Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of β-Catenin. Since several anagen-inductive genes are regulated by β-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated β-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3β/β-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H₂O₂)-induced HDPCs. The senescence-associated β-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H₂O₂-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.

中文翻译：

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间苯三酚增强人真皮乳头细胞中生长期信号传导并减轻 H2O2 诱导的氧化应激。

间苯三酚（PG）是褐藻中丰富的异构苯三醇之一。由于其多酚结构，PG表现出多种生物活性。然而，PG 对人真皮乳头细胞 (HDPC) 生长期信号传导和氧化应激的影响尚不清楚。在这项研究中，我们研究了 PG 改善脱发的治疗潜力。非细胞毒性浓度的 PG 可增加毛发生长初期诱导基因和 β-连环蛋白的转录活性。由于多个生长期诱导基因受 β-连环蛋白调节，因此进行了进一步的实验以阐明 PG 上调生长期信号传导的分子机制。各种生化分析表明，PG 上调 β-Catenin 信号传导而不影响 Wnt 的表达。特别是，PG 升高蛋白激酶 B (AKT) 的磷酸化，导致糖原合酶激酶 3 beta (GSK3β) 在丝氨酸 9 处的抑制性磷酸化增加。用选择性磷酸肌醇 3-激酶/AKT 抑制剂 LY294002 治疗，恢复 PG 诱导的增加的 AKT/GSK3β/β-Catenin 信号传导和毛发生长初期诱导蛋白。此外，PG处理的HDPC的条件培养基通过AKT信号通路促进人表皮角质形成细胞的增殖和迁移。随后，我们评估了PG的抗氧化活性。_{PG 改善了过氧化氢 (H 2} O ₂ ) 诱导的 HDPC中升高的氧化应激标记物并改善了毛发生长初期信号传导的降低。衰老相关的β-半乳糖苷酶染色实验也表明PG的抗氧化能力可以有效减轻H ₂ O ₂诱导的衰老。总的来说，这些结果表明 PG 可能增强 HDPC 中的生长期信号传导并改善氧化应激诱导的细胞损伤。因此，PG可以作为一种新型治疗成分来改善脱发症状。