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ISSN (Online): 1873-5576

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Review Article

Nordihydroguaiaretic Acid in Therapeutics: Beneficial to Toxicity Profiles and the Search for its Analogs

Author(s): Geraldine Sandana Mala John, Satoru Takeuchi, Ganesh Venkatraman* and Suresh Kumar Rayala*

Volume 20, Issue 2, 2020

Page: [86 - 103] Pages: 18

DOI: 10.2174/1568009619666191022141547

Price: $65

Abstract

Nordihydroguaiaretic acid (NDGA) is a plant lignan obtained from creosote bush, Larrea tridentata and is known to possess antioxidant, anticancer activities and is used in traditional medicine in North America and Mexico. However, its prolonged consumption leads to liver damage and kidney dysfunction. Despite its toxicity and side effects, there is little awareness to forbid its consumption and its use in the treatment of medical ailments has continued over the years. Several reports discuss its therapeutic efficiency and its medical applications have tremendously been on the rise to date. There has been a recent surge of interest in the chemical synthesis of NDGA derivatives for therapeutic applications. NDGA derivatives have been developed as better alternatives to NDGA. Although several NDGA derivatives have been chemically synthesized as evidenced by recent literature, there is a paucity of information on their therapeutic efficacies. This review is to highlight the medicinal applications of NDGA, its toxicity evaluations and discuss the chemical derivatives of NDGA synthesized and studied so far and suggest to continue research interests in the development of NDGA analogs for therapeutic applications. We suggest that NDGA derivatives should be investigated more in terms of chemical synthesis with preferred conformational structures and exploit their biological potentials with future insights to explore in this direction to design and develop structurally modified NDGA derivatives for potential pharmacological properties.

Keywords: Anticancer activity, antioxidant activity, antiviral activity, nordihydroguaiaretic acid, synthetic analogs, toxicity.

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[1]
Arteaga, S.; Andrade-Cetto, A.; Cárdenas, R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. J. Ethnopharmacol., 2005, 98(3), 231-239.
[http://dx.doi.org/10.1016/j.jep.2005.02.002] [PMID: 15814253]
[2]
Agarwal, R.; Wang, Z.Y.; Bik, D.P.; Mukhtar, H. Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab. Dispos., 1991, 19(3), 620-624.
[PMID: 1680628]
[3]
Abou-Gazar, H.; Bedir, E.; Takamatsu, S.; Ferreira, D.; Khan, I.A. Antioxidant lignans from Larrea tridentata. Phytochemistry, 2004, 65(17), 2499-2505.
[http://dx.doi.org/10.1016/j.phytochem.2004.07.009] [PMID: 15381414]
[4]
Birkenfeld, S.; Zaltsman, Y.A.; Krispin, M.; Zakut, H.; Zor, U.; Kohen, F. Antitumor effects of inhibitors of arachidonic acid cascade on experimentally induced intestinal tumors. Dis. Colon Rectum, 1987, 30(1), 43-46.
[http://dx.doi.org/10.1007/BF02556922] [PMID: 3803107]
[5]
Timmermann, B. Practical uses of Larrea.Creosote bush: Biology and Chemistry of Larrea in new world desserts; Mabry, T.; Hunziker, J; Difio, D., Ed.; Dowden Hutchinson Ross Inc, 1977, pp. 252-257.
[6]
Obermeyer, W.R.; Musser, S.M.; Betz, J.M.; Casey, R.E.; Pohland, A.E.; Page, S.W. Chemical studies of phytoestrogens and related compounds in dietary supplements: flax and chaparral. Proc. Soc. Exp. Biol. Med., 1995, 208(1), 6-12.
[http://dx.doi.org/10.3181/00379727-208-43824] [PMID: 7892296]
[7]
Sheikh, N.M.; Philen, R.M.; Love, L.A. Chaparral-associated hepatotoxicity. Arch. Intern. Med., 1997, 157(8), 913-919.
[http://dx.doi.org/10.1001/archinte.1997.00440290099011] [PMID: 9129552]
[8]
Gordon, D.W.; Rosenthal, G.; Hart, J.; Sirota, R.; Baker, A.L. Chaparral ingestion. The broadening spectrum of liver injury caused by herbal medications. JAMA, 1995, 273(6), 489-490.
[http://dx.doi.org/10.1001/jama.1995.03520300063038] [PMID: 7837368]
[9]
Li, X.; Jiang, J.H.; Chen, Q.; Xiao, S-X.; Li, C-H.; Gu, H-W.; Zhang, H.; Hu, J-L.; Yao, F-H.; Li, Q-G. Synthesis of nordihydroguaiaretic acid derivatives and their bioactivities on S. pombe and K562 cell lines. Eur. J. Med. Chem., 2013, 62, 605-613.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.028] [PMID: 23434529]
[10]
Luo, J.; Chuang, T.; Cheung, J.; Quan, J.; Tsai, J.; Sullivan, C.; Hector, R.F.; Reed, M.J.; Meszaros, K.; King, S.R.; Carlson, T.J.; Reaven, G.M. Masoprocol (nordihydroguaiaretic acid): A new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata). Eur. J. Pharmacol., 1998, 346(1), 77-79.
[http://dx.doi.org/10.1016/S0014-2999(98)00139-3] [PMID: 9617755]
[11]
Reed, M.J.; Meszaros, K.; Entes, L.J.; Claypool, M.D.; Pinkett, J.G.; Brignetti, D.; Luo, J.; Khandwala, A.; Reaven, G.M. Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of Type II diabetes. Diabetologia, 1999, 42(1), 102-106.
[http://dx.doi.org/10.1007/s001250051121] [PMID: 10027587]
[12]
Tyler, V.; Foster, S. Tyler’s Honest Herbal: A sensible guide to the use of herbs and related remedies; Haworth Herbal Press: New York, 1999.
[13]
Soriano, A.; Helfrich, B.; Chan, D.; Heasley, L.; Bunn, P.; Chou, T. Synergist effects of new chemopreventive agents against human lung cancer cell lines. Cancer Res., 1999, 59, 6178-6184.
[PMID: 10626810]
[14]
Verástegui, M.A.; Sánchez, C.A.; Heredia, N.L.; García-Alvarado, J.S. Antimicrobial activity of extracts of three major plants from the Chihuahuan desert. J. Ethnopharmacol., 1996, 52(3), 175-177.
[http://dx.doi.org/10.1016/0378-8741(96)84802-1] [PMID: 8771460]
[15]
Argueta, V. Atlas of the traditional mexican medicinal plants national indigenous institute.Ed. Mexico, Vol. II., 1994.
[16]
Ansar, S.; Iqbal, M.; Athar, M. Nordihydroguairetic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumour promotion, in mice. Carcinogenesis, 1999, 20(4), 599-606.
[http://dx.doi.org/10.1093/carcin/20.4.599] [PMID: 10223187]
[17]
Smith, A.Y.; Feddersen, R.M.; Gardner, K.D., Jr; Davis, C.J., Jr Cystic renal cell carcinoma and acquired renal cystic disease associated with consumption of chaparral tea: A case report. J. Urol., 1994, 152(6 Pt 1), 2089-2091.
[http://dx.doi.org/10.1016/S0022-5347(17)32317-0] [PMID: 7966683]
[18]
Chen, Q. Nordihydroguaiaretic acid analogues: Their chemical synthesis and biological activities. Curr. Top. Med. Chem., 2009, 9(17), 1636-1659.
[http://dx.doi.org/10.2174/156802609789941915] [PMID: 19903157]
[19]
Lambert, J.D.; Zhao, D.; Meyers, R.O.; Kuester, R.K.; Timmermann, B.N.; Dorr, R.T. Nordihydroguaiaretic acid: Hepatotoxicity and detoxification in the mouse. Toxicon, 2002, 40(12), 1701-1708.
[http://dx.doi.org/10.1016/S0041-0101(02)00203-9] [PMID: 12457882]
[20]
Sahu, S.C.; Ruggles, D.I.; O’Donnell, M.W. Prooxidant activity and toxicity of nordihydroguaiaretic acid in clone-9 rat hepatocyte cultures. Food Chem. Toxicol., 2006, 44(10), 1751-1757.
[http://dx.doi.org/10.1016/j.fct.2006.05.016] [PMID: 16839654]
[21]
Alderman, S.; Kailas, S.; Goldfarb, S.; Singaram, C.; Malone, D.G. Cholestatic hepatitis after ingestion of chaparral leaf: Confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. J. Clin. Gastroenterol., 1994, 19(3), 242-247.
[http://dx.doi.org/10.1097/00004836-199410000-00016] [PMID: 7806838]
[22]
Whiting, P.W.; Clouston, A.; Kerlin, P. Black cohosh and other herbal remedies associated with acute hepatitis. Med. J. Aust., 2002, 177(8), 440-443.
[PMID: 12381254]
[23]
Lambert, J.; Dorr, R.; Timmermann, B. Nordihydroguaiaretic acid: A review of its numerous and varied biological activities. Pharm. Biol., 2004, 42, 149-158.
[http://dx.doi.org/10.1080/13880200490512016]
[24]
Jones, S. Sistematica Vegetal; McGraw-Hill: Mexico, 1987.
[25]
Hyder, P.W.; Fredrickson, E.L.; Estell, R.E.; Tellez, M.; Gibbens, R.P. Distribution and concentration of total phenolics, condensed tannins and nordihydroguaiaretic acid (NDGA) in creosote bush (Larrea tridentata). Biochem. Syst. Ecol., 2002, 30, 905-912.
[http://dx.doi.org/10.1016/S0305-1978(02)00050-9]
[26]
Azwanida, N.N. A review on the extraction methods use in Medicinal plants, Principle, Strength and Limitation. Med. Aromat. Plants, 2015, 4, 196.
[http://dx.doi.org/10.4172/2167-0412.1000196]
[27]
Lopez-Aguirre, S.; Garcia-Lopez, J.C.; Pinos-Rodriguez, J.M.; Yanez-Estrada, L.; Lopez-Hernandez, Y. Chemical characterization and oral toxicity of an aqueous extract of Larrea tridentata. J. Nat. Prod. Resour., 2016, 2, 79-82.
[28]
Gezginci, M.H.; Timmermann, B.N. A short synthetic route to nordihydroguaiaretic acid (NDGA) and its stereoisomer using Ti-induced carbonyl-coupling reaction. Tetrahedron Lett., 2001, 42, 6083-6085.
[http://dx.doi.org/10.1016/S0040-4039(01)01182-0]
[29]
Son, J.K.; Lee, S.H.; Nagarapu, L.; Jahug, Y. A simple synthesis of nordihydroguaiaretic acid and its analogues. Bull. Korean Chem. Soc., 2005, 26, 1117-1120.
[http://dx.doi.org/10.5012/bkcs.2005.26.7.1117]
[30]
Meyers, R.O.; Lambert, J.D.; Hajicek, N.; Pourpak, A.; Kalaitzis, J.A.; Dorr, R.T. Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid. Bioorg. Med. Chem. Lett., 2009, 19(16), 4752-4755.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.063] [PMID: 19615898]
[31]
Hwu, J.R.; Hsu, C.I.; Hsu, M.H.; Liang, Y.C.; Huang, R.C.C.; Lee, Y.C. Glycosylated nordihydroguaiaretic acids as anti-cancer agents. Bioorg. Med. Chem. Lett., 2011, 21(1), 380-382.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.137] [PMID: 21123067]
[32]
Paracatu, L.C.; de Faria, C.M.; Zeraik, M.L.; Quinello, C.; Rennó, C.; Palmeira, P.; da Fonseca, L.M.; Ximenes, V.F. Hydrophobicity and antioxidant activity acting together for the beneficial health properties of nordihydroguaiaretic acid. Food Funct., 2015, 6(6), 1818-1831.
[http://dx.doi.org/10.1039/C5FO00091B] [PMID: 25927268]
[33]
Spencer, J.; Jacobs, J. Complimentary Alternative Medicine: An evidence-based approach; Mosby: Toronto, 1999.
[34]
Fujiwara, T.; Misumi, Y.; Ikehara, Y. Dynamic recycling of ERGIC53 between the endoplasmic reticulum and the Golgi complex is disrupted by nordihydroguaiaretic acid. Biochem. Biophys. Res. Commun., 1998, 253(3), 869-876.
[http://dx.doi.org/10.1006/bbrc.1998.9868] [PMID: 9918822]
[35]
Ballatori, N.; Wang, W. Nordihydroguaiaretic acid depletes ATP and inhibits a swelling-activated, ATP-sensitive taurine channel. Am. J. Physiol., 1997, 272(5 Pt 1), C1429-C1436.
[http://dx.doi.org/10.1152/ajpcell.1997.272.5.C1429] [PMID: 9176131]
[36]
Jan, C.R.; Tseng, C.J. Mechanisms of nordihydroguaiaretic acid-induced [Ca2+]i increases in MDCK cells. Life Sci., 2000, 66(18), 1753-1762.
[http://dx.doi.org/10.1016/S0024-3205(00)00498-7] [PMID: 10809172]
[37]
Nusrat, S.; Siddiqi, M.K.; Zaman, M.; Zaidi, N.; Ajmal, M.R.; Alam, P.; Qadeer, A.; Abdelhameed, A.S.; Khan, R.H. A comprehensive spectroscopic and computational investigation to probe the interaction of antineoplastic drug Nordihydroguaiaretic acid with serum albumins. PLoS One, 2016, 11(7)e0158833
[http://dx.doi.org/10.1371/journal.pone.0158833] [PMID: 27391941]
[38]
Perry, J.L.; Il’ichev, Y.V.; Kempf, V.R.; McClendon, J.; Park, G.; Manderville, R.A.; Ruker, F.; Dockal, M.; Simon, A.D. Binding of ochratoxin A derivatives to human serum albumin. J. Phys. Chem. B, 2003, 107, 6644-6647.
[http://dx.doi.org/10.1021/jp034284w]
[39]
Olson, R.E.; Christ, D.D. Plasma protein binding of drugs. Annu. Rep. Med. Chem., 1996, 31, 327-336.
[http://dx.doi.org/10.1016/S0065-7743(08)60472-8]
[40]
Zsila, F.; Bikádi, Z.; Simonyi, M. Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods. Biochem. Pharmacol., 2003, 65(3), 447-456.
[http://dx.doi.org/10.1016/S0006-2952(02)01521-6] [PMID: 12527338]
[41]
Awasthi, S.; Preethy, R.; Saraswathi, N.T. Nordihydroguaiaretic acid prevents glycation induced structural alterations and aggregation of albumin. Int. J. Biol. Macromol., 2019, 122, 479-484.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.10.173] [PMID: 30416092]
[42]
Lambert, J.D.; Meyers, R.O.; Timmermann, B.N.; Dorr, R.T. Pharmacokinetic analysis by high-performance liquid chromatography of intravenous nordihydroguaiaretic acid in the mouse. J. Chromatogr. B Biomed. Sci. Appl., 2001, 754(1), 85-90.
[http://dx.doi.org/10.1016/S0378-4347(00)00592-2] [PMID: 11318430]
[43]
Mangione, A.M.; Dearing, D.; Karasov, W. Detoxification in relation to toxin tolerance in desert woodrats eating creosote bush. J. Chem. Ecol., 2001, 27(12), 2559-2578.
[http://dx.doi.org/10.1023/A:1013639817958] [PMID: 11789959]
[44]
Hagmann, W. Lipoxygenase in human tumor cells. Pathol. Oncol. Res., 1997, 3(2), 83-88.
[http://dx.doi.org/10.1007/BF02907800] [PMID: 11173632]
[45]
Timár, J.; Rásó, E.; Döme, B.; Li, L.; Grignon, D.; Nie, D.; Honn, K.V.; Hagmann, W. Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential. Int. J. Cancer, 2000, 87(1), 37-43.
[http://dx.doi.org/10.1002/1097-0215(20000701)87:1<37:AID-IJC6>3.0.CO;2-L] [PMID: 10861450]
[46]
Shureiqi, I.; Lippman, S.M. Lipoxygenase modulation to reverse carcinogenesis. Cancer Res., 2001, 61(17), 6307-6312.
[PMID: 11522616]
[47]
Safayhi, H.; Mack, T.; Sabieraj, J.; Anazodo, M.I.; Subramanian, L.R.; Ammon, H.P. Boswellic acids: Novel, specific, nonredox inhibitors of 5-lipoxygenase. J. Pharmacol. Exp. Ther., 1992, 261(3), 1143-1146.
[PMID: 1602379]
[48]
Orafaie, A.; Matin, M.M.; Sadeghian, H. The importance of 15-lipoxygenase inhibitors in cancer treatment. Cancer Metastasis Rev., 2018, 37(2-3), 397-408.
[http://dx.doi.org/10.1007/s10555-018-9738-9] [PMID: 29882120]
[49]
Floriano-Sánchez, E.; Villanueva, C.; Medina-Campos, O.N.; Rocha, D.; Sánchez-González, D.J.; Cárdenas-Rodríguez, N.; Pedraza-Chaverrí, J. Nordihydroguaiaretic acid is a potent in vitro scavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and prevents in vivo ozone-induced tyrosine nitration in lungs. Free Radic. Res., 2006, 40(5), 523-533.
[http://dx.doi.org/10.1080/10715760500419365] [PMID: 16551579]
[50]
Yam-Canul, P.; Chirino, Y.I.; Sánchez-González, D.J.; Martínez-Martínez, C.M.; Cruz, C.; Villanueva, C.; Pedraza-Chaverri, J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem. Toxicol., 2008, 46(3), 1089-1096.
[http://dx.doi.org/10.1016/j.fct.2007.11.003] [PMID: 18155343]
[51]
Robison, T.W.; Sevanian, A.; Forman, H.J. Inhibition of arachidonic acid release by nordihydroguaiaretic acid and its antioxidant action in rat alveolar macrophages and Chinese hamster lung fibroblasts. Toxicol. Appl. Pharmacol., 1990, 105(1), 113-122.
[http://dx.doi.org/10.1016/0041-008X(90)90363-Y] [PMID: 2118282]
[52]
Youngren, J.F.; Gable, K.; Penaranda, C.; Maddux, B.A.; Zavodovskaya, M.; Lobo, M.; Campbell, M.; Kerner, J.; Goldfine, I.D. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. Breast Cancer Res. Treat., 2005, 94(1), 37-46.
[http://dx.doi.org/10.1007/s10549-005-6939-z] [PMID: 16142439]
[53]
Tong, W.G.; Ding, X.Z.; Witt, R.C.; Adrian, T.E. Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway. Mol. Cancer Ther., 2002, 1(11), 929-935.
[PMID: 12481414]
[54]
Yoshida, T.; Shiraishi, T.; Horinaka, M.; Nakata, S.; Yasuda, T.; Goda, A.E.; Wakada, M.; Mizutani, Y.; Miki, T.; Nishikawa, A.; Sakai, T. Lipoxygenase inhibitors induce death receptor 5/TRAIL-R2 expression and sensitize malignant tumor cells to TRAIL-induced apoptosis. Cancer Sci., 2007, 98(9), 1417-1423.
[http://dx.doi.org/10.1111/j.1349-7006.2007.00559.x] [PMID: 17645780]
[55]
Ding, X.Z.; Kuszynski, C.A.; El-Metwally, T.H.; Adrian, T.E. Lipoxygenase inhibition induced apoptosis, morphological changes, and carbonic anhydrase expression in human pancreatic cancer cells. Biochem. Biophys. Res. Commun., 1999, 266(2), 392-399.
[http://dx.doi.org/10.1006/bbrc.1999.1824] [PMID: 10600514]
[56]
Gonzales, M.; Bowden, G.T. Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes. Mol. Carcinog., 2002, 34(2), 102-111.
[http://dx.doi.org/10.1002/mc.10052] [PMID: 12112316]
[57]
Earashi, M.; Noguchi, M.; Kinoshita, K.; Tanaka, M. Effects of eicosanoid synthesis inhibitors on the in vitro growth and prostaglandin E and leukotriene B secretion of a human breast cancer cell line. Oncology, 1995, 52(2), 150-155.
[http://dx.doi.org/10.1159/000227447] [PMID: 7854776]
[58]
Xue, H.; Zhang, X.Y.; Liu, J.M.; Song, Y.; Liu, T.T.; Chen, D. NDGA reduces secondary damage after spinal cord injury in rats via anti-inflammatory effects. Brain Res., 2013, 1516, 83-92.
[http://dx.doi.org/10.1016/j.brainres.2013.04.016] [PMID: 23603407]
[59]
Rahman, S.; Ansari, R.A.; Rehman, H.; Parvez, S.; Raisuddin, S. Nordihydroguaiaretic acid from creosote bush (Larrea tridentata) mitigates 12-O-Tetradecanoylphorbol-13-acetate-induced inflammatory and oxidative stress responses of tumor promotion cascade in mouse skin; Evidence-based Complement Alternat. Med, 2011.
[http://dx.doi.org/10.1093/ecam/nep076]
[60]
Min, K-W.; Song, M.O.; Park, S-R.; Oh, Y-S.; Lee, C-H. Nordihydroguaiaretic acid suppresses the lipopolysaccharide-induced activation of macrophage through the down-regulation of TAK1. Anim. Cells Syst., 2013, 17, 15-22.
[http://dx.doi.org/10.1080/19768354.2012.745449]
[61]
Li, X.; Fan, S.; Pan, X.; Xiaokaiti, Y.; Duan, J.; Shi, Y.; Pan, Y.; Tie, L.; Wang, X.; Li, Y.; Li, X. Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1. Oncotarget, 2016, 7(52), 86225-86238.
[http://dx.doi.org/10.18632/oncotarget.13368] [PMID: 27863391]
[62]
Staton, C.A.; Kumar, I.; Reed, M.W.; Brown, N.J. Neuropilins in physiological and pathological angiogenesis. J. Pathol., 2007, 212(3), 237-248.
[http://dx.doi.org/10.1002/path.2182] [PMID: 17503412]
[63]
Yaqoob, U.; Cao, S.; Shergill, U.; Jagavelu, K.; Geng, Z.; Yin, M.; de Assuncao, T.M.; Cao, Y.; Szabolcs, A.; Thorgeirsson, S.; Schwartz, M.; Yang, J.D.; Ehman, R.; Roberts, L.; Mukhopadhyay, D.; Shah, V.H. Neuropilin-1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment. Cancer Res., 2012, 72(16), 4047-4059.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3907] [PMID: 22738912]
[64]
Seufferlein, T.; Seckl, M.J.; Schwarz, E.; Beil, M.; v Wichert, G.; Baust, H.; Lührs, H.; Schmid, R.M.; Adler, G. Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells. Br. J. Cancer, 2002, 86(7), 1188-1196.
[http://dx.doi.org/10.1038/sj.bjc.6600186] [PMID: 11953870]
[65]
Wagenknecht, B.; Schulz, J.B.; Gulbins, E.; Weller, M. Crm-A, bcl-2 and NDGA inhibit CD95L-induced apoptosis of malignant glioma cells at the level of caspase 8 processing. Cell Death Differ., 1998, 5(10), 894-900.
[http://dx.doi.org/10.1038/sj.cdd.4400435] [PMID: 10203695]
[66]
Siddique, Y.H.; Beg, T.; Afzal, M. Protective effect of nordihydroguaiaretic acid (NDGA) against norgestrel induced genotoxic damage. Toxicol. In Vitro, 2006, 20(2), 227-233.
[http://dx.doi.org/10.1016/j.tiv.2005.06.027] [PMID: 16061348]
[67]
Siddique, Y.H.; Ara, G.; Beg, T.; Afzal, M. Protective role of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in human lymphocytes in vitro. J. Environ. Biol., 2007, 28(2), 279-282.
[PMID: 17915765]
[68]
Madrigal-Bujaidar, E.; Díaz Barriga, S.; Cassani, M.; Molina, D.; Ponce, G. In vivo and in vitro induction of sister-chromatid exchanges by nordihydroguaiaretic acid. Mutat. Res., 1998a, 412(2), 139-144.
[http://dx.doi.org/10.1016/S1383-5718(97)00195-2] [PMID: 9539967]
[69]
Madrigal-Bujaidar, E.; Díaz Barriga, S.; Cassani, M.; Márquez, P.; Revuelta, P. In vivo and in vitro antigenotoxic effect of nordihydroguaiaretic acid against SCEs induced by methyl methanesulfonate. Mutat. Res., 1998b, 419(1-3), 163-168.
[http://dx.doi.org/10.1016/S1383-5718(98)00128-4] [PMID: 9804941]
[70]
Ahmad, M.E.; Shadab, G.G.H.A.; Azfer, M.A.; Afzal, M. Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro. Mutat. Res., 2001, 494(1-2), 13-20.
[http://dx.doi.org/10.1016/S1383-5718(01)00164-4] [PMID: 11423341]
[71]
Ramoner, R.; Rieser, C.; Bartsch, G.; Thurnher, M. Nordihydroguaiaretic acid blocks secretory and endocytic pathways in human dendritic cells. J. Leukoc. Biol., 1998, 64(6), 747-752.
[http://dx.doi.org/10.1002/jlb.64.6.747] [PMID: 9850156]
[72]
Ito, H.; Ueda, H.; Iwamoto, I.; Inaguma, Y.; Takizawa, T.; Asano, T.; Kato, K. Nordihydroguaiaretic acid (NDGA) blocks the differentiation of C2C12 myoblast cells. J. Cell. Physiol., 2005, 202(3), 874-879.
[http://dx.doi.org/10.1002/jcp.20177] [PMID: 15389564]
[73]
Zavodovskaya, M.; Campbell, M.J.; Maddux, B.A.; Shiry, L.; Allan, G.; Hodges, L.; Kushner, P.; Kerner, J.A.; Youngren, J.F.; Goldfine, I.D. Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. J. Cell. Biochem., 2008, 103(2), 624-635.
[http://dx.doi.org/10.1002/jcb.21435] [PMID: 17562544]
[74]
Rowe, D.L.; Ozbay, T.; Bender, L.M.; Nahta, R. Nordihydroguaiaretic acid, a cytotoxic IGF-1R/HER2 inhibitor in Trastuzumab-resistant breast cancer. Mol. Cancer Ther., 2008, 7, 1900-1908.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0012] [PMID: 18645000]
[75]
Gao, P.; Guan, L.; Zhai, F.; Zheng, J. NDGA upregulates the expression of p27 and p53 in cervical cancer SiHa cells. Chin. J. Cell. Biol., 2010, 32, 617-620.
[76]
Gao, P.; Zhai, F.; Guan, L.; Zheng, J. Nordihydroguaiaretic acid inhibits growth of cervical cancer SiHa cells by up-regulating p21. Oncol. Lett., 2011, 2(1), 123-128.
[http://dx.doi.org/10.3892/ol.2010.205] [PMID: 22870140]
[77]
Sare, M.; Bozkurt, S.; Onuk, E.; Oguz, M.; Gurel, M.; Ercan, S. The effects of indomethacin, NDGA, allopurinol and superoxide dismutase on prostaglandin E2 and leukotriene C4 levels after mesenteric ischemia-reperfusion injury. Prostaglandins Leukot. Essent. Fatty Acids, 1996, 55(6), 379-383.
[http://dx.doi.org/10.1016/S0952-3278(96)90120-9] [PMID: 9014215]
[78]
Liu, Y.; Wang, H.; Zhu, Y.; Chen, L.; Qu, Y.; Zhu, Y. The protective effect of nordihydroguaiaretic acid on cerebral ischemia/reperfusion injury is mediated by the JNK pathway. Brain Res., 2012, 1445, 73-81.
[http://dx.doi.org/10.1016/j.brainres.2012.01.031] [PMID: 22325100]
[79]
Okboy, N.; Yegen, C.; Aktan, A.O.; Dosluoglu, H.H.; Sav, A.; Yalin, R.; Ercan, S. The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. Prostaglandins Leukot. Essent. Fatty Acids, 1992, 47(4), 291-295.
[http://dx.doi.org/10.1016/0952-3278(92)90200-3] [PMID: 1283466]
[80]
Ramasamy, S.; Drummond, G.R.; Ahn, J.; Storek, M.; Pohl, J.; Parthasarathy, S.; Harrison, D.G. Modulation of expression of endothelial nitric oxide synthase by nordihydroguaiaretic acid, a phenolic antioxidant in cultured endothelial cells. Mol. Pharmacol., 1999, 56(1), 116-123.
[http://dx.doi.org/10.1124/mol.56.1.116] [PMID: 10385691]
[81]
Ebrahimi, A.; Schluesener, H. Natural polyphenols against neurodegenerative disorders: Potentials and pitfalls. Ageing Res. Rev., 2012, 11(2), 329-345.
[http://dx.doi.org/10.1016/j.arr.2012.01.006] [PMID: 22336470]
[82]
Siddique, Y.H.; Ali, F. Protective effect of nordihydroguaiaretic acid (NDGA) on the transgenic Drosophila model of Alzheimer’s disease. Chem. Biol. Interact., 2017, 269, 59-66.
[http://dx.doi.org/10.1016/j.cbi.2017.04.005] [PMID: 28392391]
[83]
Ma, C.J.; Lee, M.K.; Kim, Y.C. meso-Dihydroguaiaretic acid attenuates the neurotoxic effect of staurosporine in primary rat cortical cultures. Neuropharmacology, 2006, 50(6), 733-740.
[http://dx.doi.org/10.1016/j.neuropharm.2005.11.025] [PMID: 16427665]
[84]
Culver, C.A.; Michalowski, S.M.; Maia, R.C.; Laster, S.M. The anti-apoptotic effects of nordihydroguaiaretic acid: Inhibition of cPLA(2) activation during TNF-induced apoptosis arises from inhibition of calcium signaling. Life Sci., 2005, 77(19), 2457-2470.
[http://dx.doi.org/10.1016/j.lfs.2005.03.023] [PMID: 15950244]
[85]
Huang, J-K.; Chen, W-C.; Huang, C-J.; Hsu, S-S.; Chen, J-S.; Cheng, H-H.; Chang, H-T.; Jiann, B-P.; Jan, C-R. Nordihydroguaiaretic acid-induced Ca2+ handling and cytotoxicity in human prostate cancer cells. Life Sci., 2004, 75(19), 2341-2351.
[http://dx.doi.org/10.1016/j.lfs.2004.04.043] [PMID: 15350831]
[86]
Su, W.; Tseng, L-L.; Lin, M-C.; Chang, H-J.; Lee, K-C.; Chou, K-J.; Lo, Y-K.; Cheng, J-S.; Chang, H-T.; Wang, J-L.; Liu, C-P.; Chen, W-C.; Jan, C-R. Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells. Neurochem. Int., 2002, 40(3), 249-254.
[http://dx.doi.org/10.1016/S0197-0186(01)00089-4] [PMID: 11741008]
[87]
Korn, S.J.; Horn, R. Nordihydroguaiaretic acid inhibits voltage-activated Ca2+ currents independently of lipoxygenase inhibition. Mol. Pharmacol., 1990, 38(4), 524-530.
[PMID: 2172768]
[88]
Leon, D.; Parada, D.; Vargas-Uribe, M.; Perez, A.A.; Ojeda, L.; Zambrano, A.; Reyes, A.M.; Salas, M. Effect of nordihydroguaiaretic acid on cell viability and glucose transport in human leukemic cell lines. FEBS Open Bio, 2016, 6(10), 1000-1007.
[http://dx.doi.org/10.1002/2211-5463.12106] [PMID: 27761359]
[89]
Zhang, H.; Shen, W.J.; Cortez, Y.; Kraemer, F.B.; Azhar, S. Nordihydroguaiaretic acid improves metabolic dysregulation and aberrant hepatic lipid metabolism in mice by both PPARα-dependent and –independent pathways. Am. J. Physiol. Gastrointest. Liver Physiol., 2013, 304, 72-86.
[http://dx.doi.org/10.1152/ajpgi.00328.2012]
[90]
Zhang, H.; Li, Y.; Hu, J.; Shen, W.J.; Singh, M.; Hou, X.; Bittner, A.; Bittner, S.; Cortez, Y.; Tabassum, J.; Kraemer, F.B.; Azhar, S. Effect of creosote bush-derived NDGA on expression of genes involved in lipid metabolism in liver of high fructose-fed rats: Relevance to NDGA amelioration of hypertriglyceridemia and hepatic steatosis. PLoS One, 2015, 10(9)e0138203
[http://dx.doi.org/10.1371/journal.pone.0138203] [PMID: 26394137]
[91]
Zhang, H.; Shen, W-J.; Li, Y.; Bittner, A.; Bittner, S.; Tabassum, J.; Cortez, Y.F.; Kraemer, F.B.; Azhar, S. Microarray analysis of gene expression in liver, adipose tissue and skeletal muscle I response to chronic dietary administration of NDGA to high-frucose fed dyslipidemic rats. Nutr. Metab. (Lond.), 2016, 13, 1-26.
[http://dx.doi.org/10.1186/s12986-016-0121-y]
[92]
Kang, I.; Park, M.; Yang, S.J.; Lee, M. Lipoprotein lipase inhibitor, Nordihydroguaiaretic acid, aggravates metabolic phenotypes and alters HDL particle size in Western diet-fed db/db mice. Int. J. Mol. Sci., 2019, 20(12), 3057-3070.
[http://dx.doi.org/10.3390/ijms20123057] [PMID: 31234537]
[93]
Fujimoto, N.; Kohta, R.; Kitamura, S.; Honda, H. Estrogenic activity of an antioxidant, nordihydroguaiaretic acid (NDGA). Life Sci., 2004, 74(11), 1417-1425.
[http://dx.doi.org/10.1016/j.lfs.2003.08.012] [PMID: 14706572]
[94]
Koob, T.J.; Willis, T.A.; Qiu, Y.S.; Hernandez, D.J. Biocompatibility of NDGA-polymerized collagen fibers. II. Attachment, proliferation, and migration of tendon fibroblasts in vitro. J. Biomed. Mater. Res., 2001, 56(1), 40-48.
[http://dx.doi.org/10.1002/1097-4636(200107)56:1<40:AID-JBM1066>3.0.CO;2-I] [PMID: 11309789]
[95]
Koob, T.J.; Hernandez, D.J. Material properties of polymerized NDGA-collagen composite fibers: Development of biologically based tendon constructs. Biomaterials, 2002, 23(1), 203-212.
[http://dx.doi.org/10.1016/S0142-9612(01)00096-5] [PMID: 11762839]
[96]
Rioja, A.Y.; Muniz-Maisonet, M.; Koob, T.J.; Gallant, N.D. Effect of nordihydroguaiaretic acid cross-linking on fibrillar collagen: In vitro evaluation of fibroblast adhesion strength and migration. AIMS Bioeng., 2017, 4, 300-317.
[http://dx.doi.org/10.3934/bioeng.2017.2.300]
[97]
Koob, T.J.; Hernandez, D.J. Mechanical and thermal properties of novel polymerized NDGA-gelatin hydrogels. Biomaterials, 2003, 24(7), 1285-1292.
[http://dx.doi.org/10.1016/S0142-9612(02)00465-9] [PMID: 12527270]
[98]
Gong, S.Q.; Xue, Z.J.; Liao, S.T.; Wu, Y.B.; Liu, Y. The effect of NDGA-modified etchant on the enzymatic degradation resistance and mechanical properties of the collagen matrix. Chin. Chem. Lett., 2018, 29, 205-208.
[http://dx.doi.org/10.1016/j.cclet.2017.08.036]
[99]
Kato, Y.P.; Christiansen, D.L.; Hahn, R.A.; Shieh, S.J.; Goldstein, J.D.; Silver, F.H. Mechanical properties of collagen fibres: A comparison of reconstituted and rat tail tendon fibres. Biomaterials, 1989, 10(1), 38-42.
[http://dx.doi.org/10.1016/0142-9612(89)90007-0] [PMID: 2713432]
[100]
Schmidt, M.; Schmitz, H.J.; Baumgart, A.; Guédon, D.; Netsch, M.I.; Kreuter, M-H.; Schmidlin, C.B.; Schrenk, D. Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture. Food Chem. Toxicol., 2005, 43(2), 307-314.
[http://dx.doi.org/10.1016/j.fct.2004.11.001] [PMID: 15621343]
[101]
Galati, G.; Lin, A.; Sultan, A.M.; O’Brien, P.J. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic. Biol. Med., 2006, 40(4), 570-580.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.09.014] [PMID: 16458187]
[102]
Liu, Y.; Flynn, T.J.; Ferguson, M.S.; Hoagland, E.M.; Yu, L.L. Effects of dietary phenolics and botanical extracts on hepatotoxicity-related endpoints in human and rat hepatoma cells and statistical models for prediction of hepatotoxicity. Food Chem. Toxicol., 2011, 49(8), 1820-1827.
[http://dx.doi.org/10.1016/j.fct.2011.04.034] [PMID: 21569817]
[103]
Sahu, S.C.; Flynn, T.J.; Bradlaw, J.A.; Roth, W.L.; Barton, C.N.; Yates, J.G. Pro-oxidant effects of the flavonoid myricetin on rat hepatocytes in culture. Toxicol. Methods, 2001, 11, 277-283.
[http://dx.doi.org/10.1080/1537-650291895829]
[104]
Frei, B.; Higdon, J.V. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J. Nutr., 2003, 133(10), 3275S-3284S.
[http://dx.doi.org/10.1093/jn/133.10.3275S] [PMID: 14519826]
[105]
McDonald, R.W.; Bunjobpon, W.; Liu, T.; Fessler, S.; Pardo, O.E.; Freer, I.K.A.; Glaser, M.; Seckl, M.J.; Robins, D.J. Synthesis and anticancer activity of nordihydroguaiaretic acid (NDGA) and analogues. Anticancer Drug Des., 2001, 16(6), 261-270.
[PMID: 12375879]
[106]
Asiamah, I.; Hodgson, H.L.; Maloney, K.; Allen, K.J.H.; Krol, E.S. Ring substitution influences oxidative cyclisation and reactive metabolite formation of nordihydroguaiaretic acid analogues. Bioorg. Med. Chem., 2015, 23(21), 7007-7014.
[http://dx.doi.org/10.1016/j.bmc.2015.09.039] [PMID: 26439661]
[107]
Huang, L-C.S.; Chuang, H.; Kapoor, M.; Hsieh, C-Y.; Chou, S-C.; Lin, H-H.; Chen, Y-W.; Chang, C-C.; Hwu, J-R.; Liang, Y-C.; Hsu, M-H. Development of nordihydroguaiaretic acid derivatives as potential multidrug-resistant selective agents for cancer treatment. RSC Advances, 2015, 5, 107833-107838.
[http://dx.doi.org/10.1039/C5RA18827J]
[108]
Heller, J.D.; Chen, Q.; Lopez, R.A.; Morris, A.J. Tetra-Osubstituted butane-bridge modified NDGA derivatives, their synthesis and pharmaceutical use U.S. Patent Application Publication No. US 2017/0044121 A1, 2017.
[109]
Huang, R.C.C.; Mold, D.; Ruland, C.; Liang, Y.C.; Chun, J.H. Compositions comprising NDGA derivatives and Sorafenib and their use in treatment of cancer U.S.Patent 9877978 B2 2018.
[110]
Haworth, R.D.; Mavin, C.R.; Sheldrick, G. The constitutes of guaiacum resin. Part II. Synthesis of dl-guaiaretic acid dimethyl ether. J. Chem. Soc., 1934, 1423-1429.
[http://dx.doi.org/10.1039/jr9340001423]
[111]
Waller, C.W.; Gisvold, O. A phytochemical investigation of Larrea divaricata Cav. J. Am. Pharm. Assoc., 1945, 34, 78-81.
[http://dx.doi.org/10.1002/jps.3030340305]
[112]
Gisvold, O.; Thaker, E. Lignans from larrea divaricata. J. Pharm. Sci., 1974, 63(12), 1905-1907.
[http://dx.doi.org/10.1002/jps.2600631216] [PMID: 4217824]
[113]
Haworth, R.D.; Lamberton, A.H. Some derivatives of catechol and pyrogallol. J. Chem. Soc., 1946 (Nov), 1003-1005.
[http://dx.doi.org/10.1039/jr9460001003] [PMID: 20282478]
[114]
Lara, F.; Marquez, C. Medicinal plants from Mexico: Composition, uses and biological activity; UNAM: Mexico, 1996.
[115]
Xia, Y.M.; Bi, W.H.; Zhang, Y.Y. Synthesis of dibenzyl butane diol lignans and their anti-HIV, anti-HSV, anti-tumor activities. J. Chil. Chem. Soc., 2009, 54, 428-431.
[116]
Plaza, C.; Pavani, M.; Faundez, M.; Maya, J.D.; Morello, A.; Becker, M.I.; de Joannes, A.; Cumsille, M.A.; Ferreira, J. Inhibitory effect of nordihydroguaiaretic acid and its tetra-acetylated derivative on respiration and growth of adenocarcinoma TA3 and its multiresistant variant TA3MTX-R in vivo. 2008, 22, 353-362.
[117]
Plaza, C.; Pavani, M.; Araya-Maturana, R.; Pezoa, J.; Maya, J.D.; Morello, A.; Becker, M.I.; de Joannes, A.; Ferreira, J. Chemosensitizing effect of nordihydroguaiaretic acid and its tetraacetylated derivative on parental and multiresistant TA3 mouse mammary adenocarcinoma cells in vivo. 2009, 23, 959-968.
[118]
Gnabre, J.N.; Huang, R.C.C.; Bates, R.B. Characterization of Anti-HIV lignans from Larrea tridentata. Tetrahed., 1995a, 51, 12203-12210.
[http://dx.doi.org/10.1016/0040-4020(95)00794-9]
[119]
Gnabre, J.N.; Brady, J.N.; Clanton, D.J.; Ito, Y.; Dittmer, J.; Bates, R.B.; Huang, R.C. Inhibition of human immunodeficiency virus type 1 transcription and replication by DNA sequence-selective plant lignans. Proc. Natl. Acad. Sci. USA, 1995b, 92(24), 11239-11243.
[http://dx.doi.org/10.1073/pnas.92.24.11239] [PMID: 7479972]
[120]
Chen, H.; Teng, L.; Li, J-N.; Park, R.; Mold, D.E.; Gnabre, J.; Hwu, J.R.; Tseng, W.N.; Huang, R.C.C. Antiviral activities of methylated nordihydroguaiaretic acids. 2. Targeting herpes simplex virus replication by the mutation insensitive transcription inhibitor tetra-O-methyl-NDGA. J. Med. Chem., 1998, 41(16), 3001-3007.
[http://dx.doi.org/10.1021/jm980182w] [PMID: 9685239]
[121]
Craigo, J.; Callahan, M.; Huang, R.C.C.; DeLucia, A.L. Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives. Antiviral Res., 2000, 47(1), 19-28.
[http://dx.doi.org/10.1016/S0166-3542(00)00089-9] [PMID: 10930643]
[122]
Huang, R.C.C.; Chang, C.C.; Mold, D. Survivin-dependent and -independent pathways and the induction of cancer cell death by tetra-O-methyl nordihydroguaiaretic acid. Semin. Oncol., 2006, 33(4), 479-485.
[http://dx.doi.org/10.1053/j.seminoncol.2006.04.010] [PMID: 16890802]
[123]
Hwu, J.R.; Tseng, W.N.; Gnabre, J.; Giza, P.; Huang, R.C. Antiviral activities of methylated nordihydroguaiaretic acids. 1. Synthesis, structure identification, and inhibition of tat-regulated HIV transactivation. J. Med. Chem., 1998, 41(16), 2994-3000.
[http://dx.doi.org/10.1021/jm970819w] [PMID: 9685238]
[124]
Dohm, J.A.; Hsu, M.H.; Hwu, J.R.; Huang, R.C.; Moudrianakis, E.N.; Lattman, E.E.; Gittis, A.G. Influence of ions, hydration, and the transcriptional inhibitor P4N on the conformations of the Sp1 binding site. J. Mol. Biol., 2005, 349(4), 731-744.
[http://dx.doi.org/10.1016/j.jmb.2005.04.001] [PMID: 15896803]
[125]
Heller, J.D.; Kuo, J.; Wu, T.C.; Kast, W.M.; Huang, R.C. Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and exhibits tumoricidal activity in vivo. Cancer Res., 2001, 61(14), 5499-5504.
[PMID: 11454698]
[126]
Merino-Ramos, T.; Jiménez de Oya, N.; Saiz, J-C.; Martín-Acebes, M.A. Antiviral activity of nordihydroguaiaretic acid and its derivative tetra-O-methyl nordihydroguaiaretic acid against West Nile virus and Zika virus. Antimicrob. Agents Chemother., 2017, 61(8), e00376-e17.
[http://dx.doi.org/10.1128/AAC.00376-17] [PMID: 28507114]
[127]
Park, R.; Giza, P.E.; Mold, D.E.; Huang, R.C.C. Inhibition of HSV-1 replication and reactivation by the mutation-insensitive transcription inhibitor tetra-O-glycyl-nordihydroguaiaretic acid. Antiviral Res., 2003, 58(1), 35-45.
[http://dx.doi.org/10.1016/S0166-3542(02)00165-1] [PMID: 12719005]
[128]
Blecha, J.E.; Anderson, M.O.; Chow, J.M.; Guevarra, C.C.; Pender, C.; Penaranda, C.; Zavodovskaya, M.; Youngren, J.F.; Berkman, C.E. Inhibition of IGF-1R and lipoxygenase by nordihydroguaiaretic acid (NDGA) analogs. Bioorg. Med. Chem. Lett., 2007, 17(14), 4026-4029.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.092] [PMID: 17502145]
[129]
Lü, J.M.; Nurko, J.; Weakley, S.M.; Jiang, J.; Kougias, P.; Lin, P.H.; Yao, Q.; Chen, C. Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update. Med. Sci. Monit., 2010, 16(5), RA93-RA100.
[PMID: 20424564]
[130]
Eads, D.; Hansen, R.; Oyegunwa, A.; Cecil, C.; Culver, C.; Scholle, F.; Petty, I.; Laster, S. Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines. J. Inflamm. (Lond.), 2009, 6, 2.
[http://dx.doi.org/10.1186/1476-9255-6-2] [PMID: 19133137]

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