A pterocarpan and two isoflavans from alfalfa

doi:10.1016/0031-9422(91)83483-2

Phytochemistry

Volume 30, Issue 12, 1991, Pages 4147-4149

https://doi.org/10.1016/0031-9422(91)83483-2 Get rights and content

Abstract

(−)6aR,11aR-Dihydro-3-hydroxy-9,10-dimethoxy-6H-benzofuro[3,2c] [1]-benzopyran (10-methoxymedicarpin), (+)-(2,3,4,-trimethoxyphenyl)-2,3-dihydro-7-hydroxy-4H-1-benzopyran (7-hydroxy-2′,3′,4′-trimethoxyisoflavan) and (+)-(2,3,4-trimethoxy-5-hydroxyphenyl)-2,3-dihydro-7-hydroxy-4H-1-benzopyran (7,5′-dihydroxy-2′,3′,4′-trimethoxyisoflavan) were isolated for the first time from dried Medicago sativa hay. Structural assignments were based on ¹H NMR and mass spectra, X-ray crystallography, and optical rotations.

References (11)

J.L. Ingham et al.
Phytochemistry
(1979)
K.G.R. Pachler et al.
Tetrahedron
(1967)
N.W. Preston
Phytochemistry
(1977)
J.L. Ingham et al.
Phytochemistry
(1980)
K. Kurosawa et al.
Phytochemistry
(1978)

There are more references available in the full text version of this article.

Cited by (22)

Identification of triterpenoid saponin inhibitors of interleukin (IL)-33 signaling from the roots of Astragalus membranaceus
2023, Journal of Functional Foods
Interleukin-33 (IL-33) is a cytokine produced by epithelial cells that plays a key role in immune-mediated diseases, such as asthma, atopic dermatitis, and rheumatoid arthritis. In our research on the anti-allergic effects of Korean medicinal plants, we found that an ethanol extract from the roots of Astragalus membranaceus exhibited a significant IL-33 inhibitory effect. Using various chromatographic separation methods, eight compounds (1–8) were isolated from the extract. The inhibitory effect of the isolated compounds on the IL-33 protein was also investigated by ELISA. Compounds 1, 5, and 6 showed significant IL-33 inhibitory activity. Moreover, molecular docking and molecular dynamic simulations of two active compounds supported the in vitro results. Taken together, these results suggest that triterpenoid saponins from A. membranaceus roots might be useful for their pharmacological anti-allergic effects.
Nigerian propolis: chemical composition, antioxidant activity and α-amylase and α-glucosidase inhibition
2021, Natural Product Research
Propolis is an attractive natural ingredient to design health products due to its pharmacological effects. Our chemical investigation of a polar extract of Nigerian propolis (NP) led the isolation and identification of five isoflavonoids (1-4, 6), one diarylpropane (5) and one prenylated flavanone (7) by the combination of chromatographic and spectroscopic techniques. Compounds 1, 4 and 7 were found to be the main markers in NP (8.0, 5.0 and 4.0 mg/g of dry extract, respectively). Moreover, NP and its phenolic constituents exhibited in vitro free radical scavenging activity together with a promising antidiabetic effect against α-amylase and α-glucosidase enzymes. Finally, NP showed also a moderate inhibition of Helicobacter pylori growth. These results suggested that NP could be a good candidate in nutraceuticals and food products.
Profiling the metabolites of astrapterocarpan in rat hepatic 9000g supernatant
2019, Chinese Journal of Natural Medicines
Astrapterocarpan (AP) is a bioactive constituent of Astragali Radix and was selected as a model compound for investigating the in vitro metabolism of pterocarpans in this study. Its in vitro metabolism was conducted by incubation with rat hepatic 9000g supernatant (S9) in the presence of an NADPH-generating system. At first, four compounds were isolated and their structures were elucidated as 6a-hydroxy-AP (M1), astrametabolin I [M2, 1a-hydroxy-9, 10-dimethoxy-pterocarp-1(2), 4-diene-3-one], 9-demethyl-AP (M3, nissolin) and 4-methoxy-astraisoflavan (M4, 7, 2′dihydroxy-4, 3′, 4′-trimethoxy-isoflavan) on the basis of NMR data, respectively. Among them, M1, M2 and M4 were new compounds. Next, the metabolite profile of AP in rat hepatic S9 was obtained via HPLC-DAD-ESI-IT-TOF-MSⁿ, and 40 new metabolites were tentatively identified. These newly identified metabolites included 9 monohydroxylated metabolites, 1 demethylated metabolite, 7 demethylated and monohydroxylated metabolites, 4 dihydroxylated metabolites, 1 hydration metabolite, 1 didemethylated metabolite, 2 glucosylated metabolites, 1 monohydroxylated and dehydrogenated metabolite, 2 monohydroxylated and demethylated and dehydrogenated metabolites, 2 dimerized metabolites, 3 dimerized and monohydroxylated metabolites, 2 dimerized and didemethylated metabolites, and 5 dimerized and demethylated metabolites. Finally, the major metabolic reactions of AP in rat hepatic S9 were summarized and found to be hydroxylation, demethylation, dimerization, hydration, and dehydrogenation. More importantly, the biotransformation from AP to M2 and the dimerization of AP by incubation with hepatic S9 were reported for the first time. In conclusion, this is the first report on the metabolism of a pure pterocarpan in animal tissues, and these findings will provide a solid basis for further studies on the metabolism of other pterocarpans.
Bioactive constituents from Medicago sativa L. with antioxidant, neuroprotective and acetylcholinesterase inhibitory activities
2018, Journal of Functional Foods
Citation Excerpt :
The 13C NMR data (Table 1) showed 24 carbon signals, classified by the HSQC and HMBC spectra, including 15 characteristic isoflavan carbons (δC 156.6, 154.4, 147.4, 146.4, 145.5, 141.7, 130.0, 129.1, 112.6, 109.1, 108.1, 102.6, 69.3, 31.4 and 31.1), three methoxy carbons (δC 60.9, 60.8 and 60.8), and six sugar carbon signals (δC 100.6, 77.1, 77.0, 73.3, 70.0, and 61.3). The correlations (Fig. 2) of H-2 (δH 4.10, 3.96), H-3 (δH 3.29, 2.87)/C-1′ (δC 129.1), 2′-OCH3 (δH 3.73)/C-2′ (δC 145.5), 3′-OCH3 (δH 3.82)/C-3′ (δC 146.4) and 4′-OCH3 (δH 3.79)/C-4′ (δC 141.7), as well as comparation with references, indicated that the three methoxy groups were assigned to C-2′, 3′, 4′ in ring B (Spencer, Jones, Plattner, Barnekow, & Brinena, 1991). Acid hydrolysis of compound 1 followed by GC analysis and TLC comparisons with authentic D-Glucose, confirmed the presence of D-Glucose in compound 1 (Ma et al., 2004; Subarnas, Oshima, & Hikino, 1991).
Medicago sativa L. is an important source of functional foods and supplements, which can improve human health. The present work was carried out to search for potential antioxidants from M. sativa to treat neurodegeneration. Four new isoflavane glycosides (1–4) were isolated from M. sativa, along with seven known compounds (5–11). Their structures including absolute configurations were elucidated by multi-spectroscopic data analyses, chemical methods, and quantum chemical ECD calculations. The compounds (1–11) were tested for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) and Ferric reducing antioxidant power (FRAP) assays. All the isolated compounds displayed different degrees of antioxidant effects. Meanwhile, some isolates also possessed acetylcholinesterase (AChE) inhibitory activities. A possible mechanism of interaction between the active compounds and AChE was also investigated by molecular docking studies. Furthermore, compounds (1–6 and 10–11) exhibited potent neuroprotective effects against H₂O₂-induced cellular damage in human neuroblastoma SH-SY5Y cells.
Medicarpin and millepurpan, two flavonoids isolated from Medicago sativa, induce apoptosis and overcome multidrug resistance in leukemia P388 cells
2015, Phytomedicine
Citation Excerpt :
Among them, the two isoflavonoids medicarpin and millepurpan were identified as potential antiproliferative agents on several tumor cell lines. Medicarpin, a pterocarpan, and millepurpan, an isoflavone, were previously isolated from alfalfa (Spencer et al. 1991), in which they are involved in plant defense. Little data exist regarding the biological effects of millepurpan.
High consumption of flavonoids has been associated with a decrease risk of cancer. Alfalfa (Medicago sativa) leaves have been widely used in traditional medicine and is currently used as a dietary supplement because of their high nutrient content. We previously reported the cytotoxic activity of alfalfa leaf extracts against several sensitive and multidrug resistant tumor cell lines.
We aimed to determine whether medicarpin and millepurpan, two isoflavonoids isolated from alfalfa leaves, may have pro-apoptotic effects against drug-sensitive (P388) and multidrug resistant P388 leukemia cells (P388/DOX).
Cells were incubated with medicarpin or millepurpan for the appropriate time. Cell viability was assessed by the MTT assay. DNA fragmentation was analyzed by agarose gel electrophoresis. Cell cycle analysis was realized by flow cytometry technics. Caspases 3 and 9 activities were measured using Promega caspACE assay kits. Proteins and genes expression were visualized respectively by western-blot using specific antibodies and RT-PCR assay.
P-glycoprotein-expressing P388/DOX cells did not show resistance to medicarpin (IC₅₀ ≈ 90 µM for P388 and P388/DOX cells) and millepurpan (IC₅₀ = 54 µM and 69 µM for P388 and P388/DOX cells, respectively). Treatment with medicarpin or millepurpan triggered apoptosis in sensitive as well as multidrug resistant P388 cells. These effects were mediated through the mitochondrial pathway by modifying the balance pro/anti-apoptotic proteins. While 3 µM doxorubicin alone could not induce cell death in P388/DOX cells, concomitant treatment with doxorubicin and subtoxic concentration of medicarpin or millepurpan restored the pro-apoptotic cascade. Each compound increased sensitivity of P388/DOX cells to doxorubicin whereas they had no effect in sensitive P388 cells. Vinblastine cytotoxicity was also enhanced in P388/DOX cells (IC₅₀ = 210 nM to 23 and 25 nM with medicarpin and millepurpan, respectively). This improved sensitivity was mediated by an increased uptake of doxorubicin in P388/DOX cells expressing P-gp. P-gp expression was not altered by exposure to medicarpin and millepurpan.
These data indicate that medicarpin and millepurpan possess pro-apoptotic properties and potentiate the cytotoxicity of chemotherapy drugs in multidrug resistant P388 leukemia cells by modulating P-gp-mediated efflux of drugs. These flavonoids may be used as chemopreventive agents or as sensitizer to enhance cytotoxicity of chemotherapy drugs in multidrug resistant cancer cells.
Death receptor 5 targeting activity-guided isolation of isoflavones from Millettia brandisiana and Ardisia colorata and evaluation of ability to induce TRAIL-mediated apoptosis
2009, Bioorganic and Medicinal Chemistry
Death receptor 5 (DR5) is an apoptosis-inducing membrane receptor for TNF-related apoptosis-inducing ligand (TRAIL). On screening for compounds that enhance DR5 expression using a luciferase assay with DLD-1/SacI, we previously identified 4′-demethyltoxicarol isoflavone (1) isolated from the leaves of Millettia brandisiana. In this study, we revealed that 1 sensitized TRAIL-resistant human gastric adenocarcinoma (AGS) cells to TRAIL-induced apoptosis by up-regulating the expression of DR5. 1 induced DR5 expression at both the mRNA and protein level. A human recombinant DR5/Fc chimera remarkably inhibited 1-induced apoptosis. These results suggest that the enhancement of DR5 expression by 1 was critical to the cell death. Furthermore, a MeOH extract of the bark of Ardisia colorata markedly enhanced DR5 activity in this screening system. Bioassay-guided fractionation of A. colorata led to the isolation and identification of a new isoflavone, coloratanin A (3), together with ten known compounds. The chemical structure of the new compound was elucidated on the basis of a spectroscopic analysis.

View all citing articles on Scopus

¹: Present address: DowElano, Building 9001, P.O. Box 1706, Midland, MI 48641, U.S.A.

View full text

A pterocarpan and two isoflavans from alfalfa

Abstract

Phytochemistry

Tetrahedron

Phytochemistry

Phytochemistry

Phytochemistry