Journal of Holistic Integrative Pharmacy最新文献

{"title":"Methodological project (SMART-PT) for transparency and methodological characteristics of randomized controlled trials of phytotherapy interventions","authors":"Cuncun Lu ,&nbsp;Xiuxiu Deng ,&nbsp;Ziyi Wang ,&nbsp;Xiaoxiao Zhao ,&nbsp;Lixin Ke ,&nbsp;Zhifei Wang","doi":"10.1016/j.jhip.2024.01.004","DOIUrl":"10.1016/j.jhip.2024.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy and safety of medical interventions. Phytotherapy, which plays a critical role in the prevention and treatment of many clinical conditions, is also evaluated by RCTs. In recent years, the transparency, methodology, and generalizability of RCTs, as well as disparities in gender and geographical location among researchers, have attracted much attention from the scientific community. However, these aspects of RCTs in phytotherapy interventions have not been fully evaluated. Therefore, a methodological project (i.e., SMART-PT, tranSparency and Methodological chAracteristics of Randomized controlled Trials of PhytoTherapy interventions) was designed to overcome these knowledge gaps and provide key references for relevant future RCTs.</div></div><div><h3>Methods</h3><div>The SMART-PT project consists of five studies that will be conducted using RCTs derived from two high-impact phytotherapy journals, <em>Phytomedicine</em> and <em>Phytotherapy Research</em>. RCTs published in <em>Phytomedicine</em> and <em>Phytotherapy Research</em> were searched using the PubMed database from inception to February 13, 2023. Study selection was performed by two independent researchers, and data extraction and quality assessment will also be conducted independently by two researchers. First, we will investigate the reporting completeness, data-sharing level, and presence of spin among the included RCTs (Study 1). Second, we will evaluate the risk of bias in the included RCTs and the statistical fragility of primarily binary outcomes, and the likelihood ratio will be used to reinterpret statistically nonsignificant primary outcomes (Study 2). Third, we will evaluate the reporting completeness of phytotherapy interventions in the included RCTs as well as the trustworthiness of the RCTs (Study 3). Fourth, we will investigate the reporting of sociodemographic features and representation of participants in the included RCTs (Study 4). Finally, we will investigate the reporting completeness of the abstracts, the representation of gender, and geographical region of the listed authors among the included RCTs (Study 5). R 4.2.3, Stata 17/SE, and Excel 2019 will be used to analyze the data and create graphics.</div></div><div><h3>Results and Discussion</h3><div>One-hundred and fifty-two double-arm, parallel-group, superiority RCTs were included in the SMART-PT project. The results of the five meta-research studies will be submitted for publication in peer-reviewed journals.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 4","pages":"Pages 293-298"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143291710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, cytotoxicity study of novel bisacridine derivatives and their interaction with c-myc promoter G-quadruplex/i-motif","authors":"Bing Shu ,&nbsp;Wang-liang Chen ,&nbsp;Jia-lin Song ,&nbsp;Shen Fang ,&nbsp;Jiong-bang Li ,&nbsp;Shang-shi Zhang","doi":"10.1016/j.jhip.2024.01.003","DOIUrl":"10.1016/j.jhip.2024.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>To synthesize novel bisacridine derivatives <strong>A1</strong>-<strong>A4</strong> and study cytotoxicity and their interaction with <em>c-myc</em> G-quadruplex/i-motif DNA.</div></div><div><h3>Method</h3><div>Bisacridines <strong>A1</strong>-<strong>A4</strong> were synthesized according to the conventional reaction method. Fluorescence resonance energy transfer (FRET) melting assay, Surface Plasmon Resonance (SPR) measurement, CD experiments, and molecular docking were used to study the interactions between <strong>A1</strong>-<strong>A4</strong> and <em>c-myc</em> promoter G-quadruplex/i-motif. MTT cytotoxicity assay was used to evaluate the cytotoxicity of the bisacridine derivatives <strong>A1-A4</strong> against A375, Hela, A549, U2OS, HCT116, Siha, HuH7 cell lines.</div></div><div><h3>Result</h3><div>The results of FRET melting assay and SPR measurement indicated that bisacridine derivatives <strong>A1-A4</strong> could bind to and stabilize the <em>c-myc</em> G-quadruplex/i-motif structure. CD experiments and molecular docking results demonstrated the interaction between <strong>A1-A4</strong> and <em>c-myc</em> G-quadruplex/i-motif. MTT experiments showed that <strong>A1-A4</strong> exhibited strong inhibitory effects on the proliferation of human A375, Hela, A549, U2OS, HCT116, Siha, HuH7 cell lines.</div></div><div><h3>Conclusion</h3><div>Bisacridine derivatives <strong>A1-A4</strong> could bind to and stabilize the <em>c-myc</em> G-quadruplex/i-motif to inhibit the proliferation of human cancer cells and will potentially be developed into a class of small molecule ligands targeting <em>c-myc</em> G-quadruplex/i-motif.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 4","pages":"Pages 281-286"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143291712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloroplast genome of Thesium chinense: The insight into phylogeny of Santalaceae","authors":"Zhenyu Zhao ,&nbsp;Hongxiu Li ,&nbsp;Meilan Chen ,&nbsp;Meng Cheng ,&nbsp;Cadiz Quispe Gustavo Pedro ,&nbsp;Xiuteng Zhou ,&nbsp;Luqi Huang","doi":"10.1016/j.jhip.2024.01.007","DOIUrl":"10.1016/j.jhip.2024.01.007","url":null,"abstract":"<div><div><em>Thesium chinense</em> is an important and commonly used traditional Chinese medicine. The aim of this study is to obtain more bioinformatics from <em>Thesium chinense</em> and to conduct a more comprehensive and in-depth analysis of Santalaceae's phylogeny. This study sequenced the chloroplast genome of <em>Thesium chinense</em> and performed bioinformatics analysis on its key genes to reconstruct the Santalaceae phylogenetic tree. The genes of traditional Chinese medicine often affect the generation and accumulation of metabolic products. The different genes in the chloroplast genome of <em>Thesium chinense</em> have different biological characteristics. The phylogenetic system of Santalaceae and its related families differs significantly from classical classification. This study has laid a solid foundation for the better application and identification of <em>Thesium chinense</em>.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 4","pages":"Pages 310-317"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143291717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical role of signal transducers and activators of transcription-3 in the proliferation of vascular smooth muscle cells","authors":"Shuai Li,&nbsp;Chan Liu","doi":"10.1016/j.jhip.2023.11.007","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.11.007","url":null,"abstract":"<div><p>The proliferation of vascular smooth muscle cells (VSMCs) is a key pathogenic characteristic of vascular remodeling diseases. The signal transducers and activators of transcription-3 (STAT3) signaling pathway is crucial for VSMCs growth, and its role in cytokine-induced VSMCs proliferation, calcification, and phenotypic switching is essential for developing new treatment targets. VSMCs can transform from contractile to synthetic phenotypes in response to stimuli, such as mechanical forces, growth factors, pro-inflammatory cytokines, and vascular injury. Understanding the mechanism of VSMCs proliferation triggered by the STAT3 pathway is important for identifying potential therapeutic targets for vascular remodeling diseases.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 3","pages":"Pages 241-247"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823001127/pdfft?md5=bfc9f9ce462b4256522d58bda558f653&pid=1-s2.0-S2707368823001127-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138678494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the synergistic development of TCM service trade within the GBA","authors":"Qiu Zhang ,&nbsp;Chuyun Wu ,&nbsp;Xinrong Ai ,&nbsp;Mandong Huang ,&nbsp;Baifeng Zheng ,&nbsp;Yiling Li ,&nbsp;Shuli Zhang ,&nbsp;Liqing Yao ,&nbsp;Jiangyue Wang ,&nbsp;Yingying Tang","doi":"10.1016/j.jhip.2023.12.002","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.12.002","url":null,"abstract":"<div><h3>Objectives</h3><p>This study analyzed the synergistic development of the Traditional Chinese Medicine (TCM) service trade within the Greater Bay Area (GBA) in China, aiming to provide suggestions and references for the development of TCM service trade around the world.</p></div><div><h3>Methods</h3><p>Taking the typical and representative Guangdong, Hong Kong and Macao Greater Bay Area as the research object, this paper focused on four modes of “cross-border supply, offshore consumption, commercial presence, and movement of natural persons”, and explored the current situation of TCM service trade from four macroscopic aspects: political, economic, social, and technological, through case studies. The challenges in the development of TCM service trade were analyzed.</p></div><div><h3>Results</h3><p>Our study found that the degree of synergistic openness of Guangdong, Hong Kong and Macao needs to be improved. The integration of trade in TCM services is the integration of TCM services with tourism. However, there is a relative lack of human resources in TCM in Hong Kong and Macao, with weak competitiveness of service bases. The resources of TCM services are still under-utilized, and the GBA market of TCM services lacks momentum.</p></div><div><h3>Conclusions</h3><p>We have come to the conclusion that the GBA need to promptly improve the unified standard system of TCM service trade. Actively building cultivating a “Bay Area GBA brand” for TCM service trade, steadily building a social climate in support of TCM service trade and vigorously promote the development of TCM service trade through digital technology, thus promoting the synergistic development of TCM service trade within the GBA.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 3","pages":"Pages 248-255"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823001140/pdfft?md5=25f217c222d74b1c328c35ef0bcf005e&pid=1-s2.0-S2707368823001140-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139099697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dioscoreae persimilis polysaccharide ameliorates DSS-induced ulcerative colitis in mice through modulation of microbiota composition","authors":"Qian Zhang ,&nbsp;Guorong Wu ,&nbsp;Shumin Shen ,&nbsp;Chong Li","doi":"10.1016/j.jhip.2023.09.004","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.09.004","url":null,"abstract":"<div><p>Ulcerative colitis (UC) is a non-specific inflammatory bowel disease that has a high rate of recurrence, development of novel therapeutic approaches with high efficacy and few adverse effects are still needed. <em>Dioscoreae persimilis</em> is an edible plant that has been widely consumed as a remedy for gastrointestinal diseases in traditional Chinese medicine. Polysaccharides have been proven to have protective effects on UC. However, the role of polysaccharides from <em>D. persimilis</em> in UC has not been studied yet. The refined <em>D. persimilis</em> Polysaccharide (DP), which consists of glucose and galactose, was extracted and purified using three-phase partitioning (TPP) method. The primary chemical and structural characteristics of DP were investigated by UV, FT-IR, molecular weight, and monosaccharide composition. Based on dextran sulfate sodium (DSS) induced UC in mice, the alleviatory effect of DP on UC was explored. DP was found to alleviate histopathological changes of colon, improve colonic antioxidant capacity and ameliorate inflammation response in colitis mice. Moreover, 16S rDNA sequencing of fecal revealed that DP could restore the diversity and composition of gut microbiota, especially up-regulates the abundance of <em>Acetatifactor</em>, <em>Lachnospiraceae</em>, and <em>Lactobacillus</em>, and increase the ratio of Firmicutes/Bacteroidetes. According to this study, DP has the potential to serve as an effective nutritional supplement for improving colitis.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 2","pages":"Pages 157-165"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823000870/pdfft?md5=3449395a1f245bdf9f5916c92cf00ed6&pid=1-s2.0-S2707368823000870-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92047740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tianhuang formula ameliorates non-alcoholic fatty liver diseases in type 2 diabetic mice through CRLS1-ATF3/ChREBP pathway","authors":"Yi Han ,&nbsp;Yating Zhao ,&nbsp;Xuefeng Xu ,&nbsp;Zhizhong Luo ,&nbsp;Duosheng Luo ,&nbsp;Jiao Guo","doi":"10.1016/j.jhip.2023.09.002","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.09.002","url":null,"abstract":"<div><h3>Objective</h3><p>Tianhuang Formula (THF) is a hospital formula summarized by Professor Jiao Guo's 30 years of clinical experience. Some studies have shown that it can alleviate dyslipidemia in the body. The purpose of this study is to confirm whether THF can improve non-alcoholic fatty liver diseases (NAFLD) in type 2 diabetic mice induced by high-fat diet (HFD)/streptomycin (STZ) and to clarify its potential mechanism.</p></div><div><h3>Methods</h3><p>After induction of diabetes, mice were administrated with THF (60 ​mg/kg or 120 ​mg/kg) once daily for 10 weeks. Blood glucose (FBG), glucose tolerance, and insulin resistance (IR) were assayed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Blood lipids, alanine transaminase (ALT), and aspartate transaminases (AST) were detected. Serum fasting insulin (INS) and adiponectin (APN) levels were measured using ELISA. Histological changes in liver and pancreatic islets were observed by H&amp;E staining, followed by Oil Red O staining for liver lipid quantification and periodic acid-Schiff (PAS) staining to detect glycogen accumulation. Western blotting detected the levels of fatty cardiolipin synthase 1 (CRLS1), transcription factor activator 3 (ATF3), and carbohydrate-responsive element binding protein (ChREBP) in the liver. The mRNA transcripts of hepatic inflammatory factors, lipogenesis and lipolysis-related genes, and gluconeogenic enzyme-phosphoenolpyruvate carboxykinase (PEPCK), CRLS1, ATF3, and ChREBP mRNA levels were evaluated by RT-qPCR.</p></div><div><h3>Results</h3><p>THF restored impaired glucose tolerance and insulin resistance, respectively. There was an improvement in HFD/STZ-induced liver and islet damage, high serum HDL-C and ANP levels, and a significant decrease in FBG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), FFA, INS, ALT, and AST, and lipid droplet counts in the T2DM mice treated with THF. CREBBP binding protein ATF3 mediated the insulin resistance signaling pathway, which regulated glucose and lipid metabolism in the liver. THF upregulated CRLS1, and ChREBP downregulated the expression of downstream ATF3 in the liver. RT-qPCR analysis also systemically indicated that THF suppressed the pathway and key regulators related to inflammation, lipid accumulation, and gluconeogenesis.</p></div><div><h3>Conclusion</h3><p>Our findings demonstrated that THF ameliorated lipid profile and attenuated liver steatosis in T2DM mice through CRLS1-ATF3/ChREBP pathway activation.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 2","pages":"Pages 147-156"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823000857/pdfft?md5=7d230b18bbe01d2bb10e3b948adee93b&pid=1-s2.0-S2707368823000857-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92047820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of compounds and activities from mangrove Sonneratia genus and their endophytes","authors":"Bin Liu ,&nbsp;Xin Wang ,&nbsp;Yiming Wang ,&nbsp;Xiaohong Chen ,&nbsp;Xiaobao Jin ,&nbsp;Xiongming Luo","doi":"10.1016/j.jhip.2023.11.003","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.11.003","url":null,"abstract":"<div><p><em>Sonneratia</em> is an important mangrove plant, and its fruit has been used as traditional medicine and food in southeast China. With recent research focusing on its compounds and activities, an increasing number of compounds with novel structures and excellent antitumor, antioxidant, and other activities have been discovered. This review covered the compounds and activities of six species of the genus <em>Sonneratia</em> and their endophytes. To date, 116 compounds of <em>Sonneratia</em> have been reported, including 26 terpenoids, 9 flavonoids, 17 phenols, 9 lignans, 27 acid lipids, 16 steroids, and 12 other compounds. The main activities of the compounds in <em>Sonneratia</em> are antioxidant, antitumor, liver protection, antibacterial, and antidiabetic. Research on the compounds of endophytes from <em>Sonneratia</em> was first reported in 2009, and 56 compounds have been isolated, which mainly include sesquiterpenes, peptides, phenanthropyran ring-structured acids, pyrones, and anthracene derivatives. Individual compounds have been produced in <em>Sonneratia</em> and their endophytes that have the same structural fragments, and their interactions with small molecules and sources require further study. Recent advances in the bioactivities and compounds in the <em>Sonneratia</em> genus and their endophytes were summarized in this review, which is useful for the future isolation and discovery of active compounds and research regarding chemical ecology from the perspective of secondary metabolites.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 3","pages":"Pages 218-227"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823001085/pdfft?md5=0b29509c069669067fa3d11b3ac759ad&pid=1-s2.0-S2707368823001085-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138501085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on Prunella vulgaris and its monomers in protecting against ulcerative colitis","authors":"Fu Jinyin ,&nbsp;Yuan Yue ,&nbsp;Li Xiaojia ,&nbsp;Lin Peng ,&nbsp;Wang Shuibin ,&nbsp;Xiao Mingzhu","doi":"10.1016/j.jhip.2023.11.002","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.11.002","url":null,"abstract":"<div><p><em>Prunella vulgaris</em> is a traditional Chinese herbal medicine with many pharmacological effects, among which the anti-inflammatory effect is more significant. It is widely reported that <em>Prunella vulgaris</em> has anti-inflammatory, antioxidant, immune regulation, intestinal flora regulation and intestinal barrier protection effects on ulcerative colitis (UC). This paper collected relevant reports to further summarize the mechanisms and effective parts of <em>Prunella vulgaris</em> and its monomers in the treatment of UC and provided theoretical basis and reference for the application of <em>Prunella vulgaris</em> in UC.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 3","pages":"Pages 210-217"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823001073/pdfft?md5=4fb77f5a09d6dfca127da37aeb8f1229&pid=1-s2.0-S2707368823001073-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138480486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forsythiae Fructus attenuates cisplatin-induced cytotoxicity in IEC-6 ​cells and J774A.1 macrophages by inhibiting NLRP3/caspase-1/GSDMD mediated pyroptosis","authors":"Binbin Ye ,&nbsp;Ruifang Zhang ,&nbsp;Yihong Xian,&nbsp;Xiuxiu Liao,&nbsp;Weijian Chen,&nbsp;Ke Nie","doi":"10.1016/j.jhip.2023.09.001","DOIUrl":"https://doi.org/10.1016/j.jhip.2023.09.001","url":null,"abstract":"<div><h3>Objective</h3><p>Forsythiae Fructus (lian qiao in Chinese), the dried fruit of <em>Forsythia suspensa</em> (Thunb.) Vahl, is a commonly used traditional Chinese medicine known for its diverse biological activities, including antiemetic, anti-inflammatory, antioxidant, antiviral, and neuroprotective properties. This study investigated the protective effects of Forsythiae Fructus and its primary components, phillyrin and forsythoside A, against cisplatin-induced cytotoxicity <em>in vitro</em>, specifically focusing on the intestinal epithelial cells (IEC-6) and the J774A.1 macrophage cell line.</p></div><div><h3>Methods</h3><p>Cisplatin and <em>tert</em>-butyl hydroperoxide (tBHP) were used to induce stress in IEC-6 ​cells, while cisplatin and lipopolysaccharides (LPS)/adenosine triphosphate (ATP) were employed for J774A.1 macrophages. The protective effects of Forsythiae Fructus aqueous extract (FAE), phillyrin, and forsythoside A against cytotoxicity in these cultured cells were evaluated. Cell viability was assessed using the Cell Counting Kit-8 assay, while cell membrane permeability was determined through Hoechst 33342 and propidium iodide staining. Intracellular reactive oxygen species (ROS) levels were investigated using DCFH-DA, and the expression of mRNA and protein related to the NLRP3 inflammasome and GSDMD-induced pyroptosis was quantified through qRT-PCR and western blotting.</p></div><div><h3>Results</h3><p>In IEC-6 ​cells, combining FAE, phillyrin, or forsythrin A with a subthreshold dose of the antioxidant N-acetyl-L-cysteine (NAC) significantly mitigated cisplatin- or tBHP-induced cell necrosis and restored impaired cell viability. Additionally, the upregulation of NF-<em>κ</em>B, ASC, NLRP3, caspase-1, GSDMD, and HMGB1 at both mRNA and protein levels induced by cisplatin or tBHP was markedly reversed with the joint intervention of FAE, phillyrin, or forsythrin A with NAC. Similarly, in cisplatin- or LPS/ATP-treated J774A.1 macrophages, the effects on cell necrosis, cell viability, and the NLRP3/caspase-1/GSDMD pathway mirrored our previous findings in IEC-6 ​cells.</p></div><div><h3>Conclusion</h3><p>The study suggests that the alleviating effect of Forsythiae Fructus and its primary components, phillyrin and forsythoside A, against cisplatin-induced cytotoxicity may be attributed to inhibiting oxidative stress, downregulating the NLRP3/caspase-1/GSDMD pathway, and inhibiting pyroptosis.</p></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"4 2","pages":"Pages 166-177"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2707368823000845/pdfft?md5=27785c23603c88792c15e18d89d414b9&pid=1-s2.0-S2707368823000845-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92047741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}