Network Pharmacology and Experimental Validation Reveal the Anti-Inflammatory Effects of Schefflera octophylla via Inhibition of the PI3K-AKT Pathway

Abstract

Xiaoqin Zhou75304, Bin Yang75305, Yao Liang75306 and Xiaobu Lan75307*

Background: Ethnopharmacological relevance shows that Schefflera octophylla (Lour.) Harms is an indigenous plant and traditional Chinese medicine. WaiGan mixture II, which is a complex herbal preparation contains Schefflera octophylla as the main herb and is commonly employed in clinical practice to treat conditions associated with wind-heat colds, such as the resolution of heat, toxins and alleviation of throat symptoms. Although these uses of Schefflera octophylla highlight its potential as an anti-inflammatory agent, its efficacy and underlying mechanisms remain to be thoroughly explored.

As traditional Chinese medicines contain a multitude of ingredients, it can be challenging to determine the specific small molecular compounds responsible for their medicinal effects. Here, we aim to identify the active anti-inflammatory compounds and targets of Schefflera octophylla through network pharmacology, evaluate their efficacy using molecular docking techniques and investigate their anti-inflammatory effects and mechanisms using in vitro and in vivo experiments.

Materials and methods: Compound-disease-target-pathway network was established through network pharmacology to determine the potential anti-inflammatory mechanism pathways in Schefflera octophylla. The efficacy of the medication was assessed by injecting the toes of Kunming (KM) mice with carrageenan (an inflammatory agent) to induce swelling, before measuring the swelling inhibition rate and effects on serum Interleukin (IL)-6 and Malondialdehyde (MDA). Nitrogen Monoxide (NO) content of medicated Lipopolysaccharide (LPS)-induced RAW264.7 cells was measured using the Griess method, while the levels of IL-1 Beta (β), IL-6 and IL-10 secreted by RAW264.7 cells were measured using Enzyme Linked Immunosorbent Assay (ELISA). Western blot was used to analyze the effects of the medication on protein expression of the Phosphatidylinositol 3 Kinase/protein Kinase B (PI3K/Akt) pathway. In this study, aqueous and ethanol extracts of Schefflera octophylla were used as medication.

Results: Aqueous and ethanol extracts of Schefflera octophylla significantly reduced carrageenan-induced toe swelling, and decreased IL-6 and MDA levels. The medication also demonstrated potent anti-inflammatory properties in RAW264.7 cells by decreasing the levels of the LPS-induced inflammation-related factors NO, IL-6 and IL-1β, increasing the level of the anti-inflammatory cytokine IL-10 and decreasing LPS-induced phosphorylation of PI3K-Akt pathway proteins.

Conclusion: These results provide strong evidence for further investigation into the molecular mechanisms of Schefflera octophylla for treating acute inflammation from an anti-inflammatory perspective.

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