三七化学成分的研究历程和概况

三七Panax notoginseng为五加科人参属植物,在我国已有400多年的栽培历史,其作为一种名贵中药,具有化瘀止血、消肿止痛等功效。三七复杂的化学成分是其良好功效的基础。目前已从三七中发现了百余种化合物,其中有效成分以皂苷类成分和三七素为主。对三七中皂苷类和非皂苷类成分的研究历程和概况进行了综述,并根据不同化合物的特点,探讨了各类化合物今后的研究方向,以期为三七的进一步研究提供有益参考。     

复方丹参方对大鼠心脏细胞色素P450酶的影响

目的 研究复方丹参方及其单味药对大鼠心脏细胞色素P450酶（CYPs）主要亚型的影响。方法 雄性SD大鼠随机分为5组,分别用复方丹参方 [0.32 g/(kg?d)]、丹参 [0.27 g/(kg?d)]、三七 [0.05 g/(kg?d)]、冰片 [0.003 g/(kg?d)] 或生理盐水连续ig诱导处理28 d,取各组大鼠心脏组织,利用Real Time荧光定量PCR技术检测各组大鼠心脏CYPs各亚型mRNA表达水平的变化。结果 与对照组比较,复方丹参方对大鼠心脏CYP1B1、CYP2B1、CYP2E1、CYP4A1和CYP4F4的mRNA表达有下调趋势（P＜0.05）。丹参对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP2E1、CYP2J3、CYP4A1、CYP4F4和CYP4F5的mRNA表达有下调趋势（P＜0.05、0.01）,而对CYP4A3、CYP4F1和CYP4F6的mRNA表达有上调趋势（P＜0.05）。三七对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP2E1、CYP2J3、CYP4A1、CYP4A3、CYP4F4、CYP4F5和CYP4F6的mRNA表达均有不同程度的抑制趋势（P＜0.05、0.01）。冰片对CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP4A1和CYP4F4的mRNA表达有下调作用（P＜0.01）。结论 复方丹参方全方对心脏CYPs 亚型mRNA表达影响弱于方中各单味药对CYPs的影响,显示复方对CYPs影响可能是各单味药作用的综合和叠加,同时全方及单味药对CYP2家族和CYP4家族的影响显示其对心脏均有双向调节作用。     

三七皂苷类成分的蛋白质相互作用网络分析

三七皂苷类成分是三七发挥药效的活性部位,目前对其作用机制尚无系统的研究。该文构建了三七皂苷类成分的蛋白互作网络并对网络进行模块分析,通过模块的功能及包含的蛋白从分子水平上阐释三七皂苷类成分的作用机制。结果表明三七皂苷发挥药效主要与环磷酸腺苷代谢、血管伸缩、血液凝固、T细胞增殖与分化等生物过程相关。     

三七普通细粉与超微粉中三七皂苷R1、人参皂苷Rb1及人参皂苷Rg1体外溶出行为的比较研究

目的 研究三七普通细粉与超微粉中三七皂苷R₁、人参皂苷Rb₁及人参皂苷Rg₁的溶出行为,探讨粉体粒径对皂苷类成分溶出的影响。方法 采用桨法和HPLC技术同时分析不同粒径三七粉中三七皂苷R₁、人参皂苷Rb₁、人参皂苷Rg₁的体外溶出情况,比较不同粒径粉末的溶出速率。结果 超微粉碎后3种皂苷类成分的溶出速率均显著提高。结论 超微粉碎有助于三七饮片中皂苷类成分的溶出,粉碎粒度对有效成分的溶出有显著的影响。     

中药黄芪、女贞子、人参促毛发生长的在体研究

目的:以C57BL/6小鼠为动物模型,探讨中药黄芪、女贞子、人参混合煎剂促进C57BL/6小鼠毛发生长的可能机制。方法:中药组小鼠给予中药混合煎剂口饲,对照组给予等量生理盐水,观察小鼠背部皮肤颜色变化和毛发生长情况。同时在光镜下观察小鼠毛囊组织学变化及毛囊内细胞的凋亡的状况。结果:中药组小鼠饲饮中药煎剂后背部皮肤颜色由粉红色变为黑色比对照组提前了1d,背部皮肤颜色由黑色变为灰黑色比对照组延长了1.5d。组织学上,拔毛后第18天对照组小鼠毛囊处于退行中晚期,而中药组仍为生长Ⅵ期和退行早期毛囊。中药组小鼠毛囊内凋亡细胞数量比对照组减少(P<0.001)。结论:黄芪、女贞子、人参混合煎剂促毛发生长作用可能与抑制退行期毛囊内细胞凋亡,诱导和延长C57BL小鼠毛发的生长期有关。     

HPLC法测定人参毛状根及不同人参样品中9种人参皂苷的含量

目的采用HPLC法测定不同人参样品中9种人参皂苷(Rc、Rb1、Rb2、Re、Rd、Rg1、Rg2、Rg3和Rh2)的含量。方法色谱条件:Zorbax SB C18柱(4.6mm×250mm,5μm),保护柱Extend-C18柱(4.6mm×12.5mm,5μm);以乙腈-水为流动相,梯度洗脱;流速:1.0ml/min;检测波长:203nm;柱温:35℃。结果 9种人参皂苷Rg1、Rb1、Re、Rc、Rg2、Rh2、Rg3、Rb2和Rd在120min内基线分离。方法学表明其线性关系良好,精密度、稳定性和重复性RSD均小于2.0%,加样回收率在98.3%~102%之间。测得人参叶和人参须根中的总皂苷含量最高,分别为48.9、23.6mg/g;人参毛状根中的总皂苷与人参主根和人参果的总皂苷含量差别不大,为7.47mg/g。结论该法准确性高,操作简便、快速,重复性好,精密度高,可用于不同人参样品中9种人参皂苷的含量测定。     

n-Butanol extracts of Panax notoginseng suppress LPS-induced MMP-2 expression in periodontal ligament fibroblasts and inhibit osteoclastogenesis by suppressing MAPK in LPS-activated RAW264.7 cells

Objective

Periodontitis is a group of inflammatory diseases that affect connective tissue attachments and the supporting bone that surround the teeth. Osteoclasts are responsible for skeletal modeling and remodeling but may also destroy bone in several bone diseases, including osteoporosis and periodontitis. This study examined the anti-inflammatory effects of Panax notoginseng (PN) on periodontal ligament fibroblasts (PDLFs) and RAW264.7 cells under lipopolysaccharide (LPS) induced inflammatory conditions.

Design

The effects of PN on PDLFs were determined by measuring the cell viability and mRNA expression of tissue-destructive proteins. The effects of PN on osteoclasts were examined by measuring the following: (1) the cell viability, (2) the formation of Tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells, (3) MAPK signaling pathways, (4) mRNA expression of inflammatory-related proteins and (5) nitric oxide (NO) production.

Results

The n-butanol extracts of PN (bPN) increased the cell proliferation of the PDLFs and decreased the mRNA expression of matrix metalloproteinase (MMP)-2 in the PDLFs. bPN inhibited the formation of LPS-stimulated TRAP(+) multinucleated cells. bPN also inhibited the LPS-stimulated activation of JNK and ERK signaling, and inhibited the LPS-stimulated degradation of I_KB in the RAW264.7 cells. In addition, bPN decreased the mRNA expression of MMP-9 and iNOS, which are involved in the range of pathophysiological processes, such as inflammation in the RAW264.7 cells. NO production was also decreased via the inhibition of iNOS.

Conclusions

These findings suggest that bPN has therapeutic effects on bone-destructive processes, such as those that occur in periodontal diseases.     

三七皂苷对系统性红斑狼疮患者外周血淋巴细胞P-糖蛋白及激素效应的影响

目的 探讨系统性红斑狼疮(SLE)患者糖皮质激素耐药机制以及三七皂苷逆转耐药的作用.方法 直线相关分析SLE患者外周血淋巴细胞P-糖蛋白与SLE疾病活动指数(SLEDAI)、临床疗效的相关性.用三七皂苷干预患者外周血淋巴细胞,维拉帕米为对照,流式细胞术检测淋巴细胞P-糖蛋白、罗丹明123以及联合甲泼尼龙干预的细胞凋亡率.采用方差分析或t检验进行统计学分析.结果 SLE患者外周血淋巴细胞P-糖蛋白与SLEDAI呈正相关(r=0.490,P<0.05),缓解组P-糖蛋白(12.2±2.5)%与部分缓解或无效组(16.5±4.0)%差异有统计学意义.三七皂苷干预组P-糖蛋白(11.2±3.1)%和罗丹明123(70.1±5.8)%与对照组[分别为(15.3±2.9)%,(53.9±5.2)%]比较差异有统计学意义.三七皂苷可协同甲泼尼龙诱导淋巴细胞凋亡.结论 三七皂苷下调P-糖蛋白表达和转运活性的双重作用可能是协同甲泼尼龙诱导淋巴细胞凋亡的重要机制.

Abstract：

Objective To investigate the mechanism of glucocorticoid resistance in patients with systemic lupus erythematosus(SLE) and the effects of Panax Notoginseng Saponins(PNS) on reversing glucocorticoid resistance in lymphocytes. Methods The relevance between P-glycoprotein (P-gp, %) and SLEDAI integrals or clinical effects was analyzed by linear correlation analysis. The lymphocytes from SLE patients were intervened with PNS or verapamil. P-gp of the lymphocytes and Rhodamine 123 (Rh123, %) accumulated in the lymphocytes were assayed by flow cytometry. The percentage of the apoptosis of the lymphocytes stimulated with PNS or verapamil combined with methylprednisolone was identified by double-tagging with Annexin V and propidium iodide (PI) and detected by flow cytometry. Variance analysis or Student's t test was used for statistics. Results The P-gp in the peripheral blood lymphocytes of SLE patients was significantly related to SLEDAI integrals. The difference of P-gp between lymphocytes in the completely remission cases (12.2±2.5)% and lymphocytes in the partial remission or non-effective cases (16.5±4.0)% was statistically significantce. The difference of P-gp and Rh123 between lymphocytes treated with PNS [(11.2±3.1)%,(70.1 ±5.8)% respectively ] and lymphocytes of the control group [ (15.3±2.9)%, (53.9±5.2)% respectively ]was statistically significant. The lymphocytes apoptosis rate in the lymphocytes stimulated with methylprednisone combined with PNS increased significantly compared to the lymphocytes stimulated with methylprednisolone only. Conclusion The action of PNS in suppressing both the expression and the transfer activity of P-gp is possibly the important mechanism to increase the effects of methylprednisolone in inducing lymphocytes apoptosis.     

三七原人参三醇型总皂苷和人参三醇的4个衍生物的合成研究

目的研究三七中原人参三醇型总皂苷及人参三醇为原料的衍生物合成.方法分别将原人参三醇和人参三醇经Jones氧化、NaBH4还原和PCC氧化、NaBH4还原.结果制备了10个衍生物,其中4个化合物为新化合物.结论这4个新化合物简明易得,为得到大量衍生物并进行活性筛选奠定了基础.     

Effects of Panax Notoginseng Saponins on Homing of C-kit~+ Bone Mesenchymal Stem Cells to the Infarction Heart in Rats

Objective:To investigate the effects of panax notoginseng saponins(PNS) on homing of C-kit+ bone mesenchymal stem cells(BMSCs) to the infarction heart.Methods:The acute myocardial infraction(AMI) model was established in 140 Wistar rats,105 model rats survived after operation,and the model rats were randomly divided into five groups,21 rats in each group:Western medicine group mobilized by subcutaneous injection of human granuloctye colony stimulating factor(G-CSF) 50 μg·kg-1·d-1;sham operation group and a model group treated by subcutaneous injection of normal saline 50 μg·kg-1·d-1;Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong(血塞通)(ingredients of PNS) 150 mg·kg-1·d-1;integrative medicine group mobilized by subcutaneous injection of G-CSF 50 μg·kg-1·d-1 and intraperitoneal injection of Xuesaitong 150 mg·kg-1·d-1.Except for the sham-operated group,each group was divided into three sub-groups by three time points of 1 d,7 d and 14 d.G-CSF was injected once a day for 7 d.Xuesaitong was injected once a day until the rats were killed.The flow cytometry was used for detection of C-kit + cells in the peripheral blood in different time points,and immunohistochemical method was used for detection of the changes of C-kit + cell and Ki-67+ cell numbers in the marginal zone of AMI.Results:Twenty-four hours after the operation,C-kit + cells had a slight increase in the model group compared with the sham operation group(P>0.05).The peripheral blood C-kit+ cells in the integrative group increased significantly compared with the other groups on 7 d and 14 d(all P<0.05).Meanwhile the expression of C-kit + cells and Ki-67+ cells in the marginal zone of AMI in the integrative group increased significantly compared with the Chinese medicine group,the western medicine group and the model group on 1 d,7 d and 14 d(all P<0.05),and the cells in the integrative group decreased significantly on 14 d compared with that on 7 d(P<0.05).Conclusion:PNS can cooperate with G-CSF to mobilize C-kit+ BMSCs from the marrow into the peripheral blood and promote them "homing" to the infarction heart.