Chinese Herbal Medicine Interventions in Neurological Disorder Therapeutics by Regulating Glutamate Signaling

Abstract

Glutamate is the major excitatory neurotransmitter in the central nervous system, and its signaling is critical for excitatory synaptic transmission. The well-established glutamate system involves glutamate synthesis, presynaptic glutamate release, glutamate actions on the ionotropic glutamate receptors (NMDA, AMPA, and kainate receptors) and metabotropic glutamate receptors, and glutamate uptake by glutamate transporters. When the glutamate system becomes dysfunctional, it contributes to the pathogenesis of neurodegenerative and neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, and ischemic stroke. In this review, based on regulating glutamate signaling, we summarize the effects and underlying mechanisms of natural constituents from Chinese herbal medicines on neurological disorders. Natural constituents from Chinese herbal medicine can prevent the glutamate-mediated excitotoxicity via suppressing presynaptic glutamate release, decreasing ionotropic and metabotropic glutamate receptors expression in the excitatory synapse, and promoting astroglial glutamate transporter expression to increase glutamate clearance from the synaptic cleft. However, some natural constituents from Chinese herbal medicine have the ability to restore the collapse of excitatory synapses by promoting presynaptic glutamate release and increasing ionotropic and metabotropic glutamate receptors expression. These regulatory processes involve various signaling pathways, which lead to different mechanistic routes of protection against neurological disorders. Hence, our review addresses the underlying mechanisms of natural constituents from Chinese herbal medicines that regulate glutamate systems and serve as promising agents for the treatment of the above-mentioned neurological disorders.

Natural Product Isoliquiritigenin Activates GABAB Receptors to Decrease Voltage-Gate Ca2+ Channels and Glutamate Release in Rat Cerebrocortical Nerve Terminals

“…To date, no data documenting the effect of ISL on glutamate release was available. Several reports have indicated that natural products may effectively reduce the release of glutamate [20][21][22][23]. We examined whether ISL exhibited an effect on glutamate release in rat cerebrocortical nerve terminals.…”

“…Thus, reduced glutamatergic transmission through the inhibition of released glutamate has been proposed as a neuroprotective mechanism [17][18][19]. Studies have reported that several natural products with neuroprotective effects may reduce presynaptic glutamate release [20][21][22][23].…”

Potential Herb–Drug Interactions in the Management of Age-Related Cognitive Dysfunction

“…Age-related brain disorders, such as dementia and its most prevalent form Alzheimer’s disease, are a burden with limited pharmacological therapies available [ 5 ]. Multiple mechanisms have been proposed to underlie the causes of dementia, and therefore there are a variety of potentially valid treatment strategies from the broad concepts of improving angiogenesis and cerebral blood flow [ 6 ] or the antioxidant and neuroprotective effect against oxidative stress [ 7 ], to more specific targets such as modulating the brain glutamatergic and cholinergic neurotransmission [ 8 ] or improving the hippocampal brain-derived neurotrophic factor mRNA levels [ 9 , 10 ]. At present, licensed drugs include cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and a glutamate NMDA ( N -methyl- d -aspartate) receptor antagonist (memantine) [ 4 , 11 ]; a range of other nonspecific drugs often prescribed include tranquilizers, antipsychotics, antidepressants, and hypnotics.…”

Different Traditional Herbal Medicines for the Treatment of Gastroesophageal Reflux Disease in Adults

“…The use of traditional Chinese medicine (TCM) has a long history and was first documented by the Sheng Nong Classic of Materia Medica. Currently, traditional Herbal Medicines (THM) are widely used in cardio-cerebrovascular, endocrine, gastrointestinal, neuropsychiatric, and respiratory disorders (Dai et al, 2018;Jiang et al, 2019;Kong et al, 2019;Qin et al, 2019;Gao et al, 2020;Liu et al, 2020;Zhang et al, 2020). Several studies have evaluated the efficacy and safety of THM in treating GERD (Ling et al, 2015;Dai et al, 2017;Shih et al, 2019).…”