Maimendong decoction modulates the PINK1/Parkin signaling pathway alleviates type 2 alveolar epithelial cells senescence and enhances mitochondrial autophagy to offer potential therapeutic effects for idiopathic pulmonary fibrosis

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-03-02 DOI:10.1016/j.jep.2025.119568

Yuhe Zhou , Wen Su , Mengzhen Xu , Aijun Zhang , Shaoli Li , Hong Guo , Kai Gong , Kaihui Lu , Xin Yu , Jiang Zhu , Qingjun Zhu , Chuanguo Liu

{"title":"Maimendong decoction modulates the PINK1/Parkin signaling pathway alleviates type 2 alveolar epithelial cells senescence and enhances mitochondrial autophagy to offer potential therapeutic effects for idiopathic pulmonary fibrosis","authors":"Yuhe Zhou , Wen Su , Mengzhen Xu , Aijun Zhang , Shaoli Li , Hong Guo , Kai Gong , Kaihui Lu , Xin Yu , Jiang Zhu , Qingjun Zhu , Chuanguo Liu","doi":"10.1016/j.jep.2025.119568","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Maimendong decoction (MMDD) originates from the ancient Chinese medical text <em>Synopsis of the Golden Chamber</em> and is a well-established remedy for treating lung diseases. It has demonstrated efficacy in the long-term clinical management of idiopathic pulmonary fibrosis (IPF); however, its underlying mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study investigates whether MMDD alleviates IPF by reducing type 2 alveolar epithelial cell (AEC2) senescence and enhancing mitochondrial autophagy. It also explores whether these effects are mediated through the PTEN-induced putative kinase 1 (PINK1)/Parkinson juvenile disease protein 2 (Parkin) pathway.</div></div><div><h3>Materials and methods</h3><div>An IPF mouse model was established with bleomycin (BLM). Mice were administered MMDD, pirfenidone (PFD), or saline for 7 or 28 days. Body weight, lung coefficient, and lung appearance were monitored, and lung tissue pathology was assessed. The expression levels of p53, p21, p16, SA-β-gal activity, and senescence-associated secretory phenotype (SASP) markers were measured. Ultrastructural changes in AEC2 mitochondria were analyzed using transmission electron microscopy. Protein levels of autophagy markers sequestosome-1 and light chain 3 were assessed. The protein levels of PINK1, Parkin, and phosphorylated Parkin were further assessed using network pharmacology analysis and molecular docking technology.</div></div><div><h3>Results</h3><div>MMDD alleviated BLM-induced IPF by improving body weight, lung appearance, and histopathological features. It reduced AEC2 senescence markers, including p53, p21, p16, SA-β-gal, and SASP, while enhancing mitochondrial autophagy and repairing mitochondrial damage. Network pharmacology and molecular docking identified PINK1 as a major target, and Western blot (WB) analysis confirmed that MMDD regulates the PINK1/Parkin signaling pathway in the treatment of IPF.</div></div><div><h3>Conclusions</h3><div>MMDD regulates the PINK1/Parkin signaling pathway, alleviates AEC2 senescence, and enhances mitochondrial autophagy, providing significant therapeutic potential for IPF treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119568"},"PeriodicalIF":5.4000,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874125002521","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Ethnopharmacological relevance

Maimendong decoction (MMDD) originates from the ancient Chinese medical text Synopsis of the Golden Chamber and is a well-established remedy for treating lung diseases. It has demonstrated efficacy in the long-term clinical management of idiopathic pulmonary fibrosis (IPF); however, its underlying mechanisms remain unclear.

Aim of the study

This study investigates whether MMDD alleviates IPF by reducing type 2 alveolar epithelial cell (AEC2) senescence and enhancing mitochondrial autophagy. It also explores whether these effects are mediated through the PTEN-induced putative kinase 1 (PINK1)/Parkinson juvenile disease protein 2 (Parkin) pathway.

Materials and methods

An IPF mouse model was established with bleomycin (BLM). Mice were administered MMDD, pirfenidone (PFD), or saline for 7 or 28 days. Body weight, lung coefficient, and lung appearance were monitored, and lung tissue pathology was assessed. The expression levels of p53, p21, p16, SA-β-gal activity, and senescence-associated secretory phenotype (SASP) markers were measured. Ultrastructural changes in AEC2 mitochondria were analyzed using transmission electron microscopy. Protein levels of autophagy markers sequestosome-1 and light chain 3 were assessed. The protein levels of PINK1, Parkin, and phosphorylated Parkin were further assessed using network pharmacology analysis and molecular docking technology.

Results

MMDD alleviated BLM-induced IPF by improving body weight, lung appearance, and histopathological features. It reduced AEC2 senescence markers, including p53, p21, p16, SA-β-gal, and SASP, while enhancing mitochondrial autophagy and repairing mitochondrial damage. Network pharmacology and molecular docking identified PINK1 as a major target, and Western blot (WB) analysis confirmed that MMDD regulates the PINK1/Parkin signaling pathway in the treatment of IPF.

Conclusions

MMDD regulates the PINK1/Parkin signaling pathway, alleviates AEC2 senescence, and enhances mitochondrial autophagy, providing significant therapeutic potential for IPF treatment.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

麦门冬汤调节PINK1/Parkin信号通路，缓解2型肺泡上皮细胞衰老，增强线粒体自噬，对特发性肺纤维化具有潜在的治疗作用

脉门冬汤（MMDD）起源于中国古代医学文献《金匮要论》，是治疗肺部疾病的一种公认的药物。它在特发性肺纤维化（IPF）的长期临床治疗中已被证明有效；然而，其潜在机制尚不清楚。本研究探讨MMDD是否通过减少2型肺泡上皮细胞（AEC2）衰老和增强线粒体自噬来减轻IPF。它还探讨了这些作用是否通过pten诱导的推定激酶1 (PINK1)/帕金森少年病蛋白2 （Parkin）途径介导。材料与方法用博来霉素（BLM）建立IPF小鼠模型。小鼠分别给予MMDD、吡非尼酮（PFD）或生理盐水7天或28天。监测体重、肺系数和肺外观，并评估肺组织病理。检测p53、p21、p16、SA-β-gal活性和衰老相关分泌表型（SASP）标志物的表达水平。透射电镜观察AEC2线粒体超微结构变化。检测自噬标志物sequestosome-1和轻链3的蛋白水平。通过网络药理学分析和分子对接技术进一步评估PINK1、Parkin和磷酸化Parkin的蛋白水平。结果smmdd通过改善体重、肺外观和组织病理学特征减轻blm诱导的IPF。降低AEC2衰老标志物p53、p21、p16、SA-β-gal、SASP，增强线粒体自噬，修复线粒体损伤。网络药理学和分子对接鉴定PINK1为主要靶点，Western blot （WB）分析证实MMDD调控PINK1/Parkin信号通路治疗IPF。结论smmdd调节PINK1/Parkin信号通路，减轻AEC2衰老，增强线粒体自噬，对IPF治疗具有重要的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.