Curcumin and Curcumol Inhibit NF-κB and TGF-β1/Smads Signaling Pathways in CSE-Treated RAW246.7 Cells

E-Zhu (Curcuma zedoaria) is known as a classical traditional Chinese medicine and widely used in the treatment of cancers, cardiovascular disease, inflammation, and other diseases. Its main components include curcumol and curcumin, which have anti-inflammatory and antifibrosis effects. Here we established an in vitro inflammatory injury model by stimulating RAW246.7 cells with cigarette smoke extract (CSE) and detected the intervention effects of curcumin and curcumol on CSE-treated Raw246.7 macrophage cells to explore whether the two compounds inhibited the expression of inflammatory cytokines by inhibiting the NF-κB signaling pathway. We detected the antifibrosis effects of curcumin and curcumol via TGF-β1/Smads signaling pathways. The model of macrophage damage group was established by CSE stimulation. Curcumol and curcumin were administered to Raw246.7 macrophage cells. The efficacy of curcumol and curcumin was evaluated by comparing the activation of proinflammatory factors, profibrotic factors, and NF-κB and TGF-β1/Smads signaling pathway. In addition, CSE-treated group was employed to detect whether the efficacy of curcumol and curcumin was dependent on the NF-κB signaling via the pretreatment with the inhibitor of NF-κB. Our findings demonstrated that curcumol and curcumin could reduce the release of intracellular ROS from macrophages, inhibit the NF-κB signaling pathway, and downregulate the release of proinflammatory factor. Curcumol and curcumin inhibited the TGF-β1/Smads signaling pathway and downregulated the release of fibrotic factors. Curcumin showed no anti-inflammatory effect in CSE-treated cells after the inhibition of NF-κB. Curcumol and curcumin showed an anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

[1]  Li Tang,et al.  The anti-inflammatory effects of curcumin on renal ischemia-reperfusion injury in rats , 2018, Renal failure.

[2]  Amirhossein Sahebkar,et al.  Therapeutic potential of curcumin in diabetic complications , 2018, Pharmacological research.

[3]  Xin-hua Wang,et al.  Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1
. , 2018, Clinical nephrology.

[4]  Reza Salarinia,et al.  Effects of curcumin on NF‐κB, AP‐1, and Wnt/β‐catenin signaling pathway in hepatitis B virus infection , 2018, Journal of cellular biochemistry.

[5]  A. Iraji,et al.  Inhibition of LPS-induced inflammatory responses by Satureja hortensis extracts in J774.1 macrophages , 2018, Journal of immunoassay & immunochemistry.

[6]  Yongjian Xu,et al.  Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study , 2018, The Lancet.

[7]  Chunhong Ma,et al.  Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome , 2018, The Journal of Immunology.

[8]  Weigang Gan,et al.  Curcumol attenuates epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via TGF-β1 , 2018, Molecular medicine reports.

[9]  Do-Hee Kim,et al.  Comparative Effects of Curcumin and Tetrahydrocurcumin on Dextran Sulfate Sodium-induced Colitis and Inflammatory Signaling in Mice , 2018, Journal of cancer prevention.

[10]  T. Tsuda Curcumin as a functional food-derived factor: degradation products, metabolites, bioactivity, and future perspectives. , 2018, Food & function.

[11]  Chuan Zhang,et al.  Inhibition of autophagy attenuated curcumol-induced apoptosis in MG-63 human osteosarcoma cells via Janus kinase signaling pathway , 2017, Oncology letters.

[12]  W. Shumin,et al.  Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway , 2017, Inflammation.

[13]  Lixin Wei,et al.  Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-κB-IL1α/β-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis. , 2017, Cancer letters.

[14]  Qi Huang,et al.  Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression , 2016, Acta Pharmacologica Sinica.

[15]  Zhiguo Zheng,et al.  Curcumol Promotes Vascular Endothelial Growth Factor (VEGF)-Mediated Diabetic Wound Healing in Streptozotocin-Induced Hyperglycemic Rats , 2017, Medical science monitor : international medical journal of experimental and clinical research.

[16]  Yu Cheng,et al.  Iranian Journal of Basic Medical Sciences Anti-inflammatory Effect of Yu-ping-feng-san via Tgf-β1 Signaling Suppression in Rat Model of Copd , 2022 .

[17]  A. Józkowicz,et al.  TGF-β1/Smads and miR-21 in Renal Fibrosis and Inflammation , 2016, Mediators of inflammation.

[18]  K. Raafat,et al.  Phytotherapeutic activity of curcumol: Isolation, GC–MS identification, and assessing potentials against acute and subchronic hyperglycemia, tactile allodynia, and hyperalgesia , 2016, Pharmaceutical biology.

[19]  C. Cingi,et al.  Antioxidant activities of curcumin in allergic rhinitis , 2016, European Archives of Oto-Rhino-Laryngology.

[20]  Hui Ma,et al.  Curcumol Suppresses Breast Cancer Cell Metastasis by Inhibiting MMP-9 Via JNK1/2 and Akt-Dependent NF-κB Signaling Pathways , 2016, Integrative cancer therapies.

[21]  J. Soriano,et al.  Global burden of COPD , 2016, Respirology.

[22]  M. Filippo Evidence-Based Complementary and Alternative Medicine , 2016 .

[23]  Sharmistha Banerjee,et al.  The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[24]  Juan Wang,et al.  Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway , 2015, International journal of molecular sciences.

[25]  Xi Zheng,et al.  Curcumin, Inflammation, and Chronic Diseases: How Are They Linked? , 2015, Molecules.

[26]  Q. Jin,et al.  The effect of curcumin on NF-κB expression in rat with lumbar intervertebral disc degeneration. , 2015, European review for medical and pharmacological sciences.

[27]  Yinghang Wang,et al.  Curcumol induces HSC-T6 cell death through suppression of Bcl-2: involvement of PI3K and NF-κB pathways. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[28]  Wim E Hennink,et al.  Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. , 2014, Biomaterials.

[29]  Yongkyu Lee,et al.  Cytotoxic Activity from Curcuma zedoaria Through Mitochondrial Activation on Ovarian Cancer Cells , 2013, Toxicological research.

[30]  S. Malek,et al.  In Vitro Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of Curcuma zedoaria. , 2013 .

[31]  Syarifah Nur Syed Abdul Rahman,et al.  In Vitro Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of Curcuma zedoaria , 2013, Evidence-based complementary and alternative medicine : eCAM.

[32]  K. Yamaguchi,et al.  The danger signal plus DNA damage two-hit hypothesis for chronic inflammation in COPD , 2013, European Respiratory Journal.