Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases

Abstract

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan obtained from Larrea tridentata, the creosote bush found in Mexico and USA deserts, that has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals and this may explain part of its therapeutic action. Additional effects include inhibition of lipoxygenases (LOXs) and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2). On the other hand, the oxidation of the catechols to the corresponding quinones my elicit alterations in proteins and DNA that raise safety concerns. This review describes the current knowledge on NDGA, its targets and side effects, and its synthetic analogs as promising therapeutic agents, highlighting their mechanism of action and clinical projection towards therapy of neurodegenerative, liver, and kidney disease, as well as cancer.

Characterization of protease activity of Nsp3 from SARS-CoV-2 and itsin vitroinhibition by nanobodies

“…Other prominent overlapping interactors include the IFITs (Interferoninduced protein with tetratricopeptide repeats), IFIT1 and IFIT2, antiviral proteins that function as sensors of viral single-stranded RNAs to inhibit expression of viral messenger RNAs (Diamond & Farzan, 2013). Nsp3 DTM also interacts with the antiviral proteins SAMHD1, which binds to nucleotides and depletes cellular dNTPs, and 1'-5'-oligoadenylate synthase 3 (OAS3), another interferon-induced gene that inhibits viral replication by degrading viral RNA (Li et al, 2016). In addition, both PLpro and Nsp3 DTM interact with the multifunctional ATP-dependent RNA helicase DDX3X, which promotes IRF3 activation leading to the production of the type I interferons, IFNa and IFN-b (Soulat et al, 2008).…”

“…Disulfiram is a thiocarbamate drug (commercially available as Antabuse®) that has received FDA approval for the treatment of alcoholism and has been in use for more than 60 years (Johansson, 1992). Disulfiram has been previously identified by in silico screening and fluorescence resonance energy transfer assay to inhibit the main SARS-CoV-2 Cys-protease, Mpro (Lobo-Galo et al, 2020;Jin et al, 2020). Disulfiram also inhibits PLpro CoV2 and Nsp3 with similar potencies, 0.69 and 0.66 µM in the MALDI-TOF-based assay, and between 1 and 2.5 µM when assessed by gel-based orthogonal assay ( Figure 3D-E).…”

Nordihydroguaiaretic Acid as a Novel Substrate and Inhibitor of Catechol O-Methyltransferase Modulates 4-Hydroxyestradiol-Induced Cyto- and Genotoxicity in MCF-7 Cells

“…NDGA belongs to the class of lignans with catecholic structures ( Figure 1 ). It has a wide range of biological activities [ 23 ]. To date, no studies have reported the biological effects of NDGA on COMT.…”

New Drug Repositioning Candidates for T-ALL Identified Via Human/Murine Gene Signature Comparison

“…NDGA/Masoprocol is exerting pleiotropic actions in many systems, particularly cancer cells. It is a phenolic ligand from the plant genus Larrea, used in traditional medicine in Mexico and SouthWest USA to treat many diseases as different as rheumatism, diabetes, pain, inflammation (31). NDGA has anti-oxidant and electrophilic properties and therefore has been reported to interfere with many cellular enzymes such as Lipoxygenases (LOX) but also with several tyrosine kinases (Insulin Receptor, HER2) or phosphatases such as PTEN or DUSPs.…”