人参药性菌质正丁醇部位化学成分(Ⅰ)

目的:对人参药性菌质中正丁醇部位化学成分进行研究,阐明其药效物质基础。方法:采用薄层色谱、硅胶柱色谱、Sephadex LH-20凝胶色谱、半制备液相等方法进行分离纯化,通过波谱数据和理化常数鉴定其化合物结构。结果:从人参药性菌质正丁醇部位中分离并鉴定得到5个化合物,分别为20(S)-人参皂苷-Rg2(1),20(R)-人参皂苷-Rg2(2),人参皂苷Rg1(3),20(S)-人参皂苷Rf(4),人参皂苷Rb1(5)。结论:所有化合物均为首次从人参药性菌质中分离得到。     

人参总皂苷对野百合碱诱导的大鼠右室肥厚及ERK通路的影响

目的:观察人参总皂苷(Total Ginsenosides,TG)对野百合碱(Monocrotaline,MCT)所致大鼠右心室肥厚的影响并探讨其与细胞外信号调节激酶(ERK)信号通路的关系。方法:雄性SD大鼠随机分为正常对照组,MCT模型组,TG 20 mg/(kg·d)、40 mg/(kg·d)、60 mg/(kg·d)剂量组,各组动物均给药18 d。测定各组大鼠的右室肥厚指数(RVHI)、右心重/体重(RVW/BW);透射电镜观察心肌细胞超微结构的改变;Real time RT-PCR检测心肌组织ERK1mRNA的表达,Western blotting检测心肌组MKP-1蛋白质的表达。结果:TG预防给药均使RVHI、RV/BW表达明显降低,改善超微结构损伤,降低心肌组织ERK1mRNA和提高MKP-1蛋白质的表达。结论:TG能明显改善MCT诱导的大鼠右心室肥厚,其抗心肌肥厚作用至少与抑制ERK1信号转导通路有关。     

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure–activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as “the King of all herbs” could be regarded as a well‐characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.     

Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides

BACKGROUND: Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro. METHODS: We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds. RESULTS: 25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies. CONCLUSIONS: The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent.     

Differential regulations of blood pressure and perturbed metabolism by total ginsenosides and conventional antihypertensive agents in spontaneously hypertensive rats

Aim:

To investigate the regulatory effects of total ginsenosides and the conventional antihypertensive agents (captopril, amlodipine, terazosin and hydrochlorothiazide) on the blood pressure and perturbed metabolism in spontaneously hypertensive rats (SHRs) and to analyze the cause-effect relationships between high blood pressure and the metabolic disorders of hypertension.

Methods:

SHRs were administrated with total ginsenosides or the antihypertensive agents for eight weeks. Systolic blood pressure (SP) was measured every week and low-molecular-weight compounds in blood plasma were quantitatively analyzed using a nontargeted high-throughput metabolomic tool: gas chromatography/time of flight mass spectrometry (GC/TOFMS) . The metabolic patterns were evaluated using principal components analysis and potential markers of hypertension were identified.

Results:

Total ginsenosides and the antihypertensive agents differentially regulated SP and the metabolic pattern in SHRs. Total ginsenosides caused a progressive and prolonged reduction of SP and markedly normalized the perturbed metabolism with 14 of 27 (51.8%) markers of hypertension which were regulated toward normal. Total ginsenosides also reduced free fatty acids'' level toward normal levels. In contrast, captopril, amlodipine and terazosin efficiently depressed SP, but had little effect on metabolic perturbation with only 8 (29.6%), 4 (14.8%), and 4 (14.8%) markers, respectively, which were regulated.

Conclusion:

The metabolic changes persisted when the blood pressure was lowered by the conventional antihypertensive agents, suggesting that hypertension may not be the cause of the metabolic perturbation in SHRs.     

生脉散组分配伍对热损伤大鼠糖皮质激素受体的影响

目的：研究生脉散组分配伍对热损伤大鼠糖皮质激素受体（glucocorticoid receptor,GR）的影响。 方法：雄性SD大鼠32只随机分为正常对照组、模型组、人参总皂苷组和生脉散组分配伍组（简称组分配伍组）,每组8只,连续灌胃1周进行预处理。除正常对照组外,其余各组大鼠于末次给药30min后复制大昂热损伤模型。随后立即断头处死动物,收集血清和肝、肺、肾脏组织。酶联免疫吸附测定法（enzyme-linked immkinosorbent assay,ELISA）检测血清皮质酮（corticosterone,CS）的浓度,放射免疫检测法（radioimmunoassay,RIA）检测血清促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）的浓度;放射性配体受体结合法（radioligand receptor binding assay,RRA）检测肝、肺、肾细胞液GR结合容量。 结果：模型组肝、肺、肾胞液GR明显低于正常对照组（P〈0.01）。组分配伍组肝和肺胞液GR结合容量明显高于模型组（P〈0．01）,肾胞液GR结合容量与模型组比较,差异无统计学意义。组分配伍组肝胞液GR明显高于人参总皂苷组（P〈0．01）,肺和肾胞液GR结合容量与人参总皂苷组比较有上升的趋势．但差异无统计学意义。正常大鼠CS及ACTH水平与模型组、组分配伍组和人参总皂苷组比较,差异有统计学意义（P〈0．01）,模型组CS及ACTH水平与各给药组比较,差异无统计学意义。 结论：生脉散组分配伍可增强人参总皂苷上调热损伤大鼠GR水平的作用。     

人参皂甙改善老龄小鼠学习记忆的研究

目的探讨人参皂甙对自然衰老的C57BL/6J小鼠学习记忆的改善作用及其机制。方法20月龄的C57BL/6J小鼠80只,随机分为老年对照组和25、50、100mg/(kgbw·d)人参皂甙干预组,另设3月龄青龄对照组(n=20)。人参皂甙随饮水摄入,共干预6个月。干预结束后应用Morris水迷宫试验检测小鼠的空间学习记忆能力;并检测各组小鼠血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及MDA含量;Nissl染色观察海马神经元数量的改变;Westernblot方法观察海马区脑源性神经营养因子(BDNF)的表达。结果50,100mg/(kgbw·d)人参皂甙干预6个月后能明显提高小鼠的空间学习记忆能力;血清中SOD、GSH-Px活性明显增强,MDA含量显著下降;海马BDNF蛋白的表达明显增强。25mg/(kgbw·d)人参皂甙干预后血清GSH-Px的活性显著提高。各组动物海马神经元数量无明显差别。结论50、100mg/(kgbw·d)人参皂甙干预能够延缓老龄小鼠学习记忆功能的减退,减轻机体氧化损伤,增强海马区BDNF蛋白的表达可能是其重要的作用机制。     

Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes

1. The effects of four individual ginsenosides (Rb1, Rb2, Rc and Rd), two ginkgolides (A and B) and one flavonoid (quercetin) on CYP2C19-dependent S-mephenytoin 4 cent-hydroxylation and CYP2D6-mediated bufuralol 1 cent-hydroxylation were evaluated in human liver microsomes. 2. Increasing concentrations of each test compound were added to microsomal incubation mixtures containing a well-characterized marker substrate (S-mephenytoin for CYP2C19 or bufuralol for CYP2D6) to determine their IC(50) values (compound concentration yielding 50% inhibition of a marker enzyme activity), which were estimated by graphical inspection. 3. For CYP2C19, the IC(50) values were 46, 46 and 62 micromol/L for ginsenoside Rd, quercetin and ginsenoside Rb2, respectively, whereas only ginsenoside Rd had an IC(50) value of 57 micromol/L for CYP2D6. 4. The data suggest that the tested compounds are not likely to inhibit the metabolism of the concurrent use of a given drug whose primary route of elimination is through CYP2C19 or CYP2D6.     

人参总皂甙对缺血性急性肾功能衰竭大鼠肾脏的保护作用

目的 探讨人参总皂甙对缺血性急性肾功能衰竭肾脏的保护作用.方法 采用钳夹右肾蒂1 h再灌注并切除左肾法制备缺血性急性肾功能衰竭大鼠模型,观察再灌注24h后血清BUN、Scr含量,ET-1、NO水平和肾组织病理改变.结果 治疗组大鼠血清BUN、Scr含量与I/R组比较明显下降并有显著差异(P＜0.05),与对照组无差异(P＞0.05);治疗组血清NO水平与I/R组比较明显提高亦有显著差异(P＜0.05);肾组织病理示:治疗组肾小管病变明显轻于I/R组(P＜0.01).结论 人参总皂甙对缺血性肾功能衰竭肾脏有明显保护作用,其对NO水平的调节可能是这一保护作用的机理之一.     

HPLC法测定人参、西洋参和三七不同部位中人参皂苷的含量

目的:为了探讨人参、西洋参和三七中人参皂苷的资源含量,以确保人参、西洋参和三七中人参皂苷资源充分被利用,为开发以人参皂苷为主的创新药物提供科学数据。方法:采用高效液相色谱法对人参、西洋参和三七不同部位中人参皂苷的含量进行测定。色谱条件为:Agilent 1100 Series 高效液相色谱仪;色谱柱为德国 Nucleosil-C_(18)(4.6 mm×150 mm,5μm);流动相为水-乙腈梯度洗脱,流速1.5 mL·min~(-1);A为水,B为乙腈;梯度洗脱程序为:0～16 min,56%B;16～20 min,56%→100%B;20～38 min,100%B;38～45 min,100%→56%B;45～60 min,56%B;60～70 min,56%B。所有组分均70 min 内出完。检测波长203 nm,柱温35℃,灵敏度为0.02AUFS。线性关系考察r=0.9994;精密度试验 RSD=0.26%,平均回收率为99.88%,重现性试验 RSD=2.0%,分离度为R=3.042。结果:人参须根含有较高的人参皂苷 Rb_1(1.082%),人参茎叶则含有较高的人参皂苷 Rc(1.002%)、Re(3.430%)和 Rg_1(1.303%);西洋参根含有较高的人参皂苷 Rb_1(2.213%)和 Re(0.9188%),西洋参芦头中含有较高的人参皂苷 Rb_1(2.840%)和Re(1.224%);三七根含有较高的人参皂苷 Rb_1(2.163%)和 Rg_1(2.633%),三七芦头中含有较高的人参皂苷 Rb_1(4.376%)和 Rg_1(4.145%)。结论:高效液相色谱法分离、分析人参皂苷效果好、准确、迅速、简便,也可作为评价人参属植物质量的有效分析方法。建议对人参、西洋参和三七中含量较高的人参皂苷进行提取分离,直接用于创新药物的开发。