Abstract
Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-α in colon tissues, but not that of mucosal barrier-associated proteins occludin, E-cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of IL-6 and TNF-α as well as nuclear translocation and DNA binding activity of NF-κB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARγ antagonist GW9662 and siPPARγ. Subsequently, bergenin was identified as a PPARγ agonist. It could enter into macrophages, bind with PPARγ, promote nuclear translocation and transcriptional activity of PPARγ, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-κB-p65 and increased association NF-κB-p65 and IκBα. Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARγ/SIRT1/NF-κB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and offer a paradigm for the recognization of anti-UC mechanisms of compound with similar structure occurring in traditional Chinese medicines.
Highlights
Ulcerative colitis (UC) is a chronic inflammatory disease, which mainly occurs at the colon site and spreads from rectum to proximal colon and even ileum (Baumgart and Sandborn, 2007)
Bergenin was purchased from Nanjing JingZhu Biological Technology Co., Ltd. (Nanjing, China); dextran sulfate sodium (DSS, molecular weight 36–50 kDa) was purchased from MP Biomedical (OH, United States); 5-aminosalicylic acid (5-ASA) sustained release granules were purchased from Ipsen Pharma (Houdan, France); Rosiglitazone was purchased from Ampere Reagent Co., Ltd. (Shenzhen, China); GW9662 and LPS were purchased from Sigma Chemical Co., Ltd
MO, United States); myeloperoxidase (MPO) activity kit was purchased from JianCheng Bioengineering Institute (Nanjing, China); TNF-α and IL-6 enzyme-linked immunosorbent assay (ELISA) kits were purchased from Dakewe Biotech Co., Ltd. (Shenzhen, China); siPPARγ was purchased from RiboBio Co. (Guangzhou, China); enhanced chemiluminescent (ECL) plus reagent kit was purchased from DiZhao Biotech Co., Ltd (Shanghai, China); LanthaScreen R TRFRET PPAR-γ competitive binding assay Kit was purchased from Thermo Fisher Scientific Co. (Waltham, MA, United States); TRIzol reagent was purchased from Invitrogen (Carlsbad, CA, United States); HiScriptTM reverse transcriptase system and SYBR@ green master mix were purchased from Vazyme Biotech Co., Ltd. (Nanjing, China); Luciferase Reporter Gene Assay Kit was purchased from Beyotime (Shanghai, China)
Summary
Ulcerative colitis (UC) is a chronic inflammatory disease, which mainly occurs at the colon site and spreads from rectum to proximal colon and even ileum (Baumgart and Sandborn, 2007). It has been reported with high incidences in many regions: Northern Europe (24.3 per 100000), Canada (19.2 per 100000), and Australia (17.4 per 100000) (Ungaro et al, 2017). Data indicate that many activated macrophages exist in colonic mucosa, secret inflammatory cytokines such as IL1β, IL-6 and TNF-α, and control persistent inflammation. Repairment of mucosal barrier and inhibition of inflammation are effective strategies for UC treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
