Chemico-Biological Interactions最新文献

{"title":"Profiling CCR3 target pathways for discovering novel antagonists from natural products using label-free cell phenotypic assays","authors":"Hao Chai ,&nbsp;Fangfang Xu ,&nbsp;Jixia Wang ,&nbsp;Yuxin Zhang ,&nbsp;Xiaomin Xie ,&nbsp;Han Zhou ,&nbsp;Yanfang Liu ,&nbsp;Xinmiao Liang ,&nbsp;Aoxue Wang","doi":"10.1016/j.cbi.2023.110732","DOIUrl":"10.1016/j.cbi.2023.110732","url":null,"abstract":"<div><p><span>CC chemokine<span><span><span> receptor 3 (CCR3) plays important roles in atopic dermatitis<span> (AD) and other related allergic diseases. Activation of CCR3 receptor signaling pathways regulates the recruitment of </span></span>eosinophils to related tissues, releasing inflammatory mediators and causing inflammatory responses. However, none of the known CCR3 antagonists exhibit promising efficacy in </span>clinical trials<span>. In this work, we sought new natural CCR3 antagonists for drug development. To construct a high-throughput screening model, we established a stably transfected CHO-K1-Gα15-CCR3 cell line, and receptor expression was demonstrated by real-time quantitative PCR</span></span></span><strong>,</strong> confocal detection and flow cytometry analysis. Then, we applied a label-free cell phenotyping technique to profile and deconvolute CCR3 target pathways in CHO-K1-Gα15-CCR3 cells and found that activation of CCR3 triggered the Gq-PLC-Ca²⁺<span> and MAPK-P38-ERK pathways. By in vitro and in silico experiments, we discovered a novel CCR3 antagonist emodin, with an IC</span>₅₀<span> value of 27.28 ± 1.71 μM out of 266 compounds that were identified in 15 traditional Chinese medicines used in the clinical treatment of skin diseases. Molecular docking graphically presented the binding mode of emodin on CCR3. This work reports a new approach for CCR3 antagonist screening and pathway detection and identifies a new antagonist that would benefit future drug development.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110732"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of AKR1Cs by liquiritigenin and the structural basis","authors":"Huan Liu ,&nbsp;Ziqing Yao ,&nbsp;Mingna Sun ,&nbsp;Chao Zhang ,&nbsp;Yi-you Huang ,&nbsp;Hai-bin Luo ,&nbsp;Deyan Wu ,&nbsp;Xuehua Zheng","doi":"10.1016/j.cbi.2023.110654","DOIUrl":"10.1016/j.cbi.2023.110654","url":null,"abstract":"<div><p><em>In vivo</em> and <em>in vitro</em><span><span><span> studies have confirmed that liquiritigenin<span> (LQ), the primary active component of licorice, acts as an </span></span>antitumor agent<span>. However, how LQ diminishes or inhibits tumor growth is not fully understood. Here, we report the enzymatic inhibition of LQ and six other flavanone analogues towards AKR1Cs (AKR1C1, AKR1C2 and AKR1C3), which are involved in </span></span>prostate cancer<span>, breast cancer, and resistance of anticancer drugs. Crystallographic studies revealed AKR1C3 inhibition of LQ is related to its complementarity with the active site and the hydrogen bonds net in the catalytic site formed through C</span></span>₇–OH, aided by its nonplanar and compact structure due to the saturation of the C₂<img>C₃<span> double bond. Comparison of the LQ conformations in the structures of AKR1C1 and AKR1C3 revealed the induced-fit conformation changes, which explains the lack of isoform selectivity of LQ. Our findings will be helpful for better understanding the antitumor effects of LQ on hormonally dependent cancers and the rational design of selective AKR1Cs inhibitors.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110654"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes” [Chem Biol Interact. 324 (2020 Jun 1) 109062]","authors":"Qing Xiao ,&nbsp;Shujun Zhang ,&nbsp;Huina Ren ,&nbsp;Ruoyang Du ,&nbsp;Jiajun Li ,&nbsp;Jinqiu Zhao ,&nbsp;Yue Gao ,&nbsp;Yali Zhu ,&nbsp;Wenxiang Huang","doi":"10.1016/j.cbi.2023.110697","DOIUrl":"10.1016/j.cbi.2023.110697","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110697"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009279723003642/pdfft?md5=5e6f6ee90326316df98f42af2df37c6d&pid=1-s2.0-S0009279723003642-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pinostrobin modulates FOXO3 expression, nuclear localization, and exerts antileukemic effects in AML cells and zebrafish xenografts","authors":"Pei-Yi Chen ,&nbsp;Ching-Yen Lin ,&nbsp;Chia-Ling Wu ,&nbsp;Pei Ying Keak ,&nbsp;Je-Wen Liou ,&nbsp;Wan-Yun Gao ,&nbsp;Liang-In Lin ,&nbsp;Jui-Hung Yen","doi":"10.1016/j.cbi.2023.110729","DOIUrl":"10.1016/j.cbi.2023.110729","url":null,"abstract":"<div><p><span>Acute myeloid leukemia<span> (AML) is a disease characterized by abnormal cell proliferation in the bone marrow and is the most common quickly progressive leukemia in adults. Pinostrobin, a </span></span>flavonoid<span><span> phytochemical, has been reported to exhibit antioxidant, anti-inflammatory, and anticancer properties. In this study, we aimed to investigate the antileukemic effects of pinostrobin and its molecular mechanisms in human AML cells. Our study found that pinostrobin (0–80 μM) significantly reduced the viability of human AML cells, with the pronounced cytotoxic effects observed in MV4-11 &gt; MOLM-13 &gt; HL-60 &gt; U-937 &gt; THP-1 cells. Pinostrobin was found to suppress leukemia cell proliferation, modulate cell cycle progression, promote cell apoptosis, and induce monocytic differentiation in MV4-11 cells. In animal studies, pinostrobin significantly suppressed the growth of leukemia cells in a zebrafish xenograft model. Microarray-based </span>transcriptome<span> analysis showed that the differentially expressed genes (DEGs) in pinostrobin-treated cells were strongly associated with enriched Gene Ontology (GO) terms related to apoptotic process, cell death, cell differentiation, cell cycle progression, and cell division. Combining DisGeNET and STRING database analysis revealed that pinostrobin upregulates forkhead box 3 (FOXO3), a tumor suppressor in cancer development, and plays an essential role in controlling AML cell viability<span><span>. Our study demonstrated that pinostrobin increases FOXO3 gene expression and promotes its nuclear translocation, leading to the inhibition of cell growth. Finally, the study found that pinostrobin, when combined with cytarabine, synergistically reduces the viability of AML cells. Our current findings shed light on pinostrobin's mechanisms in inhibiting leukemia cell growth, highlighting its potential as a chemotherapeutic agent or </span>nutraceutical supplement for AML prevention or treatment.</span></span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110729"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential hypothalamic role in mediating cisplatin-induced negative energy balance","authors":"Yang Tae Kim ,&nbsp;Byong Seo Park ,&nbsp;Hye Rim Yang ,&nbsp;Seon Yi ,&nbsp;Il Seong Nam-Goong ,&nbsp;Jae Geun Kim","doi":"10.1016/j.cbi.2023.110733","DOIUrl":"10.1016/j.cbi.2023.110733","url":null,"abstract":"<div><p>Cisplatin is a chemotherapeutic drug commonly used for treating different types of cancer. However, long-term use can lead to side effects, including anorexia, nausea, vomiting, and weight loss, which negatively affect the patient's quality of life and ability to undergo chemotherapy. This study aimed to investigate the mechanisms underlying the development of a negative energy balance during cisplatin treatment. Mice treated with cisplatin exhibit reduced food intake, body weight, and energy expenditure. We observed altered neuronal activity in the hypothalamic nuclei involved in the regulation of energy metabolism in cisplatin-treated mice. In addition, we observed activation of microglia and inflammation in the hypothalamus following treatment with cisplatin. Consistent with this finding, inhibition of microglial activation effectively rescued cisplatin-induced anorexia and body weight loss. The present study identified the role of hypothalamic neurons and inflammation linked to microglial activation in the anorexia and body weight loss observed during cisplatin treatment. These findings provide insight into the mechanisms underlying the development of metabolic abnormalities during cisplatin treatment and suggest new strategies for managing these side effects.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110733"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punicalagin attenuates myocardial oxidative damage, inflammation, and apoptosis in isoproterenol-induced myocardial infarction in rats: Biochemical, immunohistochemical, and in silico molecular docking studies","authors":"Muthana M. Jghef ,&nbsp;Khadija Boukholda ,&nbsp;Yassine Chtourou ,&nbsp;Bernd L. Fiebich ,&nbsp;Mohammed Kebieche ,&nbsp;Rachid Soulimani ,&nbsp;Fatiha Chigr ,&nbsp;Hamadi Fetoui","doi":"10.1016/j.cbi.2023.110745","DOIUrl":"10.1016/j.cbi.2023.110745","url":null,"abstract":"<div><p><span>Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Punicalagin (PU), the major </span>ellagitannin<span> found in pomegranates<span><span>, is characterized by multiple antioxidant activities<span>. The aim of this study is to assess the protective effects of PU against isoproterenol (ISO)-induced acute </span></span>myocardial damage and to investigate its underlying vascular mechanisms using rat model.</span></span></p></div><div><h3>Methods</h3><p><span>Rats were randomly divided into five groups and were treated orally (p.o.) with PU (25 and 50 mg/kg) for 14 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 15th and 16th days to induce Myocardial infarction. Cardiac markers, oxidative stress markers, and inflammatory cytokines levels were determined in the heart tissue. Immunohistochemistry analysis was performed to determine the protein expression pathways of inflammation, apoptosis and oxidative stress (Nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) in all the groups. </span><em>In silico</em> study was carried out to evaluate the molecular interaction of PU with some molecular targets.</p></div><div><h3>Results</h3><p>Our results showed that ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I<span><span><span> (cTnI), and lactate dehydrogenase (LDH), associated with several histopathological changes. ISO also induced an increase of </span>MDA, PCO, NO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), along with a decrease of antioxidant </span>enzyme activities in the myocardial tissues. In addition, an increase of TNF-α, NF-κB, IL-6, IL-1β, iNOS, Nrf2 and (HO-1) was observed. Pre-treatment with PU reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, PU remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Molecular docking analysis of PU with protein targets showed potent interactions with negative binding energies.</span></p><p>In conclusion, PU can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110745"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “An updated lymphohematopoietic and bladder cancers risk evaluation for occupational and environmental exposures to 1,3-butadiene” [Chem. Biol. Interact. 366 (2022) 1–10]","authors":"C. Valdez-Flores ,&nbsp;N. Erraguntla ,&nbsp;R. Budinsky ,&nbsp;S. Cagen ,&nbsp;C.R. Kirman","doi":"10.1016/j.cbi.2023.110736","DOIUrl":"10.1016/j.cbi.2023.110736","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110736"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009279723004039/pdfft?md5=bec36c7aa8fcc1fb7265c58bd33f0680&pid=1-s2.0-S0009279723004039-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of acrolein exposure inhibited the release of neutrophil extracellular traps: By reducing respiratory burst and Raf/MEK/ERK pathway and promote cell apoptosis","authors":"Dongliu Luo ,&nbsp;Yiming Lu ,&nbsp;Jintao Zhang ,&nbsp;Xixi Wang ,&nbsp;Yixuan Wang ,&nbsp;Shiping Li ,&nbsp;Shu Li","doi":"10.1016/j.cbi.2023.110744","DOIUrl":"10.1016/j.cbi.2023.110744","url":null,"abstract":"<div><p><span>Acrolein<span><span> (AC) is a highly toxic volatile substance in the environment, and studies have found that excessive AC had a toxic effect on the immune system. Neutrophils are the first line of defense against </span>pathogen<span> invasion. The release of neutrophil extracellular traps (NETs) is a protective mechanism for neutrophils, and its release is affected by environmental pollutants. However, the effect of AC on NETs release and its mechanism remains unclear. In this study, chicken peripheral blood neutrophils were pretreated with 20 μM AC and treated with 5 μM Phorbol 12-myristate 13-acetate (PMA) to stimulate the release of NETs. The results showed that AC exposure significantly inhibited the release of NETs induced by PMA, respiratory burst, and the expression levels of phospho-rapidly accelerated fibrosarcoma<span><span> (p-Raf), phospho-mitogen-activated extracellular signal-regulated kinase (p-MEK) and phospho-extracellular regulated protein kinases (p-ERK). In addition, AC exposure significantly inhibited the expression of B-cell lymphoma-2 (Bcl-2) and promoted the expression of apoptotic factors Bcl2-Associated X (Bax), </span>cytochrome </span></span></span></span><em>c</em><span><span> (Cyt C), cysteinyl aspartate<span> specific proteinase 9 (Casp 9) and cysteinyl aspartate specific </span></span>proteinase 3<span> (Casp 3). Further inhibition of neutrophil apoptosis significantly improved the release of NETs. The above results indicated that AC exposure led to a decrease in the formation of NETs, which is caused by excessive AC-induced neutrophil apoptosis. Our study clarified the immune toxicity mechanism of AC on chickens, which is of great significance and reference value for protecting the ecological environment and poultry health.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110744"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrosphelides from Antarctic fungus Pseudogymnoascus sp. (strain SF-7351) and their neuroprotective effects on BV2 and HT22 cells","authors":"Zhiming Liu ,&nbsp;Le Ba Vinh ,&nbsp;Nguyen Quoc Tuan ,&nbsp;Hwan Lee ,&nbsp;Eunae Kim ,&nbsp;Youn-Chul Kim ,&nbsp;Jae Hak Sohn ,&nbsp;Joung Han Yim ,&nbsp;Ha-Jin Lee ,&nbsp;Dong-Sung Lee ,&nbsp;Hyuncheol Oh","doi":"10.1016/j.cbi.2023.110718","DOIUrl":"10.1016/j.cbi.2023.110718","url":null,"abstract":"<div><p><span><span>Strategies for reducing inflammation in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the </span>neuroprotective potential of fungal metabolites isolated from the Antarctic fungus </span><em>Pseudogymnoascus</em> sp. (strain SF-7351). The chemical investigation of the EtOAc extract of the fungal strain isolate revealed a novel naturally occurring <em>epi</em>-macrosphelide J (<strong>1</strong><span>), a novel secondary metabolite macrosphelide N (</span><strong>2</strong>), and three known compounds, namely macrosphelide A (<strong>3</strong>), macrosphelide B (<strong>4</strong>), and macrosphelide J (<strong>5</strong><span><span>). Their structures were established unambiguously using spectroscopic methods, such as one-dimensional and two-dimensional nuclear magnetic resonance (1D and 2D-NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and gauge-including </span>atomic orbital (GIAO) NMR chemical shift calculations, with the support of the advanced statistical method DP4+. Among the isolated metabolites, the absolute configuration of </span><em>epi</em>-macrosphelide J (<strong>1</strong><span>) was further confirmed using single-crystal X-ray diffraction analysis. The neuroprotective effects of the isolated metabolites were evaluated in lipopolysaccharide (LPS)-induced BV2 and glutamate-stimulated HT22 cells. Only macrosphelide B (</span><strong>4</strong><span>) displayed substantial protective effects in both BV2 and HT22 cells. Molecular mechanisms underlying this activity were investigated using western blotting and molecular docking studies. Macrosphelide B (</span><strong>4</strong>) inhibited the inflammatory response by reducing the nuclear translocation of NF-κB (p65) in LPS-induced BV2 cells and induced the Nrf2/HO-1 signaling pathway in both BV2 and HT22 cells. The neuroprotective effect of macrosphelide B (<strong>4</strong>) is related to the interaction between Keap1 and p65. These results suggest that macrosphelide B (<strong>4</strong>), present in the fungus <em>Pseudogymnoascus</em> sp. (strain SF-7351), may serve as a candidate for the treatment of neurodegenerative diseases.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110718"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41108087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating β-catenin","authors":"Jinjin Liu ,&nbsp;Jinyang An ,&nbsp;Na Jiang ,&nbsp;Kuan Yang ,&nbsp;Conghui Guan ,&nbsp;Nan Zhao ,&nbsp;Jianguo Cheng ,&nbsp;Songbo Fu ,&nbsp;Chengxu Ma ,&nbsp;Xiaoni Ma ,&nbsp;Xulei Tang","doi":"10.1016/j.cbi.2023.110721","DOIUrl":"10.1016/j.cbi.2023.110721","url":null,"abstract":"<div><p><span><span><span>Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula </span>polysaccharides (CPPs) have been widely used in </span>traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis </span><em>in vivo</em><span><span><span><span>. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by </span>ALP<span> and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to </span></span>osteogenesis<span> and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting<span>, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of β-catenin, the core protein of the Wnt/β-catenin signaling pathway, in a concentration-dependent manner. Adding </span></span></span>DKK1, a mature inhibitor of the Wnt/β-catenin signaling pathway, partially suppressed CPP-stimulated β-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats </span><em>in vivo</em>, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs <em>in vitro</em>. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"385 ","pages":"Article 110721"},"PeriodicalIF":5.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}