Neolignans from Aristolochia fordiana Prevent Oxidative Stress-Induced Neuronal Death through Maintaining the Nrf2/HO-1 Pathway in HT22 Cells

Abstract

Bioassay-guided fractionation of the ethanolic extract of the stems of Aristolochia fordiana led to the isolation of six new dihydrobenzofuran neolignans (1-3 and 7-9), three new 2-aryldihydrobenzofurans (4-6), a new 8-O-4' neolignan (10), and 14 known analogues (11-24). The structures of compounds 1-10 were established by spectroscopic methods, and their absolute configurations were determined by analyses of the specific rotation and electronic circular dichroism data. The neuroprotective effects of compounds 1-24 against glutamate-induced cell death were tested in hippocampal neuronal cell line HT22. Compounds 17 and 20-24 exhibited moderate neuroprotective activity by increasing the endogenous antioxidant defense system. In addition, the neolignans activated the Nrf2 (nuclear factor E2-related factor 2) pathway, resulting in the increase of the expression of endogenous antioxidant protein HO-1 (heme oxygenase-1). The active compounds also preserved the levels of antiapoptotic protein Bcl-2 (B cell lymphoma/leukemia-2), which was decreased by glutamate. Collectively, these results suggested that the active neolignans protect neurons against glutamate-induced cell death through maintaining the Nrf2/HO-1 signaling pathway as well as preserving the Bcl-2 protein and might be promising novel beneficial agents for oxidative stress-associated diseases.

A New Neolignan, and the Cytotoxic and Anti-HIV-1 Activities of Constituents from the Roots of Dasymaschalon sootepense

“…Compound 4 exhibited a positive optical rotation; [] 25 D 103.9 (c 0.30, MeOH), which is in agreement in sign with that of 5a {[] 20 D 111 (c 0.1, MeOH)}, while the known compound 6b [15] (the enantiomer of 5a) showed a negative optical rotation; [] 20 D 108 (c 0.1, MeOH). Additionally, compound 4 showed a similar CD curve to that of 5a (positive Cotton effect at 310 nm and 274 nm, negative Cotton effect at 234 nm for 4; positive Cotton effect at 274 nm, negative Cotton effect at 235 nm for 5a), but opposite to that of 6b (negative Cotton effect at 274 nm, positive Cotton effect at 234 nm for 6b) [15]. Thus, the structure of compound 4 was assigned as (+)-(2S,3S)-2,3-dihydro-2-(4hydroxyphenyl)-3-methylbenzofuran-5-carbaldehyde or (+)decurrenal.…”

“…The bioactive compounds from the ethyl acetate extract of D. sootepense roots were separated and purified using chromatographic and crystallization techniques to yield one new dihydrobenzofuran neolignan (5) and eleven known compounds (1-4, and 6-12). The 1 H and 13 C NMR spectral data of the known compounds, including (2S,3S)-2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-methyl-5-(E)-propenyl-benzofuran (1) [11,12], (+)-conocarpan (2) [13,14], (2S,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-methyl-5-(E)propenylbenzofu-ran (3) [15], benzyl benzoate (7) [16], dasytrichone (8) [5], 3,5,7,3,5-pentahydroxyflavane (9) [17], dicentrinone (10) [18], ()-sinactine (11) [19] and discretine (12) [20] were directly compared with those reported in the literature. Compounds 4 [21,22] and 6 [23] were only partially characterized in the previous reports.…”

“…In this communication, the absolute configuration of 4 was determined as 2S,3S upon direct comparison of its specific optical rotation value and circular dichroism (CD) properties ( Figure 2) with those of (2S,3S)-2,3-dihydro-2-(4-methoxyphenyl)-3-methylbenzofuran-5carbaldehyde (5a) [15]. Compound 4 exhibited a positive optical rotation; [] 25 D 103.9 (c 0.30, MeOH), which is in agreement in sign with that of 5a {[] 20 D 111 (c 0.1, MeOH)}, while the known compound 6b [15] (the enantiomer of 5a) showed a negative optical rotation; [] 20 D 108 (c 0.1, MeOH). Additionally, compound 4 showed a similar CD curve to that of 5a (positive Cotton effect at 310 nm and 274 nm, negative Cotton effect at 234 nm for 4; positive Cotton effect at 274 nm, negative Cotton effect at 235 nm for 5a), but opposite to that of 6b (negative Cotton effect at 274 nm, positive Cotton effect at 234 nm for 6b) [15].…”

A Ligand‐Free Pt3Cluster Catalyzes the Markovnikov Hydrosilylation of Alkynes with up to 106Turnover Frequencies

“…20 %). The selective formation of vinylsilane 30 illustrates the generality of the method shown here and its potential use in advanced intermediates for synthesis (see Figure S9 in the SupportingI nformation for the preparation of the startinga lkyne in seven steps and the structure of ar elatedn atural product) [24] because the bromide and alkene functionalities are both preserved during the Pt 3 -catalyzed hydrosilylation reaction. In any case, we can conclude that Pt 3 clusters are very active catalysts for the Markovnikov hydrosilylation of terminal alkynes, and that theseP t 3 clusters can be introduced by using [NEt 4 ] 2 [Pt 3 (CO) 6 ] 3 ,N a 2 [Pt 3 (CO) 6 ] 5 ,a nd Na 2 [Pt 3 (CO) 6 ] 10 .A ne xample of the exceptional activity of the clusters is the TOF 1.0 10 6 h À1 for the hydrosilylation of 1-octyne with 4equiv of triethylsilane.…”

Bioactivity-Guided Investigation of the Anti-Inflammatory Activity of Hippophae rhamnoides Fruits

“…This type of lignan was identified for the first time from sea buckthorn and from the Elaeagnaceae family. Previously, these compounds were reported from different Myristicaceae, Saururaceae, Magnoliaceae, Lauraceae, Piperaceae, and Poaceae species [12,20]. Previously, other types of lignan, secoisolariciresinol and matairesinol, were isolated from sea buckthorn berries, and both compounds were detected in seeds, fruit pulp, and peel [21].…”