Molecular Mechanisms and Clinical Applications of Nordihydroguaiaretic Acid (NDGA) and Its Derivatives: an Update

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2010 Apr 29

PMID 20424564

Citations 64

Authors

Jian-Ming Lu

Jacobo Nurko

Sarah M Weakley

Jun Jiang

Panagiotis Kougias

Peter H Lin

Qizhi Yao

Changyi Chen

Affiliations

Soon will be listed here.

Abstract

Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Nordihydroguaiaretic acid (NDGA), the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders and cancers. Creosote bush is a promising agent of North American herbal medicine, and it has extensive pharmacological effects and specific mechanisms of actions. This review provides an update of recent in vitro and in vivo research about NDGA and describes experimental studies using NDGA as antioxidant. Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed.

Citing Articles

Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines.

Chipon C, Riffo P, Ojeda L, Salas M, Burgos R, Ehrenfeld P Int J Mol Sci. 2024; 25(21).

PMID: 39519155 PMC: 11546251. DOI: 10.3390/ijms252111601.

A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).

Ahluwalia M, Ozair A, Rudek M, Ye X, Holdhoff M, Lieberman F Cell Rep Med. 2024; 5(7):101630.

PMID: 38955178 PMC: 11293336. DOI: 10.1016/j.xcrm.2024.101630.

Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.

Cui Q, Huang C, Liu J, Zhang J J Med Chem. 2023; 66(24):16515-16545.

PMID: 38092421 PMC: 11588358. DOI: 10.1021/acs.jmedchem.3c01130.

Classic Phytochemical Antioxidant and Lipoxygenase Inhibitor, Nordihydroguaiaretic Acid, Activates Phospholipase D through Oxidant Signaling and Tyrosine Phosphorylation Leading to Cytotoxicity in Lung Vascular Endothelial Cells.

Parinandi N, Liaugminas A, Oliver P, Varadharaj S, Yenigalla A, Elliott A Cell Biochem Biophys. 2023; 81(2):205-229.

PMID: 36820994 DOI: 10.1007/s12013-023-01128-1.

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities.

Osmakov D, Kalinovskii A, Belozerova O, Andreev Y, Kozlov S Int J Mol Sci. 2022; 23(11).

PMID: 35682715 PMC: 9181380. DOI: 10.3390/ijms23116031.

References

Lambert J, Zhao D, Meyers R, Kuester R, Timmermann B, Dorr R . Nordihydroguaiaretic acid: hepatotoxicity and detoxification in the mouse. Toxicon. 2002; 40(12):1701-8. DOI: 10.1016/s0041-0101(02)00203-9. View

Moussy Y, Guegan E, Davis T, Koob T . Transport characteristics of a novel local drug delivery system using nordihydroguaiaretic acid (NDGA)-polymerized collagen fibers. Biotechnol Prog. 2007; 23(4):990-4. DOI: 10.1021/bp0700509. View

GOODMAN Y, Steiner M, Steiner S, Mattson M . Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation. Brain Res. 1994; 654(1):171-6. DOI: 10.1016/0006-8993(94)91586-5. View

Wagenknecht B, Gulbins E, Lang F, Dichgans J, Weller M . Lipoxygenase inhibitors block CD95 ligand-mediated apoptosis of human malignant glioma cells. FEBS Lett. 1997; 409(1):17-23. DOI: 10.1016/s0014-5793(97)00468-7. View

Park R, Chang C, Liang Y, Chung Y, Henry R, Lin E . Systemic treatment with tetra-O-methyl nordihydroguaiaretic acid suppresses the growth of human xenograft tumors. Clin Cancer Res. 2005; 11(12):4601-9. DOI: 10.1158/1078-0432.CCR-04-2188. View

Hofmanova J, Soucek K, Pachernik J, Kovarikova M, Hoferova Z, Minksova K . Lipoxygenase inhibitors induce arrest of tumor cells in S-phase of the cell cycle. Neoplasma. 2003; 49(6):362-7. View

Eads D, Hansen R, Oyegunwa A, Cecil C, Culver C, Scholle F . Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines. J Inflamm (Lond). 2009; 6:2. PMC: 2631502. DOI: 10.1186/1476-9255-6-2. View

Smolewski P . Terameprocol, a novel site-specific transcription inhibitor with anticancer activity. IDrugs. 2008; 11(3):204-14. View

Seufferlein T, Seckl M, Schwarz E, Beil M, V Wichert G, Baust H . Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells. Br J Cancer. 2002; 86(7):1188-96. PMC: 2364182. DOI: 10.1038/sj.bjc.6600186. View

10.

Arteaga S, Andrade-Cetto A, Cardenas R . Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. J Ethnopharmacol. 2005; 98(3):231-9. DOI: 10.1016/j.jep.2005.02.002. View

11.

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. DOI: 10.1093/carcin/20.4.599. View

12.

Boston-Howes W, Williams E, Bogush A, Scolere M, Pasinelli P, Trotti D . Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo: therapeutic implications for amyotrophic lateral sclerosis. Exp Neurol. 2008; 213(1):229-37. PMC: 2600491. DOI: 10.1016/j.expneurol.2008.06.010. View

13.

Meyer A, McAndrew C, Donoghue D . Nordihydroguaiaretic acid inhibits an activated fibroblast growth factor receptor 3 mutant and blocks downstream signaling in multiple myeloma cells. Cancer Res. 2008; 68(18):7362-70. PMC: 2745924. DOI: 10.1158/0008-5472.CAN-08-0575. View

14.

Aktan S, Aykut C, Yegen B, Okar I, Ozkutlu U, Ercan S . The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes. Prostaglandins Leukot Essent Fatty Acids. 1993; 49(2):633-41. DOI: 10.1016/0952-3278(93)90171-r. View

15.

Kumar S, Sun X, Wedgwood S, Black S . Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity through the inhibition of AP-1 activity. Am J Physiol Lung Cell Mol Physiol. 2008; 295(2):L370-7. PMC: 2519847. DOI: 10.1152/ajplung.90205.2008. View

16.

Alderman S, Kailas S, Goldfarb S, Singaram C, Malone D . Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. J Clin Gastroenterol. 1994; 19(3):242-7. DOI: 10.1097/00004836-199410000-00016. View

17.

Lambert J, MEYERS R, Timmermann B, Dorr R . 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. DOI: 10.1016/s0378-4347(00)00592-2. View

18.

Domin J, Higgins T, Rozengurt E . Preferential inhibition of platelet-derived growth factor-stimulated DNA synthesis and protein tyrosine phosphorylation by nordihydroguaiaretic acid. J Biol Chem. 1994; 269(11):8260-7. View

19.

Konno C, Lu Z, Xue H, Erdelmeier C, Meksuriyen D, Che C . Furanoid lignans from Larrea tridentata. J Nat Prod. 1990; 53(2):396-406. DOI: 10.1021/np50068a019. View

20.

Camirand A, Lu Y, Pollak M . Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells. Med Sci Monit. 2002; 8(12):BR521-6. View