Total tanshinones extract alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying intestinal flora and suppressing the LPS-TLR4 axis.

BACKGROUND

Total tanshinones (T-Tan) extract, a class of lipophilic abietane diterpenes isolated from Salvia miltiorrhiza Bunge, exhibits anti-inflammatory effects. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urologic disorder. Dysbiosis of gut microbiota is closely related to CP/CPPS. However, whether T-Tan extract can regulate the intestinal flora to improve CP/CPPS remains unclear.

PURPOSE: The aim of this study was to investigate the effect of T-Tan extract on CP/CPPS and elucidate the mechanisms through which T-Tan extract modulates gut microbiota to ameliorate CP/CPPS.

METHODS

The pseudo-germ-free model was established by administering antibiotics (abx) water, and the experimental autoimmune prostatitis (EAP) model was induced via subcutaneous injections of prostate protein extract emulsified with Freund's adjuvant. The 16S rDNA method was used to analyze the structure and differential species of rat intestinal flora. Chronic pelvic pain was assessed by applying von Frey filaments. Inflammatory factors were detected by ELISA, qPCR and IHC. HE staining was used to evaluate histopathology. Immune cell markers were localized using IF. The expression levels of TLR4 pathway were detected by WB, IHC and qPCR. The graphical abstract is made by Figdraw.

RESULTS

T-Tan extract and its major compound tanshinone IIA (Tan IIA) alleviated abnormal pain and reduced inflammation. Moreover, they restored intestinal flora composition, reduced LPS levels, and downregulated the TLR4 pathway. In addition, fecal microbiota transplantation (FMT) preserved the protective effects of T-Tan extract, reduced inguinal pain, attenuated inflammatory responses, and inhibited the LPS-TLR4 signaling axis. Besides, we further confirmed that the role of intestinal flora in the treatment of CP/CPPS.

CONCLUSION

T-Tan extract could alleviate CP/CPPS by modulating the intestinal flora and then inhibiting the LPS-TLR4 axis, which is helpful for developing novel, microbiota-focused therapeutic strategies to treat CP/CPPS.