A novel cytotoxic lignan from Seseli annuum L

A new tetrahydrofuranoid lignan named seselinone was isolated from the aerial parts of Seseli annuum, together with three known lignans (eudesmin, magnone A and hernone) and prenylated coumarin umbelliprenin. Seselinone and eudesmin showed cytotoxic activity against C6 rat glioma cell cultures.     

Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells – Study of structure–activity relationship

A panel of nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, γ-schizandrin and wuweizisu C was examined for their effect on multidrug resistance, as well as their anti-proliferative activities. COR-L23/R, a multidrug resistant sub-line, which has been reported to over-express multidrug resistance-associated protein (MRP1), was used for the experiments together with its parent cell line COR-L23 (human lung cell carcinoma). We found that lignans deoxyschizandrin and γ-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin to COR-L23/R cells. Deoxyschizandrin and γ-schizandrin also significantly enhanced the accumulation of doxorubicin in drug resistant cells. Both lignans alone had no effect on the cell cycle; however, when combined with sub-toxic doses of doxorubicin, they induced cell cycle arrest in the G2/M phase, which is typical for toxic doses of doxorubicin. Our results suggest that deoxyschizandrin and γ-schizandrin potentiate the cytotoxic effect of doxorubicin in doxorubicin resistant lung cancer cells COR-L23/R by increasing the accumulation of doxorubicin inside the cells. The common structural feature of both active lignans is the R-biaryl configuration and the absence of a hydroxy group at C-8. Unlike the reversal effect, the cytotoxicity of lignans with the R-biaryl configuration was similar to that observed for lignans with the S-biaryl configuration.     

Protective effects of Eucommia lignans against hypertensive renal injury by inhibiting expression of aldose reductase

Aim of the study

To investigate the protective effects and the underlying mechanism of Eucommia lignans against hypertensive renal injury.

Material and methods

Ten-week-old Wistar Kyoto rats and age matched spontaneously hypertension rats were used in the study. The SHR were randomly divided into 4 groups (n = 7 for each group) and received different treatment for 16 weeks, which including saline, Captopril, Epalrestat and Eucommia lignans, respectively. System blood pressures of the rats were monitored once every 4 weeks. N-Acetyl-β-d-glucosaminidase (NAG) activity and the ratio of albumin and urinary creatinine were chosen as the indices of kidney function. Then the structure and renal collagen type III expression of glomerular basement membrane were observed by microscopy and the renal aldose reductase (AR) expression was measured by immunohistochemistry. In vitro, the proliferation of mesangial cells induced by AngII was assayed by MTT, and the mRNA expression of AR was measured by RT-real-time PCR.

Results

The renal function, evaluated by NAG enzyme activity and the ratio of albumin to urinary creatinine, was significantly ameliorated by Eucommia lignans treatment. Meanwhile, Eucommia lignans decreased both the protein (P < 0.05) and the mRNA expressed lever of AR (P < 0.05). Eucommia lignans also decreased the high expression of collagen type III in SHR (P < 0.05) and inhibited the proliferation of renal mesangial cells induced by AngII (P < 0.05).

Conclusion

Eucommia lignans have protective effects against hypertensive renal injury, and the protective effects may be partly due to inhibition of aldose reductase.     

Dibenzylbutane- and butyrolactone-type lignans as apoptosis inducers in human hepatoma HuH-7 cells

Seven lignans, previously isolated from Pycnanthus angolensis or obtained by derivatization, namely the dibenzylbutane-type lignans threo-4,4'-dihydroxy-3-methoxylignan (1), 4'-hydroxy-3,3',4-trimethoxylignan (2), (-)-dihydroguaiaretic acid (3), 3,3',4,4'-tetramethoxylignan (4), 4,4'-diacetyl-3,3'-dimethoxylignan (5), heliobuphthalmin (6) and the butyrolactone lignan hinokinin (7), were evaluted for their ability as apoptosis inducers in human hepatoma HuH-7 cells. Cell viability assays, morphological evaluation of apoptosis and enzymatic analyses of caspase activity in HuH-7 cells were carried out. Using the lactate dehydrogenase lactate dehydrogenase (LDH) assay, it was demonstrated that the lignans (1-7) tested significantly reduced viability of HuH-7 cells. Morphologic evaluation of HuH-7 cells using Hoechst staining and fluorescence microscopy revealed that lignans 1-7 were strong inducers of apoptosis. In fact, HuH-7 cells developed morphological changes of apoptosis, including chromatin condensation, nuclear fragmentation and formation of apoptotic bodies. However, lignans 2 and 7 were the most promising compounds in this study, inducing 2.4- and 2.5-fold increases in apoptotic cells as compared to controls. Caspase-3-like activity assays confirmed the morphologic data.     

Lignans with anti-hepatitis B virus activities from Phyllanthus niruri L

One new lignan, nirtetralin B, along with its two known stereoisomers were isolated from Phyllanthus niruri L. The structure of the new compound was determined by spectroscopy experiments and x‐ray diffraction analysis. These lignans were assayed for anti‐hepatitis B virus activities in vitro. Nirtetralin and nirtetralin A, B effectively suppressed the secretion of the HBV antigens in a dose‐dependent manner with IC₅₀ values for HBsAg of 9.5 µm (nirtetralin A), 16.7 µm (nirtetralin B) and 97.2 µm (nirtetralin), IC₅₀ values for HBeAg of 17.4 µm (nirtetralin A), 69.3 µm (nirtetralin B) and 232.0 µm (nirtetralin), respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

CD在木脂素类化合物绝对构型测定中的应用

目的介绍圆二色谱(circular dichroism,CD)在木脂素类化合物绝对构型测定中的应用规律。方法在查阅国内外相关文献的基础上,对CD在芳基萘类、联苯环辛烯类、二苄基丁内酯类、双四氢呋喃类、苯并呋喃类等木脂素类化合物绝对构型测定中的应用规律进行综述。结果 CD在木脂素类化合物绝对构型测定中的应用具有一定的规律性。结论初步总结了CD在木脂素类化合物绝对构型测定中的应用规律,以期为该类化合物绝对构型测定提供有益的参考。     

HPLC法同时测定不同产地五味子中8种木脂素类成分

目的 测定产自辽宁、河北和黑龙江省的五味子中五味子醇甲、戈米辛J、五味子醇乙、戈米辛G、五味子酯甲、五味子甲素、五味子乙素和五味子丙素8种木脂素成分,为其质量控制提供检测手段.方法 五味子用甲醇超声提取,色谱柱为依利特ODS-C18(250 mm ×4.6 mm,5μm);流动相为乙腈(A)-水(B),梯度洗脱(0～17 min,A为50％;17 ～ 25 min,,A为50％ ～55％;25～30 min,A为55％～75％;30 ～ 35 min,A为75％;35 ～ 40 min,A为75％ ～65％;40～45 min,A为65％ ～50％);体积流量1.0 mL/min;柱温30℃;检测波长217 nm.结果 8种被测木脂素成分分离度良好;各成分质量浓度与峰面积在测定范围内均呈良好的线性关系(r ＞0.999 5);重复性良好;加样回收率(RSD)(n=9)分别为99.75％(0.38％)、100.69％ (2.31％)、100.46％( 1.39％)、99.87％( 1.15％)、100.22％( 1.45％)、100.15％(0.99％)、100.61％(0.25％)和101.31％(1.03％).结论 本实验所建立的HPLC方法稳定可靠、简便可行,可用于五味子中木脂素类成分的同时定量分析.     

化学计量学方法研究北五味子中木脂素含量与抗氧化活性的相关性

目的:通过五味子抗氧化活性与木脂素含量的相关性分析,建立五味子抗氧化活性的快速评价方法。方法:采用高效液相色谱测定了采自吉林省不同地区的37批不同五味子样品中的5种木脂素的含量,并分别从抑制肝、肾、脑中脂质过氧化能力和清除.DPPH自由基能力几方面测定了上述样品的抗氧化活性。以SPSS 11.5软件进行了双变量相关性(biva-riate)分析及多元线性回归的逐步回归(stepwise)分析。结果:双变量相关性分析结果表明,五味子醇甲与抑制肝脏、脑脂质过氧化、.DPPH清除能力具有显著的相关性(P<0.01),均呈正相关;五味子醇乙与4种抗氧化活性均有相关性(P<0.05或0.01),均呈正相关;而五味子甲素与抑制肝脏、脑脂质过氧化、.DPPH清除能力具有显著的负相关性(P<0.01),五味子乙素仅与抑制脑脂质过氧化能力具有负相关性(P<0.05)。逐步回归分析结果与Bivariate分析结果基本一致,并分别得出木脂素与不同模型中抗氧化活性相关性的线性回归方程。采用另外10批样品的测定结果经回归方程模拟,所得的抗氧化活性与测定的抗氧化活性基本一致。结论:采用相关性分析和线性逐步回归分析法建立的抗氧化活性评价模型,从而确定五味子抗氧化活性的物质基础,同时还可根据所测定的五味子中木脂素的含量来推测样品的抗氧化活性。     

瑶山润楠根的化学成分研究

对樟科润楠属植物瑶山润楠Machilus yaoshansis根乙醇提取物的化学成分进行研究。利用多种色谱技术从瑶山润楠的醋酸乙酯萃取物中分离得到15个化合物;通过理化性质和波谱数据鉴定其结构为12个木脂素类(+)-愈创木素(1),kadsuralignan C(2),(+)-异落叶松脂素(3),(+)-5’-甲氧基异落叶松脂素(4),南烛木树脂酚(5),内消旋-裂环异落叶松树脂酚(6),异落叶松脂素-9’-O-β-D-吡喃木糖苷(7),5’-甲氧基-异落叶松脂素-9’-O-β-D-吡喃木糖苷(8),南烛木树脂酚9’-O-β-D-吡喃木糖苷(9),(2R,3R)-2,3-二氢-2-(4-羟基-3-甲氧基苯基)-7-甲氧基-3-甲基-5-(E)-丙烯基苯并呋喃(10),3,5’-二甲氧基-4’,7-环氧-8,3’-新木脂素-4,9,9’-三醇(11),甘密树皮素B(12),和3个黄烷类(+)-儿茶素(13),(-)-表儿茶素(14),bis-8,8’-catechinylmethane(15)。化合物1～15均为首次从该植物中分离得到。