• 2019-10
  • 2020-03
  • 2020-07
  • 2020-08
  • br Conflict of interest br There


    Conflict of interest
    There are no conflicts of interests.
    Bruneton, J., 1999. Généralités, in: Pharmacognosie, phytochimie, plantes médicinales.
    Dhamgaye, S., Devaux, F., Vandeputte, P., Khandelwal, N.K., Sanglard, D., Mukhopadhyay, G., Prasad, R., 2014. Molecular mechanisms of action of herbal antifungal alkaloid Ber-berine, in Candida albicans. PLoS One 9, e104554. Du, J., 2017. Berberine and evodiamine act synergistically against human breast cancer MCF-7 cells by inducing Chloramphenicol arrest and apoptosis. Anticancer Res. 37.
    Havelek, R., Seifrtova, M., Kralovec, K., Bruckova, L., Cahlikova, L., Dalecka, M., Vavrova, J., Rezacova, M., Opletal, L., Bilkova, Z., 2014. The effect of Amaryllidaceae alkaloids haemanthamine and haemanthidine on cell cycle progression and apoptosis in p53-negative human leukemic Jurkat cells. Phytomedicine 21, 479–490.
    Heath, R.L., Packer, L., 1968. Photoperoxidation in isolated chloroplasts. Arch. Biochem.
    Iizuka, N., 2000. Inhibitory effect of coptidis rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett. 148, 19–25. Imanshahidi, M., Hosseinzadeh, H., 2008. Pharmacological and therapeutic effects of Ber-beris vulgaris and its active constituent, berberine. Phytother. Res. 22, 999–1012. International Agency for Research on Cancer, World Health Organization, 2014. Latest World Cancer Statistics Global Cancer Burden Rises to 14.1 million New Cases in 2012: Marked Increase in Breast and Cervix Cancers must be Addressed (press report no. 223). World Health Organization 07/pr223_E.pdf.
    Ivanovska, N., Philipov, S., 1996. Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. Int. J. Immunopharmacol. 18, 553–561.
    Kutchan, T.M., 1995. Alkaloid biosynthesis—the basis for metabolic engineering of medic-inal plants. Plant Cell Online 7, 1059–1070.
    Li, P.-F., 1999. p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J. 18, 6027–6036.
    Mantena, S.K., 2006. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol. Cancer Ther. 5, 296–308.
    Meeran, S.M., Katiyar, S., Katiyar, S.K., 2008. Berberine-induced apoptosis in human pros-tate cancer cells is initiated by reactive oxygen species generation. Toxicol. Appl. Pharmacol. 229, 33–43. Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63. Mutsuga, M., Kojima, K., Yamashita, M., Ohno, T., Ogihara, Y., Inoue, M., 2002. Inhibition of cell cycle progression through specific phase by pancratistatin derivatives. Biol. Pharm. Bull. 25, 223–228.
    Pierpaoli, E., Damiani, E., Orlando, F., Lucarini, G., Bartozzi, B., Lombardi, P., Salvatore, C., Geroni, C., Donati, A., Provinciali, M., 2015. Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/ neu-positive mammary carcinoma. Carcinogenesis 36, 1169–1179.
    Wang, C., Li, S., Wang, M., 2010. Evodiamine-induced human melanoma A375-S2 cell death was mediated by PI3K/Akt/caspase and Fas-L/NF-κB signaling pathways and augmented by ubiquitin–proteasome inhibition. Toxicol. In Vitro 24, 898–904.
    Antifungal activity of alkaloids from the seeds of Chimonanthus praecox. Chem.
    Contents lists available at ScienceDirect
    Bioorganic & Medicinal Chemistry
    journal homepage:
    Betulinic acid induces apoptosis and inhibits metastasis of human colorectal T cancer cells in vitro and in vivo
    Anqi Zeng1, Hua Hua1, Li Liu, Junning Zhao
    Institute of Translational Pharmacology and Clinical Application of Sichuan Academy of Chinese Medicine Sciences, Sichuan Center for Translational Medicine of Traditional Chinese Medicine, Sichuan Engineering Technology Research Center of Genuine Regional Drug, Biological Assay Key Laboratory of State Administration of Traditional Chinese Medicine for TCM Quality, Sichuan Provincial Key Laboratory of Quality Evaluation and New Drug Creation of Traditional Chinese Medicine, Chengdu, Sichuan 610041, China
    Betulinic acid
    Colorectal cancer cells 
    Betulinic acid (BA) is a pentacyclic triterpenoids extracted from birch with a wide range of biological properties. Recent studies have shown that BA has significant cytotoxicity to various types of human cancer cells, and shows potential in cancer treatment. However, the efficacy of BA on human colorectal cancer tumor cells is still un-clear. The purpose of our study was to evaluate the anti-cancer activity of BA in human colorectal cancer cells in vitro and in vivo to investigate the possible mechanism. In this experiment, we found that BA inhibited colorectal cancer cell lines in vitro with a time-dependent and dose-dependent manner. Moreover, BA could induce cell apoptosis by upregulating expression of Bax and cleaved caspase-3 and downregulating protein of Bcl-2. BA could increase the production of reactive oxygen species and reduce mitochondrial membrane potential of cancer cell, suggesting that BA induced cancer cells apoptosis by mitochondrial mediated pathways. Furthermore, BA significantly inhibited the migration and invasion of colorectal cancer cells, reduced the ex-pression of matrix metalloproteinase (MMPs) and increased the expression of MMPs inhibitor (TIMP-2). In addition, the growth of tumor was significantly suppressed by intraperitoneal administration of 20 mg/kg/day of BA in a xenograft tumor mouse model of HCT-116. Histopathological and immunohistochemical analysis showed that MMP-2+ cells and Ki-67+ cells were reduced and cleaved caspase-3+ cells were increased in tumor tissues of mice after BA administration. The results showed that BA not only promoted the apoptosis of colorectal cancer cells, but also inhibited the metastasis of cancer cells. Our results suggest that BA can be a potential natural drug to inhibit the growth and metastasis of colorectal cancer.