pachymic-acid and Inflammation

Articular cartilage degeneration is a characteristic pathological change of osteoarthritis (OA). Pachymic acid (PA) is an active ingredient found in Poria cocos. Previous studies have shown that PA has anti-inflammatory effects on a variety of diseases. However, the role of PA in OA and its underlying mechanisms has not been clearly elucidated. In this study, we investigated potential protective effect of PA on OA through cell experiments in vitro and animal experiments in vivo. PA inhibited interleukin-1β-induced inflammatory mediator production in chondrocytes, which includes nitric oxide, inducible nitric oxide synthase, prostaglandin E2, cyclooxygenase-2, tumor necrosis factor alpha and interleukin-6. Meanwhile, PA also reversed the up-regulation of matrix metalloproteinase-3 and thrombospondin motifs 5, and the down-regulation of collagen type II and aggrecan in IL-1β-treated chondrocytes. Mechanistically, our findings revealed that PA-mediated overexpression of SIRT6 inhibited the NF-κB signaling pathway. In vivo, PA contributes to improve cartilage damage in the mouse OA model. In summary, PA inhibited IL-1β-induced inflammation and extracellular matrix degeneration by promoting SIRT6 expression and inhibiting the NF-κB signaling pathway, which indicates that PA is beneficial for the treatment of OA.

Topics: Animals; Chondrocytes; Cyclooxygenase 2; Disease Models, Animal; Inflammation; Interleukin-1beta; Mice; NF-kappa B; Osteoarthritis; Sirtuins

To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism.. Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting.. PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa.. PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.

Topics: Animals; Apoptosis; Colitis; Crohn Disease; ErbB Receptors; Inflammation; Interleukin-6; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Tumor Necrosis Factor-alpha

Pneumonia is a common infectious disease with high morbidity and mortality. It is caused by a variety of pathogenic microorganisms that infect the lung parenchyma. Anti-infective drugs are one of the preferred choices for the treatment of pneumonia. Pachymic acid (PA) is a lanolin triterpene compound from

Topics: Animals; Apoptosis; Inflammation; Lipopolysaccharides; NF-kappa B; Pneumonia; Rats; Triterpenes

To investigate the protective effects and underlying mechanisms of pachymic acid (PA) on sepsis-induced acute kidney injury (AKI).. Sepsis-induced AKI model was made by cecal ligation and puncture (CLP) surgery in SD rats. Animals were randomly divided into 5 groups: a sham group, a CLP group, and three PA-treated groups, which received intraperitoneal injection of PA at the dosage of 5, 20 and 50 mg/kg.bw, respectively. Kidney index, Cre and BUN contents were determined to evaluate the renal function. Pathological changes of kidney tissue were observed by HE staining. Levels of inflammatory mediators (TNF-α, IL-6) were measured to assess the inflammation in renal tissue. Moreover, the expression levels of iNOS, Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were studied by Real-time PCR and Western blot.. PA treatment can significantly decrease the kidney index, and notably drop the contents of Cre and BUN. Renal pathological damage was also found to be effectively improved by PA in a dose-dependent manner. PA treatment was observed to inhibit the renal inflammation by reducing the TNF-α and IL-6 levels. Besides, PA treatment significantly decreased the expression levels of iNOS, and enhanced the expression of Nrf2 and HO-1 in the kidney.. PA had potential therapeutic effects on sepsis-induced AKI in rats, and the activity may be associated with the anti-inflammatory function and antioxidant effect via activating Nrf2/ HO-1 pathway.

Topics: Acute Kidney Injury; Animals; Heme Oxygenase-1; Inflammation; Male; NF-E2-Related Factor 2; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction; Triterpenes

Pachymic acid (PA), a lanostane-type triterpenoid and the major component of Poria cocos alcoholic extracts, has various pharmacological effects, including anti-inflammatory, anti-oxidative and anti-apoptotic. However, few studies have investigated the effects of PA on lipopolysaccharide (LPS)-induced H9c2 cell apoptosis and inflammation, or identified the possible mechanisms underlying these effects. In the present study, H9c2 cardiomyocytes were stimulated by LPS and treated with or without PA. The increased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1 and IL-6 induced by LPS were attenuated following treatment with PA. PA also attenuated LPS-induced apoptosis, as determined by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and regulated the LPS-induced protein expression levels of caspase 3, 8 and 9. Furthermore, the phosphorylations of extracellular-regulated kinase (Erk)1/2 and p38 in the LPS-treated H9c2 cells were inhibited by PA. These results suggested that treatment with PA prevented the LPS-induced inflammatory and apoptotic response in cardiomyocytes, which may be mediated by inhibition of the Erk1/2 and p38 pathways.

Topics: Animals; Apoptosis; Cell Line; Inflammation; Interleukin-1; Interleukin-6; Lipopolysaccharides; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocytes, Cardiac; p38 Mitogen-Activated Protein Kinases; Poria; Protective Agents; Rats; Real-Time Polymerase Chain Reaction; Signal Transduction; Triterpenes; Tumor Necrosis Factor-alpha