patchouli-alcohol and Colitis

The combination therapy of strengthening inflammation regression and mucosal repair may overcome the "therapeutic ceiling" of ulcerative colitis (UC). However, poor targeting is an outstanding challenge in the preparation of drug delivery systems for UC treatment. Here, we developed anti-inflammatory drug (patchouli alcohol, PA)-loaded nanoparticles (NPs) derived from natural silk fibroin (SF) and subjected to surface functionalization with cyclo RGD peptide (cRGD). Self-assembled SF NPs realized sustained drug release. Meanwhile, cRGD functionalization yielded notably targeted drug delivery to inflamed colon, and thereby enhanced the anti-inflammatory and barrier repair capabilities of NPs. Moreover, cRGD-PASFNs regulated innate immune responses and exerted a potent therapeutic efficacy against acute colitis. Surprisingly, the cRGD-PASFNs also modulated the abnormal level of amino acids which are crucial to the integrity of the intestinal barrier. Additionally, oral delivery of this nanomedicine displayed an excellent safety profile in the mouse model. This study confers confidence for the further development of targeted precision therapy for UC and other inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Fibroins; Mice; Nanoparticles; Peptides, Cyclic; Sesquiterpenes

The pregnane-X-receptor (PXR) is involved in inflammatory bowel disease (IBD). Patchouli alcohol (PA) has anti-inflammatory effects; however, the effect of PA on IBD pathogenesis remains largely unknown.. The aim of the present study was to investigate the anti-inflammatory effect of PA, primarily focused on crosstalk between PA-mediated PXR activation and NF-κB inhibition.. We evaluated the anti-inflammatory effect of PA with respect to PXR/NF-κB signalling using in vitro and in vivo models. In vitro, PA, identified as a PXR agonist, was evaluated by hPXR transactivation assays and through assessing for CYP3A4 expression and activity. NF-κB inhibition was analysed based on NF-κB luciferase assays, NF-κB-mediated pro-inflammatory gene expression, and NF-κB nuclear translocation after activation of PXR by PA. In vivo, colonic mPXR and NF-κB signalling were analysed to assess PA-mediated the protective effect against dextran sulphate sodium (DSS)-induced colitis. Furthermore, pharmacological inhibition of PXR was further evaluated by examining PA protection against DSS-induced colitis.. PA induced CYP3A4 expression and activity via an hPXR-dependent mechanism. PA-mediated PXR activation attenuated inflammation by inhibiting NF-κB activity and nuclear translocation. The anti-inflammatory effect of PA on NF-κB was abolished by PXR knockdown. PA prevented DSS-induced inflammation by regulating PXR/NF-κB signalling, whereas pharmacological PXR inhibition abated PA-mediated suppressive effects on NF-κB inflammation signalling.. PA activates PXR signalling and suppresses NF-κB signalling, consequently causing amelioration of inflammation. Our results highlight the importance of PXR-NF-κB crosstalk in colitis and suggest a novel therapeutic reagent.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Colon; Cytochrome P-450 CYP3A; Humans; Intestinal Mucosa; Male; Mice, Inbred C57BL; NF-kappa B; Pregnane X Receptor; Sesquiterpenes

Topics: Animals; Colitis; Colon; Cytokines; Dextran Sulfate; Male; Mice, Inbred BALB C; Pogostemon; Sesquiterpenes; Tryptophan