首页|"强志"中药的网络药理学分析及其改善记忆障碍的实验研究

"强志"中药的网络药理学分析及其改善记忆障碍的实验研究

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目的 归纳并分析《神农本草经》中的"强志"药物,探讨其改善记忆障碍的效果及作用机制。方法 筛选《神农本草经》中具有"强志"功效的药物,总结其性味归经。通过网络药理学检索合取强志中药共有的作用靶点,推测其可能是发挥"强志"作用的基础。开展动物实验,将80只小鼠分为空白组、模型组、木香组、远志组、杜仲组、覆盆子组、芡实组、苍耳子组、淫羊藿组(0。06 g·d-1)、鹿茸组(0。018 g·d-1),每组8只,相应药量灌胃30天。自23天起,除空白组外,各组均腹腔注射东莨菪碱(2mg·kg-1)。第31天开始对各组小鼠进行跳台实验、水迷宫实验,实验结束后处死小鼠并取材,LFB染色观察小鼠皮层及海马区神经元损伤情况,并依据网络药理学结果,使用ELISA试剂盒检测小鼠海马组织中前列腺素内过氧化物合酶2(COX-2)、单胺氧化酶A(MAOA)、5-羟色胺(5-HT)、5-羟色胺受体2A(5-HT2AR)、乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)、腺苷受体A2a(A2aR)、腺苷受体A1(A1R)的含量,Western blot法检测小鼠海马中核转录因子-κB(NF-κB)、5-HT转运体(SERT)的表达。结果《神农本草经》中"强志"药物包括木香、远志、杜仲、覆盆子、芡实、苍耳子、淫羊藿、鹿茸八种,其药味以"辛""甘"为主,药性以"温"为主,多数归于肾经,网络药理学分析其共同靶点为COX-2、MAOA、5-HT2AR、AchE、A2aR、A1R。在行为学实验中,各强志药物组小鼠相比于模型组小鼠,跳台潜伏期显著增长、跳下平台次数显著减少、水迷宫潜伏期显著缩短(P<0。05或P<0。01),并且明显更熟悉游泳路线。LFB染色结果表明各强志药物能减少小鼠皮层和海马区神经元损伤。ELISA结果显示相比于模型组,各强志药物组小鼠海马中COX-2、Ach、AchE、MAOA、A1R、A2aR含量均明显降低(P<0。05或P<0。01),5-HT和5-HT2AR含量明显增加(P<0。01)。Western blot法检测各强志药物组小鼠海马中NF-κB、SERT含量相比于模型组显著降低。结论 8种"强志"药物均在不同程度上具有改善记忆障碍的效果,其发挥强志作用、改善记忆障碍的机制可能与抑制NF-κB/COX-2炎症通路、减少5-HT水解及提高5-HT2A受体含量、稳定Ach与AchE含量、降低腺苷A1、A2a受体含量多方面、多途径有关。
Network Pharmacological Analysis of"Qiangzhi"Chinese Medicine and Its Experimental Study on Improving Memory Impairment
Objective To summarize and analyze the"Qiangzhi"drugs in Shennong's Classic of the Materia Medica,and to explore the effect and mechanism of improving memory impairment.Methods To screen the drugs with the effect of"Qiangzhi"in Shennong's Classic of the Materia Medica,and summarize their properties and tastes.By searching the common action targets of"Qiangzhi"traditional Chinese medicine through network pharmacology,it is speculated that it may be the basis for playing the role of"Qiangzhi".Animal experiments were carried out,and 80 mice were divided into blank group,model group,Radix Aucklandiae group,Radix Polygalae group,Eucommiae Cortex group,Rubi Fructus group,Euryale Semen group,Fructus Xanthii group,Epimedium group(0.06 g·d1)and Pilose Antler group(0.018 g·d1),with 8 mice in each group,and the corresponding dosage was given by gavage for 30 days.From the 23th day,scopolamine(2 mg·kg-1)was injected intraperitoneally in all groups except the blank group.On the 31th day,the platform test and water maze test were carried out on the mice in each group.After the experiment,the mice were killed and the materials were taken.The damage of neurons in the cortex and hippocampus of the mice was observed by LFB staining.According to the results of network pharmacology,Use ELISA kit to detect prostaglandin endoperoxide synthase 2(COX-2),monoamine oxidase A(MAOA),serotonin(5-HT),serotonin receptor 2A(5-HT2AR),acetylcholine(Ach),acetylcholinesterase(AchE),adenosine receptor A2a(A2aR)and adenosine receptor A1(A1R)in hippocampus of mice.Western blot was used to detect the expression of nuclear transcription factor-κB(NF-κB)and 5-HT transporter(SERT)in hippocampus of mice.Results There are eight kinds of drugs for"Qiangzhi"in Shennong's Classic of the Materia Medica,including Radix Aucklandiae,Cortex et Radix Polygalae,Eucommiae Cortex,Rubi Fructus,Euryale Semen,Fructus Xanthii,Herba Epimedii,and Cornu Cervi Pantotrichum.The main drugs are pungent and sweet,and the main drugs are warm,and most of them belong to the kidney meridian.According to the network pharmacology analysis,their common targets are COX-2,MAOA,5-HT2AR,AchE,A2aR,A1R.In the behavioral experiment,compared with the model mice,the latency of jumping off the platform was significantly increased,the number of jumping off the platform was significantly reduced,and the latency of water maze was significantly shortened(P<0.05 or P<0.01),and the mice in each Qiangzhi drug group were obviously more familiar with the swimming route.The results of LFB staining showed that each Qiangzhi drug could reduce the neuronal damage in cortex and hippocampus of mice.The results of ELISA showed that compared with the model group,the contents of COX-2,Ach,AchE,MAOA,A1R,A2aR in the hippocampus of mice in each Qiangzhi drug group were significantly decreased(P<0.05 or P<0.01),while the contents of 5-HT and 5-HT2AR were significantly increased(P<0.01).Western blot method was used to detect the contents of NF-κB and SERT in hippocampus of mice in each"Qiangzhi"drug group,which was significantly lower than that in model group.Conclusion Eight"Qiangzhi"drugs all have the effect of improving memory impairment in different degrees.The mechanism of their"Qiangzhi"effect and improving memory impairment may be related to various ways,such as inhibiting NF-κB/COX-2 inflammatory pathway,reducing 5-HT hydrolysis and increasing 5-HT2A receptor content,stabilizing the contents of Ach and AchE,and reducing the contents of adenosine A1 and A2a receptors.

Shennong's Classic of the Materia Medica"Qiangzhi"Chinese medicineMemory impairmentNF-κB/COX-2 inflammatory pathwayAcetylcholine system5-HT and 5-HT2A receptorsAdenosine A1 and A2a receptors

王法帅、陈学志、朱琳、王玉洁、孙峰山、郭闫葵

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济宁市第一人民医院 济宁 272011

广安门医院济南医院(济南市中医医院) 济南 250012

上海中医药大学研究生院 上海 201203

《神农本草经》 "强志"中药 记忆障碍 NF-κB/COX-2炎症通路 乙酰胆碱系统 5-HT及5-HT2A受体 腺苷A1A2a受体

2024

世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
年,卷(期):2024.26(9)