Research Progress in Chemical Components and Pharmacological Action of Brucea
FAN Xin-yue, YANG Lu-ming, FU Jia-li, GUO Qiao-ru, ZHOU Wen-min, ZHANG Jian-ye*
Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China
Abstract：Brucea, one of the most commonly used traditional Chinese medicine, belongs to Simaroubaceae, with a total of six species,of which Brucea javanica (B.javanica) is the main species used in medicine.The chemical components of Brucea are the important basis of its pharmacological activities. It mainly includes nigakilactones, alkaloids, triterpenes, steroids, phenylpropanoids, flavonoids and so on.About 200 single components have been isolated and identified. Modern pharmacological studies have shown that B.javanica has good anti-tumor, anti-inflammatory and anti-parasite activities. In clinic, B.javanica can be used in the treatment of warts and corns, as well as relieving dysentery and diarrhea, killing insects, intercepting malaria, clearing heat and detoxification and so on. In this paper, it was reviewed the chemical components and pharmacological effects of Brucea in recent years, hoping to provide references for its further research and application.
范欣悦, 杨璐铭, 扶佳俐, 郭乔如, 周雯敏, 张建业. 鸦胆子化学成分及药理作用研究进展[J]. 中国药学杂志, 2022, 57(14): 1137-1145.
FAN Xin-yue, YANG Lu-ming, FU Jia-li, GUO Qiao-ru, ZHOU Wen-min, ZHANG Jian-ye. Research Progress in Chemical Components and Pharmacological Action of Brucea. Chinese Pharmaceutical Journal, 2022, 57(14): 1137-1145.
TIAN J H, ZHAO Y, LI J L,et al. Network meta-analysis of 12 Chinese herb injections combined with gemcitabine and cisplatin for nonsmall cell lung cancer[J]. Chin J Drug Eval(中国药物评价),2014, 31(6): 350-355.
[3]
WANG Q, YANG Y X, LIU Q X, et al. Study on chemical constituents from seeds of Bruceae Fructus[J]. Chin Tradit Herb Drugs(中草药),2015, 46(19):2839-2842.
[4]
DING C X,SUO Y R.Research progress on chemical constituents and pharmacology of Brucea javanica[J]. Chin Tradit Pat Med(中成药), 2006,28(1): 117-120.
[5]
SHIN Y, TOSHIRO S, MASAMI I,et al. Constituents of seeds of Brucea javanica. structures of new bitter principles, Yadanziolides A, B, C, Yadanziosides F, I, J, and L[J]. Bull Chem Soc Jpn, 1985, 58(9): 2673-2679.
[6]
TOSHIRO S, SHIN Y, MASAMI I, et al. Structures of new quassinoid glycosides, Yadanziosides A, B, C, D, E, G, H, and new quassinoids, dehydrobrusatol and dehydrobruceantinol from Brucea javanica (L.) merr[J]. Bull Chem Soc Jpn, 1985, 58(9):2680-2686.
[7]
TOSHIRO S, SHIN Y, TAKAHIKO T,et al. Structures of Yadanziosides K, M, N, and O, new quassinoid glycosides from Brucea javanica (L.) merr[J]. Bull Chem Soc Jpn, 1986, 59(11):3541-3546.
[8]
SHAKILA R, NARIHIKO F, HARUKUNI T,et al. Three new quassinoid derivatives and related compounds as antitumor promoters from Brucea javanica[J]. Bull Chem Soc Jpn, 1999, 72(4):751-756.
[9]
WANG Q.Studies on chemical constituents from the dregs of Brucea fructus.[ D ]. Guangzhou:GuangDong Pharmaceutical University, 2017,
[10]
LIU J H, ZHAO N, ZHANG G J, et al. Bioactive quassinoids from the seeds of Brucea javanica[J]. J Nat Prod, 2012, 75(4):683-688.
[11]
OHNISHI S, FUKAMIYA N, OKANO M, et al. Bruceosides D, E, and F, three new cytotoxic quassinoid glucosides from Brucea javanica[J]. J Nat Prod, 1995, 58(7):1032-1038.
[12]
FUKAMIYA N, LEE K H, MUHAMMAD I, et al. Structure-activity relationships of quassinoids for eukaryotic protein synthesis[J]. Cancer lett, 2005, 220(1):37-38.
[13]
YAN X H, CHEN J, DI Y T, et al. Anti-tobacco mosaic virus (TMV) Quassinoids from Brucea javanica (L.) Merr[J]. J Agric Food Chem, 2010, 58(3):1572-1577.
[14]
ZHAN Y Z.Study on the chemical constituents and pharmacological activities of Brucea javanica. [D]. Nanchang:JiangXi University of Chinese Medicine, 2020.
[15]
CHEN H, BAI J, FANG Z F, et al. Indole alkaloids and quassinoids from the stems of Brucea mollis[J]. J Nat Prod, 2011, 74(11):2438-2445.
[16]
IMAMURA K, FUKAMIYA N, OKANO M, et al. Bruceanols D, E, and F three new cytotoxic quassinoids from Brucea antidysenterica[J]. J Nat Prod, 1993, 56(12):2091-2097.
[17]
IMAMURA K, FUKAMIYA N, NAKAMURA M, et al. Bruceanols G and H cytotoxic quassinoids from Brucea antidysenterica[J]. J Nat Prod, 1995, 58(12):1915-1919.
[18]
LIN L Z, CORDELL G A, ZHOU N C, et al. A quassinoid from Brucea javanica[J]. Pergamon, 1990, 29(8):2720-2722.
[19]
TOYOTA T, FUKAMIYA N, OKANO M,et al. Antitumor agents, 118. The isolation and characterization of bruceanic acid A, its methyl ester, and the new bruceanic acids B, C, and D, from Brucea antidysenterica[J]. J Nat Prod, 1990, 53(6):1526-1532.
[20]
SU B N, CHANG L C, PARK E J, et al. Bioactive constituents of the seeds of Brucea javanica[J]. Planta Med, 2002. 68(8):730-733.
[21]
ZHANG J S, LIN L Z, CHEN Z L,et al. Studies on the chemical constituents of Brucea javanica II Bruceine-glucopyranoside[J]. Acta Chem Sin(化学学报), 1983,(2):149-152.Doi:HXXB.0.1984-07-009.
[22]
KUPCHAN S M, BRITTON R W, LACADIE J A, et al. The isolation and structural elucidation of bruceantin and bruceantinol, new potent antileukemic quassinoids from Brucea antidysenterica[J]. J Org Chem, 1975, 40(5):648-654.
[23]
NARIHIKO F, MASAYOSHI O, TAKAAKI A, et al. Antitumor agents: LXXXVII. cytotoxic antileukemic canthin-6-one alkaloids from Brucea antidysenterica and the structure activity relationships of their related derivatives1[J]. Planta Med, 1987, 53(2):140-143.
[24]
MING Z, SIN T L, XIAO Q Z, et al. Bruceines K and L from the ripe fruits of Brucea javanica[J]. Helv Chim Acta, 2011, 94(11):2099-2105.
[25]
TUNG M H, DUC H V, HUONG T T,et al. Cytotoxic compounds from Brucea mollis[J]. Sci Pharm, 2013, 81(3):819-831.
[26]
OUYANG Y, KOIKE K,OHMOTO T.Canthin-6-one alkaloids from Brucea mollis var. tonkinensis[J]. Phytochemistry, 1994, 36(6):1543-1546.
[27]
KITAGAWA I, MAHMUD T, SIMANJUNTAK P, et al. Indonesian medicinal plants. VIII. Chemical structures of three new triterpenoids, bruceajavanin A, dihydrobruceajavanin A, and bruceajavanin B, and a new alkaloidal glycoside, bruceacanthinoside, from the stems of Brucea javanica (Simaroubaceae)[J]. Chem Pharm Bull (Tokyo), 1994, 42(7):1416-1421.
[28]
CHEN H, MA S G, FANG Z F, et al. A new indole alkaloid from the stems of Brucea mollis[J]. Acta Pharm Sin(药学学报), 2014, 49(2):225-229.
[29]
PAN L, CHIN Y W, CHAN H B, et al. Bioactivity-guided isolation of cytotoxic constituents of Brucea javanica collected in Vietnam[J]. Bioorg Med Chem, 2009, 17(6):2219-2224.
[30]
OUYANG K K,OHMOTO T.Indole alkaloids from Brucea mollis var. Tonkinensis[J]. Pergamon, 1994, 37(2):1543-1546.
[31]
OUYANG Y S, KATSUYOSHI M, KAZUO K, et al. Alkaloids and quassinoids of Brucea mollis var. tonkinensis[J]. Phytochemistry, 1995, 39(4):911-913.
[32]
DONG S H, LIU J, GE Y Z, et al. Chemical constituents from Brucea javanica[J]. Phytochemistry, 2013, 85:175-184.Doi: 10.1016/j.phytochem.2012.08.018.
[33]
LIU J H, QIN J J, JIN H Z, et al. A new triterpenoid from Brucea javanica[J]. Arch Pharm Res, 2009, 32(5):661-666.
[34]
CHEN Y Y, PAN Q D, LI D P, et al. New pregnane glycosides from Brucea javanica and their antifeedant activity[J]. Chem Biodivers, 2011, 8(3):460-466.
[35]
CHEN H, MA S G, FANG Z F, et al. Tirucallane Triterpenoids from the Stems of Brucea mollis[J]. Chem Biodivers, 2013. 10(4):695-702.
[36]
YANG J H, LIU W Y, LI S C, et al. Coumarinolignans isolated from the seeds of Brucea javanica[J]. Helv Chim Acta, 2014, 97(2):278-282.
[37]
CHEN Q J, OUYANG M A, TAN Q W,et al. Constituents from the seeds of Brucea javanica with inhibitory activity of Tobacco mosaic virus[J]. J Asian Nat Prod Res, 2009, 11(6):539-547.
[38]
HISAHIRO K, MASAKI B,TORU O.Two new megastigmanes from the leaves of cucumis sativus[J]. Chem Pharm Bull (Tokyo), 2007, 55(1):133-136.
[39]
YUMIKO Y,MASAYOSHI I.Synthesis of optically active vomifoliol and roseoside stereoisomers[J]. Chem Pharm Bull. 2005, 53(5):541-546.
[40]
ZHANG H, YANG J Y, ZHOU F, et al. Seed oil of Brucea javanica induces apoptotic death of acute myeloid leukemia cells via both the death receptors and the mitochondrial-related pathways[J]. Evid Based Complement Alternat Med, 2011.Doi: 10.1155/2011/965016.
[41]
YU Y N,LI X. Studies on the chemical constituents of Brucea javanica (L.) Merr[J]. Acta Pharm Sin( 药学学报), 1990,25(5):382-386.
[42]
YU R M, WANG S X, ZHOU X M, et al. Studies on the anticancer active components from the stem of Brucea javanica[J]. Chin Tradit Herb Drugs(中草药), 1988, 19(7):6-7.
[43]
LUO Y, SHEN H Y, ZHANG M,et al. Chemical constituents from the dregs of Brucea javanica[J]. J Trop Subtrop Bot, 2019, 27(3):294-298.
[44]
SU Z W, MA Z H, LIU K, et al. Quassilactones A and B, structural characterization of a new class of norquassinoids from Brucea javanica[J]. J Nat Med, 2020, 74(3):599-605.
[45]
MEIYANTO E, LARASATI Y A.The chemopreventive activity of indonesia medicinal plants targeting on Hallmarks of Cancer[J]. Adv Pharm Bull, 2019, 9(2):219-230.
[46]
JIN Z,EL-DEIRY W S. Overview of cell death signaling pathways[J]. Cancer Biol Ther, 2005, 4(2):139-163.
[47]
XIE J H, LAI Z Q, ZHENG X H, et al. Apoptosis induced by bruceine D in human nonsmallcell lung cancer cells involves mitochondrial ROS mediated death signaling[J]. Int J Mol Med, 2019, 44(6):2015-2026.
[48]
LIU L, LIN Z X, LEUNG P S, et al. Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells[J]. Int J Mol Med, 2012, 30(1):93-99.
[49]
ZHANG J Y, LIN M T, TUNG H Y, et al. Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway[J]. Am J Cancer Res, 2016, 6(4):819-826.
[50]
TAN B, HUANG Y, LAN L, et al. Bruceine D induces apoptosis in human non-small cell lung cancer cells through regulating JNK pathway[J]. Biomed Pharmacother, 2019, 117:109089.Doi:10.1016/j.biopha.2019.109089.
[51]
WANG S, HU H, ZHONG B, et al. Bruceine D inhibits tumor growth and stem cell-like traits of osteosarcoma through inhibition of STAT3 signaling pathway[J]. Cancer Med, 2019, 8(17):7345-7358.
[52]
LI C, WANG Y, ZHAO X L, et al. Bruceine A induces apoptosis in non-small-cell lung cancer cell line H460 by regulating mitochondria-related apoptosis signaling[J]. Chin Med Biotechnol(中国医药生物技术), 2019, 14(4):294-301.
[53]
WANG D, QU X, ZHUANG X, et al. Seed oil of Brucea javanica induces cell cycle arrest and apoptosis via reactive oxygen species-mediated mitochondrial dysfunction in human lung cancer cells[J]. Nutr Cancer, 2016, 68(8):1394-1403.
[54]
CHEN J H, KIM S H, FAN P W, et al. The aqueous extract of Chinese medicinal herb Brucea javanica suppresses the growth of human liver cancer and the derived stem-like cells by apoptosis[J]. Drug Des Devel Ther, 2016, 10:2003-2013.Doi: 10.2147/DDDT.S107909.
[55]
OTTO T,SICINSKI P. Cell cycle proteins as promising targets in cancer therapy[J]. Nat Rev Cancer, 2017, 17(2):93-115.
[56]
ZHANG H,JIANG D Q.Effects of Bruceine D on proliferation, apoptosis and cell cycle of breast cancer MDA-MB-231 cells[J]. Shaanxi J Tradit Chin Med 2019, 40(11):1495-1497.
[57]
HUANG Z, YANG G, SHEN T, et al. Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells[J]. Biomed Pharmacother, 2017, 89:623-631.Doi:10.1016/j.biopha.2017.02.055.
[58]
WANG D X, QUX Q, ZHUANG X B, et al. Seed Oil of Brucea javanica induces cell cycle arrest and apoptosis via reactive oxygen species-mediated mitochondrial dysfunction in human lung Cancer Cells[J]. Nutr Cancer, 2016, 68(8):1394-1403.
[59]
YAN Z, ZHANG B, HUANG Y Y, et al. Involvement of autophagy inhibition in Brucea javanica oil emulsion-induced colon cancer cell death[J]. Oncol Lett, 2015, 9(3):1425-1431.
[60]
YE H X, LIU X J, SUN J C, et al. Enhanced therapeutic efficacy of LHRHa-targeted Brucea javanica oil liposomes for ovarian cancer[J]. BMC Cancer, 2016, 16(1):831.Doi: 10.1186/s12885-016-2870-4.
[61]
OLAYANJU A, COPPLE I M, BRYAN H K, et al. Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2[J]. Free Radic Biol Med, 2015, 78:202-212.Doi: 10.1016/j.freeradbiomed.2014.11.003.
[62]
ROMERO-CORDOBA S L, SALIDO-GUADARRAMA I, RODRIGUEZ-DORANTES M, et al. miRNA biogenesis: biological impact in the development of cancer[J]. Cancer Biol Ther, 2014, 15(11):1444-1455.
[63]
CHENG A M, BYROM M W, SHELTON J, et al. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis[J]. Nucleic Acids Res, 2005, 33(4):1290-1297.
[64]
LAU S T, LIN Z X, LIAO Y, et al. Bruceine D induces apoptosis in pancreatic adenocarcinoma cell line PANC-1 through the activation of p38-mitogen activated protein kinase[J]. Cancer Lett, 2009, 281(1):42-52.
[65]
HUANG Z, HUANG S, WANG Q, et al. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma[J]. Cancer Res, 2011, 71(7):2582-2589.
[66]
XIAO Z G, CHOW S C, LI C H, et al. Role of microRNA-95 in the anticancer activity of Brucein D in hepatocellular carcinoma[J]. Eur J Pharmacol, 2014, 728:141-150.Doi: 10.1016/j.ejphar.2014.02.002.
[67]
LUO C, WANG Y, WEI C, et al. The anti-migration and anti-invasion effects of Bruceine D in human triple-negative breast cancer MDA-MB-231 cells[J]. Exp Ther Med, 2020, 19(1):273-279.
[68]
FOLKMAN J, BROWDER T,PALMBLAD J. Angiogenesis research: guidelines for translation to clinical application[J]. Thromb Haemost, 2001, 86(1):23-33.
[69]
SHI Y F, LI J, LI Y L. Inhibitory effect of ethanol extract from Java Brucea Fruit on cell migration mediated by platelet-derived growth factor receptor β [N]. J Jilin Univ (Med Ed)(吉林大学学报医学版), 2009, 35(04):608-611.
[70]
ZHOU J, TAN L, XIE J, et al. Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice[J]. Drug Deliv, 2017, 24(1):1667-1679.
[71]
HUANG Y F, ZHOU J T, QU C, et al., Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice[J]. J Ethnopharmacol, 2017, 198:389-398.Doi: 10.1016/j.jep.2017.01.042.
[72]
HUANG Y F, LI Q P, DOU Y X, et al. Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn′s disease in rats: Involvement of TLR4/ NF-kappaB signaling pathway[J]. Biomed Pharmacother, 2019, 114:108766.Doi: 10.1016/j.biopha.2019.108766.
[73]
ZHOU J, WANG T, DOU Y, et al. Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in rats: Involvement of NF-kappaB pathway and NLRP3 inflammasome[J]. Int Immunopharmacol, 2018, 64:264-274.Doi: 10.1016/j.intimp.2018.09.008.
[74]
HUANG Y F, ZHOU J T, QU C, et al. Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-kappaB activation on dextran sulfate sodium-induced ulcerative colitis in mice[J]. J Ethnopharmacol, 2017, 198:389-398.Doi: 10.1016/j.jep.2017.01.042.
[75]
JUNG J I, KIM S Y, PARK K Y, et al. In vitro combinatorial anti-proliferative and immunosuppressive effects of Brucea javanica extract with CX-4945 and imatinib in human T-cell acute lymphoblastic leukemia cells[J]. Biomed Pharmacother, 2018, 106:403-410.Doi: 10.1016/j.biopha.2018.06.164.
[76]
YANG Q, ZHENG L N, XIE Y Z, et al. Study on adjoint toxical mechanism of anti- inflammatory effect of different extract from fructus bruceae [J ]. Chin J Pharmacov(中国药物警戒), 2011, 8(6):333-335.
[77]
LEMMA M T, AHMED A M, ELHADY M T, et al. Medicinal plants for in vitro antiplasmodial activities: a systematic review of literature[J]. Parasitol Int, 2017, 66(6):713-720.
[78]
MOHD ABD RAZAK M R, AFZAN A, ALI R,et al. Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum[J]. BMC Complement Altern Med, 2014, 14:492.Doi: 10.1186/1472-6882-14-492.
[79]
QIN Y H, DAI X D, ZHENG L L, et al. Therapeutic effect of Brucea javanica and Fructus Psoraleae on pneumocystis carinii pneumonia in rat[J]. Chin Pharma J(中国药学杂志), 2007, 42(4):260-263.
[80]
CUI Y, QING Y H, LI Q, et al. Experimental studies on the oxidation damages of mice induced by Pneumo cystis carinii pneumonia and the trial uses of the traditional Chinese medicine[J]. Chin J Zoonoses(中国人兽共患病杂志), 2004, 20(10):858-862.
[81]
MAO G, TIAN Y, SUN Z, et al. Bruceine D Isolated from Brucea javanica (L.) Merr. as a systemic feeding deterrent for three major lepidopteran Pests[J]. J Agric Food Chem, 2019, 67(15):4232-4239.
[82]
LAN L, ZUO B, DING H, et al. Anticoccidial evaluation of a traditional Chinese medicine—Brucea javanica—in broilers[J]. Poult Sci, 2016, 95(4):811-818.
[83]
WANG Y, WU Z F, WANG G X, et al. In vivo anthelmintic activity of bruceine A and bruceine D from Brucea javanica against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus)[J]. Vet Parasitol, 2011, 177(1-2):127-133.
[84]
SUTININGSIH D, NURJAZULI N, NUGROHO D, et al. Larvicidal Activity of brusatol Isolated from Brucea javanica (L) merr on Culex quinquefasciatus[J]. Iran J Public Health, 2019, 48(4):688-696.
[85]
XIE J H, LAI Z Q, ZHENG X H,et al. Apoptosis induced by bruceine D in human non small cell lung cancer cells involves mitochondrial ROS mediated death signaling[J]. Int J Mol Med, 2019, 44(6):2015-2026.
[86]
YU X G, WANG S J, GAO X, et al. Study on the changes of lecithin cholesterol acyltransferase activity in serum of hyperlipidemic gerbils and the lipid-lowering effect of Brucea javanica oil emulsion[J]. Chin J Gerontol(中国老年学杂志), 1997,17(3):40-41.
[87]
ABLAT A, HALABI M F, MOHAMAD J, et al. Antidiabetic effects of Brucea javanica seeds in type 2 diabetic rats[J]. BMC Complement Altern Med, 2017, 17(1):94.Doi: 10.1186/s12906-017-1610-x.
[88]
LIU H.Brucea javanica in the treatment of verruca plana[J]. J Nurs Sci, 2007(17):1533.Doi: 10.1186/s12906-017-1610-x.
[89]
LU F X. 60 cases of metatarsal warts treated by external application of Brucea javanica[J]. Chin J Urban Rural Ind Hygiene, 2014, 29(5):151-152.
[90]
QIU M M, WANG S W, WEI R F, et al. Extraction and isolation of active components from Brucea javanica in the treatment of condyloma acuminatum[J]. J Guangxi Chin Med(广西中医药大学学报),1999,(4):82-88.
[91]
RYU S M, KWON J, SEO Y H, et al. Quassinoids isolated from Brucea javanica inhibit pepper mottle virus in pepper[J]. Virus Res, 2017, 227:49-56.Doi: 10.1016/j.virusres.2016.09.013.
[92]
BAEK J, JEONG H, HAM Y, et al. Improvement of spinal muscular atrophy via correction of the SMN2 splicing defect by Brucea javanica (L.) Merr. extract and Bruceine D[J]. Phytomedicine, 2019, 65:153089.Doi: 10.1016/j.phymed.2019.153089.
[93]
ZHAN Y, TAN T, QIAN K, et al. Quassinoids from seeds of Brucea Javanica and their anticomplement activities[J]. Nat Prod Res, 2019,34(8):1-6.
[94]
ZHU H J,NAN X Y.An experimental study of the therapeutic effect of brucea javanica oil emulsion on benign prostatic hyperplasia[J]. Chin J Urol(中华泌尿外科杂志), 1999, 20(11):39-41.
2022, Vol. 57 
