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

Abstract

Purpose

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 L

Abbreviations

BLM, Bleomycin; C, Ciplukan; cFLIPL, cellular FLICE-inhibitory protein; DD, Death Domain; DED, Death Effector Domain; DISK, Death-Inducing Signaling Complex; DNA, Deoxyribonucleic acid; DR, Death Receptors; ET-1, Endothelin-1; FAK, Focal Adhesion Kinase; FADD, Fas-Associated Protein with Death Domain; FasL, Fas Ligand; GAPDH, Glyceraldehyde 3-Phosphate Dehydrogenase; IL, interleukin; Klf4, Krüppel-like factor 4; LSD, Least Significant Difference; Mmp, matrix metalloproteinase; M, Mycophenolate mofetil; mRNA, Messenger RNA; mTOR, Mammalian Target of Rapamycin; Nrf2, Nuclear factor-erythroid-2 Related Factor 2; N, control; Nox4, NADPH oxidase 4 protein; PDGFR-β+, Platelet-derived growth factor receptor beta; PI3K, PhosphoInositide 3-Kinase; PMNs, Polymorphonuclear leukocytes; ROS, Reactive Oxygen Species; SASP, Senescence Associated Secretory Phenotype; TGF-β, Transforming Growth Factor Beta; UK, United Kingdom; WA, Withangulatin A.

Data Sharing Statement

Upon request, students can acquire the data underpinning this study’s findings by contacting the corresponding author.

Acknowledgment

The authors thank Dr. Aziiz Mardanarian Rosdianto, S.Kep., Ners. for kindly contributing during the animal process until its termination in the Faculty of Medicine, Universitas Padjadjaran laboratory.

Disclosure

The authors state no conflict of interest.