Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.

[Mechanisms Involved in the Inhibition of Melanin Synthesis by Bushen Quban Granule].

Objective To observe the molecular mechanism of Bushen Quban Granule (BQG) for inhibiting the synthesis of intracellular melanin. Methods Twenty SPF grade female SD rats were di- vided into four groups by completely randomized method, i.e., the control group (fed with normal saline) , high, middle, and low dose BQG groups (administered with BQG at 4. 8, 2. 4, 1. 2 g/kg by gastrogavage, equivalent to 24, 12, and 6 times clinical doses, respectively, twice per day for 3 days in total) , 5 in each group. Drug containing serum was collected. Expressions of melanocortin 1 receptor (MC1 R) , mi- crophthalmia-associated transcription factor ( MITF) , tyrosinase ( TYP) , tyrosinase-related protein I (TYRP1) , and tyrosinase-related protein 2 (TYRP2) at the mRNA level were detected by RT-PCR. Ex- pressions of phosphorylated-extracellular regulated MAP kinasel/2 (p-ERK) , TYP, TYRP1 and TYRP2 at the protein level were detected by Western blot. Intracellular melanin contents were determined by NaOH dissolving method. Activities of tyrosinase were determined by Dopa pigment method, and the cell viability was detected by MTT. Results Compared with the control group, expressions of MC1R, MITF, TYP, TYRP1 and TYRP2 at the mRNA level were down-regulated (P <0. 05), and those of TYP, TYRP1 and TYRP2 at the protein level were also down-regulated (P <0. 05), intracellular contents of melanin and the activity of tyrosinase decreased (P <0. 05) , but the level of p-ERK and the proliferation of cells increased in each medicated group (P <0. 05). When ERK was inhibited by its inhibitor PD98059, there was no sta- tistical difference in expressions of MC1 R or MITF at the mRNA level among all medicated groups (P > 0. 05). Compared with the control group, mRNA expressions of TYP, TYRP1 and TYRP2 decreased in the high dose BQG group (P <0. 05), but with no significant difference in protein expressions of p-ERK, TYP, TYRP1 and TYRP2 (P >0. 05). There was no statistical difference in the content of melanin, the activity of TYP, or the proliferation of cells between the control group and the high dose BQG group (P >0. 05). Con- clusion BQG could inhibit the synthesis of intracellular melanin through up-regulating p-ERK to inhibit the expression of tyrosinase and its related proteins.