Oh Ji Hye, Baek Seung Hwa, Seo Hee Won, Lee Seung Ho, Hwang Seock Yeon
Department of Biomedical Laboratory Science, Daejeon University, Deahak-ro, Dong-gu, Daejeon, 34520, Republic of Korea.
Korea Ginseng Corporation Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea.
J Ginseng Res. 2025 Sep;49(5):532-540. doi: 10.1016/j.jgr.2025.04.009. Epub 2025 May 2.
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer and environmental pollutant that continuously accumulates in the body, causing urogenital toxicity. Further, DEHP accumulation can cause glomerulonephritis due to nephrotoxicity as well as infertility by disturbing reproductive function. Crude saponin is the main active ingredient of ginseng and acts effectively to protect against oxidative stress by activating signaling pathways, such as NF-κB, AP-1 and IRF. Here we investigated the effect of crude-saponin on p38 MAPK/NF-κB signaling against DEHP-induced genitourinary damage in rats.
We conducted an reproductive toxicity study in 4-week-old prepubertal SD rats. DEHP was administered orally at 1000 mg/kg/b.w., for 28 days and crude saponin was administered intraperitoneally at 10, 20, and 40 mg/kg/b.w. for 21 days from 1 wk after DEHP exposure. Four weeks later, extensive analysis of the mice's blood and tissues was performed to characterize their response to DEHP and the protective effects of crude saponin.
DEHP induced inflammation, decreased testicular germ cells, and caused damage to renal tubular epithelial cells and infiltration of inflammatory cells. The expression of MCP-1, a chemokine upregulated by MAPK signaling, was significantly increased in the testicular tissue of DEHP-treated rats (68.3 % ± 4.3 %) compared with the NC group (47.3 % ± 9.8 %) ( < 0.05). In contrast, the high-dose crude saponin group showed a decrease of 60.8 % ± 3.3 %, increased testicular germ cells, and alleviated damage to seminiferous tubule epithelial cells. crude saponin alleviated inflammation by regulating MCP-1 and thereby modulating p38 MAPK/NF-κB signaling.
While the precise mechanism underlying the favorable effects of crude saponin remains to be determined, present study provides a basis for the preventive and therapeutic potential of Korean red ginseng against urogenital disorders induced by phthalate-related plasticizer.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种增塑剂和环境污染物，会在体内持续蓄积，导致泌尿生殖系统毒性。此外，DEHP蓄积可因肾毒性导致肾小球肾炎，并通过干扰生殖功能引起不育。粗皂苷是人参的主要活性成分，可通过激活NF-κB、AP-1和IRF等信号通路有效发挥抗氧化应激的作用。在此，我们研究了粗皂苷对p38丝裂原活化蛋白激酶/核因子κB（p38 MAPK/NF-κB）信号通路的影响，以对抗DEHP诱导的大鼠泌尿生殖系统损伤。
我们对4周龄的青春期前SD大鼠进行了生殖毒性研究。DEHP按1000 mg/kg体重口服给药28天，粗皂苷在DEHP暴露1周后按10、20和40 mg/kg体重腹腔注射给药21天。四周后，对小鼠的血液和组织进行了广泛分析，以表征它们对DEHP的反应以及粗皂苷的保护作用。
DEHP诱导炎症，使睾丸生殖细胞减少，并导致肾小管上皮细胞损伤和炎性细胞浸润。与阴性对照组（47.3%±9.8%）相比，经DEHP处理的大鼠睾丸组织中，由丝裂原活化蛋白激酶（MAPK）信号上调的趋化因子单核细胞趋化蛋白-1（MCP-1）的表达显著增加（68.3%±4.3%）（P<0.05）。相比之下，高剂量粗皂苷组MCP-1表达下降了60.8%±3.3%，睾丸生殖细胞增加，生精小管上皮细胞损伤减轻。粗皂苷通过调节MCP-1从而调节p38 MAPK/NF-κB信号通路减轻炎症。
虽然粗皂苷产生有益作用的确切机制尚待确定，但本研究为韩国红参对邻苯二甲酸酯相关增塑剂诱导的泌尿生殖系统疾病的预防和治疗潜力提供了依据。
