毛蕊花糖苷的生物合成研究进展

毛蕊花糖苷是由咖啡酸、羟基酪醇、葡萄糖和鼠李糖组成的苯乙醇苷类衍生物,广泛存在于多种天然药用植物中,具有抗炎、抗菌、抗病毒、抗肿瘤、抗氧化、镇痛、神经保护、改善性功能、免疫调节和改善细胞记忆等多方面的生物活性.然而,植物提取来源的毛蕊花糖苷存在含量低、环境污染问题,无法实现绿色可持续的规模化生产.利用合成生物学成功构建...     

Attenuated endothelium-mediated relaxation by acteoside in rat aorta: Role of endothelial [Ca2+]i and nitric oxide/cyclic GMP pathway

Acteoside and other phenylethanoid glycoside are contained in many plants that are widely used in traditional Chinese herbal medicine. Acteoside possesses multiple biological actions. Its effect on the vascular system is, however, incompletely understood. This study was aimed to investigate the role of endothelial [Ca²⁺]_i, nitric oxide (NO), and cyclic GMP in acteoside-induced inhibition of endothelial NO-mediated relaxation in rat aorta. Acteoside reduced endothelial NO-dependent relaxation induced by acetylcholine (Ach) or A23187. Acteoside inhibited Ach-stimulated increase in tissue content of cyclic GMP in endothelium-intact rings. L-NNA abolished the stimulatory effect of Ach. Treatment with acteoside significantly suppressed bradykinin-induced increase in [Ca²⁺]_i of cultured rat aortic endothelial cells. Acute exposure to acteoside (30 μM) did not affect the expression of eNOS mRNA in endothelium-intact rings. In summary, acteoside impairs endothelial NO-mediated aortic relaxation partially through inhibition of agonist-induced endothelial Ca²⁺ mobilization and Ca²⁺-dependent NO production and subsequent suppression of cyclic GMP formation. This novel pharmacological action if occurring in small vessels in vivo, may contribute to the reported anti-inflammatory effect of acteoside against NO-mediated vascular permeability-related acute edema.     

Verbascoside — A review of its occurrence, (bio)synthesis and pharmacological significance

Phenylethanoid glycosides are naturally occurring water-soluble compounds with remarkable biological properties that are widely distributed in the plant kingdom. Verbascoside is a phenylethanoid glycoside that was first isolated from mullein but is also found in several other plant species. It has also been produced by in vitro plant culture systems, including genetically transformed roots (so-called ‘hairy roots’). Verbascoside is hydrophilic in nature and possesses pharmacologically beneficial activities for human health, including antioxidant, anti-inflammatory and antineoplastic properties in addition to numerous wound-healing and neuroprotective properties. Recent advances with regard to the distribution, (bio)synthesis and bioproduction of verbascoside are summarised in this review. We also discuss its prominent pharmacological properties and outline future perspectives for its potential application.     

类叶升麻苷通过上调miR-204对缺氧/复氧诱导H9C2细胞凋亡的抑制作用

目的探讨类叶升麻苷对缺氧/复氧（H/R）处理大鼠心肌细胞（H9C2）损伤的影响及其分子机制。 方法体外培养H9C2细胞,H/R （4 h/20 h）建立心肌细胞损伤模型,并采用1、10、100 μmol/L类叶升麻苷,转染miR-204模拟物阴性对照（miR-NC）、转染miR-204模拟物（miR-24）,100 μmol/L类叶升麻苷干预+转染miR-204抑制剂阴性对照、100 μmol/L类叶升麻苷+转染miR-204抑制剂干预H/R细胞。分别进行RT-qPCR、MTT、流式细胞术、Western blot检测miR-204表达水平、细胞活力、细胞凋亡率和相关蛋白表达,利用相应试剂盒检测乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平,酶联免疫吸附试验（ELISA）检测白细胞介素-6 （IL-6）、白细胞介素-β （IL-β）和肿瘤坏死因子-α （TNF-α）的含量。两组间比较采用独立样本t检验,多组间比较采用单因素方差分析,组间两两比较采用SNK-q检验。 结果与心肌损伤模型比较,10、100 μmol/L类叶升麻苷的细胞凋亡率[（25.62±1.96）%比（18.17±1.27）%,（11.24±0.57）%]、Bax（0.71±0.05比0.51±0.04、0.29±0.03）、LDH [（243.16±11.31）比（121.22±4.52）,（94.39±2.82）U/g]、MDA [（1.82±0.07）比（1.13±0.04）,（0.92±0.04）nmol/mg]、IL-6 [（121.45±6.18）比（87.16±4.53）,（47.11± 2.24）pg/mL]、IL-1β [（229.82±8.48）比（175.32±8.73）,（113.14±5.63）pg/mL]和TNF-α表达水平[（138.18±6.60）比（92.24±4.04）,（61.53±4.17）pg/mL]降低,Bcl-2 （0.18±0.01比0.35± 0.03、0.52±0.04）、SOD [（18.72±1.26）比（38.81±1.51）,（45.43±1.29）U/mg]和GSH-Px表达水平[（58.74±2.28）比（89.24±2.82）,（94.66±3.05）U/mg]升高（P均< 0.05）;与miR-NC比较,转染miR-204的细胞凋亡率[（24.12±1.12）%比（9.26±0.49）%]、Bax （0.62±0.04比0.25±0.02）、LDH [（229.11±8.47）比（86.32±5.92）U/g]、MDA [（1.75±0.08）比（0.85± 0.05）nmol/mg]、IL-6 [（134.47±7.31）比（55.26±2.13）pg/mL]、IL-1β [（211.14±9.70）比（98.11±3.18）pg/mL]和TNF-α表达水平[（152.92±3.49）比（51.34±2.66）pg/mL]降低,Bcl-2 （0.22±0.01比0.57±0.03）、SOD [（20.92±1.38）比（47.68±1.76）U/mg]和GSH-Px表达水平[（62.65±2.76）比（91.13±3.80）U/mg]升高（P < 0.05）;10、100 μmol/L类叶升麻苷可提高H/R诱导H9C2细胞中miR-204的表达水平（P < 0.05）;且下调miR-204逆转了类叶升麻苷对H/R处理H9C2细胞凋亡、氧化应激和炎症因子的影响。 结论类叶升麻苷可能通过上调miR-204表达缓解H/R诱导的H9C2细胞损伤。     

Establishment of callus and cell suspension culture of Scrophularia striata Boiss.: an in vitro approach for acteoside production

In the present study, a protocol was optimized for establishment of callus and cell suspension culture of Scrophularia striata Boiss. as a strategy to obtain an in vitro acteoside producing cell line for the first time. The effects of growth regulators were analyzed to optimize the biomass growth and acteoside production. The stem explant of S. striata was optimum for callus induction. Modified Murashige and Skoog medium supplemented with 0.5 mg/l naphthalene acetic acid + 2.0 mg/l benzyl adenine was the most favorable medium for callus formation with the highest induction rate (100 %), the best callus growth and the highest acteoside content (1.6 μg/g fresh weight). Incompact and rapid growing suspension cells were established in the liquid medium supplemented with 0.5 mg/l naphthalene acetic acid + 2.0 mg/l benzyl adenine. The optimum time of subculture was found to 17–20 days. Acteoside content in the cell suspension was high during exponential growth phase and decreased subsequently at the stationary phase. The maximum content of acteoside (about 14.25 μg/g cell fresh weight) was observed on the 17th day of the cultivation cycle. This study provided an efficient way to further regulation of phenylethanoid glycoside biosynthesis and production of valuable acteoside, a phenylethanoid glycoside, on scale-up in S. striata cell suspension culture.     

Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity

We have previously reported that acteoside isolated from the leaves of Callicarpa dichotoma has significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultured rat cortical cells. To determine the essential structural moiety within this phenylethanoid glycoside needed to exert neuroprotective activity, acteoside was hydrolyzed with acid into its aglycones, caffeic acid and 3',4'-dihydroxylphenylethanol. Caffeic acid and 3',4'-dihydroxylphenylethanol also showed significant neuroprotective activities. Acteoside and its aglycones inhibited glutamate-induced intracellular Ca2+ influx resulting in overproduction of nitric oxide and reduced the formation of reactive oxygen species. These compounds preserved the mitochondrial membrane potential and the activities of antioxidative enzymes, such as superoxide dismutase, glutathione reductase and glutathione peroxidase reduced by glutamate. It was followed by the preservation of the level of glutathione and finally the inhibition of membrane lipid peroxidation.     

Altitudinal variation of UV-absorbing compounds in Plantago asiatica

UV-absorbing compounds such as flavonoids and phenolic acids are important for plants to protect their vegetative organs from harmful UV radiation at higher altitude. Two chemotypes, i.e., acteoside mainly-containing (AM) type and plantamajoside mainly-containing (PM) type were found by qualitative HPLC analysis of the phenolics in the leaves of Plantago asiatica in Mt. Norikura, Japan. Though AM type was not detected in low altitude populations, it occurred in high altitude populations. Acteoside has been reported to be more effective antioxidant than plantamajoside. On the other hand, higher accumulations of UV-absorbing substances were seen in higher altitude populations by quantitative analyses. Besides, B-ring ortho-dihydroxylated flavonoids notably increased than mono-hydroxylated flavonoids with increasing altitude. These results demonstrate that P. asiatica has chemically acclimated to high altitudes, in which severe environmental conditions such as higher UV radiation exist.     

凌霄花的化学成分与抗生育活性

对凌霄Campsisgrandiflora(Thunb .)K .Schum .的干燥花进行了化学成分研究 ,分离获得了 10个化合物 ,并且根据它们的物理化学性质及各种光谱数据鉴定了其中的 9个化合物。它们分别是 :三十一烷醇、α ,β 香树脂醇、β 谷甾醇、15 巯基 2 十五烷酮、芹菜素、胡萝卜甙、齐墩果酸、桂皮酸、acteoside。另一结构待定的化合物 ,暂定名为CG 10。除了其中的 β 谷甾醇、芹菜素和齐墩果酸外 ,其他化合物均首次从凌霄的花中获得。除化学成分的研究以外 ,我们还进一步考察了凌霄花乙醇浸膏的石油醚、乙酸乙酯、丙酮、丙酮 :甲醇 (1∶1)、甲醇 5部分的提取部位 ,以及分到的齐墩果酸、胡萝卜甙、acteoside及CG 10等 4个化合物收缩离体孕小鼠子宫肌条的活性。首次报道了凌霄花抗生育活性部位的抗生育活性 ,其中丙酮 :甲醇 (1∶1)提取部位可以极显著的增强孕小鼠的离体子宫肌条的收缩强度 (P <0 .0 0 1)。这个研究结果提示在临床上可能有一定的应用价值。     

Phytochemical study of Stachys candida Bory & Chaubard (Lamiaceae)

Phytochemical analysis of the aerial parts of Stachys candida Bory & Chaubard, growing wild in Greece led to the isolation of eleven bioactive secondary metabolites. Nine flavones, one of them methylated, one phenylethanoid glycoside and one phenolic acid were isolated from the methanol extract of this plant. The structure elucidation of the isolated compounds was achieved on the basis of NMR spectroscopy (1D and 2D spectra). The phytochemical profile was appeared to be similar with other Greek endemic Stachys species, while a strong difference was the absence of iridoids. Importantly, the chemotaxonomic significance of the isolated compounds has extensively been described.