Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis

HUA Yongjiao; LIU Lina; LI Liang; LYU Yaozhong; XIAO Wei

doi:10.13422/j.cnki.syfjx.20230436

您当前的位置：

首页 >

文章列表页 >

Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis

更新时间：2023-06-30

- Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 15, Pages: 51-59(2023)
- 作者机构：
  
  1.南京中医药大学，南京 210023
  2.江苏康缘药业股份有限公司，江苏连云港 222001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230436
  CLC： R2-0;R33;R289;R697+.33
- Published：05 August 2023，
  
  Published Online：10 March 2023，
  
  Received：02 February 2023，
- 稿件说明：
扫描看全文
花永娇,刘莉娜,李良等.泽兰提取物对慢性前列腺炎的治疗作用及调控炎性小体NLRP3信号通路的机制[J].中国实验方剂学杂志,2023,29(15):51-59.

HUA Yongjiao,LIU Lina,LI Liang,et al.Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(15):51-59.
花永娇,刘莉娜,李良等.泽兰提取物对慢性前列腺炎的治疗作用及调控炎性小体NLRP3信号通路的机制[J].中国实验方剂学杂志,2023,29(15):51-59. DOI： 10.13422/j.cnki.syfjx.20230436.

HUA Yongjiao,LIU Lina,LI Liang,et al.Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(15):51-59. DOI： 10.13422/j.cnki.syfjx.20230436.

摘要

目的

探讨泽兰提取物对慢性前列腺炎（CNP）的治疗作用，并基于炎性小体NOD样受体蛋白3（NLRP3）通路探讨其抗CNP的可能作用机制。

方法

采用5 mg·L

-1

脂多糖（LPS）诱导人正常前列腺基质细胞WPMY-1，通过酶联免疫吸附测定法（ELISA）检测3.125、6.25、12.5、25、50、100 mg·L

-1

泽兰提取物对LPS诱导WPMY-1细胞分泌IL-6含量的影响，并计算其半抑制浓度（IC

）值。WPMY-1细胞给药50、75、100 mg·L

-1

泽兰提取物后，蛋白免疫印迹法（Western blot）检测NLRP3通路关键蛋白表达。应用角叉菜胶诱导法复制CNP大鼠模型。苏木素-伊红（HE）染色观察大鼠前列腺组织病理学变化；测定大鼠前列腺器官指数；ELISA检测大鼠血清5

-二氢睾酮（5

-DHT）及前列腺组织IL-6、肿瘤坏死因子-

（TNF-

）、转化生长因子-

（TGF-

）、环氧合酶-2（COX-2）、前列腺素E

（PGE

）和诱导型一氧化氮合酶（iNOS）的含量；Western blot检测大鼠前列腺组织中COX-2、TGF-

及NLRP3通路关键蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠前列腺组织COX-2、白细胞介素-1

（IL-1

）、TGF-

、TNF-

mRNA表达。

结果

与正常组比较，模型组细胞分泌IL-6浓度显著升高（

0.01）；细胞NLRP3、ASC、Caspase-1和IL-1

的蛋白表达水平明显升高（

0.05，

0.01）；与模型组比较，泽兰提取物对LPS诱导WPMY-1细胞分泌IL-6的IC

为38.26 mg·L

-1

；泽兰提取物低、中、高剂量组NLRP3、ASC和IL-1

蛋白表达水平明显下调（

0.05，

0.01），泽兰提取物中、高剂量组细胞Caspase-1蛋白表达水平明显下调（

0.05，

0.01）。与假手术组比较，模型组大鼠前列腺器官指数显著升高（

0.01），前列腺组织大量炎细胞浸润，组织病理学评分明显升高（

0.05），血清5

-DHT含量、前列腺组织TNF-

、PGE

、IL-6、TGF-

、NOS

/iNOS、COX-2含量，COX-2、IL-1

、TGF-

mRNA表达水平明显升高（

0.05，

0.01），前列腺组织COX-2、TGF-

、NLRP3、Caspase-1、ASC及IL-1

蛋白表达水平明显上调（

0.05，

0.01）；与模型组比较，泽兰提取物低、高剂量均能有效减轻角叉菜胶所致的前列腺组织病理学改变，明显降低血清5

-DHT含量、前列腺组织TNF-

、PGE

、TGF-

及iNOS含量（

0.05，

0.01）及COX-2、IL-1

、TGF-

mRNA表达水平（

0.05，

0.01），明显下调前列腺组织COX-2、Caspase-1、ASC及NLRP3蛋白表达水平（

0.05，

0.01）。泽兰提取物低剂量组前列腺器官指数显著降低（

0.01）。泽兰提取物高剂量组前列腺组织COX-2含量明显降低，TGF-

及IL-1

蛋白表达水平明显下调（

0.05）。

结论

泽兰提取物对CNP有明显的治疗作用并可能通过抑制炎性小体NLRP3信号通路的激活来减轻炎症反应。

Abstract

Objective

To investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis （CNP） and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 （NLRP3） pathway.

Method

Normal human prostatic stromal cells， namely WPMY-1 were induced by lipopolysaccharide （LPS） of 5 mg·L

-1

， and the effects of Lycopi Herba extract of 3.125， 6.25， 12.5， 25， 50， and 100 mg·L

-1

on interleukin-6 （IL-6） level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay （ELISA）. The half-maximal inhibitory concentration （IC

） was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba

extract of 50， 75， and 100 mg·L

-1

was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5

-dihydrotestosterone （5

-DHT） in serum， as well as the levels of IL-6， tumor necrosis factor-

（TNF-

）， transforming growth factor-

（TGF-

）， cyclooxygenase-2 （COX-2）， prostaglandin E

（PGE

）， and inducible nitric oxide synthase （iNOS） in prostate tissue were detected by ELISA. The key protein expressions of COX-2， TGF-

， and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expressions of COX-2， IL-1

， TGF-

， and TNF-

mRNA in prostate tissue.

Result

Compared with the normal group， the level of IL-6 and the protein expression levels of NLRP3， ASC， Caspase-1， and IL-1

of WPMY-1 cells in the model group were increased （

0.05，

0.01）. Compared with the model group， Lycopi Herba

extract could inhibit the levels of IL-6 （

0.01） released by LPS-induced WPMY-1 cells， with IC

of 38.26 mg·L

-1

. The protein expression levels of NLRP3， ASC， and IL-1

in the low-， medium-， and high-dose groups of Lycopi Herba extract were significantly down-regulated （

0.05，

0.01）. The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba

extract were significantly down-regulated （

0.05，

0.01）. Compared with the sham operation group， the prostate organ index of rats in the model group was significantly increased （

0.01）， a large number of inflammatory cells were infiltrated in the prostate tissue， and the histopathological score was significantly increased （

0.05）； the levels of 5

-DHT in serum， the levels of TNF-

， PGE

， IL-6， TGF-

， NOS

/iNOS， and COX-2 in prostate tissue， and expression levels of COX-2， IL-1

， and TGF-

were significantly increased （

0.05，

0.01）. The mRNA expression levels of COX-2， TGF-

， NLRP3， Caspase-1， ASC， and IL-1

in prostate tissue were significantly up-regulated （

0.05，

0.01）. Compared with model group， the low and high doses of Lycopi Herba

extract could alleviate the pathological changes in prostate tissue induced by carrageenan， significantly reduce the level of 5

-DHT in serum， levels of TNF-

， PGE

， TGF-

， and iNOS in prostate tissue （

0.05，

0.01）， and mRNA expression levels of COX-2， IL-1

， and TGF-

（

0.05，

0.01）. The protein expression levels of COX-2， Caspase-1， ASC， and NLRP3 in prostate tissue were significantly down-regulated （

0.05，

0.01）. The prostate organ index of the low-dose group of Lycopi Herba

extract was significantly decreased （

0.01）. The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba

extract was significantly decreased， and the protein expression levels of TGF-

and IL-1

were significantly down-regulated （

0.05）.

Conclusion

Lycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.

关键词

泽兰提取物慢性前列腺炎炎症反应炎性小体NOD样受体蛋白3（NLRP3）信号通路

Keywords

Lycopi Herba extractchronic prostatitisinflammationinflammasome NOD-like receptor protein 3 （NLRP3） signaling pathway

references

COLL R C，ROBERTSON A A，CHAE J J，et al.A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases［J］.Nat Med，2015，21（3）：248-255.

BAE J Y，LEE S W，SHIN Y H，et al.P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer［J］.Oncotarget，2017，8（30）：48972-48982.

JO E K，KIM J K，SHIN D M，et al.Molecular mechanisms regulating NLRP3 inflammasome activation［J］.Cell Mol Immunol，2016，13（2）：148-159.

国家药典委员会.中华人民共和国药典：一部［M］.北京：中国医药科技出版社，2020：239.

刘娜，肖纯.保健食品——泽兰的研究进展［J］.食品工业科技，2016，37（7）：392-395，400.

张颖，纪晓宁，苗明三.常用妇科中药治疗前列腺炎、前列腺增生的探讨［J］.中医学报，2011，26（8）：967-970.

王敬博，杨京航，郭婉怡，等.山豆根水提物对类风湿关节炎骨破坏及PI3K/Akt信号通路的影响［J］.中国实验方剂学杂志，2022，28（23）：30-37.

YANG X，YUAN L，CHEN J，et al.Multitargeted protective effect of Abacopteris penangiana against carrageenan-induced chronic prostatitis in rats［J］.J Ethnopharmacol，2014，151（1）：343-351.

陈盛镱，朱少平，胡利，等.雷公藤多苷对角叉菜胶诱导的大鼠非细菌性前列腺炎的抗增生作用研究［J］.中国中医药科技，2020，27（4）：538-542.

臧春柳，韩福谦，佘妙华，等.从“虚、瘀、毒”论治Ⅲ型慢性非细菌性前列腺炎［J］.中医临床研究，2022，14（23）：95-97.

陈伟杰，江宁东，张清，等.基于UPOINTS的中西医结合治疗慢性前列腺炎的规范化思考［J］.上海中医药杂志，2014，48（4）：5-7.

姚飞翔，胡镜清，张亚强.慢性前列腺炎临床常见中医证候类型和症状/体征的初步研究［J］.世界中医药，2013，8（6）：672-677.

戴春福.中西医结合治疗慢性前列腺炎的思路与方法［J］.辽宁中医杂志，2001，28（11）：660-661.

朱枕砚.参苓白术散加减对慢性前列腺炎患者血液流变学指标及血清TNF-α、IL-2、IL-6水平的影响［J］.现代医学与健康研究：电子版，2020，4（19）：112-114.

邝世航，黄双艺，乐有为，等.慢性前列腺炎TGF-β1、CTGF的表达水平及其与症状指数的关系［J］.中华腔镜泌尿外科杂志：电子版，2018，12（2）：125-128.

赵聪敏，温恩懿.脑缺氧缺血损伤过程中环氧合酶2的作用及机制［J］.中国临床康复，2004，8（7）：1328-1329.

杨勇，顾方六，HABIB F K.前列腺增生及前列腺癌组织中睾酮及双氢睾酮测定及其意义［J］.中华泌尿外科杂志，1993，14（5）：369-371.

杜菲，周岩，王军浩，等.双氢青蒿素对CNP模型大鼠的治疗作用及对炎症小体NLRP3信号通路的影响［J］.中国免疫学杂志，2022，38（21）：2597-2600.

何涛，黄华武，曾永龙，等.固有免疫分子NLRP3炎性小体在慢性细菌性前列腺炎中的作用［J］.中国医药导报，2019，16（10）：157-161.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Network Meta-analysis of Oral Chinese Patent Medicine in Adjuvant Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Effect of Yunvjian with or Without Achyranthis Bidentatae Radix on Glucose and Lipid Metabolism and Inflammatory Response in Diabetic Rats with Syndrome of Yin Deficiency and Internal Heat

Clinical Comprehensive Evaluation of Qianlieping Capsules in Treatment of Chronic Prostatitis with Stagnant Dampness-heat Syndrome

Protective Effect of Shenlian Prescription on Acute Lung Injury Induced by Particulate Matter Exposure in Rats

Role of Inflammation in Development of Chronic Heart Failure： Based on "Toxic Pathogen Theory"

Related Author

YU Binyang

YANG Jing

DAI Xinyue

XU Jiaxin

LYU Xing

WANG Yiming

GAO Rui

LIANG Ruifeng

Related Institution

Xiyuan Hospital， Chinese Academy of Chinese Medical Sciences

Graduate School， China Academy of Chinese Medical Sciences

Graduate School， Beijing University of Chinese Medicine

Henan Integrative Medicine Hospital/Henan Academy of Chinese Medicine

Henan University of Chinese Medicine

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰