Wound healing and photodynamic potential of Adiantum capillus-veneris L. (Pteridaceae): An evaluation of the cellular effects and molecular insights

Linru Mou¹Banaz Jalil¹Francesca Scotti¹Majella E. Lane¹Bernd L. Fiebich²Lu Sun²Caroline Maake³Michael Heinrich^1*

• ¹University College London, London, United Kingdom
• ²Universitatsklinikum Freiburg, Freiburg, Germany
• ³Universitat Zurich, Zürich, Switzerland

Chronic and infected wounds represent a persistent global health burden. Medicinal plants offer a promising source of wound-healing agents due to their multitarget activities, long history of traditional use, and accessibility. Adiantum capillus-veneris L. (ACV), traditionally used to treat a range of ailments, such as respiratory, urinary, and skin disorders, was investigated for its in vitro wound-healing potential following methanol extraction. We evaluated the effects of methanol extracts of ACV (ACVM) on cell proliferation, migration and antioxidative capacity in human keratinocytes (HaCaT), and anti-inflammatory activity in RAW 264.7 cells. We also explored its combination with visible light phototherapy. Chemical profiling via HPTLC analysis, UV/Vis spectrophotometry and HPLC analysis, together confirmed that ACVM contained more metabolites than other extracts, yielding five visible-light absorption peaks and identifying rutin and chlorogenic acid as major metabolites. At ≤100 µg/mL, ACVM was non-toxic to HaCaT cells in the absence of visible light. However, phototoxicity was evident at 200 µg/mL. ACVM (50 µg/mL) significantly promoted HaCaT migration, with a further 2 enhancement upon exposure to light. ACVM also suppressed H₂O₂-induced ROS generation in a dose-dependent manner (≤50 µg/mL), while light exerted a bidirectional modulatory effect. Additionally, ACVM markedly inhibited LPS-induced secretion of CXCL2, CCL2, CXCL10, TNF-α, and IL-6 in RAW 264.7 macrophages, with effects evident at concentrations as low as 0.1 µg/mL. These findings suggest that ACVM, particularly in combination with light-assisted therapy, shows promise for accelerating wound healing.