Aloe Extracts Inhibit Skin Inflammatory Responses by Regulating NF-κB, ERK, and JNK Signaling Pathways in an LPS-Induced RAW264.7 Macrophages Model

Clin Cosmet Investig Dermatol. 2023 Jan 28:16:267-278. doi: 10.2147/CCID.S391741. eCollection 2023.

Abstract

Introduction: Inflammation generally refers to the body's defensive response to stimuli, and skin inflammation is still one of the major problems that affect human physical and mental health. While current pharmacological treatments are reported to have cytotoxicity and various side effects, herbal medicines with few side effects and low cytotoxicity are considered as alternative therapeutic approaches.

Methods: In order to investigate anti-inflammatory effects and mechanisms of ALOE, the potential cytotoxicity of A. vera extracts (ALOE) was determined in vitro at first. The production of the pro-inflammatory proteins (ie, IL-6, TNF-α) in lipopolysaccharides (LPS) and ultraviolet A (UVA)-stimulated HaCaT and RAW264.7 cells were then treated with ALOE to test its inhibitory effects using enzyme-linked immunosorbent assay (ELISA). To further explore the anti-inflammatory mechanisms of ALOE, quantitative Polymerase Chain Reaction (qPCR) was used to analyze the mRNA expression of inflammatory genes iNOS, COX-2 and NO production. For NF-κB and MAPK signaling pathways analysis, Western blotting and nuclear fluorescence staining were used to evaluate the expression of key factors.

Results: ALOE did not exhibit obvious cytotoxicity (0-3 mg/mL) in vitro. ALOE was able to inhibit the expression of pro-inflammatory cytokines IL-6, TNF-α and functioned more prominently in LPS-induced model. ALOE could also suppress the mRNA expression of LPS-induced iNOS and COX-2 and further down-regulate NO level. Furthermore, ALOE reduced the protein expression of P65 in NF-κB signaling pathway and suppressed LPS-induced activation of ERK and JNK, instead of p38 MAPK pathway.

Conclusion: Taken together, these results demonstrated that ALOE is a potential treatment in suppressing LPS-stimulated inflammation reactions targeting NF-κB, JNK and ERK signaling pathways. The anti-inflammatory effects of ALOE indicated that it has the potential to become an effective cosmetic ingredient.

Keywords: Aloe vera extracts; COX-2; LPS; MAPK; NF-κB; NO; P65; anti-inflammation; iNOS.

Grants and funding

This work was supported by the Yunnan Science and technology project (2018ZF005).