Impact of sesquiterpene lactones on the skin and skin-related cells? A systematic review of in vitro and in vivo evidence

• Published in: Life sciences (1973) Vol. 265; p. 118815
• Main Authors: da Silva, Laíla Pereira, Borges, Bruno Arantes, Veloso, Marcia Paranho, Chagas-Paula, Daniela Aparecida, Gonçalves, Reggiani Vilela, Novaes, Rômulo Dias
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.01.2021; Elsevier BV
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - pharmacology; Bias; Contact dermatitis; Cyclooxygenase-2; Cytokines; Dendritic cells; Dermatitis; Dermatitis, Contact - etiology; Dose-Response Relationship, Drug; Edema; Erythema; Experimental pathology; Fibroblasts; Gene expression; Guinea Pigs; Humans; Hypersensitivity; Immunomodulation; In vivo methods and tests; Inflammation; Keratinocytes; Lactones; Lactones - administration & dosage; Lactones - adverse effects; Lactones - pharmacology; Liquid oxygen; Macrophages; Mice; Natural products; NF-kappa B - metabolism; NF-κB protein; Sesquiterpene lactones; Sesquiterpenes - administration & dosage; Sesquiterpenes - adverse effects; Sesquiterpenes - pharmacology; Signal transduction; Skin; Skin - drug effects; Skin - pathology; Experimental pathology; Sesquiterpene lactones; Natural products; Dermatitis
• DOI: 10.1016/j.lfs.2020.118815
• ISSN: 0024-3205

Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based therapies. Thus, the impact of SL on the skin and skin-related cells was systematically reviewed. Studies indexed in electronic databases were screened from the PRISMA strategy. The risk of bias in all studies was verified from the SYRCLE's tool. Thirty original studies were recovered and analyzed. Mice and guinea pig, keratinocytes and fibroblasts were predominantly investigated from in vivo and in vitro studies, respectively. In vivo studies indicated that most SL induced contact dermatitis associated with edema, erythema, and inflammatory infiltrate. Conversely, in vitro evidence was consistent with a dose-dependent anti-inflammatory effect of SL in response to reduced cytokines, 5-LOX, and COX-2 levels or activity in keratinocytes, fibroblasts, macrophages and dendritic cells; which are events potentially triggered by downregulation of gene expression and/or inhibition of the NF-κB signaling pathway. In vivo studies presented uncertain to high-risk of bias mainly associated with underreporting of randomization and experimental blinding. The current evidence supports potent cutaneous immunomodulatory properties of SL. Although in vitro and in vivo studies indicate opposite anti- or proinflammatory effects, this contradiction exhibits a dose-dependent component. In addition, the anti-inflammatory pathways activated by SL are better understood from in vitro evidence. However, additional studies are required to elucidating specific anti-inflammatory and proinflammatory mechanisms triggered by SL in vivo. Thus, controlling the sources of bias described in this review can contribute to improving the quality of the evidence in further investigations. [Display omitted]