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OBJECTIVE To observe the anti-aging effects of SOD mimicAEOL-10150 in anti-senescence accelerated mouse resistant 1 (SAMR1) strain. METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL-101502 mg·kg- 1 once a week. Morris water maze, new object recognition, nesting and forced swimming were used to observe the behavioral changes of animals. Lymphocyte subgroups and ROS were measured by Flow cytometry. The cytokines levels were determined by Luminex method. The number of DCX + neurons in brain tissue was observed by immunofluorescence. RESULTS The results showed that AEOL-10150 could prolong the mean lifespan of SAMR1 mice, but it had no obvious effect on maximal lifespan. What's more, AEOL-10150 could significantly improve the spatial learning memory of aged mice, but it could not increase the number of DCX+ neurons in the hypothalamic MBH and hippocampal DG regions. Then, we observed the effects of AEOL-10150 on peripheral blood lymphocyte subgroups and cytokines. We found that AEOL-10150 significantly modulated the lymphocyte subgroups and cytokine release. Especially, AEOL-10150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-α and IL-17. CONCLUSION The results indicate that AEOL-10150 has anti-aging effects, and the effects are closely related to modulating immunity and inhibiting SASP production.
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OBJECTIVE To investigate the effects of LW-AFC, a new formula derived from Liuwei Dihuang decoction, on gut microbiota and the behavior of learning and memory of SAMP8 mice, a mouse model of Alzheimer Disease (AD), and identify the specific intestinal microbiota correlating with cognitive ability. METHODS Morris-water maze test, novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory. 16S rRNA amplicon sequencing (Illumina, San Diego, CA, USA) was employed to investigate gut microbiota. RESULTS The treatment of LW- AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW- AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
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OBJECTIVE LW- AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction. Previous studies have showed that LW-AFC could improve learning & memory ability in amny animal models. In this study, we focused on evaluating the effect of several main active components from LW-AFC (B-B; loganin, LOG; morroniside, MOR; paeoniflorin, PF and stachyose, STA) on LTP. METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it's active components on coticorsterone (Cort) induced LTP impairment. RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment. The effect of LW-AFC was abolished when the immune function was inhibited. Single administration (ig, ip, icv) of any of the components had no effect on Cort-induced LTP impairment. Consecutively intragastric admin?istration or intraperitoneal injections (chronic administration) of B-B, LOG, MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment. Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort, while there was little improving effect when STA was administrated via intraperitoneal injection. In addition, when the intestinal microbiota was disrupted by applying the antibiotic cocktail, STA showed little protective effect against Cort. CONCLUSION In conclusion, LW-AFC and it' s components showed positive effects against cort induced LTP impairment, it seems that all displayed protective effects via indirectly, immune modulation might be the common pathway for all components; the exact pathways are different in each component, B-B, LOG, MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function, while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota. Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.
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OBJECTIVE To investigate the effect of LW- AFC, a new formula of the main active components extracted from Liuwei Dihuang decoction, on treatment of Alzheimer disease (AD) in mouse models. METHODS After treatment LW- AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β(Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Αβ deposition in the brain, and reduced the concentration of Aβ1- 42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle- stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+T cells, and reduced CD4+CD25+Foxp3+T cells in the spleen lymphocytes, down- regulated interleukin(IL)- 1β, IL- 2, IL- 6, IL- 23, granulocyte- macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.
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China is abundant in natural medicinal resources. Natural medicine (NP), especially traditional Chinese medicine (TCM), have been widely employed in prevention and treatment of diseases in China for thousands of years, which make a great contribution to health care of Chinese people and the prosperity of the Chinese nation. TCM is the excellence culture inheritance of China and a medicine system with long history, tradition and unique theory and technique. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among which the theory of compatibility is the essential part. Clinical application and modern pharmacological study both demonstrated that TCM prescription possesses unique effect in comparison with chemical drugs. However, the pharmacological study of TCM prescription is very difficult due to multiple herbs which contain complicated chemical components in the prescription. So, the key point for the pharmacological study of TCM prescription is to elucidate its integrative effect and the mechanism of action. In recent years, great advances have been achieved in the research on TCM prescription and modern study of TCM prescription, including pharmacological and chemical studies, has becoming a hot research field in China. The pharmacological studies of TCM and NP are conducted with different ways and methods including holistic approaches in various experimental model animals and in vitro experiments in tissue, organ and cell models. In addition, a lot of new technics and methods such as″ omics″ technologies were employed in the molecular level studies, for example, researches on the mechanism of action of TCM and NP. In addition, a lot of new drugs have been developed from TCM prescriptions in China. The classical preparations of TCM, including decoction, pill, powder, ointment and pellet, etc, are prepared with traditional methods. While, the new preparations are similar to modern pharmaceutical preparations such as tablet, capsule, oral liquid, even injection and manufactured under the condition of modern pharmaceutical industry according to the requirements of GMP. To elucidate the activity mechanism and the active fractions or components are very important basis for the development of new drugs from TCM prescription. Although pharmacological study of TCM has made great progresses, it is still a great challenge to elucidate the active components and the mechanism of action of TCM prescription due to the complexity of the prescription. However, with the rapid development of science and technology and their continuous application in this research field, the pharmacological study on TCM prescription has been progressing and getting deeper rapidly.