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Published on: November 17, 2018
Isodon rosthornii accelerates wound healing via dual antimicrobial activity and NF-κB/MAPK suppression
Yaqian Yang1, Yuze Li2, Yulei Qin1
1Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, P. R. China.
Ethnopharmacological Relevance:
Isodon rosthornii (Diels) Kudo is a traditional medicinal plant used by the Yi, Miao and Hui peoples in southwestern China to treat traumatic injuries and bruises, conditions often complicated by microbial infection and inflammation. However, its wound-healing potential and mechanisms remain scientifically unvalidated.
Aim Of The Study:
To investigate the wound-healing activity of the bioactive fraction of I. rosthornii (IRE), identify and quantify its key bioactive constituents, and elucidate the underlying antimicrobial and anti-inflammatory mechanisms in non-infected and infected wound settings.
Materials And Methods:
IRE was characterized by UHPLC-Q-TOF-MS and standardized by HPLC-DAD. Network pharmacology and molecular docking were used to predict active compounds and targets. Antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis and Cutibacterium acnes was evaluated. Anti-inflammatory mechanisms were investigated in LPS-stimulated RAW 264.7 macrophages. Wound healing efficacy was assessed in rat excisional and S. aureus-infected wound models, including early inflammatory time-point analysis.
Results:
UHPLC-Q-TOF-MS identified 150 compounds, predominantly kaurane diterpenoids and flavonoids; oridonin and nodosin were confirmed and quantified. Network pharmacology predicted enrichment in NF-κB and MAPK pathways. IRE exhibited bactericidal activity against all tested skin pathogens, inhibited biofilm formation, and disrupted membrane integrity. In macrophages, IRE suppressed NO production and pro-inflammatory cytokine release, and attenuated NF-κB and MAPK phosphorylation. In vivo, IRE accelerated wound closure, enhanced collagen deposition, and reduced macrophage infiltration. Notably, in S. aureus-infected wounds, IRE reduced bacterial burden and improved healing, with anti-inflammatory effects evident at an early stage. Head-to-head comparison confirmed that oridonin and nodosin contribute to but only partially account for the extract's activity.
Conclusion:
Isodon rosthornii extract promotes wound healing through combined antimicrobial and anti-inflammatory actions associated with reduced NF-κB and MAPK activation. These findings provide scientific support for its traditional use and support its further development as a topical wound-healing agent.