1.Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability
Fulu PAN ; Yang LIU ; Huining LIU ; Shuang YU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Xiaoyu CHAI ; Qianqian WANG ; Zirong YI ; Yanli PAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):116-124
ObjectiveTo examine the inhibitory effects of berberine compounds, including columbamine, on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier (BBB) permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration (IC50) of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters (Koff) of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds (including medicinal herbs and compound formulas) was conducted using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). ResultBerberine compounds, including columbamine, exhibited strong inhibition of acetylcholinesterase, with IC50 values in the nanomolar range. Moreover, they displayed better drug-target binding kinetics characteristics (with smaller Koff values) than the positive control of donepezil hydrochloride (P<0.01), indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer, as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance, this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease, providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.
2.Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism
Shuang YU ; Yanli PAN ; Huining LIU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Fulu PAN ; Qianqian WANG ; Xiaoyu CHAI ; Guopeng WANG ; Tao MA ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):114-123
ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus(SCF) based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism, intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration, and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS) was used to analyze and compare the differences in the spectra of SCF extract, blank plasma, administered plasma, blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column(2.1 mm×100 mm, 1.7 µm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-7 min, 95%B; 7-12 min, 95%-35%B; 12-17 min, 35%-15%B; 17-20 min, 15%-12%B; 20-22 min, 12%-5%B; 22-23 min, 5%B; 23-25 min, 5%-95%B; 25-28 min, 95%B). And heated electrospray ionization(HESI) was used with positive and negative ion modes, the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time, characteristic fragments, molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF, including lignans, flavonoids, amino acids, tannins, and others, of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation, methylation, demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats, it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.
3.Recent advances in bioactivity evaluation methods of uric acid-lowering compounds
Danhui QI ; Xiaoyu SHI ; Xinyong LIU ; Peng ZHAN
Journal of China Pharmaceutical University 2024;55(2):167-180
Abstract: Hyperuricemia is a metabolic disease caused by elevated uric acid in the body, and is closely related to the increased risk of cardiovascular disease, metabolic disorders, and renal complications. In the development process of uric acid-lowering drugs, activity evaluation is a crucial step. At present, the activity screening methods of uric acid-lowering drugs can be roughly divided into two categories: in vitro and in vivo. In vitro screening is mainly for such targets as xanthine oxidase, urate transporters, and purine nucleoside phosphorylase, etc.; while in vivo screening is achieved by rodent, poultry and organoid models. In this article, the activity evaluation methods for uric acid-lowering compounds are comprehensively summarized both in vitro and in vivo, aiming to provide some insight for the development of uric acid-lowering drugs.
4.Establishment and validation of the Sprague-Dawley rat model of osteoarthritis with kidney deficiency and blood stagnation
Cheng YANG ; Yusheng LI ; Hongzhuo JIAO ; Man SHANG ; Qi LIU ; Linzhen LI ; Fangyang FAN ; Chenglong ZHANG ; Xiaoyu ZHANG ; Juntao ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(27):4273-4280
BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.
5.Design and simulation of a UAV with portable folding wings for search and rescue
Qi QIU ; Weihua SU ; Xi WEN ; Junjie WANG ; Xiaoyu LI
Military Medical Sciences 2024;48(2):136-142
Objective To design a search and rescue UAV that is portable and user-friendly in order to meet the needs of rescue personnel on the battlefield.Methods Three-dimensional design software CATIA was used to complete the structural design of the UAV body.In order to make full use of the internal space of the UAV body,folding wings were adopted to reduce the volume of the UAV.By using ABAQUS,the finite elements of the key parts of the UAV were analyzed before the modal analysis of the whole vehicle was conducted to verify the reliability of the structure.The robot simulation software Webots was used for motion simulation of the UAV.Results Simulation analysis and test verification suggested that the structural design of the UAV was well-grounded.It could be quickly and properly deployed by means of hand launch or barrels,which made it easier for rescuers to use the UAV.Conclusion The design and simulation research of UAVs with portable folding wings for search and rescue is of great significance for the research and development of physical prototypes.This study is expected to stimulate new ideas for the development of rescue equipment in the PLA,and contribute to miniaturization of UAVs.
6.Constitution identification model in traditional Chinese medicine based on multiple features
Anying XU ; Tianshu WANG ; Tao YANG ; Xiao HAN ; Xiaoyu ZHANG ; Ziyan WANG ; Qi ZHANG ; Xiao LI ; Hongcai SHANG ; Kongfa HU
Digital Chinese Medicine 2024;7(2):108-119
Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions,thereby offering optimized guidance for clinical diagnosis and treatment plan-ning,and ultimately enhancing medical efficiency and treatment outcomes. Methods First,TCM full-body inspection data acquisition equipment was employed to col-lect full-body standing images of healthy people,from which the constitutions were labelled and defined in accordance with the Constitution in Chinese Medicine Questionnaire(CCMQ),and a dataset encompassing labelled constitutions was constructed.Second,heat-suppres-sion valve(HSV)color space and improved local binary patterns(LBP)algorithm were lever-aged for the extraction of features such as facial complexion and body shape.In addition,a dual-branch deep network was employed to collect deep features from the full-body standing images.Last,the random forest(RF)algorithm was utilized to learn the extracted multifea-tures,which were subsequently employed to establish a TCM constitution identification mod-el.Accuracy,precision,and F1 score were the three measures selected to assess the perfor-mance of the model. Results It was found that the accuracy,precision,and F1 score of the proposed model based on multifeatures for identifying TCM constitutions were 0.842,0.868,and 0.790,respectively.In comparison with the identification models that encompass a single feature,either a single facial complexion feature,a body shape feature,or deep features,the accuracy of the model that incorporating all the aforementioned features was elevated by 0.105,0.105,and 0.079,the precision increased by 0.164,0.164,and 0.211,and the F1 score rose by 0.071,0.071,and 0.084,respectively. Conclusion The research findings affirmed the viability of the proposed model,which incor-porated multifeatures,including the facial complexion feature,the body shape feature,and the deep feature.In addition,by employing the proposed model,the objectification and intel-ligence of identifying constitutions in TCM practices could be optimized.
7.Research Progress in the Role of Advanced Glycation End Products in the Pathogenesis of Sarcopenia
Xingyu ZHANG ; Qi GUO ; Xiaoyu CHEN
Acta Academiae Medicinae Sinicae 2024;46(1):111-118
Sarcopenia is an age-related condition characterized by a decrease in muscle mass and a de-cline in muscle strength.Sarcopenia increases the risk of falls,severely affecting the quality of life of patients,and it may be associated with various age-related chronic diseases.Advanced glycation end products(AGEs)are a class of stable glycation products produced by condensation,rearrangement,cleavage,and oxidative modifica-tion between the free amino groups of proteins,lipids or nucleic acids and the free carbonyl groups of reducing sugars.Studies have revealed associations of AGEs with muscle mass,muscle strength,and sarcopenia.AGEs can lead to hardening of the extracellular matrix of skeletal muscle through glycation cross-linking.The binding of AGEs to receptors induces inflammation and oxidative stress,consequently resulting in decreases in muscle mass and muscle strength.Therefore,AGEs may play a role in the occurrence and development of sarcopenia.This re-view summarizes the role of AGEs in the pathogenesis of sarcopenia,offering theoretical support for probing into the mechanisms underlying sarcopenia.
8.Effects of Personalized Exercise Prescriptions on Sarcopenia in Patients Undergoing Hemodialysis
Shengjie LI ; Qi GUO ; Xiaoyu CHEN
Acta Academiae Medicinae Sinicae 2024;46(2):247-253
Sarcopenia is a major factor affecting the health and quality of life of the patients undergoing hemodialysis.Exercise can effectively ameliorate sarcopenia in these patients.However,the type,intensity,time,and frequency of exercise influence the effect of exercise.This review describes the effects of different exer-cise prescriptions on sarcopenia in the patients undergoing hemodialysis.It aims to assist medical staff in develo-ping personalized exercise prescriptions,guiding patients to engage in exercise,and provide effective strategies for the prevention and treatment of sarcopenia in the patients undergoing hemodialysis.
9.Research Progress in Pathogenesis,Nutrition and Exercise Intervention of Patients With Protein Energy Wasting
Mengze GAO ; Qi GUO ; Xiaoyu CHEN
Acta Academiae Medicinae Sinicae 2024;46(2):281-286
Protein energy wasting(PEW)is common in maintenance hemodialysis(MHD)patients,and it is associated with a variety of adverse clinical outcomes,including weight loss and increased protein catab-olism.There are many studies on health interventions for MHD patients through nutrition strategies,exercise pat-terns and the combination of both.This article reviews the pathogenesis,diagnostic criteria and intervention meas-ures of PEW,aiming to provide a reference for early clinical diagnosis,identification and intervention of PEW.
10.Comparing the Anti-oxidative Effects of "Three Decoctions for COVID-19"
Ximeng LI ; Yuan KANG ; Yuan GAO ; Zhuangzhuang LIU ; Wenjing LI ; Zhenlu XU ; Xiaoyu ZHANG ; Runlan CAI ; Yun QI
Chinese Journal of Modern Applied Pharmacy 2024;41(7):887-894
OBJECTIVE
To compare the anti-oxidative effects of "three decoctions for COVID-19" (Qingfei Paidu decoction, Huashi Baidu decoction, Xuanfei Baidu decoction) in parallel experimental models.
METHODS
In the cell-free system, the total antioxidant capacity was investigated by FRAP method. The scavenging effects of DPPH radicals and superoxide anions were evaluated by DPPH and NBT reduction method, respectively. The scavenging effect of hydroxyl radicals was determined by a fluorescence method based on the end-product MDA. The anti-lipid peroxidation activity was investigated using the FeSO4-induced rat liver homogenate MDA method. Based on these five antioxidant indicators, the antioxidant capabilities of the extracts of three decoctions were parallelly compared in the cell-free system. Furthermore, in lipopolysaccharide-activated RAW264.7 cells, the productions of intracellular and mitochondrial reactive oxygen species(ROS) were detected using the L-012 probe and the MitoSOX mitochondrial superoxide red fluorescence probe, respectively; and intracellular NADPH oxidase activity was measured using the lucigenin probe. These three indicators were used to parallelly compare the antioxidant capabilities of the extracts of three decoctions.
RESULTS
In the cell-free system, three decoctions for COVID-19 could concentration-dependently scavenge DPPH radicals, superoxide anions and hydroxyl radicals, and potently inhibit the lipid peroxidation. At the equal extract concentration, their scavenging effects on DPPH radicals and superoxide anions and the total antioxidant capacity were comparable; while Huashi Baidu decoction exhibited the strongest ability to scavenge hydroxyl radicals and inhibit lipid peroxidation. In the cell system, three decoctions could reduce lipopolysaccharide-elevated intracellular ROS level by weakening NADPH oxidase activity; meanwhile, they could decrease mitochondrial ROS productions, among which Qingfei Paidu decoction possessed the most comprehensive effection.
CONCLUSION
Collectively, three decoctions for COVID-19 exert diverse antioxidant effects in both cell-free and cell systems, and each of them possesses the distinct advantages. Given that oxidative stress is pivotal during the pathological process of COVID-19, the results may suggest that the antioxidant ability of three decoctions is one of the pharmacodynamic basis for their clinical use.


Result Analysis
Print
Save
E-mail