Isoamericanoic Acid B from Acer tegmentosum as a Potential Phytoestrogen

Abstract

Phytoestrogens derived from plants have attracted the attention of the general public and the medical community due to their potentially beneficial role in relieving menopausal symptoms. The deciduous tree Acer tegmentosum Maxim (Aceraceae) has long been utilized in Korean folk medicine to alleviate many physiological disorders, including abscesses, surgical bleeding, and liver diseases. In order to explore structurally and/or biologically new constituents from Korean medicinal plants, a comprehensive phytochemical study was carried out on the bark of A. tegmentosum. One new phenolic compound with a 1,4-benzodioxane scaffold, isoamericanoic acid B (1), as well as with nine known phenolic compounds (2–10), were successfully isolated from the aqueous extracts of the bark of A. tegmentosum. A detailed analysis using 1D and 2D NMR spectroscopy, electronic circular dichroism (ECD) spectral data, and LC/MS afforded the unambiguous structural determination of all isolated compounds, including the new compound 1. In addition, compounds 2, 4, 5, and 9 were isolated and identified from the bark of A. tegmentosum for the first time. All isolated compounds were tested for their estrogenic activities using an MCF-7 BUS cell proliferation assay, which revealed that compounds 1, 2, and 10 showed moderate estrogenic activity. To study the mechanism of this estrogenic effect, a docking simulation of compound 1, which showed the best estrogenic activity, was conducted with estrogen receptor (ER) -α and ER-β, which revealed that it interacts with the key residues of ER-α and ER-β. In addition, compound 1 had slightly higher affinity for ER-β than ER-α in the calculated Gibbs free energy for 1:ER-α and 1:ER-β. Thus, the present experimental evidence demonstrated that active compound 1 from A. tegmentosum could be a promising phytoestrogen for the development of natural estrogen supplements.

Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis

“…In a previous study on this natural source, anti-inflammatory, anti-obesity, anti-photoaging, and antihyperglycemic activities were reported from crude extracts of C. walteri [7,8]. As part of our ongoing endeavor to find structurally and/or biologically novel natural products from a variety of natural resources [9,10,11,12,13], we found that MeOH extract of stem and stem bark of C. walteri showed considerable cytotoxicity against several cancer cell lines, including A549, SK-OV-3, and SK-MEL-2 [14], which led to the phytochemical investigation on the MeOH extract to identify the bioactive compounds responsible for the observed effects. Chemical analysis of the MeOH extract by our group led to the identification of cytotoxic compounds, including δ -valerolactones, tirucallane, and lupane triterpenoids [14,15].…”

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons

“…Previous phytochemical investigations of A. tegmentosum have revealed that its extracts contain various pharmacological metabolites, including flavonoids, lignans, and phenolic compounds [15,16]. In a recent study, we successfully isolated and identified a new phenolic compound, isoamericanoic acid B, and nine phenolic compounds from the bark of A. tegmentosum [17]. Intriguingly, we observed that a coumarin glycoside, fraxin, isolated from A. tegmentosum , displayed potent hepatoprotective effects via the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzyme system [18].…”

Fridamycin A, a Microbial Natural Product, Stimulates Glucose Uptake without Inducing Adipogenesis

“…M39 [13]. As part of our continuing objective to discover biologically therapeutic natural products [14,15,16,17,18], we focused on the termite-associated Actinomadura sp. RB99, isolated from the fungus-growing termite Macrotermes natalensis .…”