IDENTIFICATION AND USE: Marmesin is a furocoumarin and a component of Afraegle paniculata used to treat gut disturbances and Azadirachta indica used as an antimalarial in Nigeria. HUMAN STUDIES: Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin beta1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. It was observed that marmesin exhibited an IC50 value of 40 uM in human leukemia cell line U937 and exerted its cytotoxic effects in a dose-dependent manner (IC50 value is a measurement of cytotoxicity). However, the cytotoxic effects of marmesin were comparatively lower for the normal human monocytes as evident from the IC50 of 125 uM. It was observed that marmesin treatment triggered upregulation of Bax and downregulation of Bcl-2 causing significant increase in the Bax/Bcl-2 ratio, marmesin could also induce ROS mediated alterations in mitochondrial membrane potential. Additionally, marmesin induced G2/M cell cycle arrest and significantly inhibited cell migration potential of leukemia cells. ANIMAL STUDIES: Marmesin was screened on 6 Ames tester strains (TA92, TA94, TA97, TA98, TA100, TA102). Marmesin was mutagenic in all tester strains except TA94 and TA102. Mutagenicity was highest in TA98 and TA100. In the in vitro tests in mammalian cells, marmesin was relatively more cytotoxic than other furocoumarins studied, with a 50% lethal dose of less than 0.5 ug/mL, but it was also found to be not as mutagenic or potentially carcinogenic as other furocoumarins.
Marmesin was isolated from the medicinal plant, Afraegle paniculata. Its cytotoxicity and mutagenicity in Chinese hamster V79 cells when sensitized to near ultraviolet (NUV) and long wavelength ultraviolet light or black light (BL) were assayed. Marmesin was extremely cytotoxic in the dark. This cytotoxicity was photoenhanced in NUV and BL; the photoenhanced lethality being higher in NUV than in BL. The LD50 of marmesin under NUV and BL photosensitization were 0.002 uM and (0.012 uM), respectively. In the absence of NUV and BL, marmesin's LD50 was 0.013 uM.NUV and BL without marmesin were not significantly cytotoxic at the fluence rates of 0.29 W/sq m and 4.2 W/sq m, respectively, for up to 20 min. In contrast to the observed high cytotoxicity of marmesin, its mutagenicity at the HGPRT locus (Asub(z)Gsup(r)) was weak. The implication of this result in the high incidence of skin cancer in Nigeria in which A. paniculata is used as a medicinal plant is discussed.
Mutation by aflatoxin B1 (AFB1), imperatorin, marmesin, chalepin, and 8-methoxypsoralen (MOP), with and without black light (BL; long-wavelength ultraviolet light) activation, was determined at the hypoxanthine-guanine phosphoribosyltransferase locus (8-azaguanine resistance) in Chinese hamster V79 cells and at the ouabain locus in mouse C3H/1OT1/2 cells. Transformation by these furocoumarins under the same activation conditions was also investigated in C3H/1OT1/2 cells. In V79 cells, AFB1 induced a 4-fold maximum mutation frequency over controls under BL activation at a concentration of 5 ug/mL; marmesin induced a 2-fold increased mutation frequency at 1.5 ug/mL; MOP induced a 19-fold increase at 10 ug/mL; chalepin induced a 3-fold increase at 5 ug/mL; and imperatorin induced a 20-fold increase at 10 ug/mL. Essentially no mutation was observed at the ouabain-resistant (Ouar) locus in C3H/1OT1/2 cells with any of these compounds. In the transformation assays, type II and type III foci were observed at a 1 ug/mL addition of AFB1 with or without BL activation; while with MOP and imperatorin, these types of foci were observed only with BL activation. Marmesin, although relatively more cytotoxic than the other furocoumarins studied, with a 50% lethal dose of less than 0.5 ug/mL, was not as mutagenic or potentially carcinogenic as were AFB1, imperatorin, or MOP with BL activation. These furocoumarins are considered to be involved in the etiology of the high incidence of skin cancer in Nigeria. Our experiments reinforce that concept and suggest that exposure to these furocoumarins may constitute a real carcinogenic hazard.
OBJECTIVES: The aim of this study was to evaluate the hepatoprotective potential of a methanolic extract and of marmesin isolated from the root bark of Feronia limonia. METHODS: Activity levels of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), cell viability and cell death were evaluated in HepG2 cells (human liver hepatoma cells) treated with CCl4 in the presence or absence of F. limonia extract or marmesin. Plasma activity levels of AST, ALT, bilirubin, alkaline phosphatase, protein, hepatic antioxidants, lipid peroxidation and histopathological evaluations were carried out in rats treated with CCl4 alone or co-supplemented with F. limonia extract /200 or 400 mg/kg once daily for 7 days/ or marmesin /50 or 100 mg/kg once daily for 7 days/ in a dose-dependent manner. KEY FINDINGS: In-vitro co-supplementation of F. limonia methanolic extract or marmesin significantly minimized alteration in levels of AST and ALT and improved cell viability. Oral administration of F. limonia methanolic extract or marmesin significantly prevented CCl4-induced elevation in the plasma markers of hepatic damage and hepatic lipid peroxidation and a decrease in hepatic antioxidants. In-vivo hepatoprotective potential of F. limonia methanolic extract and marmesin was evident from the minimal alterations in the histoarchitecture of liver. ...
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
S-(+)-Marmesin ((+)-marmesin) shows affinity at the recombinant psoralen synthase, with a K
m
of 1.5 ± 0.5 μM, exceeding the substrate affinities of other enzymes of the CYP71 subfamily involved in plant secondary metabolism. S-(+)-Marmesin ((+)-marmesin) shows COX-2/5-LOX dual inhibitory activity.
Glycosides from the Methanol Extract of<i>Notopterygium incisum</i>
作者：Mei You、Juan Xiong、Yun Zhao、Lei Cao、Shi-Biao Wu、Gang Xia、Jin-Feng Hu
DOI：10.1055/s-0031-1279995
日期：2011.11
Five new (1–5) and twelve known (6–17) different types of glycosides together with a known sesquiterpene triol (18) were isolated from the methanol extract of the rhizomes of Notopterygium incisum. The new structures were elucidated by means of spectroscopic and chemical methods to be pregn-5-en-3β,20(S)-diol-3-O-bis-β-D-glucopyranosyl-(l → 2,1 → 6)-β-D-glucopyranoside (1), oleuropeic aldehyde 8-O-β-D-glucopyranoside (2), 2(R)-(3,4-dimethoxyphenyl)-propane-1,3-diol-1-O-β-D-glucopyranoside (3), eudesman-3α,4α,11-triol-11-O-β-D-glucopyranoside (4), and marmesin-11-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (5). The absolute configuration of the aglycone in compound 3 was assigned by application of Klyne's rule.
The enantioselectivetotalsyntheses of (+)-decursin (1) and related natural dihydropyranocoumarins (−)-prantschimgin (3), (+)-decursinol (4), and (+)-marmesin (5) were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. Catalytic asymmetric epoxidation of the enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O-i-Pr)3
首次实现（+）-地精（1）和相关天然二氢吡喃香豆素（-）-花木素（3），（+）-地精醇（4）和（+）-marmesin（5）的对映选择性合成使用烯酮的催化不对称环氧化作为关键步骤。由La（O- i- Pr）3，BINOL和Ph 3 As generatedO以1：1：1的比例生成的新型多功能不对称催化剂可有效促进烯酮的催化不对称环氧化，以94％的收率得到环氧化物和96％ee，将其重结晶得到光学纯的环氧化物。转换为通用关键中间体（-）-二十二烷醇（7），所有天然的二氢吡喃香豆素都是通过钯催化的分子内C-O偶联反应合成的。基于X射线分析，激光解吸/电离飞行时间质谱，动力学研究和不对称扩增研究，还描述了烯类催化不对称环氧化的可能反应机理。
Enantioselective total syntheses of novel PKC activator (+)-decursin and its derivatives using catalytic asymmetric epoxidation of an enone
The catalytic asymmetric totalsyntheses of (+)-decursin and three related natural products, (+)-decursinol, (−)-prantschimgin and (+)-marmesin, were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. The catalytic asymmetric epoxidation of enone was found to be promoted effectively by novel multifunctional asymmetric catalyst generated from La(O-i-Pr)3
Asymmetric Synthesis of 2-Substituted Dihydrobenzofurans and 3-Hydroxydihydrobenzopyrans through the Enantioselective Epoxidation of O-Silyl-Protected ortho-Allylphenols
The Shi‐type epoxidation of O‐tert‐butyldiphenylsilyl (TBDPS) protected o‐allylphenols serves as an efficient strategy to construct the dihydrobenzofurans and dihydrobenzopyrans in up to 97% ee. This methodology led to the enantioselective synthesis of (+)‐marmesin, (−)‐(3′R)‐decursinol, and (+)‐lomatin.
Accumulation of coumarins in elicitor-treated cell suspension cultures of Ammi majus
作者：Daria Hamerski、Ross C. Beier、Richard E. Kneusel、Ulrich Matern、Karl Himmelspacht
DOI：10.1016/0031-9422(90)85418-f
日期：1990.1
Heterotrophic cellsuspensioncultures were initiated from hypocotyls of young Ammimajus L. seedlings. When these cultures were propagated continuously in the dark, they produced only traces of the coumarin umbelliferone. Upon addition of fungal cell wall fractions, i.e. a skieroglucan or an elicitor from either Phytophthora megasperma f. sp. glycinea or Alternaria carthami , the cells excreted large
摘要 异养细胞悬浮培养是从幼年 Ammi majus L. 幼苗的下胚轴开始的。当这些培养物在黑暗中连续繁殖时，它们只产生痕量的香豆素伞形酮。在添加真菌细胞壁部分后，即来自巨型疫霉 f. 的一种skieroglucan 或诱导物。sp. 甘氨酸或红花链孢菌，细胞分泌大量伞形酮，此外还有异匹匹林、( S )-marmesin、( R )-ammirin、伞形酮-[3'-methyl-buta-1 t .3-dien-1'-yl ]-醚和伞形酮-[3'-羟甲基-1 t.-丁烯-1'-基]-醚。最后两种化合物是新化合物，似乎源自 7-O-异戊二烯酮，一种已从其他植物中鉴定出的香豆素。疫霉属诱导剂是最有效的香豆素积累诱导剂。当已引发 3 小时的培养物用 1-[U- 14 C]苯丙氨酸脉冲 7 小时时，提取物中的所有香豆素和另外一种仍未鉴定的化合物都被有效标记。我们的结果表明，A. majus 细胞
