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alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 268-283页

作者： Ruijie Chen Yuan-Yuan Zhai Lining Sun Zeqing Wang Xing Xia Qing Yao Longfa Kou Department of Pharmacy the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027China School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhou 325035China

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells.Recent studies showed that Signal Transducer and Activator of Transcription 3(STAT3),which plays an important role in cell survival,proliferation,differentiation,angiogenesis,and immune responses,is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions.In addition,STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production,thereby exacerbating the condition of psoriasis.alantolactone(ALT)is a sesquiterpene lactone compound that could selectively suppress STAT3 activation,but its effectiveness and application in psoriasis treatment have not been determined.In this study,we developed ALT loaded chitosan/hyaluronic acid nanoparticles(CHALT),and investigated its therapeutic potential for psoriasis therapy.CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrialmembrane potential,and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line.In an Imiquimod(IMQ)-induced psoriasis model,the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis.In addition,it was found that CHALT restricted the recruitment of immune cells.These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

关键词： Psoriasis alantolactone STAT3 Chitosan Nanoparticle

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alantolactone inhibits proliferation,metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

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Genes & Diseases 2022年第2期9卷 466-478页

作者： Chunmei Yang Lulu Zhang Huakun Huang Xiaohui Yuan Ping Zhang Caihong Ye Mengqi Wei Yanran Huang Xiaoji Luo Jinyong Luo School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016PR China Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042PR China

Although there are many therapeutic strategies such as surgery and chemotherapy,the prognosis of osteosarcoma(OS)is still far from being satisfactory.It is urgent to develop more effective,tolerable and safe drugs for the treatment of OS.In the present study,we investigated the anti-OS activity of alantolactone(ALT),a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium,and probed the possible mechanism involved.We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells.Then,we validated that ALT reduced migration,decreased invasion possibly through reversing epithelial mesenchymal transition(EMT)process and suppressing Matrix metalloproteinases(MMPs).Moreover,we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro.In addition,we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo.Mechanistically,ALT inhibited the activity of Wnt/β-catenin and p38,ERK1/2 and JNK Mitogen Activated Protein Kinases(MAPKs)signal pathway.Notably,the combination of ALT and Wnt/β-catenin inhibitor,as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation,migration and invasion of OS cells.Collectively,our results validate the ALT may inhibit proliferation,metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.

关键词： alantolactone ERK1/2 JNK Mitogen activated protein kinases Osteosarcoma p38 Wnt/β-catenin

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Inhibitory Effects of Natural Compound alantolactone on Human Non-small Cell Lung Cancer A549 Cells

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Chemical Research in Chinese Universities 2011年第2期27卷 241-244页

作者： ZONG Min-ru ZHAO Ying-hao ZHANG Kun YANG Long-fei ZHENG Yong-chen HE Cheng-yan China-Japan Union Hospital of Jilin University Changchun 130033 P. R. China The Second Hospital of Jilin University Changchun 130041 P. R. China

alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer（NSCLC） A549 cells. The an-tiproliferative effect of alantolactone on A549 cells was investigated via MTT[3′-（4,5dimethylthiazol-2-yl）-2,5- diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect was determined by Hoechst staining and flow cytometry. We found that alantolactone significantly inhibited the proliferation of A549 cells and induced morphological changes typical for apoptosis. Flow cytometry analysis indicates dose-dependent cell cycle retardation at G0/G1 and S stages. The results indicate that alantolactone could be an attractive small-molecular natural compound for further development as a therapeutic drug against NSCLC.

关键词： alantolactone Non-small cell lung cancer（NSCLC） A549 Proliferation Apoptosis

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