Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain

Abstract

Given the advantages of being stable in the ambient environment, being permeable to the blood–brain and/or blood–eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague–Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer’s disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, preclinical data to justify bringing such therapeutic compounds to clinical trials in humans is feasible.

Tetramethylpyrazine inhibits production of nitric oxide and inducible nitric oxide synthase in lipopolysaccharide-induced N9 microglial cells through blockade of MAPK and PI3K/Akt signaling pathways, and suppression of intracellular reactive oxygen species

“…Considering the dose range of TMP (1-10 mg/kg) used in in vivo studies, efficient permeability to blood-brain barrier, and comparable protein binding in serumsupplemented media and plasm (Liang et al, 1999;Tan, 2009;Tsai and Liang, 2001), we consider that the concentrations of TMP used for cell culture experiments might be relevant to plasma and tissue levels achievable clinically.…”

“…In addition, recent studies in vivo and in vitro suggest that TMP protects central nervous system from injuries challenged by exogenous stimuli. For example, systemic administration of TMP significantly blocked neuronal degeneration in brains of rats (Tan, 2009). TMP might provide neuroprotection against ischemic brain injury in rats through suppression of inflammatory reaction (Kao et al, 2006).…”

A novel tetramethylpyrazine bis-nitrone (TN-2) protects against 6-hydroxyldopamine-induced neurotoxicity via modulation of the NF-κB and the PKCα/PI3-K/Akt pathways

“…Chuanxiong (Ligusticum wallichii Franchat), a traditional herb medicine, has been used extensively in Asian countries for hundreds of years to treat heart, kidney, and brain diseases (Tan, 2009). Tetramethylpyrazine (TMP, Fig.…”

Therapeutic Effects of Multifunctional Tetramethylpyrazine Nitrone on Models of Parkinson’s Disease <i>in Vitro</i> and <i>in Vivo</i>

“…It also protected kainic acid (KA)-caused massive neuronal cell death in rat brains. 12,20) TMP reduced the L-dopa induced brain oxidative damage in PD rats. 21) Nitrones were developed as free radical-trapping agents in free radical chemistry and have been tested as therapeutic agents for neural and systemic dysfunctions including atherosclerosis, septicemia, stroke, and AD.…”

“…11) Chuanxiong (Ligusticum wallichii FRANCHAT), a traditional Chinese medicinal herb, has been used extensively in Asian countries for hundreds of years to treat heart, kidney, and brain diseases, etc. 12) Tetramethylpyrazine (TMP, Fig. 1) is an alkaloid extracted from Chuanxiong.…”