Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis

Abstract

Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF). To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P < 0.05). Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P < 0.05) and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P < 0.01). In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.

Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats

“…Practitioners of traditional Chinese medicine have developed several formulations to help promote blood circulation to accelerate wound healing. For over a thousand years in China, an essential oil derived from Rhizoma curcumae aeruginosae has been prescribed for removing blood stasis and alleviating pain [ 13 ]. Curcumol is one of the major ingredients of this essential oil with the structure of a guaiane-type sesquiterpenoid hemiketal [ 14 ].…”

Curcumol Induces Apoptosis in SPC-A-1 Human Lung Adenocarcinoma Cells and Displays Anti-neoplastic Effects in Tumor Bearing Mice

“…Similar to curcumin, curcumol also displayed a variety of beneficial pharmacological activities in preclinical studies, including anti-inflammation , anti-rheumatism (Wang et al, 2012;Wang et al, 2014;Yu et al, 2014) and anti-seizure (Ding et al, 2014) and hepato-protection . Moreover, the anti-neoplastic effects of curcumol have been well reported in various cell culture models Zhang et al, 2011;Tian et al, 2012;Jing et al, 2013;Guo et al, 2014).…”

A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Wu Tou Tang Acting on Rheumatoid Arthritis by Integrating Network Analysis

“…Among seven known STAT proteins, STAT3 has been demonstrated to be active in synovial lining cells in adjuvant arthritis and RA and in freshly isolated RA SFs [53]. It is activated by a number of cytokines and growth factors expressed in RA synovitis, including IL-6, oncostatin M, EGF, and PDGF [54]. STAT3 is one of components in the Janus kinase (JAK)-STAT signal transduction pathway, which functionally regulates gene expression and various cellular processes, including cell activation, proliferation, and differentiation.…”