Abstract
Aging is a natural biological process associated with cognitive decline and neuroendocrine–immune system changes; the neuroendocrine–immune system plays crucial role in brain aging and neurodegeneration, and it is essential to discern beneficial attempts to delay the aging progress based on immunological aging. In this study, we have investigated the effects of Traditional Chinese Medicine (TCM)—Liuwei Dihuang decoction (LW)—and donepezil, memantine, and melatonin on cognitive decline in aging mice. The aged SAMR1 mice received oral administration of donepezil (1mg/kg), memantine (10 mg/kg), melatonin (10 mg/kg), and LW (10 g/kg) for 3 months. A shuttle box, Morris water maze, and elevated-zero maze were performed to assess cognitive function, and flowcytometry, Luminex, and radioimmunoassay were performed to measure the lymphocyte subsets, inflammatory factors, and hormones. We observed that survival days of mice was increased with melatonin and LW, the anxiety behavior was significantly improved by memantine, melatonin, and LW treatment, active avoidance responses significantly improved by LW, donepezil, and memantine, the spatial learning ability was significantly improved by donepezil, and LW and melatonin were beneficial to the spatial memory of old mice. For immune function, LW increased CD4+ and CD4+CD28+ cells and reduced TNF-α, IL-1β, and G-CSF in plasma, and it also promoted the secretion of anti-inflammatory factors IL-4, IL-5, and IL-10 by regulating the active of Th2 cells in spleen. Donepezil and memantine exerted protective effects against CD4+CD28+ cell decrease caused by aging and reduced the pro-inflammatory factors TNF-α, IL-1β, and G-CSF in plasma. Melatonin could reverse CD8+CD28+ cell imbalances and increased B cells. For endocrine factors, LW increased TSH levels in the pituitary, and melatonin increased the GH level in blood. Our findings indicated that LW improved the cognitive decline in aging mice, and this might be associated with modulation of the active T cells and HPG axis hormones as well as increasing anti-inflammatory factors. Meanwhile, donepezil and memantine have advantages in regulating adaptive immunity, melatonin has advantages in the regulation of B cells and pituitary hormones, and LW exhibits a better effect on neuroendocrine immune function compared with the others from a holistic point of view. LW might be a potential therapeutic strategy for anti-aging-related syndromes, and it can also provide a value on medication guidance about drug combinations or treatment in clinic.
Highlights
Aging is a natural and an irreversible process of life that is associated with cognitive decline
The results showed that the survival days of SAMR1 mice was significantly increased with Liuwei Dihuang (LW) treatment (Figure 1E), and an analysis of the survival curve indicated that chronic administration of melatonin and LW might improve the survival rate in the elderly (Figure 1D)
There was no significant difference in overall evaluation of aging degree of mice (Figure 1F) during drug administration, but, from the appearance of mice in pictures, we could see that the mice treated with LW and melatonin were significantly better than those treated with donepezil and memantine
Summary
Aging is a natural and an irreversible process of life that is associated with cognitive decline. Evidence has shown that age-related cognitive decline is associated with oxidative stress, inflammatory responses, and innate and adaptive immune disorders, and it is subjected to the effects of stress hormones and alterations of the hypothalamic-pituitary axis (HPA) function. Memantine and donepezil are the effective drugs for alleviating the progress of AD in clinic, but the preparations of these drugs are commonly used to treat patients with particular chronic diseases, and they have not been used/evaluated for the pharmacological potential of aging-related decline in cognitive and physiological functions, especially immune and endocrine functions, in the absence of clinical manifestations of particular diseases. Immunological aging includes changes in the adaptive immune system, inflammation response, and disruptions in the hormone axis, altered cortisol levels and glucocorticoid signaling (Reed, 2019), and evidence has indicated than growth hormone deficits have been linked to deficits in memory (Sonntag et al, 2005). Studying the effects of the drugs on the immune and endocrine systems would likely provide a strategy for preventing or treating specific conditions that are associated with aging in the performance of antiaging drugs
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