Integrative Network Pharmacology and <i>In Vitro</i> Wound Healing Potential of Two Neglected Invasive Weed from Mizoram, India

Background: Wound healing is undoubtedly a challenging clinical problem since regenerating healthy and functional skin is difficult, and modern allopathy-based formulations have their limitations in treating wounds. Aim: The current objective of the study aims to explore the network pharmacology and in vitro wound healing potential of two weeds of Mizoram, India, namely, Chromolaena odorata (L.) R.M. King and H. Rob. (CO) and Mikania micrantha Kunth (MM). Methods: Plant leaves were extracted successively, and methanolic extracts of both plants were used to carry out the experiment. Quantitative phytochemical screening, like Total Phenolic Content (TPC) and Total Flavonoid Content (TFC), was performed. A network pharmacology approach was performed using various computational tools. In-vitro albumin denaturation inhibition, proteinase inhibition, and heat-induced haemolysis were performed to assess the in-vitro anti-inflammatory activity, followed by an angiogenesis study using the Chorioallantois Membrane (CAM) assay. Results: Phenolic and flavonoid content was found in both extracts, and network pharmacology revealed the involvement of both plants in wound healing through signalling pathways like EGFR and HIF1 signalling pathways. These pathways help in the reduction of inflammation and angiogenesis, and both in vitro anti-inflammatory and angiogenesis studies support the computational claims. Conclusion: Our study concludes that CO and MM may have the potential benefits for faster wound healing and may be further evaluated for in vivo efficacy in animals. Major Findings: TPC and TFC were present in both plant extracts, and the network pharmacology revealed interaction between the phytoconstituents with various inflammatory genes. This evidence shows the faster wound healing potential of CO and MM.