title: Anti-inflammatory Actions of (+)-3'α-Angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) against Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice.
abstract: The immunoregulatory protective properties of (+)-3'α-angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) isolated from Bupleurum malconense has not been reported. In the present study, the therapeutic effect of Pd-Ib (30, 60, and 120 mg/kg/day) was examined in a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Administration of Pd-Ib significantly reduced the disease activity index, inhibited the shortening of colon length, reduced colonic tissue damage, and suppressed colonic myeloperoxidase activity and nitric oxide levels in mice with DSS-induced colitis. Moreover, Pd-Ib greatly suppressed the secretion of pro-inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17A while enhancing the level of anti-inflammatory cytokine IL-4. The protein levels of phosphorylated STAT3 (p-STAT3) and phosphorylated p38 (p-p38) were down-regulated in the colonic tissues of DSS-treated mice. Importantly, the anti-inflammatory effect of Pd-Ib against acute colitis was comparable to the anti-inflammatory sulfa drug sulfasalazine (300 mg/kg). Furthermore, the in vitro study showed that the inhibitory effect of Pd-Ib on p-STAT3 and IL-6 protein levels was accompanied by the reduction of MAPKs (JNK and p38). In conclusion, this study suggested that Pd-Ib attenuated DSS-induced acute colitis via the regulation of interleukins principally through the STAT3 and MAPK pathways.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Huai-Xue
authors.initials: HX
authors.lastname: Mu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.|School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Fatima
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Shi
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Xiao
authors.affiliation: YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University , Kunming, 650500, People's Republic of China.
authors.forename: Bao-Min
authors.initials: BM
authors.lastname: Fan
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR, People's Republic of China.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D029972:Bupleurum / Q000737:chemistry*; D003092:Colitis / Q000139:chemically induced*; D003106:Colon / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000627:therapeutic use; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000187:drug effects; D013237:Stereoisomerism; D012460:Sulfasalazine / Q000494:pharmacology
chemical_list: C000610553:(+)-3'alpha-angeloxy-4'-keto-3',4'-dihydroseselin; D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016207:Cytokines; C508717:IL17A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D015847:Interleukin-4; D012460:Sulfasalazine; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D020929:Mitogen-Activated Protein Kinase Kinases