Frontiers in Pharmacology
·
2025
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IF 4.8
Jinpeng Lv,Duo Meng,Huansha Zhang,Wenhui Xu,Xiaohong An,Chuanwei Yin,Kun Zou,Rongyin Gao
Introduction: Apigenin, a natural flavonoid with well-established antioxidant, anticancer, and anti-inflammatory activities, has recently attracted attention for its pigmentation-promoting effects. However, the underlying molecular mechanisms driving its melanogenic activity remain incompletely understood.Method: To investigate apigenin‘s effects on melanogenesis, human epidermal melanocytes (HEMCs), zebrafish embryos, and human skin explants were treated with apigenin. Melanin content, dendrite formation, and melanosome maturation were evaluated using spectrophotometry and transmission electron microscopy. Key signaling molecules and proteins involved in melanogenesis and melanosome transport were assessed by Western blotting and immunohistochemistry. The role of the c-KIT receptor was further explored through pharmacological inhibition and genetic knockdown approaches. Functional pigmentation was evaluated by assessing UVB-induced DNA damage markers.Results: Apigenin (10 μM) significantly increased melanin production by 1.8-fold in HEMCs, enhanced dendritic morphology, and promoted stage III–IV melanosome formation. Mechanistically, apigenin induced melanogenesis independently of the MC1R/cAMP/PKA pathway by directly binding to the c-KIT receptor, activating the Raf-1/ERK/RSK cascade, and upregulating MITF. This led to elevated expression of tyrosinase, TRP-1, TRP-2, and melanosome transport proteins Rab27a and Cdc42. Inhibition or knockdown of c-KIT abrogated these effects. In vivo, apigenin restored pigmentation in PTU-induced depigmented zebrafish and increased melanin content by 1.3-fold in human skin explants. Histological analysis confirmed effective melanin transfer to keratinocytes. Additionally, apigenin-treated skin showed reduced UVB-induced DNA damage, indicating enhanced photoprotection.Discussion: These findings demonstrate that apigenin stimulates melanogenesis through a novel c-KIT-dependent signaling pathway and promotes functional pigmentation with photoprotective benefits. Given its dietary origin, favorable safety profile, and multifaceted mechanisms, apigenin holds promise as a therapeutic agent for vitiligo and a natural pigmentation enhancer for dermatological use.
研究领域:
细胞生物学
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皮肤病学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xu Yao,Jie Zhu,Lin Li,Bo Yang,Bixia Chen,Endong Bao,Xiaohui Zhang
Severe heat stress can cause human and animal heart failure and sudden death, which is an important issue of public health worldwide. Our previous studies in animals showed that myocardial cells injury was critical in the above process, and Hsp90 induction has a definite anti-myocardial injury effect, especially through aspirin (ASA). But the mechanism has not been fully clarified. In this study, an in vitro heat stress model of chicken primary myocardial cells (CPMCs) most sensitive to heat stress was used to explore the cell injuries and corresponding molecular resistance mechanism. We found that heat stress resulted in serious oxidation stress and calcium overload in mitochondria, which destroyed the mitochondrial structure and function and then triggered the cell death mechanism of CPMCs. Hsp90 was proven to be a central regulator for resisting heat-stress injury in CPMCs mitochondria using its inhibitor and inducer (geldanamycin and ASA), respectively. The mechanism involved that Hsp90 could activate Akt and PKM2 signals to promote Bcl-2 translocation into mitochondria and its phosphorylation, thereby preventing ROS production and subsequent cell apoptosis . In addition, Hsp90 inhibited mitochondrial calcium overload to overcome MPTP opening and MMP suppression through the inhibitory effect of Raf-1-ERK activation on the CREB-IP3R pathway. This study is the first to reveal a pivotal reason for heat-stressed damage in chicken myocardial cells at subcellular level and identify an effective regulator, Hsp90, and its protective mechanisms responsible for maintaining mitochondrial homeostasis.
研究领域:
细胞生物学
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分子生物学
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心脏病学
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应激生物学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2020
·Vol. 45
·期 5
·1107-1119
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IF 3.038
Xiao Zhang Hong,Wang Li,Gan Ping,He Jing,Yan Bing Chun,Ding Li Dong
miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia–reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how miR-126 changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism miR-126 involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of miR-126-3p and miR-126-5p expression in mice and gerbils after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of miR-126-3p exacerbated the OGD/R-induced cell death and reduced cell viability. After miR-126-3p inhibition, the levels of SPRED1 and VEGFA expression were increased, and p -Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of miR-126-3p inhibition, we found that the expression of p -Raf-1 was significantly increased after the intervention of siSPRED1 , while it was not statistically significant after intervention of siVEGFA . The reduction of miR-126 expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.
研究领域:
神经科学
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分子生物学
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脑血管疾病
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产品关联
DOI
PubMed
高影响因子
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