The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats

Lishi Jie; Zhenyuan Ma; Yifan Gao; Xiaoqing Shi; Likai Yu; Jun Mao; Peimin Wang

doi:10.3389/fmed.2023.1153360

The mechanism of palmatine-mediated intestinal flora and host metabolism intervention in OA-OP comorbidity rats

Front Med (Lausanne). 2023 Apr 20:10:1153360. doi: 10.3389/fmed.2023.1153360. eCollection 2023.

Authors

Lishi Jie^#^{1

2}, Zhenyuan Ma^#^{1

2}, Yifan Gao^{1

2}, Xiaoqing Shi^{1

2}, Likai Yu^{1

2}, Jun Mao¹, Peimin Wang¹

Affiliations

¹ Department of Orthopaedics and Traumatology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
² Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

^# Contributed equally.

Abstract

Background: ErXian decoction is a Chinese herbal compound that can prevent and control the course of osteoarthritis (OA) and osteoporosis (OP). OP and OA are two age-related diseases that often coexist in elderly individuals, and both are associated with dysregulation of the gut microbiome. In the initial study, Palmatine (PAL) was obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacological screening techniques, followed by 16S rRNA sequencing and serum metabolomics of intestinal contents, to explore the mechanism of PAL in the treatment of OA and OP.

Methods: The rats selected for this study were randomly divided into three groups: a sham group, an OA-OP group and a PAL group. The sham group was intragastrically administered normal saline solution, and the PLA group was treated with PAL for 56 days. Through microcomputed tomography (micro-CT), ELISA, 16S rRNA gene sequencing and non-targeted metabonomics research, we explored the potential mechanism of intestinal microbiota and serum metabolites in PAL treatment of OA-OP rats.

Results: Palmatine significantly repair bone microarchitecture of rat femur in OA-OP rats and improved cartilage damage. The analysis of intestinal microflora showed that PAL could also improve the intestinal microflora disorder of OA-OP rats. For example, the abundance of Firmicutes, Bacteroidota, Actinobacteria, Lactobacillus, unclassified_f_Lachnospiraceae, norank_f_Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Muribaculaceae increased after PAL intervention. In addition, the results of metabolomics data analysis showed that PAL also change the metabolic status of OA-OP rats. After PAL intervention, metabolites such as 5-methoxytryptophol, 2-methoxy acetaminophen sulfate, beta-tyrosine, indole-3-carboxylic acid-O-sulfate and cyclodopa glucoside increased. Association analysis of metabolomics and gut microbiota (GM) showed that the communication of multiple flora and different metabolites played an important role in OP and OA.

Conclusion: Palmatine can improve cartilage degeneration and bone loss in OA-OP rats. The evidence we provided supports the idea that PAL improves OA-OP by altering GM and serum metabolites. In addition, the application of GM and serum metabolomics correlation analysis provides a new strategy for uncovering the mechanism of herbal treatment for bone diseases.

Keywords: gut microbiota; metabonomics; osteoarthritis; osteoporosis; palmatine.

Grants and funding

This research was supported by the Peak Academic Talent Project of Jiangsu Province Hospital of Chinese Medicine (y2021rc02) and the Research and Practice Innovation Program for Postgraduates in Jiangsu Province (KYCX21_1684).