PMID- 30940568 OWN - NLM STAT- MEDLINE DCOM- 20200113 LR - 20231213 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 238 DP - 2019 Jun 28 TI - Natural dietary antioxidants containing flavonoids modulate keratinocytes physiology: In vitro tri-culture models. PG - 111844 LID - S0378-8741(19)30190-4 [pii] LID - 10.1016/j.jep.2019.111844 [doi] AB - 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 dermal-epidermal cellular components and microvascular endothelium. Specifically, Opuntia and MT are good alternatives to synthetic compounds in skin repair promotion. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Bassino, Eleonora AU - Bassino E AD - Department of Life Sciences and Systems Biology, University of Torino, Italy. Electronic address: eleonora.bassino@unito.it. FAU - Gasparri, Franco AU - Gasparri F AD - Department of Pharmacy, University of Salerno, Italy. FAU - Munaron, Luca AU - Munaron L AD - Department of Life Sciences and Systems Biology, University of Torino, Italy. LA - eng PT - Journal Article DEP - 20190330 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Antioxidants) RN - 0 (Culture Media, Conditioned) RN - 0 (Flavonoids) SB - IM MH - Antioxidants/*pharmacology MH - Cell Culture Techniques MH - Cell Line MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Coculture Techniques MH - Culture Media, Conditioned MH - Diet MH - Endothelial Cells/*drug effects/physiology MH - Fibroblasts/*drug effects/physiology MH - Flavonoids/*pharmacology MH - Humans MH - Keratinocytes/*drug effects/physiology MH - *Silybum marianum MH - *Opuntia MH - Wound Healing/drug effects OTO - NOTNLM OT - Endothelial cells OT - Keratinocytes OT - Milk thistle OT - Opuntia ficus-Indica (L.) Mill. OT - Wound-healing EDAT- 2019/04/04 06:00 MHDA- 2020/01/14 06:00 CRDT- 2019/04/04 06:00 PHST- 2019/01/14 00:00 [received] PHST- 2019/03/21 00:00 [revised] PHST- 2019/03/27 00:00 [accepted] PHST- 2019/04/04 06:00 [pubmed] PHST- 2020/01/14 06:00 [medline] PHST- 2019/04/04 06:00 [entrez] AID - S0378-8741(19)30190-4 [pii] AID - 10.1016/j.jep.2019.111844 [doi] PST - ppublish SO - J Ethnopharmacol. 2019 Jun 28;238:111844. doi: 10.1016/j.jep.2019.111844. Epub 2019 Mar 30.