2. Academic Validation
  3. Traditional Chinese Medicine Danzhi qing'e decoction inhibits inflammation-associated prostatic hyperplasia via inactivation of ERK1/2 signal pathway

Traditional Chinese Medicine Danzhi qing'e decoction inhibits inflammation-associated prostatic hyperplasia via inactivation of ERK1/2 signal pathway

  • J Ethnopharmacol. 2023 Mar 9;309:116354. doi: 10.1016/j.jep.2023.116354.
Yang Liu 1,  Rui Shao 2,  Tongchuan Suo 3,  Junjie Zhu 4,  Erwei Liu 4,  Yajing Wang 2,  Lin Miao 5,  Xiumei Gao 6
Affiliations

Affiliations

  • 1 Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 2 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 3 College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 4 Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 5 Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: mmmlin@tjutcm.edu.cn.
  • 6 Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: gaoxiumei@tjutcm.edu.cn.
PMID: 36906158 DOI: 10.1016/j.jep.2023.116354
Abstract

Ethnopharmacological relevance: Inflammation plays a critical role during benign prostatic hyperplasia (BPH) development. Danzhi qing'e (DZQE) decoction is a traditional Chinese medicine that has been widely used for estrogen and androgen-related diseases. However, its effect on inflammation-related BPH remains unclear.

Aim of the study: To investigate the effect of DZQE on inhibition of inflammation-related BPH, and further identify the possible mechanism involved.

Methods and materials: Experimental autoimmune prostatitis (EAP)-induced BPH was established and then 2.7 g/kg of DZQE was administrated orally for 4 weeks. The prostate sizes, weights and prostate index (PI) values were recorded. Hematoxylin and eosin (H&E) was performed for pathological analyses. Macrophage infiltrate was evaluated by Immunohistochemical (IHC). The inflammatory cytokine levels were measured by RT-PCR and ELISA methods. The phosphorylation of ERK1/2 was examined by Western blot. The expression differences of mRNA expressions between EAP-induced and oestrogen/testosterone (E2/T)-induced BPH was investigated by RNA Sequencing analyses. In vitro, human prostatic epithelial BPH-1 cells were stimulated with the conditioned medium from monocyte THP-1-derived M2 macrophages (M2CM), followed by treatment of Tanshinone IIA (Tan IIA), Bakuchiol (Ba), ERK1/2 antagonist PD98059 or ERK1/2 agonist C6-Ceramide. The ERK1/2 phosphorylation and cell proliferation were then detected by Western blotting and CCK8 assay.

Results: DZQE significantly inhibited the prostate enlargement and decreased PI value in EAP rats. Pathological analysis showed that DZQE alleviated prostate acinar epithelial cell proliferation by decreasing and reduction of CD68+ and CD206+ macrophage infiltration in the prostate. The levels of cytokines TNF-α, IL-1β, IL-17, MCP-1, TGF-β, and IgG in EAP rats' prostate or serum were significantly suppressed by DZQE as well. Moreover, mRNA Sequencing data showed that the expressions of inflammation-related genes were elevated in EAP-induced BPH but not in E2/T-induced BPH. ERK1/2-related genes expression has been found in both E2/T and EAP-induced BPH. ERK1/2 is one of the core signal pathways involved in EAP-induced BPH, which was activated in EAP group but inactivated in DZQE group. In vitro, two active components of DZQE Tan IIA and Ba inhibited M2CM-induced BPH-1 cell proliferation, similarly to ERK1/2 inhibitor PD98059 did. Meanwhile, Tan IIA and Ba inhibited M2CM-induced ERK1/2 signal activation in BPH-1 cells. When re-activated the ERK1/2 by its activator C6-Ceramide, the inhibitory effects of Tan IIA and Ba on BPH-1 cell proliferation were blocked.

Conclusion: DZQE suppressed inflammation-associated BPH via regulation of ERK1/2 signal by Tan IIA and Ba.

Keywords

Bakuchiol; Benign prostatic hyperplasia; Danzhi qing'e decoction; Tanshinone IIA; Traditional Chinese medicine.

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