{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:59:47Z","timestamp":1793109587953,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF), South Africa","award":["Incentive Funding for Rated Researchers"],"award-info":[{"award-number":["Incentive Funding for Rated Researchers"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Altern Med"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s12906-018-2372-9","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T08:07:08Z","timestamp":1542182828000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Croton gratissimus leaf extracts inhibit cancer cell growth by inducing caspase 3\/7 activation with additional anti-inflammatory and antioxidant activities"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-7202","authenticated-orcid":false,"given":"Emmanuel","family":"Mfotie Njoya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus N.","family":"Eloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndy J.","family":"McGaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"2372_CR1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.redox.2016.08.010","volume":"9","author":"A G\u0119gotek","year":"2016","unstructured":"G\u0119gotek A, Nikli\u0144ski J, \u017darkovi\u0107 N, \u017darkovi\u0107 K, Waeg G, \u0141uczaj W, Charkiewicz R, Skrzydlewska E. Lipid mediators involved in the oxidative stress and antioxidant defence of human lung cancer cells. Redox Biol. 2016;9:210\u20139.","journal-title":"Redox Biol"},{"key":"2372_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2013.02.011","volume":"60","author":"SI Liochev","year":"2013","unstructured":"Liochev SI. Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med. 2013;60:1\u20134.","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"2372_CR3","first-page":"219","volume":"2","author":"K Rahman","year":"2007","unstructured":"Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging. 2007;2(2):219\u201336.","journal-title":"Clin Interv Aging"},{"key":"2372_CR4","doi-asserted-by":"crossref","unstructured":"Islam S, Samima N, Muhammad AK, Sakhawat Hossain A, Farhadul I, Proma K, Haque Mollah MN, Mamunur R, Golam S, Md Aziz AR, et al. Evaluation of antioxidant and anticancer properties of the seed extracts of Syzygium fruticosum Roxb. Growing in Rajshahi, Bangladesh. BMC Complement Altern Med. 2013;13.","DOI":"10.1186\/1472-6882-13-142"},{"key":"2372_CR5","doi-asserted-by":"publisher","first-page":"21138","DOI":"10.3390\/molecules201219753","volume":"20","author":"Y-J Zhang","year":"2015","unstructured":"Zhang Y-J, Gan R-Y, Li S, Zhou Y, Li A-N, Xu D-P, Li H-B. Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules. 2015;20:21138\u201356.","journal-title":"Molecules"},{"issue":"10","key":"2372_CR6","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.2174\/187152012803833026","volume":"12","author":"H Wang","year":"2012","unstructured":"Wang H, Khor TO, Shu L, Su ZY, Fuentes F, Lee JH, Kong AN. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anti Cancer Agents Med Chem. 2012;12(10):1281\u2013305.","journal-title":"Anti Cancer Agents Med Chem"},{"key":"2372_CR7","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s00423-006-0073-1","volume":"91","author":"H Bartsch","year":"2006","unstructured":"Bartsch H, Nair J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair. Langenbeck's Arch Surg. 2006;91:499\u2013510.","journal-title":"Langenbeck's Arch Surg"},{"key":"2372_CR8","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.4161\/cc.8.13.8985","volume":"8","author":"TA Gonda","year":"2009","unstructured":"Gonda TA, Tu S, Wang TC. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle. 2009;8:2005\u201313.","journal-title":"Cell Cycle"},{"issue":"11","key":"2372_CR9","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","volume":"49","author":"S Reuter","year":"2010","unstructured":"Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603\u201316.","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"2372_CR10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1590\/S0103-50532007000100002","volume":"18","author":"A Salatino","year":"2007","unstructured":"Salatino A, Salatino MLF, Negri G. Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae). J Braz Chem Soc. 2007;18(1):11\u201333.","journal-title":"J Braz Chem Soc"},{"key":"2372_CR11","first-page":"35","volume":"15","author":"MC Kapingu","year":"2012","unstructured":"Kapingu MC, Mbwambo ZH, Moshi MJ, Magadula JJ. Brine shrimp lethality of alkaloids from Croton sylvaticus Hoechst. East and Central African Journal of Pharmaceutical Sciences. 2012;15:35\u20137.","journal-title":"East and Central African Journal of Pharmaceutical Sciences"},{"key":"2372_CR12","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.3390\/molecules18021916","volume":"18","author":"AR Ndhlala","year":"2013","unstructured":"Ndhlala AR, Aderogba MA, Ncube B, Van Staden J. Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species. Molecules. 2013;18:1916\u201332.","journal-title":"Molecules"},{"key":"2372_CR13","doi-asserted-by":"crossref","unstructured":"Langat M, Mulholland DA, Crouch N: New diterpenoids from Croton sylvaticus and Croton pseudopulchellus (Euphorbiaceae) and antiplasmodial screening of ent-kaurenoic acid. Planta Med 2008, 74(09):PB126.","DOI":"10.1055\/s-0028-1084471"},{"issue":"4","key":"2372_CR14","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S0031-9422(02)00034-1","volume":"60","author":"BT Ngadjui","year":"2002","unstructured":"Ngadjui BT, Abegaz BM, Keumedjio F, Folefoc GN, Kapche GW. Diterpenoids from the stem bark of Croton zambesicus. Phytochemistry. 2002;60(4):345\u20139.","journal-title":"Phytochemistry"},{"issue":"7","key":"2372_CR15","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1055\/s-2002-32903","volume":"68","author":"S Block","year":"2002","unstructured":"Block S, Stevigny C, De Pauw-Gillet MC, de Hoffmann E, Llabres G, Adjakidje V, Quetin-Leclercq J. Ent-trachyloban-3beta-ol, a new cytotoxic diterpene from Croton zambesicus. Planta Med. 2002;68(7):647\u20139.","journal-title":"Planta Med"},{"key":"2372_CR16","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1016\/j.phytochem.2010.05.014","volume":"71","author":"DA Mulholland","year":"2010","unstructured":"Mulholland DA, Langat MK, Crouch NR, Coley HM, Mutambi EM, Nuzillard JM. Cembranolides from the stem bark of the southern African medicinal plant, Croton gratissimus (Euphorbiaceae). Phytochemistry. 2010;71:1381\u20136.","journal-title":"Phytochemistry"},{"key":"2372_CR17","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1021\/np2002012","volume":"74","author":"MK Langat","year":"2011","unstructured":"Langat MK, Crouch NR, Smith PJ, Mulholland DA. Cembranolides from the leaves of Croton gratissimus. J Nat Prod. 2011;74:2349\u201355.","journal-title":"J Nat Prod"},{"issue":"3","key":"2372_CR18","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/S0378-8741(98)00185-8","volume":"66","author":"N Lall","year":"1999","unstructured":"Lall N, Meyer JJ. In vitro inhibition of drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis by ethnobotanically selected south African plants. J Ethnopharmacol. 1999;66(3):347\u201354.","journal-title":"J Ethnopharmacol"},{"key":"2372_CR19","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10811-006-9048-4","volume":"18","author":"Q Zhang","year":"2006","unstructured":"Zhang Q, Zhang J, Shen J, Silva A, Dennis D, Barrow C. A simple 96-well microplate method for estimation of total polyphenol content in seaweeds. J Appl Phycol. 2006;18:445\u201350.","journal-title":"J Appl Phycol"},{"key":"2372_CR20","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.foodchem.2006.01.014","volume":"101","author":"J Lin","year":"2007","unstructured":"Lin J, Tang C. Determination of total phenolic and flavonoid contents in selected fruits and vegetables, as well as their stimulatory effects on mouse splenocyte proliferation. Food Chem. 2007;101:140\u20137.","journal-title":"Food Chem"},{"issue":"1","key":"2372_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","volume":"28","author":"W Brand-Williams","year":"1995","unstructured":"Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. Lebensmittel Wissenschaftund Technologie. 1995;28(1):25\u201330.","journal-title":"Lebensmittel Wissenschaftund Technologie"},{"key":"2372_CR22","first-page":"1057","volume":"28","author":"R Re","year":"1999","unstructured":"Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolourization assay. Free Radic Biol Med. 1999;28:1057\u201360.","journal-title":"Free Radic Biol Med"},{"key":"2372_CR23","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.jep.2014.11.034","volume":"160","author":"JP Dzoyem","year":"2015","unstructured":"Dzoyem JP, Eloff JN. Anti-inflammatory, anticholinesterase and antioxidant activity of leaf extracts of twelve plants used traditionally to alleviate pain and inflammation in South Africa. J Ethnopharmacol. 2015;160:194\u2013201.","journal-title":"J Ethnopharmacol"},{"issue":"1\u20132","key":"2372_CR24","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1\u20132):55\u201363.","journal-title":"J Immunol Methods"},{"issue":"15","key":"2372_CR25","doi-asserted-by":"publisher","first-page":"5956","DOI":"10.1021\/jf070537x","volume":"55","author":"MC Pinto","year":"2007","unstructured":"Pinto MC, Tejeda A, Duque AL, Macias P. Determination of lipoxygenase activity in plant extracts using a modified ferrous oxidation-xylenol orange assay. J Agric Food Chem. 2007;55(15):5956\u20139.","journal-title":"J Agric Food Chem"},{"key":"2372_CR26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/1472-6882-12-173","volume":"12","author":"AS Ravipati","year":"2012","unstructured":"Ravipati AS, Zhang L, Koyyalamudi SR, Jeong SC, Reddy N, Bartlett J, Smith PT, Shanmugam K, Munch G, Wu MJ, et al. Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complement Altern Med. 2012;12:173.","journal-title":"BMC Complement Altern Med"},{"issue":"(118)","key":"2372_CR27","first-page":"11","volume":"11","author":"SK Choudhari","year":"2013","unstructured":"Choudhari SK, Chaudhary M, Bagde S, Amol R Gadbail AR, Joshi V. Nitric oxide and cancer: a review. World Journal of Surgical Oncology. 2013;11((118)):11.","journal-title":"World Journal of Surgical Oncology"},{"issue":"3","key":"2372_CR28","doi-asserted-by":"publisher","first-page":"283","DOI":"10.2174\/156802607779941369","volume":"7","author":"L Goossens","year":"2007","unstructured":"Goossens L, Pommery N, Henichart JP. COX-2\/5-LOX dual acting anti-inflammatory drugs in cancer chemotherapy. Curr Top Med Chem. 2007;7(3):283\u201396.","journal-title":"Curr Top Med Chem"},{"key":"2372_CR29","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jep.2006.10.021","volume":"111","author":"D Dufour","year":"2007","unstructured":"Dufour D, Pichette A, Mshvildadze V, H\u00e9bert M-EB, Lavoie S, Longtin A, Laprise C, Legault J. Antioxidant, anti-inflammatory and anticancer activities of methanolic extracts from Ledum groenlandicum Retzius. J Ethnopharmacol. 2007;111:22\u20138.","journal-title":"J Ethnopharmacol"},{"issue":"16","key":"2372_CR30","doi-asserted-by":"publisher","first-page":"122","DOI":"10.4103\/0973-7847.134247","volume":"8","author":"K Sak","year":"2014","unstructured":"Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 2014;8(16):122\u201346.","journal-title":"Pharmacogn Rev"},{"key":"2372_CR31","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s13205-013-0117-5","volume":"3","author":"P Batra","year":"2013","unstructured":"Batra P, Sharma A. Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 2013;3:439\u201359.","journal-title":"3 Biotech"},{"issue":"11","key":"2372_CR32","doi-asserted-by":"publisher","first-page":"12771","DOI":"10.3390\/molecules171112771","volume":"17","author":"M Wink","year":"2012","unstructured":"Wink M. Medicinal plants: a source of anti-parasitic secondary metabolites. Molecules. 2012;17(11):12771\u201391.","journal-title":"Molecules"},{"issue":"1","key":"2372_CR33","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s12291-013-0313-4","volume":"29","author":"F Namvar","year":"2014","unstructured":"Namvar F, Baharara J, Mahdi AA. Antioxidant and anticancer activities of selected Persian gulf algae. Ind J Clin Biochem. 2014;29(1):13\u201320.","journal-title":"Ind J Clin Biochem"},{"issue":"5","key":"2372_CR34","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S2221-1691(12)60058-6","volume":"2","author":"M Sasipawan","year":"2012","unstructured":"Sasipawan M, Natthida W, Sahapat B. Anticancer effect of the extracts from Polyalthia evecta against human hepatoma cell line (HepG2). Asian Pac J Trop Biomed. 2012;2(5):368\u201374.","journal-title":"Asian Pac J Trop Biomed"},{"issue":"1","key":"2372_CR35","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1158\/0008-5472.CAN-09-3324","volume":"70","author":"KH Chow","year":"2010","unstructured":"Chow KH, Sun RW, Lam JB, Li CK, Xu A, Ma DL, Abagyan R, Wang Y, Che CM. A gold(III) porphyrin complex with antitumor properties targets the Wnt\/beta-catenin pathway. Cancer Res. 2010;70(1):329\u201337.","journal-title":"Cancer Res"},{"issue":"9","key":"2372_CR36","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1038\/cdd.2011.30","volume":"18","author":"M Olsson","year":"2011","unstructured":"Olsson M, Zhivotovsky B. Caspases and cancer. Cell Death Differ. 2011;18(9):1441\u20139.","journal-title":"Cell Death Differ"},{"key":"2372_CR37","first-page":"407","volume":"7","author":"G Singh","year":"2016","unstructured":"Singh G, Passsari AK, Leo VV, Mishra VK, Subbarayan S, Singh BP, Kumar B, Kumar S, Gupta VK, Lalhlenmawia H, et al. Evaluation of phenolic content variability along with antioxidant, antimicrobial, and cytotoxic potential of selected traditional medicinal plants from India. Front Plant Sci. 2016;7:407.","journal-title":"Front Plant Sci"}],"container-title":["BMC Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-018-2372-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12906-018-2372-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-018-2372-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T19:08:33Z","timestamp":1573672113000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-018-2372-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["2372"],"URL":"https:\/\/doi.org\/10.1186\/s12906-018-2372-9","relation":{},"ISSN":["1472-6882"],"issn-type":[{"value":"1472-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]},"assertion":[{"value":"2 October 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests. Prof Jacobus N Eloff is a Section Editor and Prof Lyndy J McGaw is an Associate Editor of BMC Complementary and Alternative medicine.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"305"}}