were explored. Efficacy of medicinal plants as antiviral agents was critically assessed and revealed that the complexity and variability of herbal formulations, and safety concerns regarding toxicity levels, pose challenges in drug development. However, research on medicinal plants is often hindered by limited understanding of phytochemical mechanisms, the complexity and variability of herbal formulations, and safety concerns regarding toxicity and interactions with other medications. The way forward in harnessing full potential of medicinal plants as antiviral agents underscores the need for further research into developing models that seek to enhance the selectivity of plant extracts in order to minimize toxicity levels.
{"title":"Medicinal Plants as Effective Antiviral Agents and Their Potential Benefits","authors":"Gabriel Atampugbire, Eureka Emefa Ahadjie Adomako, Osbourne Quaye","doi":"10.1177/1934578x241282923","DOIUrl":"https://doi.org/10.1177/1934578x241282923","url":null,"abstract":"This paper explores a diverse field of medicinal plants as potential antiviral agents, and delves into utilization of plant medicine for combating viral infections, emphasizing recent surge in research on natural products from plants as antiviral agents. Specific plant-derived compounds, like phyllanthin and iscador, have been proven to exhibit antiviral properties with great potential for pharmaceutical development. Mechanisms of antiviral action by phytochemicals that are present in medicinal plants, including direct viral inhibition, degradation of viral capsid, and immunomodulation were identified, and a combination therapy of medicinal plants with conventional antiviral drugs were explored. Efficacy of medicinal plants as antiviral agents was critically assessed and revealed that the complexity and variability of herbal formulations, and safety concerns regarding toxicity levels, pose challenges in drug development. However, research on medicinal plants is often hindered by limited understanding of phytochemical mechanisms, the complexity and variability of herbal formulations, and safety concerns regarding toxicity and interactions with other medications. The way forward in harnessing full potential of medicinal plants as antiviral agents underscores the need for further research into developing models that seek to enhance the selectivity of plant extracts in order to minimize toxicity levels.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"195 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1177/1934578x241284430
Shuting Zhao, Jingying Xv, Miaomiao Tang, Wei Hou
Background and PurposePlatycodon grandiflorum is a traditional Chinese herbal medicine, which can disperse lung, promote pharynx, dispel phlegm and expel pus. Its processing history was first seen in the “Zhou Hou Bei Ji Fang” of the Jin Dynasty in China. Through processing, effective substances in plants can be enriched and negative substances can be reduced. Therefore, this study explored the effects of different processing methods on the antitussive and expectorant effects of Platycodon grandiflorum through metabolomics and pharmacology, aiming to provide a theoretical basis for clinical application.Experimental ApproachThe changes of metabolites before and after processing of Platycodon grandiflorum were analyzed by Nexera UHPLC LC-30A-HILIC-Orbitrap-Q Exactive HF-X platform. The antitussive and expectorant effects of processed Platycodon grandiflorum were verified by mouse concentrated ammonia induced cough method and tracheal phenol red drainage method.Key ResultsAfter processing, some metabolites of Platycodon grandiflorum changed, among which 24 kinds of terpenoid metabolites changed significantly. Through the experiment of ammonia-induced cough in mice and phenol red expectorant experiment, it was found that fresh JZI 40%, fresh CZ 80%, dry JZZ 40% and dry JZI 80% had obvious antitussive effect, and dry JZZ 40% had obvious expectorant effect.Conclusions and ImplicationsSome processing methods can indeed further improve the antitussive and expectorant effects of Platycodon grandiflorum, which may be due to the effect of increasing the content of triterpenoids after processing, but the mechanism of processing to improve the effect of relieving cough and expectorant needs further study.
{"title":"Exploring the Effects of Different Processing Techniques on the Antitussive Expectorant of Platycodon grandiflorus by Metabonomics and Pharmacologic Methods","authors":"Shuting Zhao, Jingying Xv, Miaomiao Tang, Wei Hou","doi":"10.1177/1934578x241284430","DOIUrl":"https://doi.org/10.1177/1934578x241284430","url":null,"abstract":"Background and PurposePlatycodon grandiflorum is a traditional Chinese herbal medicine, which can disperse lung, promote pharynx, dispel phlegm and expel pus. Its processing history was first seen in the “Zhou Hou Bei Ji Fang” of the Jin Dynasty in China. Through processing, effective substances in plants can be enriched and negative substances can be reduced. Therefore, this study explored the effects of different processing methods on the antitussive and expectorant effects of Platycodon grandiflorum through metabolomics and pharmacology, aiming to provide a theoretical basis for clinical application.Experimental ApproachThe changes of metabolites before and after processing of Platycodon grandiflorum were analyzed by Nexera UHPLC LC-30A-HILIC-Orbitrap-Q Exactive HF-X platform. The antitussive and expectorant effects of processed Platycodon grandiflorum were verified by mouse concentrated ammonia induced cough method and tracheal phenol red drainage method.Key ResultsAfter processing, some metabolites of Platycodon grandiflorum changed, among which 24 kinds of terpenoid metabolites changed significantly. Through the experiment of ammonia-induced cough in mice and phenol red expectorant experiment, it was found that fresh JZI 40%, fresh CZ 80%, dry JZZ 40% and dry JZI 80% had obvious antitussive effect, and dry JZZ 40% had obvious expectorant effect.Conclusions and ImplicationsSome processing methods can indeed further improve the antitussive and expectorant effects of Platycodon grandiflorum, which may be due to the effect of increasing the content of triterpenoids after processing, but the mechanism of processing to improve the effect of relieving cough and expectorant needs further study.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"53 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1177/1934578x241276960
Haijin Wang, Mengxiao Wang, Wuxia Yang, Runfeng Ni, Lin Ma, Dan Wang, Chao Yan, Yuhong Wu, Baoshan Liu, Aidi Wang
ObjectiveImmune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The immune imbalance of T cells is an essential pathological mechanism of ITP, more specific, the balance of Effector T cells (Teff)/Regulatory T cell (Treg) maintains T cell immune homeostasis. Dendritic cells (DC), the largest antigen-presenting cell, interfere with T cell differentiation pathways and exert immune regulatory functions. Our team created and applied the “ NingXueShengBan” (NXSB) decoction. According to our prior studies, we found that NXSB decoction could restore Th17/Treg balance in ITP mice by regulating protein expression in Notch pathway. Therefore, we further research the mechanism of NXSB decoction that regulates ITP immune homeostasis through affecting the interaction between DC and T cells.MethodsIn this study, we collected peripheral blood from health donors and ITP patients and extracted DC and CD4 + T cells then grouped in control group, model group and NXSB group. Moreover, we established a co-culture model simulating the immune environment in ITP patient to further investigate whether NXSB had therapeutic effects by the interaction between DC and CD4 + T cells.ResultsIn the current study, we found that NXSB decoction potently regulated interaction between DC and T cells by inhibiting DC development and function, specifically, the differentiation of CD4+ T cells was inhibited after NXSB decoction intervened. Our data showed that NXSB decoction inhibited Toll-like receptor 4 (TLR-4), reduced the expression of Nuclear factor kappa-B (NF-κB) and led to the reduction of downstream inflammatory factors, thereby inhibiting the inflammatory response. More importantly, NXSB decoction reduced the DC surface expression of activation and maturation markers. Moreover, we detected that the decreased expression of the phosphorylated Phosphatidylinositol 3-kinase (PI3 K), Protein kinase B (Akt), Mammalian target of rapamycin (mTOR), and their downstream effectors indicated, we found that NXSB decoction could inhibit PI3 K/Akt/mTOR signaling pathways significantly.ConclusionsCollectively, our data suggested that NXSB decoction ameliorates ITP-induced immune imbalance via its anti-inflammation and immunosuppressive by regulating TLR-4/ NF-κB and PI3 K/Akt/mTOR signaling pathways.
目的免疫性血小板减少症（ITP）是一种自身免疫性出血性疾病。T细胞的免疫失衡是ITP的重要病理机制，具体而言，效应T细胞（Teff）/调节T细胞（Treg）的平衡维持着T细胞的免疫平衡。树突状细胞（DC）是最大的抗原递呈细胞，能干扰T细胞分化途径并发挥免疫调节功能。我们的团队创造并应用了 "宁血生煎"。根据之前的研究，我们发现宁血生煎可通过调节 Notch 通路蛋白的表达，恢复 ITP 小鼠 Th17/Treg 的平衡。因此，我们进一步研究了NXSB煎剂通过影响DC和T细胞之间的相互作用来调节ITP免疫平衡的机制。结果 在本研究中，我们发现 NXSB 水煎剂通过抑制 DC 的发育和功能，有效调节 DC 和 T 细胞之间的相互作用，特别是在 NXSB 水煎剂干预后，CD4+ T 细胞的分化受到抑制。我们的数据显示，NXSB 水煎剂抑制了 Toll 样受体 4（TLR-4），降低了核因子卡巴-B（NF-κB）的表达，导致下游炎症因子减少，从而抑制了炎症反应。更重要的是，NXSB 水煎剂降低了直流电表面活化和成熟标志物的表达。此外，我们还检测到磷酸化磷脂酰肌醇3-激酶（PI3 K）、蛋白激酶B（Akt）、哺乳动物雷帕霉素靶标（mTOR）及其下游效应物的表达减少，表明NXSB水煎剂能显著抑制PI3 K/Akt/mTOR信号通路。结论综上所述，我们的数据表明，NXSB煎剂通过调节TLR-4/ NF-κB和PI3 K/Akt/mTOR信号通路，具有抗炎和免疫抑制作用，可改善ITP诱导的免疫失衡。
{"title":"NingXueShengBan Decoction Regulates Immune Homeostasis by PI3 K/Akt/mTOR and TLR4/NF-κB Signaling Pathways in Immune Thrombocytopenia Patients","authors":"Haijin Wang, Mengxiao Wang, Wuxia Yang, Runfeng Ni, Lin Ma, Dan Wang, Chao Yan, Yuhong Wu, Baoshan Liu, Aidi Wang","doi":"10.1177/1934578x241276960","DOIUrl":"https://doi.org/10.1177/1934578x241276960","url":null,"abstract":"ObjectiveImmune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The immune imbalance of T cells is an essential pathological mechanism of ITP, more specific, the balance of Effector T cells (Teff)/Regulatory T cell (Treg) maintains T cell immune homeostasis. Dendritic cells (DC), the largest antigen-presenting cell, interfere with T cell differentiation pathways and exert immune regulatory functions. Our team created and applied the “ NingXueShengBan” (NXSB) decoction. According to our prior studies, we found that NXSB decoction could restore Th17/Treg balance in ITP mice by regulating protein expression in Notch pathway. Therefore, we further research the mechanism of NXSB decoction that regulates ITP immune homeostasis through affecting the interaction between DC and T cells.MethodsIn this study, we collected peripheral blood from health donors and ITP patients and extracted DC and CD4 <jats:sup>+ </jats:sup>T cells then grouped in control group, model group and NXSB group. Moreover, we established a co-culture model simulating the immune environment in ITP patient to further investigate whether NXSB had therapeutic effects by the interaction between DC and CD4 <jats:sup>+ </jats:sup>T cells.ResultsIn the current study, we found that NXSB decoction potently regulated interaction between DC and T cells by inhibiting DC development and function, specifically, the differentiation of CD4<jats:sup>+</jats:sup> T cells was inhibited after NXSB decoction intervened. Our data showed that NXSB decoction inhibited Toll-like receptor 4 (TLR-4), reduced the expression of Nuclear factor kappa-B (NF-κB) and led to the reduction of downstream inflammatory factors, thereby inhibiting the inflammatory response. More importantly, NXSB decoction reduced the DC surface expression of activation and maturation markers. Moreover, we detected that the decreased expression of the phosphorylated Phosphatidylinositol 3-kinase (PI3 K), Protein kinase B (Akt), Mammalian target of rapamycin (mTOR), and their downstream effectors indicated, we found that NXSB decoction could inhibit PI3 K/Akt/mTOR signaling pathways significantly.ConclusionsCollectively, our data suggested that NXSB decoction ameliorates ITP-induced immune imbalance via its anti-inflammation and immunosuppressive by regulating TLR-4/ NF-κB and PI3 K/Akt/mTOR signaling pathways.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"39 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Postmenopausal osteoporosis (PMOP) is an important part of primary osteoporosis, and the current clinical treatment program for PMOP is easily limited by side effects and adverse reactions, so it is particularly important to seek more efficient, safe, and economical drug treatment for PMOP. In recent years, with the change of disease treatment mode and the gradual deepening of Traditional Chinese medicine (TCM) research on PMOP, a review of the literature reveals that there is a huge number of studies on the use of TCM in the treatment of PMOP, but there are no relevant systematic studies on the rules of its formulas and the specific mechanisms by which the core drugs exert their therapeutic effects. Therefore, in this study, we collected a total of 141 formulas used by TCM clinicians to treat PMOP, statistically analyzed their high-frequency medications, Four Qi, Five Flavors, meridians, and efficacies, and analyzed the core medications based on the association rules, which were Rehmanniae Radix Praeparata, Epimedium, Eucommia ulmoides, Rhizoma Drynariae, Angelica sinensis, Achyranthes, Astragalus propinquus, Psoralen, Cornus officinalis and licorice. A total of 87 drug pairs were obtained from the correlation analysis, and a total of 8 groups of potential core combination drugs and 4 potential new prescriptions were derived based on the cluster analysis. Subsequently, a network pharmacological analysis of the core drugs was conducted to obtain 173 active ingredients in the core drugs, including kaempferol, β-sitosterol, quercetin, etc. 298 targets of action, including MAPK3, STAT1, HSP90AA1, etc. 170 signaling pathways including AGE-RAGE, PI3 K/Akt, TNF, HIF-1 and others. The molecular docking results showed that 11 key active ingredients in the core drugs had stable binding to the target targets. This study showed that TCM treatment of PMOP is mainly based on “reinforcing liver and kidney, warmly invigorating spleen and stomach, activating blood and resolving stasis.” Core drugs therapy for PMOP is a comprehensive intervention through multi-component, multi-target, and multi-pathway approaches. The minimum binding energies between the 11 key active ingredients and the 11 key targets were calculated in a comprehensive analysis, which shows that the core drugs have good binding activities to their therapeutic targets, proving that the predictions of this study are reliable. In the future, it will provide certain medication basis and data support for TCM treatment of PMOP.
{"title":"To Explore the Rule and Mechanism of Traditional Chinese Medicine in the Treatment of Postmenopausal Osteoporosis Based on Data Mining, Network Pharmacology and Molecular Docking Technology","authors":"Hao Zeng, Keqi Huang, Yuan Chai, Hua Liu, Yongjin Li, Zhengpeng Li, Xiaoyun Zhang","doi":"10.1177/1934578x241281303","DOIUrl":"https://doi.org/10.1177/1934578x241281303","url":null,"abstract":"Postmenopausal osteoporosis (PMOP) is an important part of primary osteoporosis, and the current clinical treatment program for PMOP is easily limited by side effects and adverse reactions, so it is particularly important to seek more efficient, safe, and economical drug treatment for PMOP. In recent years, with the change of disease treatment mode and the gradual deepening of Traditional Chinese medicine (TCM) research on PMOP, a review of the literature reveals that there is a huge number of studies on the use of TCM in the treatment of PMOP, but there are no relevant systematic studies on the rules of its formulas and the specific mechanisms by which the core drugs exert their therapeutic effects. Therefore, in this study, we collected a total of 141 formulas used by TCM clinicians to treat PMOP, statistically analyzed their high-frequency medications, Four Qi, Five Flavors, meridians, and efficacies, and analyzed the core medications based on the association rules, which were Rehmanniae Radix Praeparata, Epimedium, Eucommia ulmoides, Rhizoma Drynariae, Angelica sinensis, Achyranthes, Astragalus propinquus, Psoralen, Cornus officinalis and licorice. A total of 87 drug pairs were obtained from the correlation analysis, and a total of 8 groups of potential core combination drugs and 4 potential new prescriptions were derived based on the cluster analysis. Subsequently, a network pharmacological analysis of the core drugs was conducted to obtain 173 active ingredients in the core drugs, including kaempferol, β-sitosterol, quercetin, etc. 298 targets of action, including MAPK3, STAT1, HSP90AA1, etc. 170 signaling pathways including AGE-RAGE, PI3 K/Akt, TNF, HIF-1 and others. The molecular docking results showed that 11 key active ingredients in the core drugs had stable binding to the target targets. This study showed that TCM treatment of PMOP is mainly based on “reinforcing liver and kidney, warmly invigorating spleen and stomach, activating blood and resolving stasis.” Core drugs therapy for PMOP is a comprehensive intervention through multi-component, multi-target, and multi-pathway approaches. The minimum binding energies between the 11 key active ingredients and the 11 key targets were calculated in a comprehensive analysis, which shows that the core drugs have good binding activities to their therapeutic targets, proving that the predictions of this study are reliable. In the future, it will provide certain medication basis and data support for TCM treatment of PMOP.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"1 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Buyang-Huanwu Decoction is often used as an adjuvant therapy for ischemic stroke in clinical practice. At the same time, various laboratories have found that it has the potential to treat ischemic heart failure, lower extremity varicose veins, pulmonary hypertension, pulmonary fibrosis, and hyperlipidemia. Previous studies in our laboratory have found that different concentrations of ethanol were used to separate the polar components of Buyang-Huanwu decoction, and the therapeutic effects of each group on pulmonary fibrosis and hyperlipidemia were different. Therefore, we analyzed and explored Buyang Huanwu decoction and its products. Methods: The isolated components were obtained by treatment with absolute ethanol, 30% (v/v), 50% (v/v), 75% (v/v), and 90% (v/v) ethanol, and the components were analyzed by UPLC-MS. Results: The separation method used in our laboratory could well separate the components of Buyang Huanwu Decoction, and simply enrich carbohydrates, organic acids, phenylpropanoid compounds, lipids, nucleotides, and lignans. Conclusions: The products treated with different concentrations of ethanol have different therapeutic potentials. The high content components of 30% ethanol eluate and 50% ethanol eluate have good therapeutic effects on osteoarthritis and bone loss, while the high content components of the precipitate components and 75% eluate are more likely to be related to glucose and lipid metabolism disorders and cardiovascular diseases.
{"title":"The Components of Buyang Huanwu Decoction with UPLC-MS","authors":"Shijian Fang, Yuxue Ma, Shuaihu Yang, Ruihong Yang, Xingtong Chen, Jinbiao Yang, Yunyue Zhou, Hongbin Xiao, Yukun Zhang, Wenying Niu","doi":"10.1177/1934578x241275820","DOIUrl":"https://doi.org/10.1177/1934578x241275820","url":null,"abstract":"Objective: Buyang-Huanwu Decoction is often used as an adjuvant therapy for ischemic stroke in clinical practice. At the same time, various laboratories have found that it has the potential to treat ischemic heart failure, lower extremity varicose veins, pulmonary hypertension, pulmonary fibrosis, and hyperlipidemia. Previous studies in our laboratory have found that different concentrations of ethanol were used to separate the polar components of Buyang-Huanwu decoction, and the therapeutic effects of each group on pulmonary fibrosis and hyperlipidemia were different. Therefore, we analyzed and explored Buyang Huanwu decoction and its products. Methods: The isolated components were obtained by treatment with absolute ethanol, 30% (v/v), 50% (v/v), 75% (v/v), and 90% (v/v) ethanol, and the components were analyzed by UPLC-MS. Results: The separation method used in our laboratory could well separate the components of Buyang Huanwu Decoction, and simply enrich carbohydrates, organic acids, phenylpropanoid compounds, lipids, nucleotides, and lignans. Conclusions: The products treated with different concentrations of ethanol have different therapeutic potentials. The high content components of 30% ethanol eluate and 50% ethanol eluate have good therapeutic effects on osteoarthritis and bone loss, while the high content components of the precipitate components and 75% eluate are more likely to be related to glucose and lipid metabolism disorders and cardiovascular diseases.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"12 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The massive production of agro-industrial waste has become a global concern. Approximately 3.6 million tons of citrus waste are disposed of annually after processing, despite most bioactive molecules being found in fruit peels. Objectives/methodology: This work explored the biochemical and carbohydrate polymer profile of methanolic extract of the soft, spongy Citrus reticulata ( C. reticulata) albedo through proximate analysis, antioxidant and scavenging potential analysis, carbohydrate analysis, antioxidant enzyme and genotoxicity analysis, which were further quantified by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and Fourier transform infrared spectroscopy (FTIR) analysis. Results: The results revealed that the citrus albedo comprised an ample amount of ash (3.30 g/100−g of fresh weight (FW), moisture (52.67 g/100−g FW), fiber (30.80 g/100−g FW), lipid (5.58 g/100−g FW), protein (9.62 Kcal/ 100−g FW) and carbohydrate contents, ie, pectin (18.5 mg/g of dry weight (DW), glucosamine (5.05 mg/g DW), maltose (6.5 mg/g DW), D-xylose (35.5 mg/g DW), cellulose (12.2 mg/g DW), total soluble sugars (13.5 mg/g DW), starch (29% w/w). The antioxidant enzyme exhibited excellent activities (23.06 IU/mL for superoxide dismutase, 37.10 IU/mL for catalase and 1.27 IU/mL for peroxidase). The bioactive molecules of the citrus albedo showed maximum total phenolic content (TPC) (2.30 mg gallic acid equivalent (GAE)/ g DW), total flavonoid contents (TFC) (1.71 mg quercetin equivalent (QE)/ g DW) and scavenging potential (50.67% inhibition) when used at a higher concentration of 100 mg/mL. FTIR and liquid chromatography-mass spectrometry (LC-MS) findings concluded that the citrus albedo was rich in polysaccharides including pectin, glucosamine and antioxidants like caffeic acid, quercitin, naringenin, hesperidin and resveratrol. Moreover, the MTT assay showed that the hepatoblastoma cell line (HepG2) underwent apoptosis after 72-h exposure to C. reticulata albedo extract at varied concentrations. Conclusion: These findings suggest that citrus albedo can be a potential chemotherapeutic agent against hepatocellular carcinoma.
{"title":"LC-MS/MS Profiling, Antioxidant Potential and Cytotoxicity Evaluation of Citrus reticulata Albedo","authors":"Javaid Aftab, Mazhar Abbas, Sumaira Sharif, Aqsa Mumtaz, Kinza Zafar, Naveed Ahmad, Osama A. Mohammed, Arif Nazir, Shahid Iqbal, Munawar Iqbal","doi":"10.1177/1934578x241272471","DOIUrl":"https://doi.org/10.1177/1934578x241272471","url":null,"abstract":"Background: The massive production of agro-industrial waste has become a global concern. Approximately 3.6 million tons of citrus waste are disposed of annually after processing, despite most bioactive molecules being found in fruit peels. Objectives/methodology: This work explored the biochemical and carbohydrate polymer profile of methanolic extract of the soft, spongy Citrus reticulata ( C. reticulata) albedo through proximate analysis, antioxidant and scavenging potential analysis, carbohydrate analysis, antioxidant enzyme and genotoxicity analysis, which were further quantified by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and Fourier transform infrared spectroscopy (FTIR) analysis. Results: The results revealed that the citrus albedo comprised an ample amount of ash (3.30 g/100<jats:sup>−g</jats:sup> of fresh weight (FW), moisture (52.67 g/100<jats:sup>−g</jats:sup> FW), fiber (30.80 g/100<jats:sup>−g</jats:sup> FW), lipid (5.58 g/100<jats:sup>−g</jats:sup> FW), protein (9.62 Kcal/ 100<jats:sup>−g</jats:sup> FW) and carbohydrate contents, ie, pectin (18.5 mg/g of dry weight (DW), glucosamine (5.05 mg/g DW), maltose (6.5 mg/g DW), D-xylose (35.5 mg/g DW), cellulose (12.2 mg/g DW), total soluble sugars (13.5 mg/g DW), starch (29% w/w). The antioxidant enzyme exhibited excellent activities (23.06 IU/mL for superoxide dismutase, 37.10 IU/mL for catalase and 1.27 IU/mL for peroxidase). The bioactive molecules of the citrus albedo showed maximum total phenolic content (TPC) (2.30 mg gallic acid equivalent (GAE)/ g DW), total flavonoid contents (TFC) (1.71 mg quercetin equivalent (QE)/ g DW) and scavenging potential (50.67% inhibition) when used at a higher concentration of 100 mg/mL. FTIR and liquid chromatography-mass spectrometry (LC-MS) findings concluded that the citrus albedo was rich in polysaccharides including pectin, glucosamine and antioxidants like caffeic acid, quercitin, naringenin, hesperidin and resveratrol. Moreover, the MTT assay showed that the hepatoblastoma cell line (HepG2) underwent apoptosis after 72-h exposure to C. reticulata albedo extract at varied concentrations. Conclusion: These findings suggest that citrus albedo can be a potential chemotherapeutic agent against hepatocellular carcinoma.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"15 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1177/1934578x241282866
Muhannad Hasan, Imad Hwija, Yaseer Mossa
Objective/Background: Phlomis longifolia Boiss. & C.I. Blanche. is one of the significant medicinal plants extensively utilized in folk medicine in Syria. So, this study aimed to identify the chemical components with potential pharmacological properties of essential oils extracted from the aerial parts of the Syrian P. longifolia plant for the first time. Methods: The aerial parts of the plant were collected from a mountainous area in Latakia Province, Syria. Subsequently, the essential oils were obtained using hydrodistillation with a yield of (0.14% for flowers, 0.075% for calyxes, and 0.19% for leaves) using a Clevenger-type apparatus and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Results: A total of 63, 61, and 48 compounds, which represent (98.0%, 97.1%, and 97.9%) of the total oils, were identified for flowers, calyxes, and leaves, respectively. The major compounds identified in the flower's essential oil were: widdrol (29.8%), β-caryophyllene (9.7%), and (E)-nerolidyl acetate (5.8%). While in the calyx's essential oil were: (E)-nerolidyl acetate (8.6%), α-humulene (8.1%), and β-caryophyllene (7.7%). As for the leave's essential oil were: (E)-nerolidyl acetate (11.4%), β-caryophyllene (9.5%), α-amorphene (8.8%), caryophyllene oxide (6.7%), α-humulene (5.3%), and 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one (5.2%). Additionally, the majority of the identified compounds have various biological activities, according to the published literature. Conclusion: In this work, the chemical composition of essential oils extracted from the aerial parts of P. longifolia was determined for the first time by GC-MS. Terpenes were the dominant chemical content of essential oils (83.3% for flowers, 72.7% for calyxes, and 80.9 for leaves), and sesquiterpenes had the highest concentration among them (77.3% for flowers, 65.7% for calyxes, and 77.1% for leaves). These compounds are known for their diverse biological activities and promote the use of such plants in phytopharmaceuticals.
{"title":"Essential Oils from Phlomis longifolia Boiss. & C.I. Blanche. Aerial Parts (Flowers, Calyxes, Leaves): GC-MS Analyzes and Biological Properties","authors":"Muhannad Hasan, Imad Hwija, Yaseer Mossa","doi":"10.1177/1934578x241282866","DOIUrl":"https://doi.org/10.1177/1934578x241282866","url":null,"abstract":"Objective/Background: Phlomis longifolia Boiss. & C.I. Blanche. is one of the significant medicinal plants extensively utilized in folk medicine in Syria. So, this study aimed to identify the chemical components with potential pharmacological properties of essential oils extracted from the aerial parts of the Syrian P. longifolia plant for the first time. Methods: The aerial parts of the plant were collected from a mountainous area in Latakia Province, Syria. Subsequently, the essential oils were obtained using hydrodistillation with a yield of (0.14% for flowers, 0.075% for calyxes, and 0.19% for leaves) using a Clevenger-type apparatus and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Results: A total of 63, 61, and 48 compounds, which represent (98.0%, 97.1%, and 97.9%) of the total oils, were identified for flowers, calyxes, and leaves, respectively. The major compounds identified in the flower's essential oil were: widdrol (29.8%), β-caryophyllene (9.7%), and (E)-nerolidyl acetate (5.8%). While in the calyx's essential oil were: (E)-nerolidyl acetate (8.6%), α-humulene (8.1%), and β-caryophyllene (7.7%). As for the leave's essential oil were: (E)-nerolidyl acetate (11.4%), β-caryophyllene (9.5%), α-amorphene (8.8%), caryophyllene oxide (6.7%), α-humulene (5.3%), and 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one (5.2%). Additionally, the majority of the identified compounds have various biological activities, according to the published literature. Conclusion: In this work, the chemical composition of essential oils extracted from the aerial parts of P. longifolia was determined for the first time by GC-MS. Terpenes were the dominant chemical content of essential oils (83.3% for flowers, 72.7% for calyxes, and 80.9 for leaves), and sesquiterpenes had the highest concentration among them (77.3% for flowers, 65.7% for calyxes, and 77.1% for leaves). These compounds are known for their diverse biological activities and promote the use of such plants in phytopharmaceuticals.","PeriodicalId":19019,"journal":{"name":"Natural Product Communications","volume":"17 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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