The theory that "the kidney nourishes marrow and brain is the sea of marrow" has been instructing traditional Chinese medical doctors in preventing and treating dementia in aged people for thousands of years. However, the modern biological basis of this theory has not been systemically studied. In this review, we summarized our serial pharmacological studies on the treatment of Alzheimer's disease (AD) with Chinese medicinal herbs, using multiple kinds of AD-like animal and cell models. The results show that "kidney-reinforcing" herbs of traditional Chinese medicine play a very important role in the anti-AD effects; and different "kidney-reinforcing" herbs have different effects in brain functions. The common effects of "kidney-reinforcing" herbs are improving cellular energy metabolism, increasing neurotrophic factors and the number of cholinergic neurons, and decreasing neurotoxin production. Based on above results, we propose that the essence of "brain marrow" is the neurons and neurotrophic factors in the brain; "the deficiency of brain marrow" is induced by the decrease in neurotrophic factors and the atrophy and loss of neurons in the brain, thus resulting in cognitive impairment and dementia. The modern biological basis of "reinforcing kidney to replenish marrow" by traditional Chinese medicine includes improving cellular energy metabolism and utilization, enhancing endogenous neurotrophic effects and decreasing neurotoxin production, thus reducing the cell death and increasing the survival and regeneration of neurons.
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