Lifespan-increasing drug nordihydroguaiaretic acid
Nordihydroguaiaretic acid (NDGA) is an important antioxidant.
The anticancer and antiviral properties of NDGA and its derivatives have recently been reported: for example, the compound 3'-O-methyl-NDGA, has anti-HIV activities inhibiting HIV (Human Immunodeficiency Virus), while other methylated/acetylated NDGA analogs show promising antiviral activities against HIV, herpes simplex and human papilloma. In addition, it is one of the semi-desert plant species best adapted to dry environmental conditions, with a very wide distribution range compared to that of other species.
The beneficial effects of NDGA have been essentially attributed to its antioxidant properties. NDGA is an effective in vitro inactivator of peroxynitrite, hydroxyl radical, and hypochlorous acid. It has been shown that NDGA is able to protect rats exposed to oxidative stress induced by ozone and potassium dichromate.
In addition, NDGA also protects primary rat neuronal cultures against damage generated by hydrogen peroxide and iodine acetate. It is well established that oxidative stress is implicated in pathologies such as cancer, diabetes, and inflammation. Oxidative stress is an imbalance in the redox state that is generated by the exacerbated production of reactive oxygen species (ROS) or decreased protective systems, such as enzymes or scavenger molecules.
In fact, increased ROS production causes cell damage and even cell death, and antioxidants can help prevent or alleviate diseases in which oxidative stress is involved.
NDGA also protected cultured neurons against cell death-induced oxidative stress by enhancing ATP generation, mitochondrial morphology, and function. It also restored mitochondrial membrane potential, mitochondrial structure, and synapse structure in the striatum of R6/2 mice and increased their lifespan.
The findings suggest that further therapeutic studies using NDGA are warranted in Huntington's disease (HD) and other neurodegenerative diseases characterized by increased oxidative stress and impaired mitochondrial function. NDGA therapy, which reduces lipid peroxidation and mitochondrial dysfunction, was shown to reduce the pathological phenotype in HD mice as well.
In other studies, NDGA administration resulted in a beneficial effect on neurons by modulating mitochondrial function and oxidative stress. In addition, NDGA has improved neuropathology and also extended the survival of R6 /2 transgenic mice.