Preparation and antitussive, expectorant, and antiasthmatic activities of verticinone's derivatives

To prepare verticinone derivatives with significant antitussive, expectorant, and antiasthmatic activities, the compounds 3beta-acetylverticinone (1), 3-ketoverticinone (2), 3beta-benzoylverticinone (3), 3beta-propionylverticinone (4), 3beta-butyrylverticinone (5), and 3beta-butoxycarbonylverticinone (6) have been prepared. All of these are new compounds. Among them, 1-6 exhibited potent antitussive and expectorant activities; 1 and 3-6 displayed various antiasthmatic activities. The antitussive activity of 1-6, the expectorant activity of 1-2 and 4-6, and the antiasthmatic activity of 1 are higher than those of verticinone. The results demonstrated that 1 had dominant biological activities, suggesting that it would be a potential antitussive, expectorant, and antiasthmatic agent.     

Preparation and antitussive, expectorant, and antiasthmatic activities of verticinone's derivatives.

To prepare verticinone derivatives with significant antitussive, expectorant, and antiasthmatic activities, the compounds 3beta-acetylverticinone (1), 3-ketoverticinone (2), 3beta-benzoylverticinone (3), 3beta-propionylverticinone (4), 3beta-butyrylverticinone (5), and 3beta-butoxycarbonylverticinone (6) have been prepared. All of these are new compounds. Among them, 1-6 exhibited potent antitussive and expectorant activities; 1 and 3-6 displayed various antiasthmatic activities. The antitussive activity of 1-6, the expectorant activity of 1-2 and 4-6, and the antiasthmatic activity of 1 are higher than those of verticinone. The results demonstrated that 1 had dominant biological activities, suggesting that it would be a potential antitussive, expectorant, and antiasthmatic agent.     

浙贝乙素胆汁酸盐的制备及其镇咳、祛痰和平喘活性的筛选

为了寻找具有优良镇咳、祛痰和平喘活性且毒性较低的药物，将贝母中的主要药效成分之一浙贝乙素和蛇胆中各主要药效成分进行酸碱反应,得到一系列浙贝乙素胆汁酸盐并对所得的盐进行镇咳、祛痰和平喘活性的筛选。活性筛选结果显示，浙贝乙素胆酸盐和浙贝乙素鹅去氧胆酸盐的镇咳、祛痰和平喘活性较强，尤其是二者显示出比磷酸可待因还强的镇咳活性值得关注。借鉴药物化学中的结构拼合思路有望在中药复方的研究开发中开辟出一条新的途径。     

Antitussive,expectorant, and anti-inflammatory activities of four caffeoylquinic acids isolated from Tussilago farfara

Context: The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and asthmatic conditions.

Objective: The objective of this study is to isolate four caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate their antitussive, expectorant, and anti-inflammatory activities.

Materials and methods: The structures of compounds 1–4 isolated from EtE were determined by spectral analysis. Mice were orally treated with these compounds and their mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20?mg/kg once daily for 3 d. The antitussive and expectorant activities were evaluated separately with the ammonia liquor-induced model and the phenol red secretion model. The anti-inflammation activity was evaluated using leukocyte count in the bronchoalveolar lavage fluid after ammonia liquor-induced acute airway inflammation.

Results: The four compounds were identified as chlorogenic acid (1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5-dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition in cough frequency), showed a significant antitussive effect. However, the mixture was the most effective to inhibit the cough frequency by 61.7%. All compounds also showed a significant expectorant effect, while compound 2 was the most potent to enhance the phenol red secretion by 35.7%. All compounds significantly alleviated inflammation, but compound 4 showed the strongest effect to inhibit the leukocytosis by 49.7%.

Discussion and conclusion: The caffeoylquinic acids and their mixture, exhibiting significant antitussive, expectorant, and anti-inflammatory effects, could be considered as the main effective ingredients of FTF, and they may act in a collective and synergistic way.     

Speciosaperoxide,a new triterpene acid,and other terpenoids from Chaenomeles speciosa

Investigation on the EtOH extract of the fruits of Chaenomeles speciosa led to the isolation of a new triterpene acid bearing an unusual hydroperoxyl substitute group at C-11, speciosaperoxide (1), along with six known triterpenoids, 3β-acetoxyurs-11-en-13β,28-olide (2), 3-O-acetyl ursolic acid (3), oleanolic acid (4), ursolic acid (5), masilinic acid (6), and tormentic acid (7), and three known norsesquiterpenoids, roseoside (8), vomifoliol (9) and (6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-[β-d -xylopyranosyl (1 → 6)-glucopyranoside] (10). Their structures were elucidated on the basis of spectroscopic data and comparison with reference data. Besides compound 1, compounds 2, 8–10 were obtained from this genus for the first time. None of these compounds exhibited inhibitory activity against T-and B-lymphocyte proliferation.     

紫苏子镇咳、祛痰、平喘作用的药理研究

目的 对紫苏子及其炮制品的梯度溶媒提取物进行了镇咳、祛痰、平喘的对比性研究。方法 浓氨水喷雾法、毛细玻管法、喷雾致喘法。结果 1．紫苏子水提物、醇提物和醚提物均显示了程度不同的镇咳作用。2．紫苏子和炒紫苏子水提物的小剂量组均有良好的祛痰作用。3．对1％氯化乙酰胆碱诱导的豚鼠哮喘未发现其有平喘作用。但对用2％氯化乙酰胆碱和0．1％磷酸组胺的等量混合液诱喘的哮喘模型，炒紫苏子水提物和醚提物的小剂量组都显示出显著的平喘效果。结论 紫苏子具有一定的镇咳、祛痰和平喘作用，其镇咳成分较分散。平喘成分的水溶性大。存在于炒紫苏子的平喘成分其极性较分散，既存在于极性大的部分也存在于极性小的部分。     

Cryptoporic acid S,a new drimane-type sesquiterpene ether of isocitric acid from the fruiting bodies of Cryptoporus volvatus

A new drimane-type sesquiterpene with an isocitric acid moiety, cryptoporic acid S (1), together with six known compounds, cryptoporic acid D (2), β-sitosterol (3), β-daucosterol (4), stigmast-4-en-3-one (5), ergosterol (6), and (22E,24R)-ergosta-7,22-diene-3β,5α,6β-triol (7), was isolated from the fruiting bodies of Cryptoporus volvatus. The structures of these compounds were established on the basis of UV, IR, MS, 1D and 2D NMR analysis. In the meanwhile, compounds 1 and 2 were evaluated for antioxidant activity using the methods of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (DPPH-RSA) and ferric reducing antioxidant power (FRAP) assay, and they exhibited moderate antioxidant activities.     

Addictive evaluation of cholic acid-verticinone ester,a potential cough therapeutic agent with agonist action of opioid receptor

Aim:

The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver.

Methods:

Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver''s central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver''s addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum.

Results:

The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response.

Conclusion:

These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.     

Three new sesquiterpenes from the stems of Nicotiana tabacum and their bioactivities

Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4–6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1–6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC₅₀ values in the range of 6.7–9.6 μM.     

Sesquiterpene lactones from Ixeris sonchifolia Hance and their cytotoxicities on A549 human non-small cell lung cancer cells

A new sesquiterpene lactone glucoside, 11,13-dihydroixerinoside (1), together with the five known sesquiterpene lactones, ixerinoside (2), ixerin Z (3), 11,13α-dihydroixerin Z (4), ixerin Z1 (5), and 3-hydroxydehydroleucodin (6), respectively, were isolated from the whole plants of Ixeris sonchifolia Hance. The compounds were identified by spectral analysis and comparison with spectroscopic data reported in the literatures. When the in vitro cytotoxic activities of compounds 1–6 were evaluated against A549 human non-small cell lung cancer cells, all six compounds exhibited cytotoxic activity against A549 cells, with compounds 2, 3, and 6 showing good activities (inhibitory concentration (IC₅₀ values < 30 μg/ml) that are comparable with well-established chemotherapeutic drug, 5-fluorouracil.     

Chemical constituents from the leaves of Boehmeria rugulosa with antidiabetic and antimicrobial activities

Three new flavonoid glycosides, named chalcone-6′-hydroxy-2′,3,4-trimethoxy-4′-O-β-d-glucopyranoside (1), isoflavone-3′,4′,5,6-tetrahydroxy-7-O-{β-d-glucopyranosyl-(1 → 3)-α-l-rhamnopyranoside} (2), and isoflavone-3′,4′,5,6-tetrahydroxy-7-O-{β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl-(1 → 3)-α-l-rhamnopyranoside} (3), were isolated from the leaves of Boehmeria rugulosa, together with five known compounds, β-sitosterol, quercetin, 3,4-dimethoxy-ω-(2′-piperidyl)-acetophenone (4), boehmeriasin A (5), and quercetin-7-O-β-d-glucopyranoside. The structures of the isolated compounds were determined by means of chemical and spectral data including 2D NMR experiments. The ethanolic extract of leaves showed significant hypoglycemic activity on alloxan-induced diabetic mice. Glibenclamide, an oral hypoglycemic agent (5 mg/kg, p.o.), was used as a positive control. The ethanolic extract of the plant as well as the isolated compounds 1–3 (25 μg/ml) showed potent antimicrobial activity against two bacterial species (Staphylococcus aureus and Streptococcus mutans) and three fungus pathogens (Microsporum gypseum, Microsporum canis, and Trichophyton rubrum). The activities of the isolated compounds 1–3 have been compared with positive controls, novobiocin, and erythromycin (15 μg/ml).     

One new ergostane-type steroid and three new phthalide derivatives from cultures of the basidiomycete Albatrellus confluens

One new ergostane-type steroid, (12β,15β,22R,23S,24S)-22,25-epoxy-12,15,23-trihydroxyergost-4,6,8(14)-trien-3-one (1), three new phthalide derivatives, 5-(2′,3′-epoxy-3′,3′-dimethylpropoxy)-7-methoxy-6-methylphthalide (2), (2′)-(Z)-5-(3′-hydroxymethyl-3′-methylallyloxy)-7-methoxy-6-methylphthalide (3), and 5-(3′,3′-dimethylallyloxy)-7-hydroxy-6-methylphthalide (4), along with one known phthalide derivative, 5-(3′,3′-dimethylallyloxy)-7-methoxy-6-methylphthalide (5), were isolated from cultures of the basidiomycete Albatrellus confluens. The structures of the new compounds were established on the basis of extensive spectroscopic data (IR, MS, 1D, and 2D NMR) analyses. All compounds were evaluated for their cytotoxic activities on five tumor cell lines.     

Antioxidant and α-amylase inhibitory activities of extract and isolates from Zygogynum pancheri subsp. arrhantum

One new sesquiterpenoid (5R^*,8R^*,9R^*,10R^*)-cinnamolide (8), and seven known compounds, 5-hydroxy-7-methoxyflavonone (1), 8-hydroxy-3-(4′-hydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (2), 8-hydroxy-3-(3′,4′-dihydroxyphenyl)-6,7-(2″,2″-dimethylchromene)-tetralone (3), 1β-E-O-p-methoxycinnamoyl-bemadienolide (4), 1β-O-(E-cinnamoyl)-6α-hydroxy-9-epi-polygodial (5), 1β-O-(E-cinnamoyl)-6α-hydroxypolygodial (6), and 1β-O-E-cinnamoylpolygodial (7) were isolated from the ethyl acetate extract of barks of Zygogynum pancheri subsp. arrhantum (Winteraceae). The structures of these molecules were assigned predominantly based on spectral data. The structure of compound 8 was confirmed by X-ray crystallographic analysis. Compounds 2 and 3 exhibited significant antioxidant activity, whereas compounds 1 and 4–7 showed significant α-amylase inhibitory activity.     

Chemical constituents of the Annona glabra fruit and their cytotoxic activity

Abstract

Context: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. Annona glabra Linn (Annonaceae) is used in traditional medicine as an anticancer drug. Phytochemical investigation of this plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids. In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria.

Objective: Isolation, structure determination, and cytotoxic activity evaluation of compounds from the methanol extract from A. glabra fruits.

Materials and methods: Using chromatographic methods to isolate compounds from the A. glabra methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds which showed significant cytotoxic activity were chosen for further study apoptosis characteristics.

Results: One new, (2E,4E,1′R,3′S,5′R,6′S)-dihydrophaseic acid 1,3′-di-O-β-d-glucopyranoside, and eight known compounds, (2E,4E,1′R,3′S,5′R,6′S)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (2), icariside D₂ (3), icariside D₂ 6′-O-β-d-xylopyranoside (4), 3,4-dimethoxyphenyl O-β-d-glucopyranoside (5), 3,4-dihydroxybenzoic acid (6), blumenol A (7), cucumegastigmane I (8), and icariside B₁ (9), were isolated from the fruits of A. glabra. Icariside D₂ (3) was found to show significant cytotoxic activity on the HL-60 cell line with the IC₅₀ value of 9.0?±?1.0?µM and did not show cytotoxic activity on the Hel-299 normal cell line. The further test indicated that compound 3 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells.

Discussion and conclusion: The results suggested that the constituents from A. glabra may contain effective compounds which can be used as anticancer agents.     

Triterpenes from Astilbe chinensis

Six new triterpenes, 3β,6β-dihydroxyurs-12-en-27-oic acid (1), 3β,6β,24-trihydroxyurs-12-en-27-oic acid (2), 3β,6β,7α-trihydroxyurs-12-en-27-oic acid (3), 3β-acetoxy-6β-hydroxyurs-12-en-27-oic acid (4), 3β,6β,24-trihydroxyolean-12-en-27-oic acid (5), and 3β,6β,7α-trihydroxyolean-12-en-27-oic acid (6), were isolated from the rhizomes of Astilbe chinensis. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses and HR-MS experiments. The isolated compounds exhibited significant cytotoxic activities against the SK-N-SH and HL-60 cell lines.     

Chromone glycosides from Knoxia corymbosa

Four new chromone glycosides, corymbosins K₁-K₄ (3–6), together with two known compounds, noreugenin (1) and undulatoside A (2), were isolated from the whole plant of Knoxia corymbosa (Rubiaceae). The structures of the new compounds were established through extensive NMR or X-ray spectroscopic analysis as 7-O-β-d-allopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₁, 3), 7-O-β-d-6-acetylglucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₂, 4), 7-O-[6-O-(4-O-trans-caffeoyl-β-d-allopyranosyl)]-β-d-glucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K₃, 5) and 7-O-[6-O-(4-O-trans-feruloyl-β-d-allopyranosyl)]-β-d-glucopyranosyl-5-hydroxy-2- methylchromone (corymbosin K₄, 6). Compounds 2–5 were subjected to test their immunomodulatory activity in vitro.     

Compounds from Sedum caeruleum with antioxidant,anticholinesterase, and antibacterial activities

Context: This is the first study on the phytochemistry, antioxidant, anticholinesterase, and antibacterial activities of Sedum caeruleum L. (Crassulaceae).

Objective: The objective of this study is to isolate the secondary metabolites and determine the antioxidant, anticholinesterase, and antibacterial activities of S. caeruleum.

Materials and methods: Six compounds (1–6) were isolated from the extracts of S. caeruleum and elucidated using UV, 1D-, 2D-NMR, and MS techniques. Antioxidant activity was investigated using DPPH^?, CUPRAC, and ferrous-ions chelating assays. Anticholinesterase activity was determined against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the Ellman method. Antibacterial activity was performed according to disc diffusion and minimum inhibitory concentration (MIC) methods.

Results: Isolated compounds were elucidated as ursolic acid (1), daucosterol (2), β-sitosterol-3-O-β-d-galactopyranoside (3), apigenin (4), apigetrin (5), and apiin (6). The butanol extract exhibited highest antioxidant activity in all tests (IC₅₀ value: 28.35?±?1.22?µg/mL in DPPH assay, IC₅₀ value: 40.83?±?2.24?µg/L in metal chelating activity, and IC₅₀ value: 23.52?±?0.44?µg/L in CUPRAC), and the highest BChE inhibitory activity (IC₅₀ value: 36.89?±?0.15?µg/L). Moreover, the chloroform extract mildly inhibited (MIC value: 80?µg/mL) the growth of all the tested bacterial strains.

Discussion and conclusion: Ursolic acid (1), daucosterol (2), β-sitosterol-3-O-β-d-galactopyranoside (3), apigenin (4), apigetrin (5), and apiin (6) were isolated from Sedum caeruleum for the first time. In addition, a correlation was observed between antioxidant and anticholinesterase activities of bioactive ingredients of this plant.     

Antibacterial sesquiterpene lactone glucoside from seed pods of Bauhinia retusa

From the seed pods of Bauhinia retusa, a new eudesmane sesquiterpene glucoside, 1-O-β-D-glucopyranosyl-9β,15-dihydroxy-5α,6βH-eudesma-3-ene-6α,12-olide (1), has been isolated together with three known compounds, 4′-hydroxy-7-methoxy flavane (2), β-sitosterol (3), and stigmasterol (4). The structures of isolated compounds were verified with the help of 1D, 2D NMR, and HR-ESI-MS spectroscopies. Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa and Escherichia coli when a disc diffusion method is used.     

野马追抗菌、止咳、平喘作用

目的 :研究野马追药效学作用。方法 :采用常规咳嗽、喘息模型以及体外抑菌试验。结果 :小鼠灌服野马追45 1g、22 6g和11 3g(生药 )/kg,能明显镇咳、祛痰、平喘 ,还能抑制临床常见病菌。结论 :野马追具镇咳、平喘和祛痰作用     

化痰降气胶囊化痰、止咳、平喘的实验研究

目的初步探讨化痰降气胶囊化痰止咳平喘的功效。方法化痰降气胶囊按小鼠剂量3.8 g生药.kg-1,7.5 g生药.kg-1,15 g生药.kg-1,大鼠和豚鼠剂量2.9 g生药.kg-1,5.8 g生药.kg-1,11.6 g生药.kg-1ig给药,观察化痰降气胶囊的化痰、止咳、平喘作用。结果化痰降气胶囊能明显促进小鼠酚红分泌量,增加大鼠痰液排出量,显著减少浓氨水致小鼠咳嗽次数,延长咳嗽潜伏期,显著减少枸橼酸喷雾致豚鼠咳嗽次数,延长氯化乙酰胆碱和组胺混合液喷雾引喘豚鼠潜伏期。结论化痰降气胶囊具有化痰止咳平喘的作用。