Constituents of Laurus nobilis L. inhibit recombinant human lanosterol synthase

Abstract

Extracts from 37 kinds of foods and foodstuffs were tested for inhibitory activity against recombinant human lanosterol synthase. Among them, extracts from five samples showed significant inhibition. Potent activity (55%) was found in 95% ethanol extract of Laurus nobilis L. Therefore, large-scale methanol extraction of the plant was carried out, and the constituents were separated by partition and fractionation by silica gel chromatography and HPLC. Four flavonoids, kaemperol 3-O-[2¢¢,4¢¢-O-di-E-p-coumaroyla-L-pyranorhamnoside] (1); 3,3¢,4¢,5,6,7,8-heptamethoxyflavone (2); 3¢, 4¢,5,6,7,8-hexamethoxyflavone (nobiletin) (3); and 4¢,5,6,7,8-pentamethoxyflavone (tangeretin) (4); and six sesquiterpens, eremanthine (5), dehydrocostus lactone (6), costunolide (7), zaluzanin C (8), zaluzanin D (9) and reynosin (10) were isolated. Eremanthine (5) showed the most potent activity, 70% inhibition, at the concentration of 500 lM.

Phytochemicals and Biological Activities of Laurel Tree (Laurus nobilis)

“…Sesquiterpenoids: It was reported in 1971 [35] the isolation from laurel roots of the first sesquiterpene lactone: laurenobiolide (11). Since then, ten more lactones with a germacrane skeleton (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) have been isolated from roots [36,37], fruits [38,39] and leaves [37,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] (Figure 4). Dehydrocostus lactone (22), zaluzanin D (24) and eremanthin (26) were the first lactones isolated from laurel with a guaiane skeleton [38], and santamarine (28) and reynosin (31) the first ones with a eudesmane skeleton [40].…”

“…In addition to this group of sesquiterpene lactones, which represent a characteristic group of phytochemicals in L. nobilis, other sesquiterpenoids have been isolated from methanol or chloroform extracts of laurel fruits [38,39] and leaves [41][42][43][44]47,[52][53][54] such as compounds 50-72 ( Figure 4). Eleven of all the sesquiterpenoids found in laurel tree were new natural products (25,27,29,49,50,52,58,(65)(66)(67)72) when isolated.…”

Chemical Inhibition of Sterol Biosynthesis

“…Several studies have screened and prioritized potential LSS inhibitory compounds, including extracts from foods, in different model systems [117][118][119]. These include the experimental compound BIBB-515, which induced 24(S),25 epoxycholesterol and resulted in decreased human rhinovirus replication [120] and sensitized chronic lymphocytic leukemia cells to chemotherapeutics [121].…”

“…Due to their focus on microorganisms, many of the studies assessing LSS inhibition are solely in vitro analyses. Although many of these studies suggested LSS inhibition, it should be noted that the concentrations of chemical administered were widely variable: from 500 µM eremanthine [119] to screening several compounds at 20-50 µM [118] and 0.25-0.5 µM diacylglycerols [125].…”

Regulatory science of natural products

“…We found its potent inhibitory activity against lanosterol synthase and isolated its constituents to obtain four flavonols and six sesquiterpenes. Of these, eight compounds had moderate inhibitory activity, and eremanthine, a sesquiterpene, was the most potent [ 49 ]. In addition, we screened Brazilian herbs for inhibitory activity against lanosterol synthase, and Paffia paniculata , Trichilia catigua , and Maytenus ilicifolia showed the most potent activity [ 50 ].…”