Deciphering the underlying wound healing mechanisms of Streptocaulon juventas (Lour.) Merr. by integrating network pharmacology, transcriptomics, and experimental validation

Abstract

Ethnopharmacological relevance: Streptocaulon juventas (Lour.) Merr. (SJ), a traditional Chinese folk medicine, has been widely used for the treatment of dysentery and traumatic injuries since ancient times. However, the mechanisms underlying its wound healing activity remain unclear.

Aim of the study: The aim of this study was to evaluate the wound healing activity of SJ and clarify the underlying molecular mechanisms.

Materials and methods: The wound healing activity of an ethanol extract of SJ (ESJ) was confirmed in rat full-thickness wound models. UPLC-Q-TOF-MS/MS was used to analyze the composition of ESJ. Potential molecular targets and signaling pathways involved in the wound healing activity of ESJ were predicted using network pharmacology and transcriptomic analyses. In addition, the L929 cells were used to evaluate the in vitro wound healing activity of ESJ and to verify the predicted pathways.

Results: In rat wound models, ESJ significantly accelerated wound healing and promoted hydroxyproline production in wounds. Network pharmacology and transcriptomic analyses results revealed that ESJ might promote wound healing by activating the AKT and MAPK pathways. In L929 cells, ESJ significantly promoted cell proliferation, migration, and expression of collagen I and α-SMA. Additionally, ESJ treatment increased the phosphorylation of AKT, mTOR, ERK, and p38 in a time- and dose-dependent manner.

Conclusions: ESJ significantly promoted wound healing in vivo and in vitro. AKT-mTOR and ERK-p38 signaling pathways were involved in the wound healing activity of ESJ.

Keywords: AKT-mTOR signaling pathway; ERK-p38 signaling pathway; L929; Streptocaulon juventas (Lour.) Merr.; Wound healing.