Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4

AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.

玄参中苯丙素苷Acteoside对小鼠高尿酸血症的影响

目的探讨玄参中苯丙素苷Acteoside对小鼠高尿酸血症的影响及可能的作用机理。方法从玄参根中分离提取苯丙素苷成分Acteoside,采用次黄嘌呤造成小鼠高尿酸血症,观察Acteoside对小鼠高尿酸血症的影响,并进一步从体外观察Acteoside对黄嘌呤氧化酶的抑制作用。结果Acteoside能显著降低高尿酸血症小鼠体内的尿酸水平,体外实验显示其对黄嘌呤氧化酶有明显的抑制作用,IC50为12.25μgml-1。结论玄参中Acteoside在小鼠高尿酸血症中的降尿酸作用可能与其抑制黄嘌呤氧化酶作用有关。

Isolation and Purification of Plantamajoside and Acteoside from Plant Extract of Plantago asiatica L. by High Performance Centrifugal Partition Chromatography

Two phenylethanoid glycosides（PhGs）, plantamajoside and acteoside, were isolated and purified from the aerial parts ofPlantago asiatica for the first time by high performance centrifugal partition chromatography（HPCPC） with ethyl acetate, n-butanol, ethanol and water（0.5：0.5：0.1：1, volume ratio） as solvent system. A total of 45.6 mg of plantamajoside and 293.8 mg of acteoside were purified from 1341 mg of the n-butanol extract of P. asiatica, with a purity of 〉93.3% as determined by HPLC. The HPCPC fractions were analyzed by HPLC-DAD and the structures were identified by their retention time, UV, electrospray ionization multi stage tandem mass spectrometry（ESI-MSn） in the negative ion mode, and confirmed by NMR experiments. The characteristic fragment ions of ESI-MS of the two PhGs isolated from Plantago asiatica were discussed, which are specific and useful for the identification of the structures of PhGs.

Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs

Acteoside(verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a phamacokinetic(PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve(AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg·min·L-1 for oral administration of 10, 20, and 40 mg·kg-1, respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

Neuroprotective effect of chitosan nanoparticle gene delivery system grafted with acteoside (ACT) in Parkinson's disease models

Developing new drugs to treat Parkinson's disease efficiently is challenging. Here we report that chitosan nanoparticles(APPDNs) could serve as novel candidates for the design of anti-PD drugs. In this study, we investigated the effects of chitosan poly ethyleneglycol-poly lactic acid(PEG-PLA) nanoparticles conjugated with nerve growth factor(NGF), acteoside(ACT) and plasmid DNA(p DNA) for PD therapy using in vitro and in vivo models. Using PD cell models, we demonstrated that APPDN had good neuroprotective effects. More significantly, experiments using mouse PD models demonstrated that APPDNs could ameliorate the behavioral disorders of sick mice. Immunohistochemical and western blot(WB) analyses demonstrated that APPDNs could significantly reverse dopaminergic(DA) neuron loss in the substantia nigra and striatum of sick mice. This study opens up a novel avenue to develop anti-PD drugs.

紫珠的水溶性成分(英文)

目的:研究中药紫珠的水溶性成分。方法:运用多种色谱技术进行分离纯化,运用光谱技术鉴定化合物结构。结果:从紫珠的水溶性提取物中分离到4个苯丙素苷类化合物,分别鉴定为连翘苷(forsythoside B,1),arenarioside(2),类叶升麻苷(acteoside,3)和异类叶升麻苷(isoacteoside,4)。结论:这4个化合物都是首次从该植物中分离得到。

短腺小米草水溶性化学成分的研究

目的 :研究短腺小米草水溶性部分的化学成分。方法 :大孔吸附树脂和硅胶柱色谱 ;IR和NMR等技术鉴定结构。结果 :分离鉴定了 2个特殊的、结构非常接近的苯丙素苷 ,acteoside和eukovoside。结论

短茎马■蒿化学成份研究

目的研究短茎马芙蒿的有效化学成份，为临床应用提供依据。方法通过冷浸、革取及硅胶柱层析获得单体化合物，用波谱分析及与标准样品对照的方法，确定其化学结构。结果从短茎马蒿中分离获得3个单体化合物，鉴定为：红景天甙（Ⅰ）、acteoside（Ⅱ）、β-胡萝卜甙（Ⅲ）。结论短茎马蒿中含有苯丙素我类化合物。

凌霄花的化学成分与抗生育活性(英文)

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。

苯丙素苷化合物的合成研究进展

生物活性有机化合物的合成是有机化学的重要前沿领域之一。苯丙素苷是一类天然糖苷类化合物的总称,具有抗肿瘤、抗病毒、抗氧化、消炎等生物活性,其全合成是一项具有重要科学意义和挑战性的研究工作。本论文对具有广泛生物活性的天然化合物糖苷苯丙素苷全合成研究进展进行了概述。

Isolation and Identification of Antioxidative Active Component from Total Flavonoids of Mimenghua

In this study, bioassay-guided isolation, identification and biological evaluation of antioxidant components from total flavonoids of Chinese herbal plant Mimenghua were performed. 1, 1-Diphenyl-2-picrylhydrazyl(DPPH) radical scavenging test was adopted as the bioassay-guided method, Sephadex LH-20 column chromatography and high performance liquid chromatography were used as the purification tools for the acquisition of antioxidant components. One compound was obtained and identified as acteoside by its physicochemical properties and spectral characteristics. Antioxidant activity in vitro of acteoside was determined by evaluation of the scavenging activity on DPPH radical and hydroxyl radical, reducing power and total antioxidant capability.The results showed that acteoside had significant antioxidative activity and possessed higher activity with the increase of concentration, which provides the potential application of acteoside in food, pharmaceutical and cosmetic industries.

Brain protection of AC in PTZ-induced epileptic rats

Objective:To investigate the neuroprotective effect and mechanism of Acteoside(AC)on brain injury in epileptic rats.Methods:30 Sprague-Dawlay rats(SPF grade,healthy males,about 200g)were randomly divided into epilepsy group,AC group and blank control group.The epileptic group and the AC group were given 28 days of intraperitoneal injection of pentaerythritazine(PTZ),and the remaining groups were given normal saline injection.The changes of electroencephalogram(EEG),learning and memory ability,pathological changes of brain tissue,superoxide dismutase(SOD)and malondialdehyde(MDA)were observed in all rats.Results:Compared with the epilepsy group,the AC group showed significantly reduced degeneration and necrosis of nerve cells in brain tissue,significantly improved learning and memory ability,and the EEG was dominated by wavelet and slow wave,replacing the typical spike and spike waves.SOD increased and MDA decreased in oxygen radical(P<0.05).Conclusions:Epilepsy are closely related to Oxidative stress.AC can play a protective role in the brain by improving EEG,learning and memory ability,regulating changes in SOD and MDA content,and inhibiting the generation of oxygen free radicals.

Complete biosynthesis of the phenylethanoid glycoside verbascoside

Verbascoside,which was first discovered in 1963,is a well-known phenylethanoid glycoside(PhG)that exhibits antioxidant,anti-inflammatory,antimicrobial,and neuroprotective activities and contributes to the therapeutic effects of many medicinal plants.However,the biosynthetic pathway of verbascoside remains to be fully elucidated.Here,we report the identification of two missing enzymes in the verbascoside biosynthesis pathway by transcriptome mining and in vitro enzymatic assays.Specifically,a BAHD acyltransferase(hydroxycinnamoyl-CoA:salidroside hydroxycinnamoyltransferase[SHCT])was shown to catalyze the regioselective acylation of salidroside to form osmanthuside A,and a CYP98 hydroxylase(osmanthuside B 3,30-hydroxylase[OBH])was shown to catalyze meta-hydroxylations of the p-coumaroyl and tyrosol moieties of osmanthuside B to complete the biosynthesis of verbascoside.Because SHCTs and OBHs are found in many Lamiales species that produce verbascoside,this pathway may be general.The findings from the study provide novel insights into the formation of caffeoyl and hydroxytyrosol moieties in natural product biosynthetic pathways.In addition,with the newly acquired enzymes,we achieved heterologous production of osmanthuside B,verbascoside,and ligupurpuroside B in Escherichia coli;this work lays a foundation for sustainable production of verbascoside and other PhGs in micro-organisms.

Application of ~1H NMR-based metabolomics for discrimination of different parts and development of a new processing workflow for Cistanche deserticola

Cistanche deserticola(CD) is one of the two authoritative source plants of Cistanches Herba, a well-known medicinal plant. Herein,~1H NMR spectroscopy was employed to characterize the chemical profile and to distinguish the different parts, as well as to propose a new processing workflow for CD.Signal assignment was achieved by multiple one and two dimensional NMR spectroscopic techniques in combination with available databases and authentic compounds. The upper parts of the plant were distinguished from the lower parts by combining ~1H NMR spectroscopic dataset with multivariate statistical analysis. A new processing method that hyphenated steaming with freeze-drying, was demonstrated to be superior to either steaming coupled with oven-drying or direct freeze-drying via holistic ~1H NMR-based metabolomic characterization. Phenylethanoid glycosides, mainly echinacoside and acteoside, were screened out and confirmed as the chemical markers responsible for exhibiting the superiority of the new processing workflow, whereas serial primary metabolites, especially carbohydrates and tricarboxylic acid cycle metabolites, were found as the primary molecules governing the discrimination between the upper and lower parts of the plant. Collectively,~1H NMR spectroscopy was demonstrated as a versatile analytical tool to characterize the chemical profile and to guide the indepth exploitation of CD by providing comprehensive qualitative and quantitative information.