Sun Dalin, Xing Dong, Wang Dandan, Liu Yuanyuan, Cai Bin, Deng Weimin, Hu Qinglin, Ma Wenjun, Jin Baofang
Andrology Department of Integrative Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
School of Medicine, Southeast University, Nanjing, China.
Front Pharmacol. 2024 Jan 4;14:1281002. doi: 10.3389/fphar.2023.1281002. eCollection 2023.
Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP and by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. , BSDZG effectively reduced the prostate index. and , BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, and , BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 . To sum up, the and therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.
慢性非细菌性前列腺炎（CNP）是泌尿外科最常见的慢性病之一，可导致前列腺疼痛和排尿困难，严重影响患者的身心健康。然而，临床上尚无治疗CNP的标准方法。虽然补肾导浊颗粒（BSDZG）的临床应用为中国的CNP患者带来了希望，但其治疗CNP的机制仍不完全清楚。因此，我们旨在研究BSDZG治疗CNP的新机制。在本研究中，我们首先检测了大鼠的前列腺指数，然后通过酶联免疫吸附测定试剂盒和TUNEL染色确定了BSDZG对CNP的抗炎和抗凋亡作用。接下来，我们借助蛋白质免疫印迹法研究了BSDZG对前列腺蛋白诱导的大鼠和脂多糖（LPS）诱导的RWPE-1细胞的抗炎和抗凋亡机制是否与AKT、p38丝裂原活化蛋白激酶（MAPK）和核因子κB（NF-κB）信号通路有关。最后，借助酶联免疫吸附测定试剂盒和蛋白质免疫印迹法，采用脱氢紫堇碱（DHC，p38 MAPK激活剂）探索了BSDZG对LPS诱导的RWPE-1细胞中p38 MAPK和NF-κB信号通路之间相互作用的影响。结果显示，BSDZG有效降低了前列腺指数。此外，BSDZG显著降低了两种促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的水平以及凋亡率。而且，BSDZG显著上调了磷酸化AKT（p-AKT）的表达水平，并显著下调了磷酸化p38 MAPK和NF-κB2的表达水平。p38 MAPK的激活显著逆转了BSDZG对TNF-α和IL-1β水平以及磷酸化p38 MAPK和NF-κB2表达水平的调节作用。综上所述，BSDZG治疗CNP的机制表现为通过抑制促炎细胞因子TNF-α和IL-1β的水平来调节AKT、p38 MAPK和NF-κB信号通路，从而形成抗炎和抗凋亡作用，且BSDZG的抗炎作用是通过抑制p38 MAPK信号通路来抑制下游的NF-κB信号通路实现的。
