Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents

Taghreed S Alnusaire; Ibrahim Lahbib Sabouni; Hanan Khojah; Sumera Qasim; Mohammad M Al-Sanea; Sadaf Siddique; Fatma Alzahraa Mokhtar; Shaimaa R Ahmed

doi:10.1021/acsomega.3c02940

Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents

ACS Omega. 2023 Aug 29;8(36):32544-32554. doi: 10.1021/acsomega.3c02940. eCollection 2023 Sep 12.

Authors

Taghreed S Alnusaire¹, Ibrahim Lahbib Sabouni², Hanan Khojah³, Sumera Qasim⁴, Mohammad M Al-Sanea⁵, Sadaf Siddique³, Fatma Alzahraa Mokhtar⁶, Shaimaa R Ahmed^{3

7}

Affiliations

¹ Biology Department, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
² Olive Research Center, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia.
³ Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia.
⁴ Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia.
⁵ Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida, Sharkia 44813, Egypt.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el-Aini street, Cairo 11562, Egypt.

Abstract

The purpose of this study is to explore the anti-inflammatory activity of Pterocarpus dalbergioides fruit extract (PFE) and the underlying mechanism. Chemical profiling using ultraperformance liquid chromatography/mass spectrometry identified 28 compounds in PFE (12 flavonoids, 5 fatty acids, 4 phenolic compounds, 3 alkaloids, 2 sesquiterpenes, and 2 xanthophylls). PFE (2 g/kg) significantly inhibited carrageenan-induced rat paw edema after 4 h of administration (42% inhibition). A network-based strategy and molecular docking studies were utilized to uncover the anti-inflammatory mechanism. Out of the identified compounds, 16 compounds with DL ≥ 0.18 and F ≥ 30% were selected using bioavailability (F) and drug-likeness (DL) metrics. The network analysis revealed that 90 genes are considered key targets for the selected compounds and linked to the anti-inflammatory effect. Among all compounds, linoleic acid was found to be the top-most active constituent as it targets maximum genes. Four targets (TNF, IL6, AKT1, and CCL2) among the top 10 genes were found to be the main target genes that may contribute to the anti-inflammatory potential of PFE. Furthermore, KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis revealed that PFE might regulate inflammation through five pathways: neuroactive ligand-receptor interaction, lipid and atherosclerosis, fluid shear stress and atherosclerosis, TNF signaling pathway, and rheumatoid arthritis. The docking study predicted the significant binding affinity between the top four active constituents (linoleic acid, 9-octadecenoic acid, 11,12,13-trihydroxy-9-octadecenoic acid, and rhamnetin-3-O-rhamnoside) and the selected target proteins (TNF and AKT1). The findings highlight PFE as a promising drug lead for controlling inflammation.