Screening of anti-inflammatory and antipyretic activity of Vitex leucoxylon Linn

Objective:

This study was designed to evaluate the anti-inflammatory and antipyretic activity of ethyl acetate extract of Vitex leucoxylon Linn. in various animal experimental models.

Materials and Methods:

Ethyl acetate extract of V. leucoxylon Linn. evaluated for anti-inflammatory activity in carrageenan, mediator-induced rat paw edema, and cotton pellet-induced granuloma model. The antipyretic activity was evaluated by yeast-induced pyrexia model.

Results:

Single administration of the ethyl acetate extract of V. leucoxylon Linn. at dose of 500 mg/kg p.o. showed significant (P < 0.001) inhibition of rat paw edema. The ethyl acetate extract showed significant antipyretic activity in brewer yeast-induced pyrexia in rats throughout the observation period of 4 h.

Conclusion:

This study shows that ethyl acetate extract of V. leucoxylon Linn. has significant anti-inflammatory and antipyretic activity.     

Studies on the alkaloid constituents of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang and their acute toxicity in mice

Six alkaloids (1–6) have been isolated from the fruits of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang, two of which are new compounds, identified as 2-undecyl-4(1H)-quinolone (4) and 1-methyl-2-undecanone-10′-4(1H)-quinolone (5); the known compounds were identified as rutaecarpine (1), evodiamine (2), 1-methyl-2-undecyl-4(1H)-quinoline (3) and 2-undecanone-10′-4(1H)-quinolone (6). Compounds 1–5 were evaluated for their acute toxicity.     

Indoloquinazoline alkaloids from Euodia rutaecarpa and their cytotoxic activities

Nine indoloquinazoline alkaloids (1–9) were isolated from the dried and nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth. (Euodiae Fructus), along with limonin and β-sitosterol. Their structures were elucidated on the basis of their spectroscopic data. Among them, compounds 1 and 2 were new compounds and characterized as (7R,8S)-7-hydroxy-8-methoxy-rutaecarpine and (7R,8S)-7-hydroxy-8-ethoxy-rutaecarpine, respectively, and 1-hydroxy-rutaecarpine (3) and (7R,8S)-7,8-dihydroxy-rutaecarpine (4) were isolated from Euodiae Fructus for the first time. The nine indoloquinazoline alkaloids were evaluated for their cytotoxic activities against human promyelocytic leukemia HL-60 cells and human gastric carcinoma N-87 cells.     

Two novel dammarane-type compounds from the leaves and stems of Panax quinquefolium L.

Two new dammarane-type compounds were isolated from the leaves and stems of Panax quinquefolium L. The new compounds were named as pseudo-ginsenoside RT₆ (1) and pseudoginsengenin R₁ (2). The structures of the new compounds were elucidated by the combined analysis of NMR and HR-ESI-MS as (20S,24R)-6-O-β-d-glucopyranosyl-dammar-3-one-20,24-epoxy-6α,12β,25-triol (1) and (20S,24R)-dammar-3-one-20,24-epoxy-6α,12β,25-triol (2).     

New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine

Three new C₂₀-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1–4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations.     

Cancer Preventive Agents. 7. Antitumor-Promoting Effects of Seven Active Flavonolignans from Milk Thistle (Silybum marianum.) on Epstein-Barr Virus Activation

Abstract

Seven pure flavonolignans were isolated from an extract of milk thistle [Silybum marianum.(L.) Gaertn (Asteraceae)], by semipreparative reverse-phase HPLC, and identified based on spectroscopic and LC-MS/IT-TOF data. All seven compounds were screened as potential antitumor-promoting agents by using the in vitro. short-term 12-O.-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. They showed good inhibitory activity (87.7–94.9%) at 1000 mol ratio/TPA. Silychristin A (1) and silychristin B (2) were slightly more potent than the well-known antitumor promoter β.-carotene. Silychristins A (1) and B (2) and isosilybins A (6) and B (7) were more active than the clinically proven cancer prevention components silybins A (4) and B (5).     

Evaluation of in vitro antiprotozoal activity of Ajuga laxmannii and its secondary metabolites

Context Some Ajuga L. (Lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases.

Objective In the continuation of our studies on the identification of antiprotozoal secondary metabolites of Turkish Lamiaceae species, we have investigated the aerial parts of Ajuga laxmannii.

Materials and methods The aerial parts of A. laxmannii were extracted with MeOH. The H₂O subextract was subjected to polyamide, C₁₈-MPLC and SiO₂ CCs to yield eight metabolites. The structures of the isolates were elucidated by NMR spectroscopy and MS analyses. The extract, subextracts as well as the isolates were tested for their in vitro antiprotozoal activities against Plasmodium falciparum, Trypanasoma brucei rhodesiense, T. cruzi and Leishmania donovani at concentrations of 90–0.123?μg/mL.

Results Two iridoid glycosides harpagide (1) and 8-O-acetylharpagide (2), three o-coumaric acid derivatives cis-melilotoside (3), trans-melilotoside (4) and dihydromelilotoside (5), two phenylethanoid glycosides verbascoside (6) and galactosylmartynoside (7) and a flavone-C-glycoside, isoorientin (8) were isolated. Many compounds showed moderate to good antiparasitic activity, with isoorientin (8) displaying the most significant antimalarial potential (an IC₅₀ value of 9.7?μg/mL).

Discussion and conclusion This is the first report on the antiprotozoal evaluation of A. laxmannii extracts and isolates. Furthermore, isoorientin and dihydromelilotoside are being reported for the first time from the genus Ajuga.     

New cycloartanes and new iridoids from Dolichandrone spathacea collected in the mangrove forest of Soc Trang province,Vietnam

Abstract

Two new cycloartanes, named dolichandrone A (1) and dolichandrone B (2), as well as two new iridoids, named [6-O-[(E)-4-methoxycinnamoyl]-1β-hydroxy-dihydrocatalpolgenin (3) and 6-O-[(E)-4-methoxycinnamoyl]-1α-hydroxy-dihydrocatalpolgenin (4), together with four known iridoids (5–8), were isolated from the leaves and barks of Dolichandrone spathacea. Their structures were elucidated by means of extensive analysis of their HRESIMS, 1D and 2D NMR spectroscopic data. All of these compounds have been isolated for the first time from this plant. Compounds 1, 2, 5, and 7 were evaluated for their cytotoxic activity in vitro against four human cancer cell lines KB, Lu, HepG2, and MCF7. The results showed that only compound 2 exhibited a good cytotoxicity against KB cell line with IC₅₀ of 18.77 μM.     

Aromatic acid derivatives from the lateral roots of Aconitum carmichaelii

Seven new aromatic acid derivatives (1–7), together with five known analogs, were isolated from the lateral roots of Aconitum carmichaelii. Structures of the new compounds were determined by spectroscopic and chemical methods as 4-methyl ( ? )-(R)-hydroxyeucomate (1), 4-butyl ( ? )-(R)-hydroxyeucomate (2), 4-butyl-1-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (3), 1-butyl-4-methyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (4), dimethyl (+)-(R)-2-O-(4′-hydroxy-3′-methoxybenzoyl)malate (5), dimethyl (+)-(R)-2-O-(4′-hydroxybenzoyl)malate (6), and methyl ( ± )-3-(4′-hydroxy-3′-methoxyphenyl)-3-sulfopropionate (7), respectively. Compounds 1 and 2 are 2-benzylmalates (eucomate derivatives), 3–6 belong to 2-O-benzoylmalates, and 7 is a rare phenylpropionate containing a sulfonic acid group. The absolute configurations of eucomate derivatives were confirmed by X-ray crystallographic analysis of 4-methyl eucomate (11).     

Microbial deglycosylation and ketonization of ginsenosides Rg1 and Rb1 by Fusarium oxysporum

Two major ginsenosides, ginsenoside-Rg₁ (1) and ginsenoside-Rb₁ (2), were transformed by the fungus Fusarium oxysporum f. sp. Lycopersici (Z-001). 1 was converted into five metabolites, ginsenoside-F₁ (3), 6α,12β-dihydroxydammar-3-one-20(S)-O-β-d-glucopyranoside (4), 3a-oxa-3a-homo-6α,12β-dihydroxydammar-3-one-20(S)-O-β-d-glucopyranoside (5), 20(S)-protopanaxatriol (6), and 3-oxo-20(S)-protopanaxatriol (7). 2 was converted into four metabolites, ginsenoside-Rd (8), ginsenoside-F₂ (9), compound K (10), and 12β-hydroxydammar-3-one-20(S)-O-β-d-glucopyranoside (11). The structures of these metabolites were determined by the analysis of extensive spectroscopic data. Among them, 4 and 5 were two new compounds. Deglycosylation and ketonization at C-3 were recognized as the characteristic reactions of this strain.     

Immunosuppressive effects of new cyclolanostane triterpene diglycosides from the aerial part of <Emphasis Type="Italic">Cimicifuga foetida</Emphasis>

Two new cyclolanostane diglycosides, cimifoetiside A (1) and cimifoetiside B (2), were isolated from an 80% ethanolic extract of the aerial part of Cimicifuga foetida L. (Ranuculaceae). Using spectral data and chemical analysis, the structures of 1 and 2 were identified as (23R, 24S) cimicigenol 3-O-β-D-glucopyranosyl-(1″→3′)-β-D-xylopyranoside and (23R, 24S) cimicigenol 3-O-β-D-glucopyranosyl-(1″→2′)-β-D-xylopyranoside, respectively. The in vitro immunosuppressive effects of the two new compounds 1 and 2, as well as four other known cyclolanostane saponins 3–6 on T cells were evaluated. All the agents tested effectively inhibited the proliferation of murine splenocytes induced by Concanavalin A (ConA), with IC₅₀ values ranging from 12.7 nM to 33.3 nM.     

Two new dammarane-type triterpenoid saponins from notoginseng medicinal fungal substance

Two new dammarane-type triterpenoid saponins, namely ginsenoside Rk₆ (1) and ginsenoside-Rh₂₂ (2), were isolated from notoginseng medicinal fungal substance. The structures of 1 and 2 were established as 3β,6α,12β,26-tetrahydroxydammar-20(21),24(25)(E)-diene-6-O-β-D-glucopyranoside and 3β,6α, 20(S)-trihydroxy-12(R),23(R)-expoxy-13(S),17(S)-dammar-24-ene-6-O-β-D-glucopyranoside on the basis of spectroscopic analysis and chemical analysis, respectively.     

Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

A new chromone and a new aliphatic ester isolated from Daldinia eschscholtzii

Abstract

A new chromone and a new aliphatic ester were isolated from the EtOAc extract of myceliums of Daldinia eschscholtzii. Their structures were elucidated as (R)-5-hydroxy-8-methoxy-2-methylchroman-4-one (1) and (E)-6-(non-3-en-1-yl) -2H-pyran-2-one (2) by interpretation of the spectroscopic evidence.     

Two pairs of phenylpropanoid enantiomers from the leaves of Eucommia ulmoides

Abstract

Two pairs of phenylpropanoid enantiomers, (+)-(7S,8S)-alatusol D (1a), (?)-(7R,8R)-alatusol D (1b), (?)-(7S,8R)-alatusol D (2a) and (+)-(7R,8S)-alatusol D (2b) were isolated from the leaves of Eucommia ulmoides Oliver. Among them, 1a and 2b were firstly obtained by chiral enantiomeric resolution. Their structures were elucidated based on extensive spectroscopic analysis and the induced CD (ICD) spectrum caused by adding Mo₂(AcO)₄ in DMSO. All compounds were tested on Hep G2 tumor cell lines. However, none of the compounds showed potential cytotoxic activity against Hep G2 in vitro.     

5-Alkylresorcinol glucosides from the leaves of <Emphasis Type="Italic">Grevillea robusta</Emphasis> Allan Cunningham

From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Grevillea robusta Allan Cunningham, two 5-alkylresorcinol glucosides, named grevillosides G and H (1, 2), and grevilloside E methyl ester (3) were isolated, along with one known megastigmane glucoside, staphylionoside D (4). The structures of the new compounds were elucidated by means of spectroscopic analyses. The structure of the related phenolic glucoside (1a) isolated from Veronica thymoides subsp. pseudocinerea was reported to be the same as that of 1. However, as judged on the close inspection of the spectroscopic data, its structure (1a) must be revised to 3,4-dihydroxyphenylethanol 3-O-glucoside.     

molidustat的合成工艺研究

目的对molidustat的合成工艺进行研究。方法以4,6-二氯嘧啶为原料,先后引入吗啉、肼取代基,制备获得中间体4-(6-肼基嘧啶-4-基)吗啉(2);1H-1,2,3-三氮唑和溴乙酸乙酯为原料,经烃基化、缩合反应,制备获得中间体(Z/E)-3-(二甲基氨基)-2-(1H-1,2,3-三氮唑-1-基)丙烯酸乙酯(4)。中间体2和4在三氟乙酸的催化下,经环合反应制备得到molidustat(5),然后经成盐反应得到其钠盐(6)。结果合成了目标化合物molidustat及其钠盐,并利用1H-NMR、MS确证了结构。此路线的总收率为31.5%。结论该合成工艺步骤短,操作简单,可适应未来工业化放大生产,具有良好的应用前景。     

A new lignan glycoside from <Emphasis Type="Italic">Juniperus rigida</Emphasis>

A new lignan glycoside, named juniperigiside (1) was isolated from the CHCl₃ soluble fraction of the MeOH extract of stems and leaves of Juniperus rigida S.et Z. Compound 1 was identified by 1D- and 2D-NMR spectroscopy as well as CD analysis as (2R,3S)-2,3-dihydro-7-methoxy-2-(4′-hydroxy-3′-methoxyphenyl)-3-hydroxymethyl-5-benzofuranpropanol 4′-O-(3-O-methyl)-α-L-rhamnopyranoside. Five known lignans, icariside E4 (2), desoxypodophyllotoxin (3), savinin (4), thujastandin (5), and (−)-nortrachelogenin (6) in addition to five known labdane diterpenes including trans-communic acid (7), 13-epi-torulosal (8), 13-epi-cupressic acid (9), imbricatoric acid (10), and isocupressic acid (11) were also isolated and their structures were characterized by comparing their spectroscopic data with those in the literature. All compounds were isolated for the first time from this plant, and 5 and 6 were first reported from the genus Juniperus. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay. Compounds 3, 4, 7, and 8 showed considerable cytotoxicity against four human cancer cell lines in vitro.     

Seven new dammarane triterpenes from the floral spikes of Betula platyphylla var. japonica

Seven new dammarane-type triterpenoids, including two 20(S)-hydroxy-25-methoxy-dammar-23-enes (1 and 2), two 20(S),24(R)-epoxydammaranes (3 and 4), a cabralealactone (5), and two 20(S),25-epoxydammaranes (6 and 7), together with seven known triterpenes (8–14), were isolated from the floral spikes of Betula platyphylla var. japonica. The structures for all compounds were elucidated by the analyses of extensive spectroscopic data, as well as chemical examinations.     

Isolation of megastigmane sesquiterpenes from the silkworm (<Emphasis Type="Italic">Bombyx mori</Emphasis> L.) droppings and their promotion activity on HO-1 and SIRT1

The silkworm (Bombyx mori L.) droppings were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned in succession with EtOAc, n-BuOH, and H₂O. From the EtOAc fraction, five megastigmane sesquiterpenes were isolated through repeated silica gel and ODS column chromatography. According to the results of spectroscopic data, such as NMR, MS, and IR, the chemical structures of the isolated compounds were determined as (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (1), (S)-dehydrovomifoliol (2), (6R,7E,9R) -9-hydroxy-4,7-megastigmadien-3-one (3), (3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (4), (6R,9R)-9-hydroxy-4-megastigmen-3-one (5). Compounds 2 through 5 were isolated for the first time from silkworm droppings. GC/MS analysis indicated silkworm powder contained compound 3, and mulberry leaves contained compound 4. Compounds 1 and 5 increased the expression of heme oxygenase-1 and SIRT1 in HepG2 and HEK239 cells, respectively. Heme oxygenase-1 is considered to be an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron and biliverdin, while SIRT1 is the mammalian homologue of the yeast silent information regulator (Sir)-2, which are involved in the suppression of inflammatory mediators or factors that may be used to improve atopy-related symptoms.