Ningmitai Capsule Reprograms Tryptophan Metabolism by Inhibiting the JAK2-STAT3-IDO1 Signaling Pathway to Treat Pain in Chronic Prostatitis/Pelvic Pain Syndrome
Chaoyu Hu, Yi Zhao, Zhengwei Song, Yan Wang, Dengke Yin, Xuejun Shang, Song TanIntroduction:
Ningmitai (NMT) is a Chinese patent medicine commonly used to treat Chronic Prostatitis/Pelvic Pain Syndrome (CP/CPPS). This study aimed to identify the compounds in NMT and explore their potential mechanisms of action in treating pain in CP/CPPS.
Methods:
UPLC-Q-Exactive-Orbitrap-MS combined with network analysis was used to identify relevant components, targets, and signaling pathways. A thermal shift assay validated the interaction between the active components and the target protein, consistent with the binding modes predicted by molecular docking. The analgesic effect of NMT in rats with Experimental Autoimmune Prostatitis (EAP) was verified. In vitro and in vivo experiments verified a negative correlation between NMT and the JAK2/STAT3 pathway. Meanwhile, the expression of IDO1, a downstream target of the JAK2/STAT3 pathway, and tryptophan metabolism were detected in EAP rats.
Results:
28 compounds were identified in NMT, of which wogonin and arctiin bound closely to JAK2. NMT alleviated pain in EAP rats, reduced the expression of pain-related factors p-JAK2/JAK2, p-STAT3/STAT3, and IDO1 in vivo and in vitro, and this effect was reversed by the JAK2/STAT3 agonist RO8191. Targeted metabolomics in EAP rats revealed that metabolites involved in tryptophan metabolism were upregulated in the pain state, whereas these alterations were significantly mitigated by NMT treatment. This suggests that the analgesic effect of NMT in CP/CPPS may be mediated through the modulation of tryptophan metabolism.
Discussion:
NMT demonstrates a multi-component, multi-target, and multi-pathway therapeutic profile for CP/CPPS, characterized by the suppression of pain and inflammatory mediators and the modulation of tryptophan metabolism.
Conclusion:
NMT can inhibit the JAK2/STAT3/IDO1 signaling pathway, thus reprogramming tryptophan metabolic disorders, which contributes to the treatment of pain in CP/CPPS.