No abstract

PurposeOP and OA are chronic bone diseases with high incidence in the middle-aged and elderly populations. The latest research shows that the pathological environment of OP may be involved in the aggravation of the pathological process of OA, and the pathological state of OP plays an important role in the aggravation of OA pathology. EXD is a traditional Chinese medicine decoction that has been used to treat osteoporosis. Therefore, we further study whether OA will be aggravated in the OP environment and whether EXD can alleviate OA by intervening in the OP environment. The purpose of this study was to analyze the effect of OP on OA metabolites by using metabolomic methods and to explore the intervention mechanism of EXD on osteoporotic OA.MethodThirty-two SD rats were randomly divided into normal group, OA group, OP-OA group, and EXD group. EXD was administered by gavage. Histopathological evaluation of cartilage tissue was performed using Saffron fast green and HE staining. Western blot and qRT-PCR were used to detect the expression levels of chondrogenesis genes SOX9, COL2A1, and COMP in cartilage tissue. GC-TOFMS and LC-QTRAP-MS/MS metabolomics methods were used to analyze the changes of metabolites in serum samples of rats in each group.ResultThe slice results showed that the cartilage damage in the OP-OA group was more serious than that in the OA group, which was significantly relieved after EXD intervention, indicating that the cartilage damage in the OP-OA group was more severe than that in the OA group and further reduced the protein and gene expressions of cartilage markers SOX9, COL2A1, and COMP. Thirty-seven substances were identified, and gentiopicroside, emodin, quercetin, and diosmetin were analyzed as possible active components of EXD. EXD treatment significantly reduced cartilage damage and reversed the expression of these markers. Metabolomics showed that EXD attenuated cartilage destruction by modulating the expression of cystine, chenodeoxycholate, and D-Turanose, involving glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways.ConclusionThe OP environment may promote the progression of OA through metabolic factors. The benign intervention of EXD in osteoporotic OA involves cystine, chenodeoxycholate, and D-Turanose, and their associated glycolysis/gluconeogenesis, pantothenate, and CoA biosynthesis metabolic pathways. Therefore, we have a deep understanding of the metabolic-related intervention of EXD in osteoporotic OA and are eager to better understand the mechanism of multi-targeted intervention of EXD in bone metabolic lesions.

Objectives. Chronic pain, the main symptom of knee osteoarthritis (OA), remains the primary reason for decreased functional capacity. Quzhi decoction, a TCM prescription, is effective in treating chronic pain in OA, but the potential mechanisms require further exploration. Methods. An anterior cruciate ligament transection (ACLT) rat model was established, and pain-like behavior was evaluated. Metabolomics analysis of serum samples was performed to identify differential metabolites, and network pharmacology was used to identify potential targets of Quzhi decoction for the treatment of OA. Finally, we constructed a comprehensive network of serum metabolomics and network pharmacology. At the same time, the obtained key targets were verified by molecular docking. Results. Quzhi decoction was shown to attenuate pain-like behavior and joint inflammation in OA rats. Through serum metabolomics, thirty potentially significant metabolites were found to be involved in the therapeutic effects of Quzhi decoction against OA pain. According to network pharmacology, 107 active drug components were matched with 115 disease targets, which was partly consistent with the metabolomics findings. Further analysis focused on 6 key targets, including CYP3A4, PLA2G4A, PTGS1, PTGS2, TYR, and ALOX5, and their associated core metabolites and pathways. Molecular docking results showed that the related targets had high affinity with the active pharmaceutical ingredients in Quzhi decoction. Conclusion. The effect of Quzhi decoction on OA pain may be related to the inhibition of joint inflammation, mainly through disturbing arachidonic acid metabolism, tyrosine metabolism, and leukotriene metabolism. Further systematic molecular biology experiments are needed to verify the accurate mechanism.

BackgroundErXian 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.MethodsThe 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.ResultsPalmatine 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.ConclusionPalmatine 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.