Roh Kangsan, Kim Suji, Kang Hee, Ku Jin-Mo, Park Kye Won, Lee Sukchan
Department of Genetic Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
Department of Food Science & Biotechnology, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
Pharmacol Res. 2017 Jul;121:230-239. doi: 10.1016/j.phrs.2017.05.003. Epub 2017 May 5.
Acquired lymphedema is a pathological condition associated with lymphatic dysfunction caused by surgical treatments for cancer. Although global estimates of the prevalence of acquired lymphedema have been rising, there are currently no effective therapeutics available. Since adipose tissue accumulation is a clinical hallmark of lymphedema, we hypothesized that regulation of adipogenesis in lymphedematous tissue could be used as a therapeutic intervention against lymphedema. Toward this, we investigated the possibility of anti-adipogenic 30% ethanol Rhus verniciflua Stokes (RVS) extract as a potential lymphedema treatment. Oral administration of RVS extract ameliorated volumetric symptoms of lymphedema in a mouse model. RVS administration also reduced adipose tissue accumulation in lymphedematous tissue and downregulated expression of adipocyte markers, including Pparγ and Fabp4. Sulfuretin was identified as a major bioactive compound in the 30% ethanol RVS extract in liquid chromatography-mass spectrometry analysis. Similar to the activities of RVS, sulfuretin inhibited adipocyte differentiation in 3T3-L1 preadipocytes. Moreover, treatment with sulfuretin on lymphedema-induced mice reduced lymphedema volume, decreased the expression of adipogenic markers, but induced the expression of markers associated with lymphangiogenesis. Taken together, our data raise the possibility that sulfuretin might be used in therapeutic interventions against acquired lymphedema.
后天性淋巴水肿是一种与癌症手术治疗导致的淋巴功能障碍相关的病理状况。尽管全球后天性淋巴水肿患病率的估计值一直在上升，但目前尚无有效的治疗方法。由于脂肪组织积聚是淋巴水肿的临床特征，我们推测调节淋巴水肿组织中的脂肪生成可作为对抗淋巴水肿的治疗干预措施。为此，我们研究了抗脂肪生成的30%乙醇漆树（RVS）提取物作为潜在淋巴水肿治疗方法的可能性。口服RVS提取物可改善小鼠模型中淋巴水肿的体积症状。给予RVS还可减少淋巴水肿组织中的脂肪组织积聚，并下调包括Pparγ和Fabp4在内的脂肪细胞标志物的表达。在液相色谱-质谱分析中，硫黄菊素被鉴定为30%乙醇RVS提取物中的主要生物活性化合物。与RVS的活性相似，硫黄菊素可抑制3T3-L1前脂肪细胞中的脂肪细胞分化。此外，用硫黄菊素治疗淋巴水肿诱导的小鼠可减少淋巴水肿体积，降低脂肪生成标志物的表达，但诱导与淋巴管生成相关的标志物的表达。综上所述，我们的数据表明硫黄菊素可能用于后天性淋巴水肿的治疗干预。
