Maimendong decoction regulates M2 macrophage polarization to suppress pulmonary fibrosis via PI3K/Akt/FOXO3a signalling pathway-mediated fibroblast activation. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Mai Men Dong decoction (MMDD), a traditional Chinese medicine formula, is relevant to ethnopharmacology due to its constituents and therapeutic properties. The formula contains herbs like Ophiopogon japonicus (Thunb.) Ker Gawl., Pinellia ternata (Thunb.) Makino, Panax ginseng C.A.Mey, Glycyrrhiza uralensis Fisch, and Ziziphus jujuba Mill, Oryza sativa L., which have been used for centuries in Chinese medicine. These herbs provide a comprehensive approach to treating respiratory conditions by addressing dryness, cough, and phlegm. Ethnopharmacological studies have explored the scientific basis of these herbs and identified active compounds that contribute to their medicinal effects. The traditional usage of MMDD by different ethnic groups reflects their knowledge and experiences. Examining this formula contributes to the understanding and development of ethnopharmacology. AIM OF THE STUDY:In the case of pulmonary fibrosis (PF), treating it can be challenging due to the limited treatment options available. This study aimed to assess the potential of MMDD as a treatment for PF by targeting macrophages and the PI3K/Akt/FOXO3a signaling pathway. MATERIALS AND METHODS:In a mouse model of PF, we investigated the effects of MMDD on inflammation, fibrosis, and M2 macrophage infiltration in lung tissue. Additionally, we examined the modulation of pro-fibrotic factors and key proteins in the PI3K/Akt/FOXO3a pathway. In vitro experiments involved inducing M2-type macrophages and assessing the impact of MMDD on fibroblast activation and the PI3K/Akt/FOXO3a pathway. RESULTS:Results demonstrated that MMDD improved weight, reduced inflammation, and inhibited M2 macrophage infiltration in mouse lung tissue. It downregulated pro-fibrotic factors, such as TGF-β1 and PDGF-RB, as well as markers of fibroblast activation. MMDD also exhibited regulatory effects on key proteins in the PI3K/Akt/FOXO3a signaling pathway. CONCLUSIONS:MMDD inhibited M2 macrophage polarization and released profibrotic factors that inhibited pulmonary fibrosis. As a result, the PI3K/Akt/FOXO3a signaling pathway is suppressed. MMDD is proving to be a successful treatment for PF. However, further research is needed to validate its effectiveness in clinical practice. 10.1016/j.jep.2023.117308

Mechanism of myocardial fibrosis regulation by IGF-1R in atrial fibrillation through the PI3K/Akt/FoxO3a pathway. Biochemistry and cell biology = Biochimie et biologie cellulaire Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen Ⅰ protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway. 10.1139/bcb-2022-0199