The Effect of Physalis angulata L. Administration on Gene Expressions Related to Lung Fibrosis Resolution in Mice-Induced Bleomycin

Ummul Khair Imaduddin,1 Afiat Berbudi,2,* Enny Rohmawaty3,* 1Graduate School of Master Program in Anti Aging and Aesthetic Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Parasitology Division, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Pharmacology & Therapy Division, Departement of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia*These authors contributed equally to this workCorrespondence: Enny Rohmawaty, Pharmacology & Therapy Division, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang, KM.21, Hegarmanah, Kec. Jatinangor, Kabupaten Sumedang, Bandung, West Java, 45363, Indonesia, Email [email protected]: To explore the potential therapeutic effects of Physalis angulata L. (Ciplukan) extract on lung fibrosis resolution in a Bleomycin-induced mouse model, researchers conducted a comprehensive study. The study focused on key genes associated with fibrosis progression, including Nox4, Mmp8, Klf4, and FAS, and assessed their mRNA expression levels following the administration of Ciplukan extract.Methods: A Bleomycin-induced mice model was divided into seven groups to investigate the effects of ciplukan extract on fibrosis-related gene expressions. Mice were induced with subcutaneously injected Bleomycin to generate lung fibrosis and given different doses of the Ciplukan extract for four weeks. Lung fibrosis mRNA expression was analyzed by semi-quantitative PCR for Nox4, Klf4, Mmp8, and FAS.Results: The administration of ciplukan extract resulted in a significant decrease in mRNA expression of Nox4 with p-value=0.000, Mmp8 with p-value =0.002, and Klf4 with p-value =0.007, indicating potential antifibrotic effects. However, FAS expression remained unchanged (p-value=0.127).Conclusion: Ciplukan extract exhibited promising effects on fibrosis-related gene expressions, particularly Nox4, Mmp8, and Klf4. This study suggests that the extract has the potential to intervene in fibrosis progression, offering a potential avenue for therapeutic strategies.Keywords: ciplukan, FAS, Klf4, lung fibrosis, Mmp8, Nox4, pulmonary fibrosis, Physalis angulata

Supplementary Material for: Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

<p>Helminths induce type 2 immune responses and establish an anti-inflammatory milieu in their hosts. This immunomodulation was previously shown to improve diet-induced insulin resistance which is linked to chronic inflammation. In the current study, we demonstrate that infection with the filarial nematode <i>Litomosoides sigmodontis</i> increased the eosinophil number and alternatively activated macrophage abundance within epididymal adipose tissue (EAT) and improved glucose tolerance in diet-induced obese mice in an eosinophil-dependent manner. <i>L. sigmodontis</i> antigen (LsAg) administration neither altered the body weight of animals nor adipose tissue mass or adipocyte size, but it triggered type 2 immune responses, eosinophils, alternatively activated macrophages, and type 2 innate lymphoid cells in EAT. Improvement in glucose tolerance by LsAg treatment remained even in the absence of Foxp3+ regulatory T cells. Furthermore, PCR array results revealed that LsAg treatment reduced inflammatory immune responses and increased the expression of genes related to insulin signaling (<i>Glut4</i>, <i>Pde3b, Pik3r1</i>, and<i> Hk2</i>) and fatty acid uptake (<i>Fabp4</i> and <i>Lpl</i>). Our investigation demonstrates that <i>L. sigmodontis </i>infection and LsAg administration reduce diet-induced EAT inflammation and improve glucose tolerance. Helminth-derived products may, therefore, offer new options to improve insulin sensitivity, while loss of helminth infections in developing and developed countries may contribute to the recent increase in the prevalence of type 2 diabetes.</p