2. Academic Validation
  3. Bioactive fraction from Plumeria obtusa L. attenuates LPS-induced acute lung injury in mice and inflammation in RAW 264.7 macrophages: LC/QToF-MS and molecular docking

Bioactive fraction from Plumeria obtusa L. attenuates LPS-induced acute lung injury in mice and inflammation in RAW 264.7 macrophages: LC/QToF-MS and molecular docking

  • Inflammopharmacology. 2023 Apr;31(2):859-875. doi: 10.1007/s10787-023-01144-w.
Yousra T Eloutify 1,  Riham A El-Shiekh 1,  Khaled Meselhy Ibrahim 1,  Ahmed R Hamed 2,  Ahmed A Al-Karmalawy 3,  Aya A Shokry 4,  Yasmine H Ahmed 5,  Bharathi Avula 6,  Kumar Katragunta 6,  Ikhlas A Khan 6 7,  Meselhy R Meselhy 8
Affiliations

Affiliations

  • 1 Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo, 11562, Egypt.
  • 2 Chemistry of Medicinal Plants Department and Biology Unit, Central Lab for the Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El-Bohouth St, Giza, 12622, Dokki, Egypt.
  • 3 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, 12566, Egypt.
  • 4 Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.
  • 5 Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  • 6 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
  • 7 Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
  • 8 Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo, 11562, Egypt. meselhy.meselhy@pharma.cu.edu.eg.
PMID: 36773191 DOI: 10.1007/s10787-023-01144-w
Abstract

In this study, the anti-inflammatory effects of the methanolic extract (TE) of Plumeria obtusa L. (aerial parts) and its fractions were evaluated in vitro, and active fraction was evaluated in vivo. Among tested extracts, dichloromethane fraction (DCM-F) exhibited the strongest inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 macrophages. The effect of DCM-F on LPS-induced acute lung injury (ALI) in mice was studied. The Animals were divided into five groups (n = 7) randomly; Gp I: negative control, GP II: positive control (LPS group), GP III: standard (dexamethasone, 2 mg/kg b.wt), GP IV and V: DCM-F (100 mg/kg), and DEM-F (200 mg/kg), respectively. DCM-F at a dose of 200 mg/kg suppressed the ability of LPS to increase the levels of nitric oxide synthase (iNOS), NO, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), as measured by ELISA. In addition, the expression of cyclooxygenase-2 (COX-2) was reduced (determined by immunohistochemistry) and the level of malondialdehyde (MDA) was decreased while that of catalase was restored to the normal values. Furthermore, the histopathological scores of inflammation induced by LPS were reduced. Twenty-two compounds were tentatively identified in DCM-F using LC/ESI-QToF with Iridoids, phenolic derivatives and Flavonoids as major constituents. Identified compounds were subjected to two different molecular docking processes against iNOS and prostaglandin E synthase-1 target receptors. Notably, protoplumericin A and 13-O-coumaroyl plumeride were the most promising members compared to the co-crystallized inhibitor in each case. These findings suggested that DCM-F attenuates the LPS-induced ALI in experimental Animals through its anti-inflammatory and antioxidant potential.

Keywords

Immunohistochemistry; LC/QToF; LPS-induced ALI; Molecular docking; Plumeria obtusa L.; RAW 264.7 macrophages.

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