Sesamin Metabolites Induce an Endothelial Nitric Oxide-Dependent Vasorelaxation through Their Antioxidative Property-Independent Mechanisms: Possible Involvement of the Metabolites in the Antihypertensive Effect of Sesamin

Abstract

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis (3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radicalscavenging activities against the xanthine/xanthine oxidaseinduced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m-and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthaseNeither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NO-ARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.Endothelium-derived nitric oxide (NO) is a potent vasodilator. NO synthesized by endothelial NO synthase (eNOS) diffuses into the smooth muscle cells and stimulates the soluble guanylate cyclase (sGC), leading to increased cGMP production and smooth muscle relaxation (Moncada and Higgs, 1993). Several findings have suggested that excess superoxide (O 2 . ) produced in vascular cells interacts with NO, induces the abnormality of vascular tonus regulation, and results in the development of hypertension (Rajagopalan et al., 1996;Jung et al., 2004). In addition, Laursen et al. (1997) reported that both the development of hypertension and the altered endothelium-dependent vascular relaxation were improved by the treatment with membrane-targeted forms of superoxide dismutase in angiotensin II-induced hypertensive rats. Thus, it seems likely that the suppression of oxidative stress improves the NO bioavailability and prevents the development of hypertension and end-organ damage (Zhou et al., 2003;Schmieder, 2005). Sesamin ( Fig. 1) is one of the lignans found in high concentration in sesame seeds and oil. We have obtained evidence that dietary sesamin efficiently suppressed the development and maintenance of hypertension in deoxycorticoArticle, publication date, and citation information can be found at

Antioxidant and vasorelaxant activities of theTurraeanthus africanusmethanol extract

“…Our preliminary test showed that this compound induced a relaxation on aorta precontracted with noradrenaline (results not shown). This finding has also been reported by Nakano et al (2006), who suggested that the enhancement of endotheliumdependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin. Moreover, it has been demonstrated that T. africanus contains some terpenoid compounds (Kimbu et al, 1984;Ayafor et al, 1994).…”

“…A recent study demonstrated that sesamin and its metabolites had in vitro radical scavenging activities (Nakano et al, 2006). This compound (sesamin, a lignan) and terpenoids present in T. africanus extract may be responsible in part for its antioxidative activity.…”

Antihypertensive Effects of Sesamin in Humans

“…It is also thought that sesamin may improve hypertension by its ability to induce nitric oxide and inhibit endothelin-1 production from human umbilical vein endothelial cells ( 25 ). Furthermore, it is suggested that the metabolic products had potent radical-scavenging activities in vitro ( 2 ) and that the enhancement of endotheliumdependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin ( 31 ). Taken together, it is considered that sesamin might involve several pathways in its hypotensive effects ( 26 ).…”

Development of Health Foods from Oilseed Cakes

“…Lignans are natural antioxidants present in sesame oil. Lignans have health benefits, including antioxidant activity [25], anticarcinogenic [26], blood pressure-lowering [27] and serum lipid-lowering [28]. Table 3 depicts the data for the moisture, fat, protein, carbohydrates, ash, crude fiber, oryzanol, and lignans.…”