Ursolic acid molecules dock MAPK1 to modulate gut microbiota diversity to reduce neuropathic pain.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis.

Synchrotron radiation micro-CT as a novel tool to evaluate the effect of agomir-210 in a rat spinal cord injury model.

MicroRNA-210 (miR-210) was initially reported to be associated with hypoxia and plays a vital role in modulating angiogenesis. However, the potential effect and underlying mechanisms of miR-210 activity in rat spinal cord injury (SCI) have not yet been fully illuminated. In the present study, differential microRNA expression after SCI was determined by Microarray analysis. To explore the effect of miR-210 after SCI, we intrathecally injected agomir-210 with Alzet Osmotic Pumps to up-regulated the endogenous miR-210 expression. Then, synchrotron radiation micro-CT (SRµCT) imaging was used to investigate the effect of agomir-210 in rat SCI model. We found that the endogenous miR-210 expression could be up-regulated by intrathecal agomir-210 injection. The administration of agomir-210 significantly promoted angiogenesis, as evidenced by increased vessel number and volume detected by SRµCT, attenuated the lesion size and improved functional recovery after SCI. Additionally, agomir-210 attenuated cellular apoptosis and inflammation in the injured rat spinal cord. Expression levels of pro-apoptotic protein (Bax) and pro-inflammatory cytokines (TNF-α and IL-1ß) were significantly decreased after agomir-210 treatment, whereas expression levels of anti-apoptotic (Bcl-2) and anti-inflammatory (IL-10) proteins were up-regulated. In conclusion, our results indicated that SRµCT is a powerful imaging tool to evaluate the effects of angiogenesis after agomir-210 administration in rat SCI model. The up-regulation of endogenous miR-210 expression following agomir-210 administration promoted angiogenesis and anti-apoptotic protein expression, and attenuated inflammation. MiR-210 played a positive role in neurological functional recovery and could be a potential new therapeutic target for SCI.