title: Anti-proliferative and antioxidant activities of Saposhnikovia divaricata.
abstract: The dry root of Saposhnikovia divaricata (Turcz.) Schischk. (SD, syn. Ledebouriella divaricata (Turcz.); Umbelliferae), Siler, a perennial herb of the carrot family, is also known as Fang Feng in traditional Chinese herbal medicine. It is a herbal ingredient included in many polyherb formulae. This study investigated the in vitro anti-proliferative, antioxidant and anti-inflammatory activities of the SD extract (1 g/10 ml 70% ethanol). IC50 (50% inhibition) is estimated at 1/300, 1/1400, 1/250 and 1/600 dilutions, for the K562, HL60, MCF7 and MDA-MB-468 cell lines, respectively. The combination of non-cytotoxic concentrations of SD with chemotherapeutic drugs such as camptothecin or paclitaxel showed additive anti-proliferative effects on K562, HL60 and MCF7 cells, and antagonistic effects on MDA-MB-468 cells. At a dilution of 1/2000, SD induced a differentiation of 17.5+/-2.5% in HL60 cells along the granulocyte lineage compared to 2.8+/-0.8% in the untreated controls, but not along the monocyte/macrophage lineage. At non-cytotoxic 1/10000, 1/5000 and 1/2000 dilutions, the SD extract did not affect nitric oxide (NO) production by non-stimulated RAW 264.7 cells, but dose-dependently and significantly reduced NO production by lipopolysaccharide (LPS)-activated RAW 264.7 cells. RT-PCR analyses showed that SD at a dilution of 1/2000 did not affect TNFalpha, IL-1 beta, iNOS and COX-2 mRNA expression in RAW 264.7 cells compared to the unstimulated controls, but significantly reduced (p<0.05) iNOS and its mRNA expression in LPS-activated cells. It is concluded that the SD ethanol extract possesses strong anti-proliferative properties against several human tumor cell lines, a mild granulocyte differentiation inducing property on HL60 cells, and potent antioxidant, anti-inflammatory and protective properties on LPS-activated RAW 264.7 cells. Further research is required in order to identify the major ingredients present in the Saposhnikovia divaricata root and rhizome showing the observed activities.
authors.affiliation: Child and Family Research Institute, Vancouver, British Columbia V6H 3V4, Canada. jtai@interchange.ubc.ca
authors.forename: Joseph
authors.initials: J
authors.lastname: Tai
authors.forename: Susan
authors.initials: S
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2