Lee Yeon-Ji, Choi Joo-Hee, Kang Kyung-Ku, Sung Soo-Eun, Lee Sijoon, Sung Minkyoung, Seo Min-Soo, Park Jong-Hwan
Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea.
Laboratory of Veterinary Tissue Engineering, College of Veterinary Medicine, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea.
Microorganisms. 2024 Jan 17;12(1):188. doi: 10.3390/microorganisms12010188.
Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of culture supernatant (CSK), isolated from Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control HO-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove HO-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.
过量的活性氧生成会对皮肤细胞生理产生不利影响,导致细胞生长停滞、黑色素生成和衰老。最近的临床研究发现,乳酸菌对皮肤器官有直接或间接的特殊作用,但其确切机制尚未阐明。在本研究中,我们调查了从西方蜜蜂(Apis mellifera Linnaeus)分离的培养上清液(CSK)的抗氧化保护作用和对黑色素合成的抑制作用的潜在机制。CSK在氧化应激下促进细胞迁移和伤口愈合方面表现出显著功效,超过了其他菌株。与对照HO处理的细胞相比,CSK预处理显著上调了Nrf2/HO-1(核因子红细胞2相关因子2/血红素加氧酶-1)的表达,Nrf2/HO-1是细胞抵御氧化应激的关键因子。DCF-DA(二氯二氢荧光素二乙酸酯)检测结果证实,CSK增强Nrf2和HO-1表达的能力与其清除HO诱导的活性氧的强大能力一致。此外,CSK上调了MAPK(丝裂原活化蛋白激酶)磷酸化,MAPK磷酸化是HO-1表达的上游信号,而MAPK抑制剂损害了CSK的伤口愈合效果。此外,CSK对黑色素合成具有抑制作用,下调了B16F10细胞中与黑色素生成相关的基因。因此,本研究表明,CSK通过MAPK磷酸化激活Nrf2/HO-1途径发挥抗氧化作用,从而恢复细胞迁移并对黑色素生成产生抑制作用。这些发现强调了CSK的抗氧化和抗黑色素生成潜力,表明其作为治疗剂促进伤口愈合以及作为美白化妆品活性成分的潜在用途。