College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of Korea.
Brain Busan 21 Plus Research Project Group, Kyungsung University, Busan 48434, Republic of Korea.
Biomolecules. 2024 Oct 4;14(10):1257. doi: 10.3390/biom14101257.
Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer's disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from , has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.
血小板是维持止血、防止过度出血和促进伤口愈合的重要血液成分。血小板计数减少与白血病、肝炎、癌症和阿尔茨海默病等各种疾病有关。增强巨核细胞分化是增加血小板生成的一种有前途的策略。化合物 K（CK）是 中人参皂苷的主要生物活性代谢物，具有抗癌和神经保护作用。在这项研究中，我们研究了 CK 对慢性髓系白血病（CML）细胞系 K562 和 Meg-01 中巨核细胞分化和凋亡的影响。CK 处理显著上调了关键巨核细胞分化标志物的 mRNA 表达，包括 CD61、CD41 和 CD42a，并促进了 K562 细胞中大的多核细胞的形成。此外，流式细胞术分析显示，5 µM 的 CK 在 K562 和 Meg-01 细胞中诱导凋亡，这是血小板生成的关键过程。RT Profiler PCR 阵列分析进一步确定，在 CK 处理的 K562 和 Meg-01 细胞中，与 NLRP3 炎性小体激活相关的基因表达显著增加。这项研究首次表明，CK 通过激活 ERK/EGR1 和 NLRP3 炎性小体途径促进巨核细胞分化和凋亡。这些发现表明 CK 可能增强血小板生成，表明其作为与血小板相关的疾病和其他相关疾病的治疗候选物的潜力。
