Twenty-two new lignans and neolignans (1−22), together with 14 known analogues, have been isolated from an ethanolic extract of the stem (with skin removed) of Sinocalamus affinis. Their structures ...were elucidated by spectroscopic and chemical methods. On the basis of systematic NMR and circular dichroism (CD) data analysis, the validity of J 7,8 and ΔδC8−C7 values to distinguish threo and erythro aryl glycerol units in different neolignans and the CD data particularly the Rh2(OCOCF3)4-induced CD data (the E band) to determine the absolute configurations at C-8 (C-7) of the aryl glycerol units are discussed. At a concentration of 10 μM, compounds 20 and 22 inhibited NO production in mouse peritoneal macrophages 84.2 ± 5.9% and 71.7 ± 1.0%, respectively. Compounds 19, 20, and 22 showed activity against serum deprivation induced PC12 cell damage by increasing the cell viability from 80.7 ± 2.8% to 91.6 ± 6.4%, 107.2 ± 8.0%, and 97.6 ± 8.5%, respectively.
Abstract
Background
Isotalatizidine is a representative C
19
-diterpenoid alkaloid extracted from the lateral roots of
Aconitum carmichaelii
, which has been widely used to treat various diseases on ...account of its analgesic, anti-inflammatory, anti-rheumatic, and immunosuppressive properties. The aim of this study was to evaluate the analgesic effect of isotalatizidine and its underlying mechanisms against neuropathic pain.
Methods
A chronic constrictive injury (CCI)-induced model of neuropathic pain was established in mice, and the limb withdrawal was evaluated by the Von Frey filament test following isotalatizidine or placebo administration. The signaling pathways in primary or immortalized microglia cells treated with isotalatizidine were analyzed by Western blotting and immunofluorescence.
Results
Intrathecal injection of isotalatizidine attenuated the CCI-induced mechanical allodynia in a dose-dependent manner. At the molecular level, isotalatizidine selectively increased the phosphorylation of p38 and ERK1/2, in addition to activating the transcription factor CREB and increasing dynorphin A production in cultured primary microglia. However, the downstream effects of isotalatizidine were abrogated by the selective ERK1/2 inhibitor U0126-EtOH or CREB inhibitor of KG-501, but not by the p38 inhibitor SB203580. The results also were confirmed in in vivo experiments.
Conclusion
Taken together, isotalatizidine specifically activates the ERK1/2 pathway and subsequently CREB, which triggers dynorphin A release in the microglia, eventually leading to its anti-nociceptive action.
Two sulfonated seco C20-diterpenoid alkaloids, having analgesic activities and unprecedented carbon skeletons biogenetically derived via Criegee rearrangements of the napelline-type architecture, ...were isolated from an aqueous extract of the raw material of “Fu Zi”.
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Two sulfonated seco C20-diterpenoid alkaloids, aconapelsulfonines A (1) and B (2), were isolated from an aqueous extract of the raw material of “Fu Zi” (the Aconitum carmichaelii lateral roots), of which the structures were elucidated by various spectroscopic data, combined with X-ray crystallographic analysis. The unprecedented skeletons are biogenetically proposed to be derived via Criegee rearrangements of the napelline-type architecture. The two compounds exhibited dose-depended analgesic activities on an acetic acid-induced mice writhing test.
Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A-F（1–6）, were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute ...configurations were elucidated by comprehensive spectroscopic data analysis and enzyme hydrolysis. The validity of ΔδC8-C7 values to distinguish threo and erythro aryl glycerol units and Cotton effects at 235±5 nm to determine absolute configurations at C-8 in 1–6 and their aglycones（1a–6a） are discussed.
Alkaloids from the Root of Isatis indigotica Chen, Minghua; Gan, Lishe; Lin, Sheng ...
Journal of natural products (Washington, D.C.),
06/2012, Volume:
75, Issue:
6
Journal Article
Peer reviewed
Seventeen new alkaloids (1–17) and 14 known analogues have been isolated from an aqueous extract of the root of Isatis indigotica. The structures and absolute configurations of these compounds were ...determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography using anomalous scattering of Cu Kα radiation, and electronic circular dichroism spectra calculations based on the quantum-mechanical time-dependent density functional theory. Compounds 1, 2, and 3 are the first examples of natural products with unique linkages between a molecule of 2-(4-methoxy-1H-indol-3-yl)acetonitrile and 2-(1H-indol-3-yl)acetonitrile, 2-(4-methoxy-1H-indol-3-yl)acetonitrile, and 4-hydroxyphenylethane, respectively. Compounds (−)-4 and (+)-4 represent the first natural products with the pyrrolo2,3-bindolo5,5a,6-b,aquinazoline skeleton. Some structural assignments for the new alkaloids suggest that the assignments made for certain previously reported alkaloids require revision. Compounds 1–3 and arvelexin (18) show antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2), with IC50 values of 3.70–12.35 μM, and 17 inhibits Coxsackie virus B3 replication with an IC50 of 6.87 μM.
Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons, named aconidenusulfonine A (1) and 12,16-secoaconidenusulfonine A (2), respectively, were isolated as ...minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii (“Fu Zi”). The structures of 1 and 2, representing the first two C21-diterpenoid alkaloids from nature, were determined by analysis of various spectroscopic data and chemical transformation, of which 1 was further proved by single-crystal X-ray diffraction. Especially, 1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.
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Two diterpenoid alkaloids having unique twenty-one skeletal carbons were isolated as minor chemical constituents of the lateral root of Aconitum carmichaelii “Fu Zi”
A pair of 2,7′-cyclo-8,9′-neolignan enantiomers with an unprecedented carbon skeleton and hypnotic effect were isolated and structurally characterized from an aqueous extract of the Angelica sinensis ...root heads (guitou). Biogenetically, the carbon skeleton is postulated from coupling between ferulic acid and coniferyl alcohol.
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A pair of neolignan enantiomers with an unprecedented carbon skeleton, (+)-/(−)-angelignanine (+)-/(−)-1, was isolated as minor components of an aqueous extract of the Angelica sinensis root heads (guitou). Their structures were determined by spectroscopic data analysis and the absolute configurations were assigned by the circular dichroism (CD) exciton chirality method as well as electronic CD quantum calculations. The enantiomers represent the first 2,7′-cyclo-8,9′-neolignans, of which biosynthetic pathways originating from precursors ferulic acid and coniferyl alcohol is proposed. In an in vivo test, both the enantiomers showed significant hypnotic effects at a dose of 10 mg/kg (i.g.).
Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica ...root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.
Three new C20-diterpenoid alkaloids with a sulfonic acid unit, named aconicarmisulfonines B and C (1 and 2) and chuanfusulfonine A (3), respectively, were isolated from the Aconitum carmichaelii ...lateral roots (“fu zi” in Chinese). Structures of 1–3 were determined by spectroscopic data analysis. Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids: (a) specific selective nucleophilic addition of the carbonyl (C-12) in 1 with CD3OD; (b) interconversion between 1 and 2 in D2O; (c) stereo- and/or regioselective deuterations of H-11α in 1–3 and both H-11α and H-11β in aconicarmisulfonine A (4); (d) TMSP-2,2,3,3-d4 promoted cleavage of the C-12−C-13 bond of 4 in D2O; (e) dehydrogenation of 4 in pyridine-d5, and (f) Na2SO3-assisted dehydrogenation and N-deethylation of songorine (5, a putative precursor of 1–4). Biogenetically, 1 and 2 are correlated with 4, for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13−C-16 and C-15−C-16 bonds of the napelline-type skeleton, respectively. Meanwhile, 3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1, 2, and 4. In the acetic acid-induced mice writhing assay, at 1.0 mg/kg (i.p.), compounds 1, 2, 5, 5a, and 5b exhibited analgesic effects against mice writhing.
From an aqueous extract of the Aconitum carmichaelii lateral roots (a popular Chinese medicine “fu zi”), analgesic C20-diterpenoid alkaloids with a sulfonic acid unit and intriguing chemical properties were characterized. The aconicarmisulfonine skeleton is proposed to be from semipinacol migration of different carbon bond in the precursor. Display omitted
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