ABSTRACT
Background: Aging is the primary risk factor for the onset of Alzheimer's disease (AD). Inflamma-aging is a major feature in the process of aging, and the chronic neuroinflammation caused by inflamma-aging is closely related to AD. As the main participant of neuroinflammation, the polarization of microglia (MG) could influence the development of neuroinflammation. Objective: This study aims to observe the impact of YHD on microglia (MG) polarization and neuroinflammation to delay the onset and progression of AD. Methods: In vivo experiment, four-month senescence accelerated mouse prone 8 (SAMP8) were used as the model group, the SAMR1 mice of the same age were used as the control group. In YHD group, 6.24 g/kg YHD was intragastrically administrated continuously for 12 weeks, and Ibuprofen 0.026 g/kg in positive control group. Morris Water Maze test was used to evaluate the learning and memory ability, Nissl's staining and immunofluorescence double staining for neuron damage and MG M1/M2 polarization, Enzyme-Linked Immunosorbent Assay (ELISA) for neuroinflammation biomarkers in hippocampus, Western blot for key protein expression of TREM2/NF-κB signaling pathway. In vitro experiments, 10 µM/l Aß1-42 induced BV-2 cell model was used to re-verify the effect of YHD regulating MG polarization to reduce neuroinflammation. Also, TREM2 small interfering RNA (siRNA) was used to clarify the key target of YHD. Results: YHD could improve the learning and memory ability of SAMP8 mice evaluated by the Morris Water Maze test. Like Ibuprofen, YHD could regulate the M1/M2 polarization of MG and the levels of neuroinflammatory markers TNF-α and IL-10 in hippocampus, and relieve neuroinflammation and neuron loss. In addition, YHD could also regulate the expression of PU.1, TREM2, p-NF-κB P65 in the TREM2/NF-κB signaling pathway. Further in vitro experiments, we found that YHD had a significant regulatory effect on Aß1-42-induced BV-2 cell polarization, and it could significantly increase PU.1, TREM2, decrease p-NF-κB P65, p-IKKß, TNF-α, IL-6, IL-1ß. At the same time, using siRNA to inhibit TREM2, it proved that TREM2 was a key target for YHD to promote Aß1-42-induced BV-2 cell M2 polarization to reduce neuroinflammation. Conclusions: YHD could regulate the TREM2/NF-κB signaling pathway through TREM2, thereby to adjust MG polarization and reduce AD-related neuroinflammation.
ABSTRACT
Background: As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status. Methods: This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration). Results: After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (P < 0.01), (2) CD3 and CD4/CD8 increased significantly after the test (P < 0.05), (3) IgG, IgA, IgM and WBC increased significantly in the mid-term and after the test (P < 0.01); the results of the secondary efficacy indicators: (1) TNF-α decreased significantly in the mid-term (P < 0.05), IFN-γ decreased significantly in the mid-term (P < 0.01), (2) NK increased significantly in the mid-term and after the test (P < 0.05), (3) monocyte increased significantly in the mid-term and after the test (P < 0.01). Inter-group comparison of the test group and the control group, the results of the main efficacy indicators: (1) immune related health scores were higher than that of the control group in the mid-term and after the test (P < 0.01), (2) IgA of the test group was higher than that of the control group in the mid-term and after the test (P < 0.05); the results of the secondary efficacy indicators: (1) WBC of the test group was higher than that of the control group in the mid-term (P < 0.05); (2) monocytes of the test group were higher than that of the control group in the mid-term and after the test (P < 0.05), neutrophils of the test group were higher than that of the control group in the mid-term (P < 0.05). Conclusion: Taking KRG has no adverse effects on the health of the subjects. According to the standard of clinical trial scheme, the immune related health scores and IgA in the main efficacy indicators were positive, which shows that KRG is helpful in enhancing human immunity.
ABSTRACT
OBJECTIVE: To explore the acupoint selection rules of acupuncture for Alzheimer's disease (AD) in modern clinical practice by complex network technology. METHODS: The relevant articles of clinical trials were retrieved from CNKI published before December 2017. Using Microsoft Excel 2010, the database was established. Using Gephi 0.8.2 software, the complex network mode was built and its topological structure was analyzed. RESULTS: Finally, 81 articles were eligible and 114 acupoint prescriptions were extracted. The constructed complex network of acupoint prescriptions for AD was characteristics as small world effect and scale-free property, the crucial acupoints included Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Yintang (GV 29), Shenmen (HT 7), Shenting (GV 24), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3). In acupoint combination, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Sanyinjiao (SP 6) were the most common, and the combination of the distal and nearby points was predominant. Using k-core for acupoint optimization, 29 core acupoints were screened and they were mostly located on the governor vessel and the head and neck, with the highest use frequency. 82.76% of acupoints were specific acupoints and the influential points were dominant. Using community structure partition, these acupoints were classified into two groups, i.e. deficiency syndrome and excess syndrome. CONCLUSION: The selection of local acupoints is the first choice in acupuncture treatment for AD. The combination of distal and nearby points is the most common and the special points are the core. In clinical practice, the great consideration is provided on mind regulation, integration of disease and symptoms, the mutual treatment of the primary and the secondary as well as the deficiency and the excess.