Itcontains alkaloid: vinblastine(vincaleukoblastine), vincristine(leurocristine, lochneridine, lochnericine, catharosine, catharanthine, vindorosine, lochnerinine, tetrahydroserpentine, leurosidine(vinrosidine), leurosine(vinleurosine), lochnerine, tetrahydroalstonine, sitsirikine, dihydrositsirikine, isositsirikine, isoleurosine, vincamicine, Catharine, vindolicine, vindolinine-2HCl, virosine, lochrovine, perimivine, vincoline, lochrovidine, lochrovicine, vincolidine, vindolinine, serpentine, leurosivine, rovidine, dihydrovindolinine, coronaridine;

It also contains inositol, succinic acid, secologanic acid, secologanoside, catharanthine, leurocolombine(2′-hydroxyvincaleukoblastine)^[1];

The roots contains alkaloid: mitraphylline, akuammicine, vinosidine, lochnerivine, cavineine sulfate, leurosivinesulfate, ammocalline, pericalline, ammorosine, perosine sulfate, cavincidinesulfate, maandrosinesulfate, cathindine sulfate, δ-yohimbine(ajmalicin, raubasine), alstonine ^[1];

The leave contains alkaloid: vindoline, vindolinine, tetrahydroalstonine, yohimbine, vinblastine, vincristine, perivine^[1];

The seeds contains tabersonine^[1].

1 An anti-tumor:periwinkle vinblastine (VBL), vincristine (VCR), epoxy vinblastine isovinblastinehas significant anti-tumor effect [1]. Herba Catharanthi alkaloids AC-875 havesignificant anti-tumor effect by intraperitoneal injection of 20 ~ 42mg/kg,significantly inhibited mouse Ehrlich ascites tumor and ascites hepatoma, sarcomarat ascites has a good effect; slightly inhibited the mouse sarcoma S180 [2].VBL had significant treatment effect on DBA/2 mice transplanted lymphocyticleukemia P1534 [3]; VCR not only extend the survival time of diseased mice, andthe diseased mice can be cured. VBL and VCR can significantly inhibit breasttumors of DBA/1 mice, VCR have a role of the adenomatous 755 [4]. VBL haveobvious therapeutic effect on murine leukemia L1210, P1534 mice transplantedlymphocytic leukemia, AKR leukemia IRC741/1398 leukemia, W256 carcinosarcoma inrats, mice meat, cancer, S180, Ehrlich ascites carcinoma and transplantation orspontaneous breast cancer, and can prevent spontaneous leukemia of AKR mice,can suffer from the cancer cells the IRC741 leukemia in rats blood quicklydisappear [5]. VCR had significant inhibition of proliferation on culturedhuman hepatoma SMMC-7721 cells, anti-personnel role, and the role ofstrengthening [6]. Ascites mouse hepatoma (in HepA) VCR-IgG can significantlyprolong survival, better than free VCR [7]. Ehrlich ascites carcinoma wassignificantly inhibited by domestic vincristine sulfate on mouse [8]. VCR and 1,2:5,6- dihydrate Euonymus alcohol (DAG) mixed had synergistic killing effect onmouse bone marrow stem cells [9 ]. The periwinkle amine can treat nasopharyngealcarcinoma KB cells cytotoxicity of murine leukemia P388 [10]. 2'-hydroxyvinblastine 2×10-2μg/ml inhibit Chinese hamster ovary cell mitosis, the 15mg/kgmice transplanted with the original Ridgeway bone meat cancer inhibition rateof 27%, 0.02μg/ml make mitotic stop in the medium term [11]. Changchunartificial semi-synthetic products VDS, the anti-tumor spectrum compared withVBL wide colorectal cancer, non-small cell lung cancer, leukemia, breastcancer, renal cell carcinoma and malignant melanoma, including used otherChangchun flower the alkaloids caught [12]. Another semisynthetic products VRBand VBL is similar for anti-human ovarian cancer A2780 activity. The VRBanti-L1210 activity is lower than the VBL and VCR, Human gastric cancer ST-4and ST-40 the role of VRB also has greater activity [13].

2 Anti-tumor mechanism:(1) tubulin binding with high affinity: VCR, VBL and VDS can impede tubulinassembled into microtubules, microtubule depolymerization, the cell mitosisstopped in the interim [1]. VBL allows leukemia cell line L1210 ascites type ofEhrlich ascites carcinoma and normal bone marrow cell mitosis stop at themedium term, leading to completely disappear after the mid-early, are notaffected, this effect can be glutamic acid or tryptophan significantly weakened[14]. Periwinkle extracts of fibroblasts in the distortion of the mitoticspindle damage in vitro allows [15]. In vitro, four kinds of vinca alkaloidswith bovine brain tubulin binding affinity order of VPD> a VCR ≌ the VDS>the VBL of VPD affinity (Ka) values than the VBL about four times higher.However, the proliferation of melanoma Bl6 cells the opposite direction. Drugsin the inhibition of cell proliferation by 50% of the concentration ofextracellular, intracellular drug concentration is still far lower than theconcentration of tubulin. All Vinca alkaloids can tubulin binding inhibits cellproliferation effect difference is mainly the intake different than Ka values [16].VRB compared with the VBL, VCR, VDS, anticancer wide spectrum, less toxicity,and think this is due VRB due to the role of microtubules. The VBL, VCR, andVRB may be the neuronal differentiation of early mouse embryos between poles inmitotic microtubule depolymerization, cells were blocked in the medium term,increasing the drug concentration can make the centromere microtubulesprogressive depolymerization. Only the VRB enable these microtubules occurcompletely depolymerization cell cycle arrest at the pre-, the same three drugson the role of axonal microtubules, produced microtubule depolymerization,while VRB cause depolymerization concentration than other Changchun floweralkaloids, so the VRB of a higher therapeutic index, the lower neurotoxicity[1,13]. (2) tumor cells: affinity and vinca alkaloids in animal or tumor cellsin vitro tests can be strong and rapid uptake into the cell, there aredifferences between the different alkaloids in freshly isolated rat hepatocytessuspension VBL accumulation in the cells than a VCR, VDS more. Human liver cellexperiments to obtain similar results, proportional to the intensity andfat-soluble vinca alkaloids in the intracellular accumulation of, andintracellular drug concentration is much higher than the extracellular. Inmurine leukemia cells, cell VCR 5 to 20 times higher concentration than theextracellular concentration. In the mouse lymphoma cell lines (Hela and S49)and the concentration of extracellular concentration within the cells of thehuman promyelocytic leukemia cell line (in HL60), the vinca alkaloid class ofl50 ~ 500. VCR and fine gowns human leukemia lines (CEM / CCRI) affinity thanthe murine leukemia cell lines (leukemia L1210, against P388) [1]. (3) inhibitionof nucleic acid and protein synthesis: once to the VBL 2mg/kg, mixed withEhrlich ascites tumor cells RNA can be significantly reduced 3H-uridine(3H-UR); the VBL 2 × 104mol / L and Ai ascites carcinoma cells hatched onehour, can be significantly inhibited 3H-the UR incorporation of RNA. VBLinhibits RNA synthesis in vivo, in vitro tests can be Valley nitric acidantagonist. VCR can inhibit the incorporation of 3H-thymidine cancer sarcomaW256DNA in rats, and tumor nucleolar DNA synthesis inhibition of non-nuclearbenevolent. A VCR 7 × 10-5mol/L could inhibit the incorporation of 3 H-the URacute lymphoblastic leukemia cell RNA; 0.5 × 10 (-4) mol/L or 1.0 × 10 (-4) mol/L,also significantly inhibited in human chronic granulocytic leukemia and sarcomapatients of leukemia, white blood cell 3H-cytidine incorporation to RNA andDNA, the VBL and VCR can inhibit Ehrlich ascites cells DNA-dependent RNApolymerase activity [17]; a VCR 25μg/ml also makes liver cancer cell membranefluidity decreased cancer cell activity decreased [6]. The VCR can alsosignificantly inhibited the human brain malignant into the RNA of glioblastomaand meningioma nucleolar ribonucleoprotein precursors generate anti-tumoreffect and inhibition of ribosomal ribosomal RNA synthesis [18]. The VCR canalso interfere with protein metabolism and inhibit RNA polymerase activity andlead to tumor cell membrane lipid composition changes [19]. The vincristinelower membrane phosphatidylinositol kinase activity affect cell nucleic acid orprotein metabolism, thereby inhibiting the early one of the biochemicalprocesses of cell proliferation [20]. (4) the membrane phospholipids ofarachidonic acid synthesis effects: VCR contact with mouse sarcoma S180 cells24 hours after the phospholipid content was significantly increased cholesterol/phospholipidratio decreased membrane phospholipids, arachidonic acid ratio wassignificantly reduced. VCR to reduce the proportion of the membranephospholipids of arachidonic acid may be an important mechanism of anti-tumoreffect [21].

3 Resistance: Catharanthusroseus alkaloid-resistant tumor cells to some chemical structure unrelated tonatural compounds such as anthracyclines (such as doxorubicin, daunorubicin)and Table podophyllum toxin, although not previously exposure to these drugs,but also the performance of cross-resistance. Vinca alkaloid or other drugresistance mechanisms is one of the P-glycoprotein-mediated, energy-dependentefflux, resulting in intracellular drug retention decreased [1]. VCR, VBL andVDS, VCR, mouse lymphocytic leukemia L5I78Y cell line cytotoxicity strongest.L5178Y cell lines resistant to VCR and VDS resistance, but does not VBLresistance, these three alkaloids in the drug-resistant cell lines the uptakeand retention of stay were significantly reduced, and this reduce the extentand antimicrobial resistance There is no correlation [22]. Lesscross-resistance between the VRB and other vinca alkaloids. Application VRB canlimit the multi-drug resistant (MDR) the occurrence of cell lines. Most casesof MDR and can take the initiative to discharge the drug within the cellsurface P-glycoprotein overexpression is directly related to many membraneactive agents such as calcium antagonists and calmodulin inhibitors to overcomethis resistance. With coronary dilatation verapamil, vinca alkaloidaccumulation within the cells in vitro and in vivo tests can be powerful.Verapamil significantly increased the concentration of VCR and VBL in the mouseleukemia cell line P388, thereby overcoming of MDR. This effect of the vincaalkaloid class than the other natural drugs such as anthracyclines and Tablepodophyllotoxin class more [1]. Resistance to Vinca alkaloids in cell lines orhuman tumor cell lines can be calmodulin inhibitor Pune Lamine, two DiclofenacClomipramine regulation. These drugs in 6.6μmo1 / L VCR 29 ~ 45-fold increasein the cytotoxicity of anti-VCR human erythroleukemia cells (K562), a VCRincrease in the accumulation of its cytotoxic increase in Trifluoperazine andclomipramine allows VCR to a high degree of accumulation of resistance to VCRin K562 cells, and Lamine Pune, however, can only make the VCR to a lower levelof accumulation in this cell. However, Pune Lamine allows the VCR cytotoxicitygreatly increased. Other drugs such as flunarizine, reserpine, vitamin A,Stephania alkali head full risperidone, quinidine, cyclosporine and itsanalogues and anti-tumor effect of vinca alkaloid class also can reverse theVinca alkaloids of MDR performance [1]. Chinese medicine Corydalis contained inL-tetrahydropalmatine 0.05mmol/L can significantly enhance the sameconcentration of VCR on human promyelocytic leukemia HL-60 and humanerythrocyte white blood cells in leukemia K562 cell lines, proliferationinhibition, suggesting that the two drugs the merger application of synergy[23]. 25 μmol/L calmodulin antagonist in vitro can increase the VBL in culturedhuman gastric adenocarcinoma MGC803 concentration within the cell lines, lowerthe VBL half inhibition of the amount, to improve its anti-cancer effect [24].

4. Depressurizationand vasodilator: Herba Catharanthi alkaloids had antihypertensiveeffect on anesthetized dogs, there is not significant effect on heart rate andbreathing in the depressurization process. Herba Catharanthi alkaloids had the expansionof coronary vessels effects [17].

5 Hypoglycemic effects: HerbaCatharanthi leaf water extract reduces blood sugar of normal or alloxandiabetic rabbits and dogs. All of alkaloids had hypoglycemic effects in variousdegrees, the role of slow, but more lasting [17].

6 Hypolipidemic: HerbaCatharanthi alkaloids monomeric indole alkaloidscan rapidly decrease serum lipids for normal orhigh cholesterol tumor-bearing mice [25].

7 The others: VCR withmitomycin mixed with equal amount can reduce the average fertility rate (onlyenable mature mice), birth the deadrat number significantlyincreased, for sex immature mice fertility was significantly delayed [26]; HerbaCatharanthi strong diuretic effect in rats [17]. Herba Catharanthi inducedmemory acquisition impairment and memory consolidation bad and anti-acutecerebral ischemia [27]. Herba Catharanthi leaf decoction can reduce micronucleusnumber of polychromatic erythrocytes induced by mutation of analgin,Metronidazole da yl, mitomycin C and safrole etc. And it had anti-mutageniceffects [28].

8 Intracorporal process: 3H-Herba Catharanthi alkaloids intravenous injection to therats, after 30 minutes, blood radioactivity is less than 1.5%, after 24 hours, theinjection volume is only 6.6% in renal excretion, quick elimination seems notdue to renal excretion, biliary excretion may be the main way to eliminate. VCRis injected to intravenous of dog and monkey for1mg/kg, after 6 hours, theplasma concentration decreased significantly, VCR elimination rate also quiterapid [17]. VCR, the VBL, and VDS in the distribution of the various organs isbasically the same, the distribution of concentration in the order: spleen>adrenal> thyroid gland> colon> small intestine> heart> liver>lung> kidney> bone marrow> skin> muscle. Very low concentrations inthe cerebrospinal fluid distribution [13]. The oral VRB quickly absorbed, thebioavailability for 40%, a VCR, the VBL and VDS oral bioavailability is poor,almost ineffective. Compared with other Herba Catharanthi alkaloids, VCR had longhalf life for terminal elimination, which is relate with lower eliminationconstant, the VRB tissue distribution of the VBL> VRB> VCR [1,13]. OralVRB, the pharmacokinetics of science and anti-tumor and that of intravenous is similar.HerbaCatharanthi alkaloids mainly through the hepatobiliary system,metabolism and elimination [1].

9 Toxicity: therapeuticdose VBL decrease leukocyte in animals. Median lethal dose VBL (LD50) for miceintravenous, intraperitoneal injection and oral is 17mg/kg, 3mg/kg and 33mg/kg,respectively. Lethal dose of Herba Catharanthi alkaloids in dogs can cause bonemarrow suppression, died of secondary infection [17]. The VCR has a relativelyweak bone marrow suppression, the amount of treatment generally does not causeleukopenia [4]. VCR dose-dependently caused the mice bone marrow cell sisterchromatid exchange, so that in the cells S phase DNA replication inhibition,SCE suppression effects and inhibition of cell division [29]. The result is similarwith normal human lymphocytes in vitro test [30]. The main side effects of VCR isneurotoxicity. symptom for no deep tendon reflexes, (toe) numbness andtingling, staggering gait. Autonomic dysfunction included abdominal pain,constipation, and paralytic ileus, orthostatic hypotension, deaths. VCR canoften cause hair loss, and occasionally urinary retention, mental confusion,depression, agitation, insomnia, hallucinations, etc. [31].

1. Advanced non-small cell lung cancer: ①26 cases were treated with vinorelbine for rapid intravenous infusion at 8, 15, 22, 29 days. 1 times Common blood tested weekly, and timely to recombinant granulocyte colony-stimulating factor elevated white blood cells. Results showed that 19 cases of cancer related symptoms (cough, hemoptysis, chest pain, chest tightness, etc.) had different degrees of reduction or remission, 7 patients weight gained. Recent objective curative effect, 6 cases had partial remission, accounting for 23.1%; 15 cases stable, accounting for 57.7%; 5 cases had carcinogenesis progression, accounting for 19.2% ^[2]. ②220 cases were treated with vinorelbine at 1, 5 days (8days) and cisplatin at 2 days. 28 day as a cycle. efficacy were evaluated after completed 2～3 courses, later followed-up. Results showed that the total effective rate was 30.9% ( 68/220 ), the efficiency of first treatment was 31.3% ( 51/163 ), the efficiency of retreatment was 29.8% ( 17/57 ). The median survival time was 8.3 months, 1 year survival rate was 39.23%, 2 year survival rate was 19.31%, 3 year survival rate was 6.32%^[1]. ③53 cases were treated with vinorelbine at 1, 8 days and cisplatin at 1~5 days. 21 day as a cycle.all were treated with 2 cycles of treatment. Results showed that 3 cases had the complete remission , 23 cases had partial remission, 19 cases stable, 7 cases had malignant progression, the total efficiency was 49.1%^[3].

2.Breast cancer: 47 cases were treated with vinorelbine at 1, 8days and cisplatin at 1～3 days. 21 day as a cycle. efficacy were evaluated after completed 2～3 courses. Results showed that 3 cases were completely relieved, accounting for 6.3%, 18 cases had partial remission, accounting for 38.5%, the total effective rate was 44.6%; 12 cases stable, accounting for 25.5%; 14 cases had carcinogenesis progression, accounting for 29.7%, the median response duration was 6 ～10 months. The main adverse reactions were myelosuppression , gastrointestinal reaction and hair loss ^[4].

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clinical test:

[6] Xu lei，Baizhonghong，Xu ruancheng，edc. Comparison on therapeutic effect on advanced metastatic breast cancer treated with TAX and NVB combining with cisplatin respectively.Practical Journal of Medicine and Pharmacy.2007，24(7):811.