Natural dietary antioxidants containing flavonoids modulate keratinocytes physiology: In vitro tri-culture models

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Several traditional medicinal herbs are widely used for dermatologic and cosmetic preparations. The beneficial skin repair activity is detected in various phases of wound-healing process, such as cell-cell, cell-matrix interactions or collagen synthesis. AIM OF THE STUDY: The study assessed the effects of Opuntia ficus-indica (L.) Mill. (Opuntia) and Milk Thistle (MT) (Silybum marianum (L.) Gaerth) on adult keratinocytes (HaCaT) functioning under basal condition or in the presence of mechanical damage (wounded cells). MATERIALS AND METHODS: The role of the natural compounds was tested on HaCaT grown in mono-culture and tri-culture configurations. In tri-cultures models, HaCaT were treated with the conditioned media (CM) obtained by Human Normal Dermal Fibroblast (NHDF) and Human Dermal Microvascular Endothelial cells (HMVEC) co-cultures. Specifically, were tested cell viability, oxidative stress mechanisms (cytokines release and lipid peroxidation) and cellular remodelling (growth factors release or metalloproteinase modulation). Moreover, the migratory potential of HaCaT was analysed by the use of wound healing in vitro assay. RESULTS: Opuntia and MT differently modified the metabolism (EGF, MMP-9), and the migratory properties of HaCaT both under physiological conditions or upon mechanical damage (wounded cells). Moreover, both compounds modulated HaCaT response to oxidative stress. The response to the natural compounds were modified, and in some cases potentiated, in tri-culture configuration systems. CONCLUSIONS: The data demonstrated that in vitro tri-culture approach is suitable to characterize the role of natural compounds on the complex communication between dermalepidermal cellular components and microvascular endothelium. Specifically, Opuntia and MT are good alternatives to synthetic compounds in skin repair promotion.

Protective Role of Nutritional Plants Containing Flavonoids in Hair Follicle Disruption: A Review

“…BC promoted endothelial proliferation, while VSD and MXD enhanced angiogenic potential. Moreover, only HSP increased VEGFR-2 phosphorylation [31].…”

Molecular Mechanisms at the Basis of Pharmaceutical Grade Triticum vulgare Extract Efficacy in Prompting Keratinocytes Healing

“…In addition, we attempted to unravel the molecular features beyond this beneficial effect, and we evaluated the key biomarkers that involved in the tissue repair. Recently, Bassino and collaborators [18] found that plant extracts modulated MMPs expression by using scratched HaCaT cells in an in vitro model. In fact, that natural compounds that contained flavonoids changed the MMP-9 expression at all doses tested, though only during wound repair, and were not modulated in physiological conditions.…”

Wound healing and photoprotection properties of Acanthus ebracteatus Vahl. extracts standardized in verbascoside

“…In short, HDF were seeded in 48-well plate for 3 days prior to additional seed of HaCaT cells seeded onto the HDF and further incubated for 24 h. Thereafter, the cocultures were treated with the samples, i.e., AE1, AE3, AE24, verbascoside and dexamethasone (D4902, Sigma, UK), incubated for 24 h, exposed with UV (UV lamp, Cole-Parmer, USA), i.e., UVA for 15 min (1 J/cm 2 ) and UVB for 25 s (30 mJ/cm 2 ), incubated for 24 h. Cell viability (%) was monitored with CellTiter-Glo luminance (Promega, USA). Cellular activity of the samples against MMP-9 (ab100610, Abcam, UK) in the coculture system was examined at the noncytotoxic concentrations (150 µg/mL for AE1, AE3, AE24 and verbascoside, 10 µg/mL for dexametasone) in a comparison with the control groups, i.e., vehicle control with UV exposures and vehicle non-UV control 29 .…”