Piper retrofractum extract and its component piperine promote lymphangiogenesis via an AKT- and ERK-dependent mechanism.
Piper retrofractum extract and its component piperine promote lymphangiogenesis via an AKT- and ERK-dependent mechanism.
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DOI：
10.1111/jfbc.14233
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发表时间：
2022-05
影响因子：
4
通讯作者：
M. Ishii;Haruka Miyata;Nao Ikeda;Takashi Tagawa;M. Nishimura
中科院分区：
文献类型：
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作者：
M. Ishii;Haruka Miyata;Nao Ikeda;Takashi Tagawa;M. Nishimura
据报道，施用胡椒提取物（PRE）可减轻水肿，但这种作用的机制尚不清楚。已知促进淋巴管生成可改善水肿，但PRE对淋巴管生成的影响尚不清楚。在本研究中，我们调查是否PRE，特别是胡椒碱，PRE的主要成分，可以诱导淋巴管生成。预处理和胡椒碱显着促进人真皮淋巴管微血管内皮细胞（HDLECs）的增殖，迁移和管的形成，但对淋巴管生成因子的表达没有影响。此外，PRE和胡椒碱显着促进HDLEC中AKT和ERK蛋白的磷酸化，并且用AKT和ERK抑制剂预处理显着减弱PRE和胡椒碱诱导的淋巴管生成。这些结果表明，PRE和胡椒碱通过AKT和ERK依赖性机制促进淋巴管生成。实际应用：淋巴系统发挥着各种作用，如维持组织液稳态，免疫防御和新陈代谢。淋巴系统的破坏导致液体排出不足，从而导致水肿。目前，对于水肿没有有效的治疗方法;因此，需要开发新的治疗策略。在这项研究中，我们发现，PRE及其主要成分胡椒碱促进淋巴管内皮细胞的淋巴管生成。因此，PRE有可能作为一种新型的缓解水肿的功能性食品。
Administration of Piper retrofractum extract (PRE) has been reported to alleviate edema, but the mechanism underlying this effect is unknown. Promotion of lymphangiogenesis is known to improve lymphedema, but the effect of PRE on lymphangiogenesis remains unclear. In the present study, we investigated whether PRE and specifically, piperine, the main component of PRE, can induce lymphangiogenesis. Treatments with PRE and piperine significantly promoted the proliferation, migration, and tube formation in human dermal lymphatic microvascular endothelial cells (HDLECs) but had no effect on the expression of lymphangiogenic factors. Furthermore, PRE and piperine significantly promoted the phosphorylation of the AKT and ERK proteins in HDLECs, and pretreatment with AKT and ERK inhibitors significantly attenuated the PRE- and piperine-induced lymphangiogenesis. These results indicate that PRE and piperine promote lymphangiogenesis via an AKT- and ERK-dependent mechanism. PRACTICAL APPLICATIONS: The lymphatic system plays various roles such as maintaining tissue fluid homeostasis, immune defense, and metabolism. Disruption of the lymphatic system results in insufficient fluid drainage, which causes edema. Currently, there are no effective treatments for lymphedema; therefore, the development of novel treatment strategies is desirable. In this study, we showed that PRE and its main component piperine promote lymphangiogenesis in lymphatic endothelial cells. Therefore, PRE has the potential to be used as a novel functional food for relieving lymphedema.