1.FLZ attenuates Parkinson's disease pathological damage by increasing glycoursodeoxycholic acid production via down-regulating Clostridium innocuu m.
Meiyu SHANG ; Jingwen NING ; Caixia ZANG ; Jingwei MA ; Yang YANG ; Yueqi JIANG ; Qiuzhu CHEN ; Yirong DONG ; Jinrong WANG ; Fangfang LI ; Xiuqi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):973-990
Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.
2.Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways.
Meiyu SHANG ; Jingwen NING ; Caixia ZANG ; Jingwei MA ; Yang YANG ; Zhirong WAN ; Jing ZHAO ; Yueqi JIANG ; Qiuzhu CHEN ; Yirong DONG ; Jinrong WANG ; Fangfang LI ; Xiuqi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2025;15(4):2024-2038
Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.
3.Erratum: Author correction to "Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways" Acta Pharm Sin B 15 (2025) 2024-2038.
Meiyu SHANG ; Jingwen NING ; Caixia ZANG ; Jingwei MA ; Yang YANG ; Zhirong WAN ; Jing ZHAO ; Yueqi JIANG ; Qiuzhu CHEN ; Yirong DONG ; Jinrong WANG ; Fangfang LI ; Xiuqi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4972-4972
[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].
4.Acupuncture and moxibustion therapy in the management of Crohn's disease: opportunities and challenges
Chunhui BAO ; Jinrong ZHANG ; Xinyi ZHU ; Zhou HAO ; Luyi WU ; Huirong LIU ; Huan'gan WU
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):286-291
With the increasing global recognition of Traditional Chinese Medicine (TCM), acupuncture, as a non-pharmacological treatment, has demonstrated promising potential in alleviating symptoms, improving quality of life, and modulating immune and neurological system functions in patients with Crohn's disease (CD). This review summarizes the theoretical foundations and recent research progress on acupuncture for CD, and introduces a personalized "Three Discriminations" diagnostic and therapeutic strategy based on syndrome differentiation, meridian differentiation, and acupoint selection. It also identifies the target patient populations and clinical application value of acupuncture in CD treatment. Despite preliminary progress, acupuncture treatment for CD still faces multiple challenges, including limited high-quality clinical research evidence, uneven resource distribution, non-standardized efficacy evaluation systems, insufficiently standardized treatment strategies, and an incomplete understanding of its underlying mechanisms. Future efforts should focus on establishing high-quality evidence systems, optimizing integrative treatment strategies combining acupuncture with conventional medicine, and conducting deep exploration of multi-dimensional mechanisms, with the goal of promoting the standardized integration of acupuncture into the management of CD and providing patients with safer, more precise, and sustainable therapeutic options.
5.Acupuncture and moxibustion therapy in the management of Crohn's disease: opportunities and challenges
Chunhui BAO ; Jinrong ZHANG ; Xinyi ZHU ; Zhou HAO ; Luyi WU ; Huirong LIU ; Huan'gan WU
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):286-291
With the increasing global recognition of Traditional Chinese Medicine (TCM), acupuncture, as a non-pharmacological treatment, has demonstrated promising potential in alleviating symptoms, improving quality of life, and modulating immune and neurological system functions in patients with Crohn's disease (CD). This review summarizes the theoretical foundations and recent research progress on acupuncture for CD, and introduces a personalized "Three Discriminations" diagnostic and therapeutic strategy based on syndrome differentiation, meridian differentiation, and acupoint selection. It also identifies the target patient populations and clinical application value of acupuncture in CD treatment. Despite preliminary progress, acupuncture treatment for CD still faces multiple challenges, including limited high-quality clinical research evidence, uneven resource distribution, non-standardized efficacy evaluation systems, insufficiently standardized treatment strategies, and an incomplete understanding of its underlying mechanisms. Future efforts should focus on establishing high-quality evidence systems, optimizing integrative treatment strategies combining acupuncture with conventional medicine, and conducting deep exploration of multi-dimensional mechanisms, with the goal of promoting the standardized integration of acupuncture into the management of CD and providing patients with safer, more precise, and sustainable therapeutic options.
6.Association of OPRMI and CYP3A gene polymorphisms with fentanyl analgesic effect on abdominal hysterec-tomy
Huixia LIANG ; Yangyang XU ; Jinrong BAO
Chinese Journal of Primary Medicine and Pharmacy 2014;(20):3078-3080
Objective To discuss the influence of μ-opioid receptor ( OPRM1) and CYP3A gene polymor-phism on analgesic effect of fentanyl for abdominal hysterectomy patients .Methods 198 cases of gynecologic anes-thesia patients who were treated by elective abdominal hysterectomy surgery ,were selected in the hospital .The rela-tionship between the fentanyl consumption of intravenous analgesia and OPRMI and CYP 3A gene polymorphisms was detected by using polymerase chain reaction-restriction fragment length polymorphism detection .Results In 198 pa-tients,OPRM1 genotyping was 186 cases,the other 10 patients failed to typing were excluded ,including 89 cases of type A/A,type A/G 76 cases,type G/G 21 cases,OPRM1 the frequency of A118G allele was 31.7%.No statistically significant differences were found in mean VAS score of CYP 3A4*1/*1,CYP3A4*1/*1G,CYP3A4*1G/*1G instantly after operation in the three groups and 24h postoperation.By using analysis of variance with body mass ,age and intraoperative volume as a covariate factors after first 24h fentanyl consumption ,the difference was statistically sig-nificant among the three groups (P<0.05),CYP3A4*1G/*1G group was significantly lower than that in CYP3A4*1/*1G group and CYP3A4*1/*1 group,there was no significant difference between CYP 3A4*1/*1G group and CYP3A4*1/*1 group (P>0.05).In addition,because the OPRM1 A118G interacts with CYP3A4*1G, reducedthe quantity of expression of opioid receptor carrying CYP 3A4*1 and OPRM1 A118G/G,and thus more fent-anyl was needed postoperation to achieve the same effect .Conclusion It provided a theoretical basis and reference for clinical application of personalized medicine by analyzing the gynecological patients μopioid receptor gene A118G and CYP3A4*1G polymorphism.

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