Ischemic stroke (IS) is one of the major global causes of death and disability. Because blood clots block the neural arteries provoking ischemia and hypoxia in the brain tissue, IS results in irreversible neurological damage. Available IS treatments are currently limited. Curcumin has gained attention for many beneficial effects after IS, including neuroprotective and anti-inflammatory; however, its precise mechanism of action should be further explored. With network pharmacology, molecular docking, and molecular dynamics (MD), this study aimed to comprehensively and systematically investigate the potential targets and molecular mechanisms of curcumin on IS. We screened 1096 IS-related genes, 234 potential targets of curcumin, and 97 intersection targets. KEGG and GO enrichment analyses were performed on these intersecting targets. The findings showed that the treatment of IS using curcumin is via influencing 177 potential signaling pathways (AGE-RAGE signaling pathway, p53 signaling pathway, necroptosis, etc.) and numerous biological processes (the regulation of neuronal death, inflammatory response, etc.), and the AGE-RAGE signaling pathway had the largest degree of enrichment, indicating that it may be the core pathway. We also constructed a protein-protein interaction network and a component-target-pathway network using network pharmacology. From these, five key targets were screened: NFKB1, TP53, AKT1, STAT3, and TNF. To predict the binding conformation and intermolecular affinities of the key targets and compounds, molecular docking was used, whose results indicated that curcumin exhibited strong binding activity to the key targets. Moreover, 100 ns MD simulations further confirmed the docking findings and showed that the curcumin-protein complex could be in a stable state. In conclusion, curcumin affects multiple targets and pathways to inhibit various important pathogenic mechanisms of IS, including oxidative stress, neuronal death, and inflammatory responses. This study offers fresh perspectives on the transformation of curcumin to clinical settings and the development of IS therapeutic agents.

Ethnopharmacological relevance: The 'cold' property herbs are commonly applied in heat syndrome. Unfortu-nately, the underlying mechanisms of the 'cold' property herbs on heat syndrome has not been investigated.Aim of the study: The study aimed to probe the activities of the four typical 'cold' property herbs on hyperthyroidism.Materials and methods: Firstly, the four typical 'heat' property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical 'cod' property herbs and the four typical 'heat' property herbs. H&E staining were used to confirmed the influence of the typical 'cold' property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical 'cold' property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na+/K+-ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-gamma, which detected by commercial kits and Western blot.Results: It is proved that the four typical 'cold' property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical 'heat' property herbs showed no benefit. Moreover, the four typical 'cold' property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca2+ and MAPK signaling pathway. And the levels of UCP-1, Na+/K+-ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-gamma were ameliorated by the four typical 'cold' property herbs. Conclusion: The four typical 'cold' property herbs could alleviate hyperthyroidism by ameliorate thyroid hor-mone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+/MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.

中药四性是中药药性理论的核心,是我国历代医药学家经过长期实践总结而成的一种临床用药经验,并经过不断发展、完善与验证,最终又指导中医临床用药.通过对四性及五味的溯本寻源,以中药四性的起源、临床应用和现代研究为主线,对四性的形成过程及其临床应用价值进行归纳和总结.并对《中国药典》2020年版一部收载的617味中药进行"性"与"味"的统计分析,解析二者的内在关联性,有助于中药性味的应用和理解,为中药药性理论的进一步研究提供思路与借鉴.

Naringenin (NR) is a kind of flavonoid which plays a great role in the treatment of autism spectrum disorder (ASD). However, the underlying mechanism of NR in treating ASD still remains unclear. This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of NR on ASD. Targets related to NR were screened from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Encyclopedia of Traditional Chinese Medicine Database (ETCM), Traditional Chinese Medicine Integrated Database (TCMID), PharmaMapper database, and targets related to ASD were screened from Online Mendelian Inheritance In Man (OMIM), Disgenet, GeneCards, Therapeutic Target Database (TTD), Drugbank, and ETCM. Screened of the intersected gene targets. Then, we used the protein–protein interaction (PPI) networks to construct a PPI network and used Network Analyzer plug-in to perform topological analysis to screen out the core target. We used Metascape platform to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and used Chem draw, Pymol, AutoDock 1.5.6 software for molecular docking verification with core targets. A total of 149 targets of NR and 1594 potential targets of ASD were screened, and 43 intersected targets and 8 key targets were obtained and screened. A total of 176 GO items were obtained by GO enrichment analysis ( P < .05), 153 entries on biological process (BP), 12 entries on BP and 11entries on cell composition (CC) were included. A total of 100 signaling pathways were obtained by KEGG pathway enrichment screening ( P < .05).The pathways that are closely related to the pathogenesis of ASD are estrogen signaling, thyroid hormone signaling pathway, prolactin signaling pathway, and endocrine resistance pathway. Molecular docking results showed that NR had the best docking activity with the core target CASP3, and had good binding ability with AKT1, ESR1, ACTB and MAPK3. Taken together, our findings support that NR exerts therapeutic effects on ASD with multi-target, and multi-pathway characteristics, which provides a preliminary theoretical basis for clinical trials. The mechanism of anti-oxidative stress response, anti-apoptosis, regulation of cell growth and metabolism, anti-inflammatory, balance hormone levels may be important for the therapeutic effect.

Herbs with a “hot” properties are frequently used to treat cold symptoms in TCM. However, the underlying mechanisms of the herbs with “hot” properties on hypothyroidism have not been investigated. This study aimed to explore four typical “hot” and “cold” property herb on hypothyroidism. Firstly, the difference efficacy between the four typical “hot” property herbs and the four typical “cold” property herbs was assessed by physical signs, thyroid function, and the metabolic profile using multivariate statistical analysis. The influence of the four typical “hot” property herbs on hypothyroidism was validated pathologically. The impact mechanism of the four typical “hot” property herbs on hypothyroidism was investigated through a metabolomics method combined with network analysis. Na+/K+-ATP, ACC1 enzyme, UCP-1, and the PI3K-Akt pathway were used to confirm the metabolite pathways and target-associated metabolites. The results showed that the four typical “hot” property herbs could significantly improve physical signs, thyroid function, and the metabolic profile in hypothyroidism rats, the four typical “cold” property herbs did not show any benefit. Moreover, the four typical “hot” property herbs could improve lipid metabolism, energy metabolism, and thyroid hormone levels by the PI3K-Akt signaling pathway, Ca2+- AMPK signaling pathways, purine metabolism, and tryptophan metabolism. Additionally, the levels of UCP-1, Na+/K + -ATP enzyme, and ACC1 were ameliorated by the four typical “hot” property herbs in hypothyroidism rats. Therefore, a metabolomics strategy combined with network analysis was successfully performed and interpreted the mechanism of the four typical “hot” property herbs on hypothyroidism based on the theory of “cold and hot” properties of TCM well.

Based on the theory of activating spleen and generating blood, this study explored the effect of Rehmanniae Radix Prae-parata on the spleen metabolome of the rat model with blood deficiency syndrome.The rat model of blood deficiency syndrome was established by combining with cyclophosphamide(CTX) and N-acetyl-phenylhydrazine(APH), and the metabolomes of the spleen samples were analyzed with ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the metabolite profiles of spleen samples.The MEV heatmap and metabolic network were established based on the potential biomarkers.Finally, the blood routine indexes were combined with the metabolomic profile to reveal the mechanism of Rehmanniae Radix Praeparata in activating spleen and generating blood.The treatment with CTX and APH decreased the blood routine indexes such as white blood cell count(WBC), red blood cell count(RBC), platelet(PLT), and hematocrit(HCT), indicating that the rat model of blood deficiency syndrome was successfully established.The administration of Rehmanniae Radix Praeparata significantly improved the blood routine indexes, which suggested that Rehmanniae Radix Praeparata played a role in replenishing blood.In addition, the metabolomics analysis identified 41 potential biomarkers.The PCA and MEV heatmap also showed significant improvement effect of Rehmanniae Radix Praeparata on the spleen metabolic profile.These potential biomarkers were mainly involved in tricarboxylic acid cycle, niacin and nicotinamide metabolism, phenylalanine metabolism, tyrosine metabolism, taurine and hypotaurine metabolism, and sphingolipid metabolism.Therefore, we hypothesize that Rehmanniae Radix Praeparata may regulate energy metabolism, peripheral blood production, and oxidative injury of hemocytes to tonify blood.

Hyperthyroidism and hypothyroidism are common diseases resulting from thyroid dysfunction, and are simple to diagnose and treat. The traditional treatment for hypothyroidism is thyroid hormone replacement therapy. The traditional treatments for hyperthyroidism include antithyroid drug, iodine radiotherapy, and surgery. Thyroid disease can be fatal in severe cases if untreated. Current statistical reference ranges used for diagnosis based on relevant biochemical parameters have been debated, and insufficient treatment can result in long-term thyroid hormone deficiency, which is associated with increased risk of cardiovascular disease and persistent symptoms. In contrast, overtreatment can result in heart disease and osteoporosis, particularly in older people and pregnant women. Therefore, under- or over-treatment should be avoided and treatment regimens should be monitored closely. A significant proportion of patients who achieve biochemical treatment goals still complain of significant symptoms. Systematic literature review was performed through the Embase (Elsevier), PubMed and Web of Science databases, and studies summarized evidence regarding treatment and management of hypothyroidism and hyperthyroidism, and reviewed clinical practice guidelines. We also reviewed the latest research on the metabolic mechanisms of hyperthyroidism and hypothyroidism, which contributed to understanding of thyroid diseases in the clinic. A reliable algorithm is needed to management, assessment, and treatment patients with hyperthyroidism and hypothyroidism, which can not only improve management efficiency, but also providing a broad application. In addition, the thyroid disorder showed a lipid metabolism tissue specificity in the Ventromedial Hypothalamus, and effect oxidative stress and energy metabolism of whole body. This review summarizes an algorithm for thyroid disease and the latest pathogenesis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition.

Cattle bile Arisaema (CBA) is a traditional medicine used for the treatment of febrile seizures (FS) for thousands of years in China. However, its application is greatly limited due to cost reasons, and pig bile Arisaema (PBA) is the main commercial product instead. Additionally, the underlying mechanism of CBA for the treatment of FS still remains unknown. In this study, we investigated the anti-convulsant effect and potential mechanism of the CBA aqueous extract for the first time through a hot-water bath-induced FS rat model. Our results showed that pre-treatment with CBA dramatically lowered the incidence rate and generation times and prolonged the latency of FS. In addition, CBA effectively ameliorated neuronal damage and regulated neurotransmitter disorder induced by FS in the rat hippocampus. The enzyme-linked immunosorbent assay, western blotting, immunohistochemical, and qRT-PCR results exhibited that CBA suppressed the expression of GFAP, TLR4, NF-κB, HMGB1, NLRP3, TNF-α, IL-1β, and IL-6 and consequently inhibited the neuroinflammation induced by FS. Interestingly, although the CBA and PBA aqueous extracts possessed the same trend on the changes caused by FS, the improvement of FS by CBA is markedly better than that by PBA. These findings indicate that CBA exerts a protective effect on febrile seizures through regulating neurotransmitter disorder and suppressing neuroinflammation.

Background:Fibromyalgia is a chronic disease characterized by widespread pain. Repetitive transcranial magnetic stimulation (rTMS) effectively relieves pain intensity in patients with fibromyalgia. The frequency and target site of rTMS have significant roles in therapy effectiveness. However, there is disagreement over the best rTMS protocol. Thus, we will conduct a thorough systematic review and network meta-analysis to rank the efficacy of these various rTMS protocols and determine which is most beneficial in lowering pain and enhancing the quality of life. Methods:Databases PubMed, Web of Science, Embase, and Cochrane Library will be searched for clinical randomized controlled trials of rTMS in fibromyalgia. The retrieval time is from the inception of the database until October 1, 2022. Following the Cochrane Handbook, 2 reviewers will independently review the literature, extract data, and evaluate the risk of bias of included articles. Pain intensity and quality of daily life are outcome indicators. Stata 17.0 and ADDIS 1.16.8 software will be used for pairwise meta-analysis and network analysis to evaluate the effectiveness of rTMS and the ranking probability of all protocols. The recommended grading assessment, development, and evaluation will be used to assess the overall quality of the evidence. Results:The meta-analysis and probability ranking of the network determined the best TMS protocol for fibromyalgia. Conclusion:This study will provide systematic support of evidence-based medicine for TMS in fibromyalgia, integrate the results of direct and indirect comparisons of the efficacy of different rTMS protocol, and provide the best one.

A UPLC-Q-TOF/MS-based metabolomics study was carried out to explore the intervening mechanism of Corallodiscus flabellatus (Craib) B. L. Burtt (CF) extract on Alzheimer's disease (AD). The AD model group consisted of senescence-accelerated mouse prone 8 (SAMP8) mice, and the control group consisted of senescence-accelerated mouse resistant 1 (SAMR1) mice. UPLC-Q-TOF/MS detection, multivariate statistical analysis, and pathway enrichment were jointly performed to research the change in metabolite profiling in the urine of AD mice. The result suggested that the metabolite profiling of SAMP8 mice significantly changed at the sixth month compared with SAMR1 mice of the same age, and the principal component analysis (PCA) score scatter plots of the CF group closely resembled those of the control and positive drug (huperzine A, HA) group. A total of 28 metabolites were considered potential biomarkers associated with the metabolism of beta-alanine, glycine, serine, threonine, cysteine, methionine, arginine, proline, and purines in AD mice. Furthermore, the CF group was clustered with the control and positive group and was clearly separated from the model group in the heat map. In conclusion, significant anti-AD effects were firstly observed in mice after treatment with the CF extract, and the urinary metabolomics approach assisted with dissecting the underlying mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE:"Treating cold syndrome with hot herbs & treating heat syndrome with cold herbs" is a fundamental medication principle of Chinese medicine. Scientists have been working hard to explore the scientific essence of this medication principle. However, researchers only focused on the herbs or syndrome individually, the intrinsic relationship between the cold/hot herbs and cold/heat syndrome received little attention. Consequently, the medication principle still lacked a scientific explanation. AIM OF THE STUDY:The aim of present study was to explore the scientific essence involved in the medication principle. MATERIALS AND METHODS:First, extracts of cold and hot herb1-7 were analyzed using UPLC-Q-TOF/MS to research the chemical composition. Second, expression of enzymes relating glucose aerobic oxidation and respiratory chain were detected to assess the metabolic state of rats in cold herb, hot herb, cold syndrome and heat syndrome groups. Lastly, metabolomic approach was utilized to screen out biomarkers and related pathways shared between the cold and hot herb groups, the cold and heat syndrome groups, as well as the herb and syndrome groups. RESULTS:The integrated results of chemistry, biochemistry and metabolomics study indicated that the cold (hot) herbs could remedy heat (cold) syndrome through inhibiting (promoting) arginine and proline metabolism and tryptophan metabolism, and the associated excessive (sluggish) material metabolism, ATP storage and generation in heat (cold) syndrome. The fundamental reason behind the differential efficacies of cold and hot herbs was the chemical composition and different contents of shared components. CONCLUSIONS:The medication principle was scientifically elucidated from perspective of material and energy metabolism. Moreover, this integrated novel strategy provides a feasible approach for future research of Chinese medicinal herb.

目的:观察右归丸联合左甲状腺素钠片治疗甲状腺功能减退症的临床疗效.方法:按照随机数字表法将80例甲状腺功能减退症患者分为治疗组和对照组各40例,对照组给予左甲状腺素钠片治疗,连续治疗3月.治疗组在服用西药的基础上加以右归丸治疗,连续治疗3月.比较2组患者的临床疗效,与治疗前后的甲状腺功能、血脂、血液流变学指标.结果:治疗组总有效率92.5％,高于对照组的80.0％,但差异无统计学意义(P＞0.05).治疗后,2组血清促甲状腺激素(TSH)均较治疗前降低,血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)均较治疗前升高,差异均有统计学意义(P＜0.05);治疗组血清TSH均低于对照组,血清FT3、FT4均高于对照组,差异均有统计学意义(P＜0.05).2组血清总胆固醇(TC)均较治疗前降低(P＜0.05),治疗组血清甘油三酯(TG)较治疗前降低(P＜0.05),对照组血清TG无明显改善(P＞0.05);治疗组血清TC、TG均低于对照组,差异均有统计学意义(P＜0.05).2组全血黏度(低切、中切、高切)、血浆黏度均较治疗前降低(P＜0.05);2组各指标比较,差异均无统计学意义(P＞0.05).结论:右归丸联合左甲状腺素钠片治疗甲状腺功能减退症具有良好的临床疗效,能够有效调节甲状腺功能、血脂及血液流变学,且不良反应少,优于单纯左甲状腺素钠片治疗.