title: Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.
abstract: The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20μg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Su-Li
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zi-Jing
authors.initials: ZJ
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Tang Center of Herbal Medicine Research, and Department of Anesthesia and Critical care, University of Chicago, Chicago, IL 60637, USA. Electronic address: zhangchunfeng67@163.com.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Tang Center of Herbal Medicine Research, and Department of Anesthesia and Critical care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Tang Center of Herbal Medicine Research, and Department of Anesthesia and Critical care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001713:Biphenyl Compounds; D002351:Carrageenan; D032364:Daphne / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004487:Edema; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010851:Picrates; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018501:Antirheumatic Agents; D001713:Biphenyl Compounds; D005419:Flavonoids; D008070:Lipopolysaccharides; D010851:Picrates; D010936:Plant Extracts; D009569:Nitric Oxide; D002351:Carrageenan; D005620:Freund's Adjuvant; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Adjuvant-induced arthritis; Daphne genkwa; Flavonoids; RAW264.7 cells; Rheumatoid arthritis