人参皂苷对心血管疾病的药理作用和药代动力学特征

人参皂苷是人参的主要活性成分,其在心血管方面的作用正在被广泛研究。本文简要介绍了人参皂苷对心血管疾病的药理作用及其药代动力学特点。人参皂苷能够控制心律失常,抑制心肌肥厚和心肌细胞凋亡,抑制炎症,保护血管内皮细胞,改善心肌缺血和心肌缺血/再灌注损伤,从而发挥其保护心血管系统的作用。肠道菌群广泛参与人参皂苷的代谢是其代谢特征之一。     

三七皂苷药物动力学及体内代谢研究进展

三七Panax notoginseng(Burk.)F.H. CHEN与人参同为名贵的古老中药,对心血管、血液、免疫系统及代谢均有一定药理作用.三七总皂苷[1](total saponins of Pnanx notoginseng,PNS)为三七根茎的有效部位,主要是达玛烷型20(S)-原人参二醇型(ppd)和20(S)-原人参三醇型(ppt)四环三萜皂苷,不含齐墩果酸型皂苷,单体的含量和比例与人参亦不同.本文对三七皂苷的药物动力学、体内代谢及其代谢产物活性的研究进展进行了简要综述.     

人参皂苷对心血管系统药理作用的研究

人参对心血管系统具有良好的保护作用,其提取物人参皂苷有明显的耐缺氧作用,可加快脂质代谢,增强心肌收缩力,减慢心率,增加心输出量与冠脉血流量,可抗心肌缺血与心律失常。本文就近年有关人参皂苷在心血管方面的药理作用研究概况做一综述。     

人参挥发油化学成分及其主要活性成分聚乙炔醇类药理作用研究进展

目的:为进一步研究及开发利用人参提供参考。方法:以"人参""挥发油""活性成分""聚乙炔醇类""药理作用""Panax ginseng""Volatile oils"等为关键词,组合查询1977年1月-2016年9月的Pub Med、Elsevier、Science Direct、中国知网、万方、维普等数据库中的相关文献,对人参挥发油化学成分及其主要活性成分聚乙炔醇类药理作用进行综述。结果与结论:共检索到相关文献108篇,其中有效文献44篇。人参挥发油化学成分包括萜类、醇类、酮类、醛类、酚类、杂环类、脂肪酸及其酯类化合物、烷烃及其他化合物等,目前对醇类所含以人参炔醇、人参环氧炔醇为代表的聚乙炔醇类物质的药理作用研究较为深入,该类物质具有营养及保护神经细胞、抗肿瘤、预防心脑血管系统疾病、抗炎止痛等药理作用。萜类中的倍半萜类是人参挥发油化学成分的主要组成物质,但对其有效部位的研究较欠缺。建议在化学成分方面,应着重围绕人参挥发油中倍半萜类有效部位、聚乙炔醇类有效部位的各单体结构确证、结构转化等方面展开研究;在药理作用方面,对聚乙炔醇类物质在神经系统保护、抗肿瘤、防治心脑血管系统疾病等的作用机制及构效关系展开研究;在开发利用方面,对人参挥发油的成药性、有效部位或有效成分制备工艺、稳定性、储存条件、安全性等展开研究。     

黑参的化学成分及药理作用研究进展与展望

黑参是将人参经微生物发酵或多次蒸晒的方法炮制而成，其在化学成分及药理作用方面发生了显著变化，增加多种药理活性。作为新的人参炮制品种，近年来国内外对黑参的研究越来越多。依据黑参加工炮制程度，黑参的化学成分较人参发生较大变化，原级皂苷含量减少，稀有皂苷含量大大提高，其中主要成分为人参皂苷20(R+S)Rg₃、Rg₅、Rk₁和Rk₃等。黑参具有抗癌、抗心力衰竭、免疫调节与抗炎、抗糖尿病、对中枢神经系统影响等药理作用。黑参与人参及红参相比，其优势在于稀有皂苷成分含量提高，药理作用增强。本文通过查阅近十年国内外文献，对黑参的化学成分、药理作用及其作用机制进展进行综述，为黑参的开发利用奠定基础。     

人参皂苷水溶液热稳定性研究

目的 研究加热时间对人参皂苷水溶液的影响及受热后人参皂苷含量的变化情况。方法 红参须浓缩液加热不同时间,采用高效液相色谱法测定其人参皂苷Rg1、Re、Rb1、Rc和Rd的含量。结果 5种人参皂苷在加热6 h内,发生不同程度的降解反应,二醇类人参皂苷Rb1、Rc和Rd在加热2-3 h时,含量呈明显下降趋势,人参皂苷Rd降解速率最慢。三醇类人参皂苷Rg1和Re在加热3 h内含量快速下降,3 h后趋于平缓。结论 在常压受热条件下,人参皂苷水溶液主要成分人参皂苷Rg1、Re、Rb1、Rc和Rd的含量,随加热时间延长而不断下降,3 h后下降速率减缓。三醇类人参皂苷较二醇类对热更为敏感。     

人参皂苷对细胞自噬信号通路调控作用的研究进展

细胞自噬是细胞在自噬相关基因(Atg)的调控下,利用溶酶体降解自身受损的细胞器和大分子物质的过程。细胞自噬的主要信号通路包括有依赖mTOR的PI3K/Akt信号通路、AMPK信号通路、以及非依赖mTOR的Beclin-1和p53信号通路。人参皂苷是一种固醇类化合物,主要存在于人参属中药材中,是人参中重要的活性成分,在肿瘤,心脑血管疾病,免疫系统等疾病的临床治疗中发挥显著地疗效。近年来研究报道,多种人参皂苷单体及其代谢产物的药理作用与细胞自噬有关,其作用机制涉及多条细胞自噬信号通路。本文综述人参皂苷对细胞自噬的作用及其相关自噬信号通路的调控作用的最新研究进展,以期为人参皂苷临床治疗相关疾病提供进一步的理论指导和实验参考。     

人参化学成分的免疫作用及其机制的研究进展

人参是我国传统名贵中药材,具有良好的免疫药理作用,对其免疫作用及机制的研究已成为热点。因此,文章综述了人参中人参总皂苷、人参皂苷单体、人参多糖和人参蛋白的免疫作用及其作用机制。旨在为人参产业化发展及应用提供一定的科学依据。     

人参皂苷Rd的药理作用研究进展

人参皂苷Rd(ginsenoside Rd,GSRd)是人参皂苷的主要活性单体之一,属于达玛烷型人参皂苷中的二醇型。GSRd在人参属植物中的含量较低,但却具有较强的生物活性,其药理作用受到国内外学者的广泛关注。研究表明,GSRd能够保护心血管及肾脏功能,发挥抗肿瘤、调节免疫等多种药理作用,对于中枢神经系统亦显示出良好的神经保护效应。文中对人参皂苷Rd的药理作用特别是人参皂苷Rd的神经保护作用进行了综述。     

基于生物分子网络的人参皂苷Rg1的生物效应

目的:运用代谢组学及生物效应网络方法研究人参皂苷Rg1的生物效应的机制.方法:采用高效液相色谱-质谱(HPLC-MS)联用技术结合偏最小二乘判别分析方法,考察空白组与人参皂苷Rg1给药组的内源性物质差异,并确定生物标志物.结果:筛选出对分组贡献较大的25种潜在生物标记物,通过数据库确定了6个目标物的结构、代谢途径,相关酶和作用靶点,分别为吡哆醛与醛氧化酶、氨基葡萄糖和已糖激酶、甲基尿酸及黄嘌呤脱氢酶、多巴醌转化酪氨酸酶、氟尿苷与胸苷磷酸化酶、卵磷脂和卵磷脂胆固醇酰基转移酶.通过网络药理学及文献解释了人参皂苷Rg1在嘧啶代谢通路中为胸苷磷酸化酶的抑制剂;还可促进卵磷脂通过血浆卵磷脂胆固醇酰基转移酶催化成血浆胆固醇酯.结论:代谢组学及生物效应网络方法能用于人参皂苷Rg1生物效应机制的研究,为进一步揭示人参皂苷Rg1药理作用机制提供了新方法.     

Effects of ginseng total saponins on pacemaker currents of interstitial cells of Cajal from the small intestine of mice

Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of ginsenosides on gastrointestinal (GI) motility. We studied the modulation of pacemaker activities by ginseng total saponins in the interstitial cells of Cajal (ICC) using the whole cell patch-clamp technique. Externally applied ginseng total saponins (GTS) produced membrane depolarization in the current-clamp mode and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid or niflumic acid abolished the generation of pacemaker currents, but only treatment with flufenamic acid inhibited the GTS-induced tonic inward currents. The tonic inward currents induced by GTS were not inhibited by the intracellular application of guanosine 5'-[beta-thio]diphosphate trilithium salt. Pretreatment with a Ca(2+)-free solution, with U-73122, an active phospholipase C inhibitor, and with thapsigargin, a Ca(2')-ATPase inhibitor of the endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the GTS-induced action. However, treatment with chelerythrine and calphostin C, protein kinase C inhibitors, did not block the GTS-induced effects on the pacemaker currents. These results suggest that ginsenosides modulate the pacemaker activities of the ICC, and the ICC can be targets for ginsenosides, and their interaction can affect intestinal motility.     

人参皂苷协同增效的研究进展

人参皂苷是人参中主要活性成分,具有多种生物活性。人参皂苷与其他药物联合使用可产生协同增效作用,作用于肿瘤、神经系统、心血管系统、免疫系统、血液和造血系统等,提升人参皂苷的临床应用价值。综述了人参皂苷与其他药物协同增效作用于肿瘤、神经系统、心血管系统、免疫系统、血液和造血系统等,为人参皂苷的临床应用提供参考。     

人参皂苷生物转化的研究进展

目的综述人参皂苷在体内及体外的生物转化研究概况。方法查阅国内外相关文献,以其中的26篇文献为依据对人参皂苷在体内的转化途径及产物加以介绍,也对体外转化中使用的酶法和微生物法加以详细阐述。结果人参皂苷在体内被代谢成为多种稀有人参皂苷,它们是人参在体内发挥药理活性作用的物质。体外生物转化人参皂苷的方法较多,并取得了许多有意义的成果。结论为人参皂苷的代谢研究及稀有人参皂苷的体外生物转化制备提供了参考。     

The protective effects of ginsenosides on human erythrocytes against hemin-induced hemolysis.

Panax ginseng has been used in traditional Chinese medicine to enhance stamina and capacity to deal with fatigue and physical stress. Many reports have been devoted to the effects of ginsenosides on many in vitro or in vivo experimental systems. The major aim of this work is to investigate the protective effects of 12 individual ginsenosides including Rb1, Rb3, Rc, Rd, Re, Rg1, Rg2, Rg3, Rh1, Rh2, R1 and pseudoginsenoside F11, together with the central structures of aforementioned ginsenosides, 20(S)-protopanaxadiol (PD) and 20(S)-protopanaxatriol (PT), on hemin-induced hemolysis of human erythrocytes. This is because hemin can induce hemolysis by accelerating the potassium leakage, dissociating skeletal proteins and prohibiting some enzymes in the membrane of erythrocyte. Thus, the structure-activity-relationship (SAR) between ginsenosides and protective effects has been screened in this in vitro experimental system. It is found that Rh2 and Rg3 intensify hemolysis in the presence of hemin, and initiate hemolysis even in the absence of hemin. All the other ginsenosides protect human erythrocytes against hemin-induced hemolysis more or less. The overall sequence is Rc>Rd>Re approximately Rb1>Rg1 approximately Rh1>Rb3 approximately Rg2 approximately R1 approximately F11 approximately PT. In addition, the protective effects of PD and PT have been detected, and found that PD promotes hemolysis appreciably, whereas PT protects erythrocytes efficiently. Moreover, the protective effects of PT ginsenosides are similar to PT itself, and the protective effects of PD ginsenosides vary remarkably, demonstrating that the positions of the sugar moieties make the protective activities of ginsenosides complicated. Especially, sugar moiety at 20-position is critical for PD ginsenosides to inhibit hemolysis, whereas hydroxyl group at 3-position is important for PT ginsenosides. The present result may be useful for understanding the SAR of ginsenosides.     

Effects of ginsenosides on rat jejunal contractility

Context: Ginsenosides are primary active ingredients of ginseng, which are believed to have various health benefits. It is found that the biotransformation of ginsenosides mainly takes place in the gastrointestinal tract and the information about ginsenosides-exerted effects on intestinal contractility is not sufficient.

Aims: The present study proposed that ginsenosides could exert stimulatory or inhibitory effects on intestinal motility depending on the assay condition-related intestinal contractile states and was to characterize the effects of ginsenosides on intestinal motility.

Methods: Jejunal contractility determination, Western blotting analysis, and real-time polymerase chain reaction were performed to test the effects of total ginsenosides isolated from Panax ginseng C. A. Mey (Araliaceae) root.

Results: The results showed that ginsenosides at the fixed concentration of 20?mg/L exerted bidirectional regulation (BR) on the contractility of isolated jejunal segment (IJS), depending on the contractile states. The contractility of IJS was increased by ginsenosides in low contractile states, which were correlated to the cholinergic activation, and the contractility of IJS was decreased by ginsenosides in high contractile states, which were correlated to the adrenergic activation and nitric oxide related mechanisms. Ginsenosides-induced BR was abolished in the absence of Ca²⁺ or by using tetrodotoxin, implicating the requirement of Ca²⁺ and the enteric nervous system. Effects of ginsenosides on myosin light chain phosphorylation and the mRNA expression of myosin light chain kinase were also bidirectional.

Discussion and conclusion: Results suggest that ginsenosides may have the potential clinical implication for reliving the symptoms of alternative hypo- and hyper-intestinal motility.     

Angiomodulatory and neurological effects of ginsenosides

Panax ginseng C.A. Meyer, one of the most popular and valued herbs, has been used extensively in traditional Chinese medicine for thousands of years. More than thirty ginsenosides, the pharmacologically active ingredients in ginseng, have been identified with various sugar moieties attached at the C-3, C-6 and C-20 positions of the steroidal skeleton. We herein review the current literature on the pharmacological effects of ginsenosides on the modulation of angiogenesis, dysregulations of which contribute towards many pathological conditions. Regarding the adaptogenic property of ginseng, the effects of ginsenosides on central nervous system are also discussed. Recent researches have pointed to the steroid hormone receptors as the target molecules to elicit the diverse cellular and physiological activities of ginseng. We believe that understanding the interaction between ginsenosides and various steroid hormone receptors may provide clues to unravel the secret of ginseng.     

Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior

Our recent study demonstrated that ginsenosides had antinociceptive effects by reducing some types of pain-related behavior in mice (Yoon et al., 1998. Ginsenosides induce differential antinociception and inhibit substance P-induced nociceptive response in mice. Life Science 62, PL319-PL325). In the present study we further investigated whether ginsenosides produce antinociceptive effects through an action at central or peripheral site(s) and whether these effects are mediated by the opioid system. Intraperitoneally injected ginsenosides suppressed in a dose-dependent manner the pain-related behavior produced by capsaicin injection into the plantar surface of the hind paw; the ED(50) was 49 mg/kg [26-92 mg/kg, 95% confidence interval (C.I.)]. Intrathecally or intracerebroventricularly administered ginsenosides also suppressed the capsaicin-induced pain-related behavior in a dose-dependent manner; the ED(50)s were 1.72 mg/kg (0.8-3.72 mg/kg, 95% C.I.) and 1. 48 mg/kg (0.8-2.6 mg/kg, 95% C.I.), respectively. On the other hand, subcutaneously injected ginsenosides to the plantar surface prior to the capsaicin injection did not alter the pain-related behavior. Naloxone pretreatment was without effect in blocking the antinociceptive effect of intrathecally administered ginsenosides. Intraperitoneally injected ginsenosides also did not significantly affect the motor response of animals. These results suggest that ginsenosides produce antinociceptive effects through their action at the spinal and/or supraspinal site(s), not at nociceptors in the periphery. In addition, the results suggest that the antinociceptive effects are not mediated by opioid receptors.     

Ginsenosides: are any of them candidates for drugs acting on the central nervous system?

The last two decades have shown a marked expansion in the number of publications regarding the effects of Panax ginseng. Ginsenosides, which are unique saponins isolated from Panax ginseng, are the pharmacologically active ingredients in ginseng, responsible for its effects on the central nervous system (CNS) and the peripheral nervous system. Recent studies have shown that ginsenosides regulate various types of ion channels, such as voltage-dependent and ligand-gated ion channels, in neuronal and heterologously expressed cells. Ginsenosides inhibit voltage-dependent Ca(2+), K(+), and Na(+) channel activities in a stereospecific manner. Ginsenosides also inhibit ligand-gated ion channels such as N-methyl-d-aspartate, some subtypes of nicotinic acetylcholine, and 5-hydroxytryptamine type 3 receptors. Competition and site-directed mutagenesis experiments revealed that ginsenosides interact with ligand-binding sites or channel pore sites and inhibit open states of ion channels. This review will introduce recent findings and advances on ginsenoside-induced regulation of ion channel activities in the CNS, and will further expand the possibilities that ginsenosides may be useful and potentially therapeutic choices in the treatment of neurodegenerative disorders.