The effects of Curcuma longa and curcumin on reproductive systems

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Objective. Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-inflammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an effort on a detailed literature survey concentrated on the protective effects of C. longa and curcumin on the reproductive organs activity. Methods. The databases such as, PubMed, Web of Science, Google Scholar, Scopus, and Iran- Medex, were considered. The search terms were “testis” or “ovary” and “Curcuma longa”, “curcumin”, “antioxidant effect”, “anti-inflammatory effect” and “anti-cancer effect”. Results. C. longa and curcumin inhibited the production of the tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) and increased the caspases (3, 8 and 9) activities in HL-60 prostate cancer. Furthermore, C. longa and curcumin suppressed the vascular endothelial growth factor (VEGF), phosphorylated signal transducers and activators of the transcription 3 (STAT) and matrix metalloproteinase-9 (MMP-9) in ovarian cancer cell line. Conclusion. C. longa and curcumin might decrease the risk of cancer and other malignant diseases in the reproductive system. C. longa and curcumin have a protective effect on the reproductive organs activity such as, anti-inflammatory, anti-apoptotic, and antioxidant effects in normal cells but showed pro-apoptotic effects in the malignant cells. Therefore, different effects of C. longa and curcumin are dependent on the doses and the type of cells used in various models studied.

Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23, 363-398, 2003.

Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) downregulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα kinase and Akt activation. Mol Pharmacol 69, 195-206, 2006.

Agga rwal BB, Harikumar KB. Potential therapeutic eff ects of curcumin, the anti-infl ammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41, 40-59, 2009.

Akram M, Uddin S, Ahmed A, Usmanghani K, Hannan A, Mohiuddin E, Asif M. Curcuma longa and curcumin: a review article. Rom J Biol Plant Biol 55, 65-70, 2010.

Akta s C, Kanter M, Erboga M, Ozturk S. Anti-apoptotic eff ects of curcumin on cadmium-induced apoptosis in rat testes. Toxicol Indust Health 28, 122-130, 2012.

Ammo n HP, Wahl MA. Pharmacology of Curcuma longa. Plant Med 57, 1-7, 1991.

Arau jo CAC, Leon LL. Biological activities of Curcuma longa L. Memorias do Instituto Oswaldo Cruz 96, 723-728, 2001.

Asho k P, Meenakshi B. Contraceptive eff ect of Curcuma longa (L.) in male albino rat. Asia J Androl 6, 71-74, 2004.

Azza M, El-Wakf ME-S, Elhabiby MW, El-kholy E-GEA. Use of tumeric and curcumin to alleviate adverse reproductive outcomes of water: Nitrate pollution in male rats. Nat Sci 9, 229-239, 2011.

Chai nani-Wu N. Safety and anti-infl ammatory activity of curcumin: a component of tumeric (Curcuma longa). J Alter Compl Med 9, 161-168, 2003.

Cohe n GM. Caspases: the executioners of apoptosis. Biochem J 326, 1-16, 1997.

Cort A, Timur M, Ozdemir E, Kucuksayan E, Ozben T. Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells. Mol Med Rep 5, 1481-1146, 2012.

Cort A, Timur M, Ozdemir E, Ozben T. Eff ects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells. J Physiol Biochem 69, 289-296, 2013.

Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 100, 72-79, 2005.

Desh pande UR, Gadre SG, Raste AS, Pillai D, Bhide SV, Samuel AM. Protective eff ect of turmeric (Curcuma long L.) extract on carbon tetrachloride-induced liver damage in rats. India J Exp Biol 36, 573-577, 1998.

Dobrovolskaia MA, Kozlov SV. Infl ammation and cancer: when NF-κB amalgamates the perilous partnership. Curr Cancer Drug Targets 5, 325-344, 2005.

Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Th erapeutic potential of curcumin in human prostate cancer. III.

Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 47, 293-303, 2001.

Eigner D, Scholz D. Ferula asa-foetida and Curcuma longa in traditional medical treatment and diet in Nepal. J Ethnopharmacol 67, 1-6, 1999.

Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO. Curcumin and kolaviron ameliorate di‐n‐butylphthalate‐induced testicular damage in rats. Basic Clin Pharmacol Toxicol 100, 43-48, 2007.

Giannessi F, Giambelluca MA, Grasso L, Scavuzzo MC, Ruff oli R. Curcumin protects Leydig cells of mice from damage induced by chronic alcohol administration. Med Sci Monitor 14, BR237-BR242, 2008.

Gururaj A, Belakavadi M, Venkatesh DA, Marme D, Salimath BP. Molecular mechanisms of antiangiogenic eff ect of curcumin. Biochem Biophys Res Commun 297, 934-942, 2002.

Hardie DG, C arling D. Th e AMP‐activated protein kinase. Eur J Biochem 246, 259-273, 1997.

Harris SL, Le vine AJ. Th e p53 pathway: positive and negative feedback loops. Oncogene 24, 2899-2908, 2005.

Holt PR, Katz S, Kirshoff R. Curcumin therapy in infl ammatory bowel disease: a pilot study. Dig Dis Sci 50, 2191-2193, 2005.

Hu M, Du Q, V ancurova I, Lin X, Miller EJ, Simms HH, Wang P. Proapoptotic eff ect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway. Crit Care Med 33, 2571-2578, 2005.

Hu J, Verkman A. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J 20, 1892-1894, 2006.

Ilbey YO, Ozb ek E, Cekmen M, Simsek A, Otunctemur A, Somay A. Protective eff ect of curcumin in cisplatininduced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Hum Reprod 24, 1717-1725, 2009.

Ji C, Cao C, Lu S, Kivlin R, Amaral A, Kouttab N, Yang H, Chu W, Bi Z, Di W, Wan Y. Curcumin attenuates EGFinduced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemother Pharmacol 62, 857-865, 2008.

Jurenka JS. A nti-infl ammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14, 141-153, 2009.

Khazdair MR, Mohebbati R, Karimi S, Abbasnezhad A, Haghshenas M. Th e protective eff ects of Curcuma longa extract on oxidative stress markers in the liver induced by Adriamycin in rat. Physiol Pharmacol 20, 31-37, 2016.

Kowluru RA, K anwar M. Eff ects of curcumin on retinal oxidative stress and infl ammation in diabetes. Nutr Metab (Lond) 4, 8, 2007.

Kunchandy E, Rao MNA. Oxygen radical scavenging activity of curcumin. Int J Pharm 58, 237-240, 1990.

Kuttan R, Bha numathy P, Nirmala K, George MC. Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett 29, 197-202, 1985.

Lantz RC, Che n G, Solyom A, Jolad S, Timmermann B. Th e eff ect of turmeric extracts on infl ammatory mediator production. Phytomedicine 12, 445-452, 2005.

Lin YG, Kunnu makkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN, Kamat AA, Spannuth WA, Gershenson DM, Lutgendorf SK, Aggarwal BB, Sood AK. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clin Cancer Res 13, 3423-3430, 2007.

Martelli AM, Z weyer M, Ochs RL, Tazzari PL, Tabellini G, Narducci P, Bortul R. Nuclear apoptotic changes: an overview.J Cell Biochem 82, 634-646, 2001.

Mishra RK, Sin gh SK. Reversible antifertility eff ect of aqueous rhizome extract of Curcuma longa L. in male laboratory mice. Contraception 79, 479-487, 2009.

Mohanty I, Sin gh Arya D, Dinda A, Joshi S, Talwar KK, Gupta SK. Protective eff ects of Curcuma longa on ischemiareperfusion induced myocardial injuries and their mechanisms. Life Sci 75, 1701-1711, 2004.

Mohebbati R, S hafei MN, Soukhtanloo M, Mohammadian Roshan N, Khajavi Rad A, Anaeigoudari A, Hosseinian S, Karimi S, Beheshti F. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney. Avicenna J Phytomed 6, 86-94, 2016.

Montopoli M, R agazzi E, Froldi G, Caparrotta L. Cell‐cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif 42, 195-206, 2009.

Moon C, Soria J- C, Jang SJ, Lee J, Obaidul Hoque M, Sibony M, Trink B, Chang YS, Sidransky D, Mao L. Involvement of aquaporins in colorectal carcinogenesis. Oncogene 22, 6699-6703, 2003.

Moussavi M, Assi K, Gomez-Munoz A, Salh B. Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells. Carcinogenesis 27, 1636-1644, 2006.

Nagata D, Takeda R, Sata M, Satonaka H, Suzuki E, Nagano T, Hirata Y. AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation 110, 444-451, 2004.

Naik RS, Mujumda r AM, Ghaskadbi S. Protection of liver cells from ethanol cytotoxicity by curcumin in liver slice culture in vitro. J Ethnopharmacol 95, 31-37, 2004.

Oguzturk H, Cift ci O, Aydin M, Timurkaan N, Beytur A, Yilmaz F. Ameliorative eff ects of curcumin against acute cadmium toxicity on male reproductive system in rats. Andrologia 44, 243-249, 2012.

Pan W, Yang H, C ao C, Song X, Wallin B, Kivlin R, Lu S, Hu G, Di W, Wan Y. AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep 20, 1553-1559, 2008.

Park MJ, Kim EH, Park IC, Lee HC, Woo SH, Lee JY, Hong YJ, Rhee CH, Choi SH, Shim BS, Lee SH, Hong SI. Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol 21, 379-384, 2002.

Purohit A. Antif ertility effi cacy of Curcuma longa (50% E to H extract) with special referance to serum biochemistry and fertility test. Anc Sci Life 18, 192-194, 1999.

Qureshi S, Shah A, Ageel A. Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med 58, 124-127, 1992.

Raj A, Singh A, Sharma A, Singh N, Kumar P, Bhatia V. Antifertility activity of medicinal plants on reproductive system of female rat. Int J Bio-Eng Sci Technol 2, 44-50, 2011.

Sahoo DK, Roy A, Chainy GB. Protective eff ects of vitamin E and curcumin on L-thyroxine-induced rat testicular oxidative stress. Chem Biol Interac 176, 121-128, 2008.

Sak ME, Soydinc HE, Sak S, Evsen MS, Alabalik U, Akdemir F, Gul T. Th e protective eff ect of curcumin on ischemiareperfusion injury in rat ovary. Int J Surg 11, 967-970, 2013.

Sharma RA, Gesch er AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 41, 1955-1968, 2005.

Sharma P, Singh R. Protective role of curcumin on lindane induced reproductive toxicity in male Wistar rats. Bull Environ Contam Toxicol 84, 378-384, 2010.

Shi M, Cai Q, Ya o L, Mao Y, Ming Y, Ouyang G. Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int 30, 221-226, 2006.

Shukla PK, Khann a VK, Khan MY, Srimal RC. Protective eff ect of curcumin against lead neurotoxicity in rat. Hum Exp Toxicol 22, 653-658, 2003.

Siddik ZH. Cispl atin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279, 2003.

Srivastava G, Me hta JL. Currying the heart: curcumin and cardioprotection. J J Cardiovasc Pharmacol Th er 14, 22-27, 2009.

Swamy MV, Citine ni B, Patlolla JMR, Mohammed A, Zhang Y, Rao CV. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nutr Cancer 60, 81-89, 2008.

Thakur S, Bawara B, Dubey A, Nandini D, Chauhan NS, Saraf DK. Eff ect of Carum carvi and Curcuma longa on hormonal and reproductive parameter of female rats. Int J Phytomed 1, 31-38, 2009.

Van Laere SJ, Va n der Auwera I, Van den Eynden GG, Elst HJ, Weyler J, Harris AL, van Dam P, Van Marck EA, Vermeulen PB, Dirix LY. Nuclear factor-KB signature of infl ammatory breast cancer by cDNA microarray validated by quantitative real-time reverse transcription-PCR, immunohistochemistry, and nuclear factor-KB DNA-binding. Clin Cancer Res 12, 3249-3256, 2006.

Verkman A. More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118, 3225-3232, 2005.

Wahl H, Tan L, G riffi th K, Choi M, Liu JR. Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells. Gynecol Oncol 105, 104-112, 2007.

Watson JL, Green shields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, Hoskin DW. Curcumin‐induced apoptosis in ovarian carcinoma cells is p53‐independent and involves p38 mitogen‐activated protein kinase activation and downregulation of Bcl‐2 and survivin expression and Akt signaling. Mol Carcinog 49, 13-24, 2010.

Wilken R, Veena MS, W ang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 10, 12, 2011.

Yamamoto Y, Gaynor RB . Th erapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J Clin Invest 107, 135-142, 2001.

Yang Yl, Ji C, Cheng L, He L, Lu CC, Wang R, Bi ZG. Sphingosine kinase‐1 inhibition sensitizes curcumin‐induced growth inhibition and apoptosis in ovarian cancer cells. Cancer Sci 103, 1538-1545, 2012.

Yu J, Zhang L. Th e transcr iptional targets of p53 in apoptosis control. Biochem Biophys Res Commun 331, 851-858, 2005.

Yu YY, Li Q, Zhu ZG. NF-ka ppaB as a molecular target in adjuvant therapy of gastrointestinal carcinomas. Eur J Surg Oncol 31, 386-392, 2005.

Yu T, Li J, Qiu Y, Sun H. 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitates curcumin-induced melanoma cell apoptosis by enhancing ceramide accumulation, JNK activation, and inhibiting PI3K/AKT activation. Mol Cell Biochem 361, 47-54, 2012.

Zhou C, Zhao XM, Li XF, Wan g C, Zhang XT, Liu XZ, Ding XF, Xiang SL, Zhang J. Curcumin inhibits AP-2γ- induced apoptosis in the human malignant testicular germ cells in vitro. Acta Pharmacol Sin 34, 1192-1200, 2013.

Zunino F, Perego P, Pilotti S , Pratesi G, Supino R, Arcamone F. Role of apoptotic response in cellular resistance to cytotoxic agents. Pharmacol Th er 76, 177-185, 1997.

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