Bergenin, Acting as an Agonist of PPARγ, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-κB-Mediated Macrophage Activation

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.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…Subsequently, SIRT1 reduces the acetylation of NF-κBp65, up-regulates the association of NF-κBp65 and IκBα. Consequently, the nuclear translocation of NF-κBp65 is prevented resulting in reduced expressions of TNF-α and IL-6 against inflammatory injury in DSS-induced mice [97].…”

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

“…The Bergenin dose was chosen based on previous research. [32][33][34] Sham groups underwent no action apart from opening and stitching of the abdominal cavity. Bergenin (dissolved in physiological saline) groups were given a corresponding dose (10, 20 or 40 mg/kg) of Bergenin by gavage at 3 days (once before the operation, once per day).…”

Sustained release of N‐acetylcysteine by sandwich structured polycaprolactone/collagen scaffolds for wound healing

“…The stage of inflammation in wounds is remarkably related to the activity of neutrophils. During this period, the recruitment and function of neutrophils have been shown to be regulated by several cytokines, including interleukin‐1β (IL‐1β) and tumor necrosis factor‐a (TNF‐a) whose expressions were regulated by nuclear factor kappa B (NFκB) . However, observed in impaired wound healing, the overproduction of ROS hinders the wound healing process by depressing NFκB activation and the subsequent synthesis and release of proinflammatory cytokines .…”

“…During this period, the recruitment and function of neutrophils have been shown to be regulated by several cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-a) whose expressions were regulated by nuclear factor kappa B (NFκB). 43,44 However, observed in impaired wound healing, the overproduction of ROS hinders the wound healing process by depressing NFκB activation and the subsequent synthesis and release of proinflammatory cytokines. 45 In this study, we found that NAC could promote wound healing and achieve repair effects, which pointed toward its impact of reducing excessive ROS production during the healing period.…”