TY - JOUR
T1 - Muntingia calabura Leaves Extracts to Ameliorate chronic obstruction pulmonary diseases by Inhibiting IL-17a Signaling
T2 - In silico and in vivo studies
AU - Nurhasanah, Nenden
AU - Phalanisong, Parichat
AU - Fadilah, Fadilah
AU - Bahtiar, Anton
N1 - Funding Information:
This research is funded by the Directorate of Research and Development, Universitas Indonesia, under Hibah PUTI 2022 (Grant No. NKB-544/UN2.RST/HKP.05.00/2022).
Publisher Copyright:
© 2023 Nenden Nurhasanah et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
PY - 2023/9
Y1 - 2023/9
N2 - Chronic obstructive pulmonary disease, or COPD, is a disease that commonly breaks the lower respiratory system triggered by continuous exposure to toxic inhalants resulting in oxidative stress accumulation and cascade inflammation process. This disease is one of the top three causes of death in the world. Therapeutic options based on COPD-causing target genes are not currently available. A desired therapeutic candidate acts as an antioxidant and anti-inflammatory and inhibits the expression of COPD-causing related genes. In recent years, using natural compounds as pharmacological therapy has been desirable. Kersen or Muntingia calabura is a tropical, evergreen, and fast-growing plant with high anti-inflammatory and antioxidant potential that investigates its effect through molecular analysis upon an in vivo COPD model. This study aims to evaluate linking the pathogenesis of COPD and the potential possessed by Kersen leaves and to analyze the mechanism of action of this plant as a therapy for improving COPD conditions. The relationship between the structures of Kersen leaf compounds and COPD was initiated through bioinformatics studies (in silico). It was found that the IL-17 signaling pathway is a pathway that Kersen’s compounds can intervene against COPD. Molecular docking reveals that quercitrin, myrtillin, and quercetin ligands can bind to IL-17a macromolecules with binding affinity values −7.3, −7.1, and −6.4 kcal/mol, respectively. For the downstream macromolecule, TNF-α successively docked with quercetin, hiravanone, and ononine with −6.7 kcal/mol binding affinity and −5.7 kcal/mol for quercetin. An in vivo study used a COPD mouse model combined with cigarette smoke for 14 weeks and Lipopolysaccharides. Meanwhile, Kersen extract started from the 9th week at three different doses, 3.5, 7, and 14 mg per 20 g weight of mice. Kersen’s leaves extract at 3.5 mg/20 g weight of mice showed the potential inhibition of cytokine IL-17a, reduced mucus production, and reduced TNF-α expression in the lungs of COPD mice models.
AB - Chronic obstructive pulmonary disease, or COPD, is a disease that commonly breaks the lower respiratory system triggered by continuous exposure to toxic inhalants resulting in oxidative stress accumulation and cascade inflammation process. This disease is one of the top three causes of death in the world. Therapeutic options based on COPD-causing target genes are not currently available. A desired therapeutic candidate acts as an antioxidant and anti-inflammatory and inhibits the expression of COPD-causing related genes. In recent years, using natural compounds as pharmacological therapy has been desirable. Kersen or Muntingia calabura is a tropical, evergreen, and fast-growing plant with high anti-inflammatory and antioxidant potential that investigates its effect through molecular analysis upon an in vivo COPD model. This study aims to evaluate linking the pathogenesis of COPD and the potential possessed by Kersen leaves and to analyze the mechanism of action of this plant as a therapy for improving COPD conditions. The relationship between the structures of Kersen leaf compounds and COPD was initiated through bioinformatics studies (in silico). It was found that the IL-17 signaling pathway is a pathway that Kersen’s compounds can intervene against COPD. Molecular docking reveals that quercitrin, myrtillin, and quercetin ligands can bind to IL-17a macromolecules with binding affinity values −7.3, −7.1, and −6.4 kcal/mol, respectively. For the downstream macromolecule, TNF-α successively docked with quercetin, hiravanone, and ononine with −6.7 kcal/mol binding affinity and −5.7 kcal/mol for quercetin. An in vivo study used a COPD mouse model combined with cigarette smoke for 14 weeks and Lipopolysaccharides. Meanwhile, Kersen extract started from the 9th week at three different doses, 3.5, 7, and 14 mg per 20 g weight of mice. Kersen’s leaves extract at 3.5 mg/20 g weight of mice showed the potential inhibition of cytokine IL-17a, reduced mucus production, and reduced TNF-α expression in the lungs of COPD mice models.
KW - COHb
KW - COPD
KW - IL-17a
KW - in silico
KW - Kersen
KW - Muntingia calabura
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=85172341266&partnerID=8YFLogxK
U2 - 10.7324/JAPS.2023.141546
DO - 10.7324/JAPS.2023.141546
M3 - Article
AN - SCOPUS:85172341266
SN - 2231-3354
VL - 13
SP - 169
EP - 189
JO - Journal of Applied Pharmaceutical Science
JF - Journal of Applied Pharmaceutical Science
IS - 9
ER -