title: Calycosin and formononetin from astragalus root enhance dimethylarginine dimethylaminohydrolase 2 and nitric oxide synthase expressions in Madin Darby Canine Kidney II cells.
abstract: Nitric oxide (NO) is a crucial vasodilator produced by nitric oxide synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor and mainly catabolized by dimethylarginine dimethylaminohydrolase (DDAH). As we reported, the antihypertensive effect of shichimotsukokato (SKT), a formula of Japanese traditional kampo medicine consisting of 7 crude drugs, in 5/6 nephrectomized rats, is mediated by the DDAH-ADMA-NO pathway. Our present study aimed to explore the effective compounds of SKT using Madin Darby Canine Kidney (MDCK) II cells. We isolated two isoflavones, calycosin and formononetin from astragalus root, one of the components of SKT, which can promote DDAH2 protein and mRNA expressions in MDCK II cells. The neuronal NOS levels were also upregulated by the treatment of calycosin and formononetin. These results suggest that calycosin and formononetin could be the active ingredients of astragalus root and SKT that cause antihypertensive effects. The increased levels of DDAH2 and NOS may enhance NO production, decrease ADMA level and improve endothelial and cardiovascular dysfunction.
authors: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
authors: Fan
authors: F
authors: Bai
authors: Toshiaki
authors: T
authors: Makino
authors: Keiko
authors: K
authors: Kono
authors: Akito
authors: A
authors: Nagatsu
authors: Takahiko
authors: T
authors: Ono
authors: Hajime
authors: H
authors: Mizukami
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D027883:Astragalus Plant / Q000737:chemistry*; D004285:Dogs; D007529:Isoflavones / Q000494:pharmacology*; D061985:Madin Darby Canine Kidney Cells; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D007529:Isoflavones; D010936:Plant Extracts; C116087:shichimotsu-koka-to; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; C007768:formononetin; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase