山荷叶中木脂素成分的研究

从陕西产山荷叶(Diphylleia sinensis Li.)根茎中分得9个木脂素和1个黄酮化合物,通过光谱分析证明化合物Ⅸ为新木脂素,即苦鬼臼素-1-乙基醚(picropodophyllin-1-ethyl ether),其它化合物分别为鬼臼毒素(podophyllotoxin,Ⅰ)、异苦鬼臼酮(isopicropodophyllone,Ⅱ)、去氢鬼臼毒素(dehydropodophyllotoxin,Ⅲ)、山荷叶素(diphyllin,Ⅳ)、苦鬼臼素(picropodophyllin,Ⅴ)、鬼臼酯酮(podophyllotoxone,Ⅵ)、4′-去甲基鬼臼毒素(4′-demethylpodophyllotoxin,Ⅶ)、苦鬼臼素葡萄糖甙(picropodophyllin slucoside,Ⅷ)和山奈酚(kaempferol,Ⅹ)。其中化合物Ⅱ,Ⅵ,Ⅶ和Ⅷ为首次从山荷叶属植物中分得。     

Determination of 8-methoxypsoralen levels in plasma and skin suction blister fluid by a new sensitive fluorodensitometric method

Summary The four lignans: podophyllotoxin, 4-demethyl-podophyllotoxin, -peltatin and -peltatin represent the podophyllin ingredients believed to exert lesional necrosis after application to condylomata acuminata. This study comparatively evaluates cutaneous cytodestructive potency of these drugs, as evaluated by measurement of epidermal and dermal ³H-thymidine incorporation and injury of dermal microcirculation at intervals in the range of 9–168 h after application to hairless mouse skin. Influence on DNA-synthesis was measured using a disc technique for isolation of standardized skin areas followed by alkali extraction of DNA from respective tissues after separation through Potassium bromide incubation. Any capillary injury was demonstrated by visual assessment of leakage of i.v. injected trypan blue to test areas. An analytical method compensating for variations in DNA synthesis in individual controls is presented. Using 0.5% preparations of the lignans, podophyllotoxin most consistently influenced the variables indicating cytodestructive effect, while 4-demethyl-podophyllotoxin exerted the weakest degree of damage.     

Lignans from the stems of Clematis armandii (“Chuan-Mu-Tong”) and their anti-neuroinflammatory activities

Ethnopharmacological relevance

The dried stems of Clematis armandii (Caulis clematidis armandii), named “Chuan-Mu-Tong” in Chinese Pharmacopoeia, have been traditionally used as an herbal remedy mainly for inflammation-associated diseases. The Aim of the study is to identify the potential anti-neuroinflammatory components from Clematis armandii.

Materials and methods

The ethanol extract of “Chuan-Mu-Tong” was suspended in H₂O and exhaustively extracted with CH₂Cl₂. The CH₂Cl₂ fraction was successively subjected to column chromatography (CC) over silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopic methods and by comparison with those reported in the literature. Their anti-neuroinflammatory activities were evaluated by inhibitory effects on pro-inflammatory mediators [e.g. nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α)] in lipopolysaccharide (LPS)-activated BV-2 cells.

Results

One new and sixteen known lignans were isolated and characterized. The absolute configuration of the new lignan, (7R,8S)-9-acetyl-dehydrodiconiferyl alcohol (1), was elucidated by a combination of 1D/2D NMR techniques and the Electronic Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules. The anti-neuroinflammatory bioassay showed that compounds 1, (7R,8S)-dehydrodiconiferyl alcohol (2), erythro-guaiacylglycerol-β-coniferyl ether (5), and threo-guaiacylglycerol-β-coniferyl ether (6) displayed significant inhibitory effects on NO production. Among them, neolignans 1 and 2 exhibited more potent activities than the positive control (N^G-monomethyl-l-arginine, l-NMMA), with an IC₅₀ value of 9.3 and 3.9 μM, respectively. Moreover, both 1 and 2 were also found to concentration-dependently suppress the TNF-α release in LPS-stimulated BV-2 cells.

Conclusion

The results revealed that lignans are the major components of “Chuan-Mu-Tong”, and their anti-neuroinflammatory activities strongly support the traditional application of this herb medicine on inflammation. Moreover, the dihydrobenzo[b]furan neolignans 1 and 2 as well as Caulis clematidis armandii could be further exploited as new therapeutic agents to treat inflammation-mediated neurodegenerative and aging-associated diseases.     

Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential

Ethanopharmacological relevance

Zanthoxylum alatum is used in traditional medicinal systems for number of disorders like cholera, diabetes, cough, diarrhea, fever, headache, microbial infections, toothache, inflammation and cancer. The aim of the present study was to evaluate Zanthoxylum alatum stem bark for its cytotoxic potential and to isolate the bioactive constitiuents.

Material and methods

Cytotoxicity of the different extracts and isolated compounds was studied on lung carcinoma cell line (A549) and pancreatic carcinoma cell line (MIA-PaCa) using MTT assay. Isolation of compounds from most active extract (petroleum ether) was done on silica gel column. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, ¹H NMR, ¹³C NMR and mass spectroscopy. The type of cell death caused by most active compound C was explored by fluorescence microscopy using the acridine orange/ethidium bromide method.

Result

Petroleum ether extract of plant has shown significant cytotoxic potential. Three lignans sesamin (A), kobusin (B), and 4'O demethyl magnolin (C) has been isolated. All lignans showed cytotoxic activities in different ranges. Compound C was the novel bioactive compound from a plant source and found to be most active. In apoptosis study, treatment caused typical apoptotic morphological changes. It enhances the apoptosis at IC₅₀ dose (21.72 µg/mL) however showing necrotic cell death at higher dose after 24 h on MIA-PaCa cell lines.

Conclusion

Petroleum ether extract (60–80 °C) of Zanthoxylum alatum has cytotoxic potential. The lignans isolated from the petroleum ether extract were responsible for the cytotoxic potential of the extract. 4'O demethyl magnolin was novel compound from Zanthoxylum alatum. Hence the Zanthoxylum alatum can be further explored for the development of anticancer drug.     

樟属植物化学成分研究进展

樟属植物在城市绿化、医药卫生和食品等领域具有重要的应用价值,樟属植物化学成分比较复杂,化学结构类型包括挥发油、二萜、木脂素、黄酮、生物碱、酚苷、丁内酯类化合物等,这些化合物具有广泛的药理活性,具有抗氧化、抗菌、消炎、抗癌、降糖、伤口愈合、抗艾滋病毒、抗抑郁和免疫抑制等作用,其中,挥发油、二萜、木脂素、黄酮是其主要结构类型。本文就国内外对樟属化学成分的研究成果进行整理总结,以期为樟属植物的进一步开发利用提供参考。     

Simultaneous quantification of eight active compounds in Sinopodophyllum hexandrum by HPLC-DAD

Sinopodophylli Fructus is the commonly used traditional Tibetan medicinal herb. In the present study, we established a reversed-phase high performance liquid chromatography method to simultaneously determine three lignans and five flavonoid constituents, namely podophyllotoxin, desoxypodophyllotoxin, 4′-demethyldesoxypodophyllotoxin, 8-prenylkaemferol, quercetin, kaempferol, 8,2'-diprenylquercetin 3-methylether and 8-prenylquercetin, in Sinopodophylli Fructus. The chromatographic separationwas achieved on a C₁₈ analytical column with a gradient mobile phase consisting of acetonitrile and 0.05% phosphoric acid at a flowrate of 1.0 mL/min. UV detection was set at 290 nm and 370 nm, and the column oven was set at 35 °C. This method provided a good reproducibility, and its overall intra- and inter-day precision was less than 3% and 4%, respectively. The recovery of the method was 98.29%–101.60%, and a good linearity (R²≥0.9992) was obtained for all the analytes over a relatively wide range of concentration. A total of 17 samples of S. hexandrum (12 fruits, 5 roots and rhizomes) were collected from different areas and then successfully quantified. The results indicated that the contents of eight compounds significantly varied (the sum content rangedfrom 16.90 to 55.68 mg/g), and prenylated flavonoids could be used as marker constituents in the identification and quality control of Sinopodophylli Fructus.     

A new lignan from the seeds of Arctium lappa

A new compound, neoarctin A (1), together with nine known compounds (2-10), were obtained from the ethanolic extract of the seeds of Arctium lappa. The structure of 1 was elucidated on the basis of spectral and chemical evidence.     

杜仲木脂素化合物降压药效学研究与机制初探

目的:研究杜仲中木脂素化合物(EUL)的降血压作用并初步探讨降压机制。方法:SHR大鼠实验组分为低、中、高3个剂量组给予EUL溶液,连续给药4周,每周定时测量血压、心率和体重。100例高血压受试者随机分为2组,实验组服用EUL胶囊,对照组服用安慰剂,连续给药4周,定期测量血压。去甲肾上腺素预收缩内皮完整的离体SD大鼠胸主动脉血管环,累积加入不同浓度EUL溶液,观察舒张变化。结果:EUL高剂量与模型组相比,能降低SHR大鼠血压(P<0.05),对大鼠体重和心率均无影响。实验组高血压患者服用EUL胶囊后,收缩压、舒张压与服用前相比显著下降(P<0.01),与对照组相比显著降低(P<0.01)。NE预收缩离体血管环,EUL累积浓度升高,舒张率增大。结论:EUL有一定的降压作用,作用是使血管扩张,为进一步阐明杜仲降血压机制提供参考。     

Dietary Phytoestrogen, Serum Enterolactone and Risk of Prostate Cancer: The Cancer Prostate Sweden Study (Sweden)

Objective

Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer.

Methods

In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer.

Results

High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57–0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15–0.55), 0.63 (95% CI: 0.35–1.14) and 0.74 (95% CI: 0.41–1.32).

Conclusions

Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.     

Antihypertensive effect of Eucommia ulmoides Oliv. extracts in spontaneously hypertensive rats

Aim of the study

To investigate the antihypertensive fractions of Eucommia ulmoides Oliv. and their underlying mechanisms in spontaneously hypertensive rats (SHRs).

Materials and methods

In vivo study, Eucommia ulmoides lignans (EuL) and Eucommia ulmoides iridoids (EuI) were administrated to Sprague–Dawley (SD) rats and SHRs, and their blood pressures were measured. Plasma level of nitric oxide (NO) was measured by colorimetric method, and renin activity (RA) and plasma concentration of angiotensin II (Ang II) were measured by radioimmunoassay. In vitro study, rat mesenteric artery was treated with EuL and the vessel relaxation responses were determined.

Results

EuL could lower blood pressures of both SD rats and SHR dose-dependently by either intravenous (i.v.) or intragastric (i.g.) administration, but EuI failed to affect blood pressure in the two kinds of rats. Meanwhile, no synergistic effect was observed with the combination of EuL and EuI. The plasma level of NO in SHR treated with EuL 300 mg/kg twice a day was markedly increased. Both plasma RA and Ang II level were decreased with long-term oral treatment of EuL 150 and 300 mg/kg twice a day. In perfusion experiment, EuL relaxed mesenteric artery quickly and dose-dependently and the effect on the artery with and without endothelium was the same.

Conclusions

EuL may be the effective fraction to lowering blood pressure and its antihypertensive effect is probably associated with regulating NO and renin–angiotensin system (RAS) and directly relaxing artery.