Qinghua decoction (清化饮) improves chronic nonbacterial prostatitis possibly via regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors

doi:10.19852/j.cnki.jtcm.20220909.001

Abstract

Abstract:

OBJECTIVE: To explore the mechanism by which Qinghua decoction (清化饮) regulates neuroendocrine inflammation in chronic nonbacterial prostatitis (CNP) model rats and provide an experimental basis for clinical treatment.

METHODS: The rats were randomly divided into six groups: normal control, model, Qianlie Tongyu capsule, low-dose Qinghua decoction, medium-dose Qinghua decoction, and high-dose Qinghua decoction group with six rats in each group. Rats in each group were sacrificed on the 29th day of treatment, and blood and prostate tissues were collected. Serum levels of tumor necrosis factor-alpha and interleukins 1-beta, 6, 8, and 10 (TNF-α and IL-1β, -6, -8, and -10, respectively) were measured using enzyme-linked immunosorbent assay. The pathological changes in the rat prostate tissue in each group were observed under a light microscope. The expression levels of chromogranin A (CgA), nerve growth factor (NGF), and tyrosine kinase A (TrkA) were detected using reverse transcription quantitative polymerase chain reaction. Western blotting was used to detect protein expression of CgA, NGF, and TrkA.

RESULTS: In the model group, the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels. TNF-α, IL-1β, -6, and -8, CgA, NGF, and TrkA levels increased, whereas the content of IL-10 decreased, which was statistically significant compared to that in the normal control group (P < 0.05). Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration. When compared with the model group, the high-dose Qinghua decoction group showed a significant improvement in these indices (P < 0.05).

CONCLUSION: Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP, regulation of inflammatory cytokine expression, and inhibition in the expression of CgA, NGF, and TrkA. This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

Key words: inflammation, interleukins, chromogranin A, nerve growth factor, chronic nonbacterial prostatitis, Qinghua decoction

HAN Yunpeng, YU Wentao, ZHANG Ying, XU Huazhou, DENG Guoxing, FANG Chaoyi. Qinghua decoction (清化饮) improves chronic nonbacterial prostatitis possibly via regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors[J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 695-703.

Figures/Tables 5

Figure 1 Diagram of the experimental protocol Control: Normal control group; Model: Model group; QLTY: Qianlie Tongyu capsule group (0.5 g·kg-1·d-1); QH-L: Qinghua decoction low-dose (1.25 g·kg-1·d-1); QH-M: Qinghua decoction medium-dose group (2.5 g·kg-1·d-1); QH-H: Qinghua decoction high-dose group (5 g·kg-1·d-1). The drug was administered by gavage once a day for 4 weeks. ELISA: enzyme-linked immunosorbent assay; PCR: polymerase chain reaction.

Figure 2 Effect of Qinghua decoction on pathomorphology of prostate in rats with CNP (HE, ×200) A: Normal control group; B: Model group; C: Qianlie Tongyu capsule group (0.5 g·kg-1·d-1); D: Qinghua decoction low-dose group (1.25 g·kg-1·d-1); E: Qinghua decoction medium-dose group (2.5 g·kg-1·d-1); F: Qinghua decoction high-dose group (5 g·kg-1·d-1); the scale is 1 mm. Normal control and model groups were given normal saline (10 mL·kg-1 d-1) by gavage for 28 d. The Qianlie Tongyu capsule group received Qianlie Tongyu capsules (0.5 g·kg-1·d-1) for 28 d, The Qinghua decoction low-, medium-, and high dose groups were given Qinghua decoction (1.25, 2.5, and 5 g kg-1·d-1, respectively) for 28 d. Each group received the drug by gavage once a day using an equal volume and unequal concentration method. Body weight was measured every seven days, and the dosage volume was adjusted according to the change in body weight. CNP: chronic nonbacterial prostatitis; HE: hematoxylin-eosin.

Table 1 Effect of Qinghua decoction on the expression of TNF-α, IL-1 β, IL-6, IL-8, IL-10 in rats with CNP (pg/mL,

\bar{x} \pm s

)

Group	n	TNF-α	IL-1β	IL-6	IL-8	IL-10
Control	6	18.1±2.0	25.0±3.2	18.4±3.3	18.6±1.2	14.8±1.2
Model	6	24.2±2.0^a	35.6±3.7^a	27.2±3.5^a	24.7±1.6^a	9.4±1.6^a
QLTY	6	20.6±3.0^b	30.4±5.5^b	21.4±2.3^c	21.9±2.0^b	12.2±1.8^c
QH-L	6	23.4±2.3	34.4±3.4	25.7±2.7	21.1±3.2^b	11.9±1.6^c
QH-M	6	21.1±1.7^b	33.0±1.3	22.9±2.5^b	22.5±1.5	12.5±1.7^c
QH-H	6	20.9±2.6^b	27.4±4.8^c	21.9±3.7^c	19.8±3.1^c	14.0±0.9^cd

Table 1 Effect of Qinghua decoction on the expression of TNF-α, IL-1 β, IL-6, IL-8, IL-10 in rats with CNP (pg/mL, $\bar{x} \pm s$ )

Group	n	TNF-α	IL-1β	IL-6	IL-8	IL-10
Control	6	18.1±2.0	25.0±3.2	18.4±3.3	18.6±1.2	14.8±1.2
Model	6	24.2±2.0^a	35.6±3.7^a	27.2±3.5^a	24.7±1.6^a	9.4±1.6^a
QLTY	6	20.6±3.0^b	30.4±5.5^b	21.4±2.3^c	21.9±2.0^b	12.2±1.8^c
QH-L	6	23.4±2.3	34.4±3.4	25.7±2.7	21.1±3.2^b	11.9±1.6^c
QH-M	6	21.1±1.7^b	33.0±1.3	22.9±2.5^b	22.5±1.5	12.5±1.7^c
QH-H	6	20.9±2.6^b	27.4±4.8^c	21.9±3.7^c	19.8±3.1^c	14.0±0.9^cd

Figure 3 Effect of Qinghua decoction on CgA, NGF and TrkA protein expression in rats with CNP A: protein bands for each group; B-D: Protein content of CgA, NGF, and TrkA, inter-group control. Control: Normal control group; Model: Model group; QLTY: Qianlie Tongyu capsule group (0.5 g kg-1· d-1); QH-L: Qinghua decoction low-dose group (1.25 g·kg-1 d-1); QH-M: Qinghua decoction medium-dose group (2.5 g· kg-1 d-1); QH-H: Qinghua decoction high-dose group (5 g· kg-1 d-1). The drug was administered by gavage once a day for 4 weeks. CgA: chromogranin A; NGF: nerve growth factor; TrkA: tyrosine kinase A; CNP: chronic nonbacterial prostatitis. Data are expressed as mean ± standard deviation (n = 6). Compared to the normal control group, aP < 0.01; compared to the model group, bP < 0.01, cP < 0.05; compared to the Qianlie Tongyu capsule group, dP < 0.05, eP < 0.01.

Figure 4 Effect of Qinghua decoction on CgA, NGF, and TrkA gene expression in rats with CNP A: the relative quantitative gene expression of CgA in lung tissue; B: the relative quantitative gene expression of NGF in lung tissue; C: the relative quantitative gene expression of TrkA in lung tissue. Control: Normal control group; Model: Model group; QLTY: Qianlie Tongyu capsule group (0.5 g·kg-1 d-1); QH-L: Qinghua decoction low-dose group (1.25 g·kg-1 d-1); QH-M: Qinghua decoction middle-dose group (2.5 g·kg-1 d-1); QH-H: Qinghua decoction high-dose group (5 g·kg-1 d-1). The drug was administered by gavage once a day for 4 weeks. CgA: chromogranin A; NGF: nerve growth factor; TrkA: tyrosine kinase A; CNP: chronic nonbacterial prostatitis. Data are expressed as mean ± standard deviation (n = 6). Compared with the normal control group, aP < 0.01; compared with the model group, bP <0.01, cP < 0.05.

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