A bibliometric and thematic analysis of the trends in the research on ginkgo biloba extract from 1985 to 2022.

Background: Ginkgo biloba extract (GBE), a complementary and alternative medicine, has been widely used for disorders such as brain infarction, dementia, and coronary heart disease, in recent decades. Given its widespread clinical use, GBE has always been a vital research topic. However, there are no bibliometric analyses on this topic; furthermore, published reviews of GBE focus only on a specific research field or lack scientific and systematic evaluation. This study combined bibliometrics with thematic reviews by visual analysis to identify the current status of GBE research and to better identify research hotspots and trends in the past 40 years to understand future developments in basic and clinical research. Methods: Articles and reviews on GBE were retrieved by topic from the Web of Science Core Collection from inception to 2022.12.01. Countries, institutions, authors, journals, references, and keywords in the field were visually analyzed using CiteSpace, Scimago Graphica, and VOSviewer software; then, these visualization results for references and keywords were clarified in detail by thematic reviews in subdivisions of the fields. Results: In total, 2015 publications were included. The GBE-related literature has high volumes of publications and citations. The majority of literature is from China, and the USA cooperates most closely with other countries. In GBE research, Christen Yves is the most cited author, Phytotherapy Research is the most prolific journal, and the Journal of Ethnopharmacology is the most co-cited journal. Through a comprehensive analysis of keywords, references, and reviews, the quality of the meta-analysis of randomized controlled clinical trials of GBE in treating dementia was evaluated by the Risk of Bias in Systematic Reviews scale (ROBIS). Current research on GBE focuses on its pharmacological mechanisms, and neuroprotective application in diseases such as Alzheimer's disease, and glaucoma. Randomized controlled trials are the current research hotspot. Conclusion: Research on GBE is flourishing; using bibliometric and thematic analysis, we identified its hotspots and trends. The pharmacological mechanisms and clinical applications of GBE are the focus of present and likely future research.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in ß-amyloid Protein-induced Alzheimer's Disease Rat Model.

OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

[Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis].

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1ß(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1ß(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1ß(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1ß(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1ß(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

[Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygium Glycosides Tablets or combined administration with methotrexate against rheumatoid arthritis].

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

Transcriptomic Analysis, Motility and Biofilm Formation Characteristics of Salmonella typhimurium Exposed to Benzyl Isothiocyanate Treatment.

Salmonella typhimurium (S. typhimurium) is a common foodborne pathogen that not only causes diseases and contaminates food, but also causes considerable economic losses. Therefore, it is necessary to find effective and feasible methods to control S. typhimurium. In this study, changes in S. typhimurium after treatment with benzyl isothiocyanate (BITC) were detected by transcriptomics to explore the antibacterial effect of BITC at subinhibitory concentration. The results showed that, in contrast to the control group (SC), the BITC-treated group (SQ_BITC) had 197 differentially expressed genes (DEGs), of which 115 were downregulated and 82 were upregulated. We screened out eight significantly downregulated virulence-related genes and verified gene expression by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). We also selected motility and biofilm formation to observe the effects of BITC on the other virulence related factors of S. typhimurium. The results showed that both swimming and swarming were significantly inhibited. BITC also had a significant inhibitory effect on biofilm formation, and showed an effect on bacterial morphology. These results will be helpful for understanding the mechanism of the antibacterial action of BITC against S. typhimurium and other foodborne pathogens.

[Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis].

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

[Clinical symptoms effect of Tripterygium Glycosides Tablets alone or combined with methotrexate in treatment of rheumatoid arthritis: a Meta-analysis].

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.

Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding.

AIM: To investigated the mechanism of the association between the TBX21 T-1993C promoter polymorphism and autoimmune hepatitis type 1 (AIH-1) development. METHODS: In vivo, In vivo, and reporter analyses were performed to determine the function of transcription factors binding to the T-1993C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor (T-bet) and interferon-γ (IFN-γ) expressions in CD4+ T cells, B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993TC and 15-1993TT genotype carriers, and healthy controls including 10-1993TC and 25-1993TT genotype carriers. Furthermore, a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients. RESULTS: TBX21-1993C allele created a strong Yin-Yang 1 (YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells. Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the -1993 TC genotype and controls with the -1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with siRNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION: The repression of TBX21 expression by high-affinity binding of YY1 to the -1993C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.

[Effect of Heixiaoyao Powder on Hippocampal Gene Expression Profile of Alzheimer's Disease Rats].

Objective To observe the effect of Heixiaoyao Powder (HP) on gene microarray profile of hippocampus in Aß23₋35 fragments induced Alzheimer's disease rat model. Methods Female SD rats were chosen to establish AD model by injecting Aß25₋35 amyloid into hippocampus ,and then they were divid- ed into 6 groups, i.e., the sham-operation group, the model group,the Western medicine (WM) group, high, middle, and low dose HP groups, 14 in each group. After 7 days of modeling, all rats were administered with respective solution at the daily dose of 3 mL/kg by gastrogavage for 28 successive days. Normal saline was administered to rats in the sham-operation group and the model group. Huperzine A Tablets wa- ter solution was administered to rats in the WM group at the daily dose of 0. 02 mL/kg. HP at the daily dose of 4. 25, 8. 50, 17. 00 g/kg was administered to rats in the low, middle, high HP groups. All rats were sacri- ficed after ending gastrogavage, and their hippocampal tissues were collected to extract tissue RNA. Rat gene microarray was used to screen differentially expressed genes, and then differentially expressed genes with partial dose-dependently changing obtained by microarry were verified by qRT-PCR. Results Compared with the sham-operation group, 538 genes were up-regulated, and 579 genes were down-regulated in the model group. mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 increased, while mRNA expressions of casq2 and bcl-2 decreased in the model group (P <0. 05). Compared with the model group, 276 genes were up-regulated, and 170 genes were down-regulated in the 3 HP groups. Of them, 71 up-regulated genes dose-dependently and 70 down-regulated genes dose-dependently. mRNA expressions of igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 in- creased in the WM group (P <0. 01). mRNA expressions of wisp1 , crebbp, igfbp-1 , znf483, zfp37, and zic4 decreased, while mRNA expressions of casq2 and bcl-2 increased in the high dose HP group (P <0. 01). mRNA expressions of crebbp, igfbp-1, znf483, zfp37, and zic4 decreased (P <0. 01, P <0. 05), while mR- NA expressions of casq2 and bcl-2 increased in the middle dose HP group (P <0. 01, P <0. 05). mRNA ex- pressions of igfbp-1 , znf483, zfp37, and zic4 decreased in the low dose HP group (P <0. 01). Compared with the middle dose HP group, mRNA expressions of crebbp, zfp37, and zic4 increased (P <0.01) , mR- NA expressions of igfbp-1 and bcl-2 decreased in the middle dose HP group (P <0. 01, P <0. 05); mRNA expressions of crebbp, znf483, and zfp37 increased (P <0. 01, P <0. 05), mRNA expressions of igfbp-1, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01). Compared with the middle HP group, mRNA expressions of casq2, zic4, and bcl-2 decreased in the low dose HP group (P <0. 01, P <0. 05). Conclusion HP could affect the occurrence of AD by regulating mRNA expressions of zfp37, znf483, and zic4, and af- fect the metabolism of Aß and abnormal phosphorylation of Tau protein by inhibiting wnt signal pathway re- lated genes such as wisp-1 , crebbp, igfbp-1 , and casq2.

[Effect of Guiqicongzhi Decoction on Expression of HSP27 and HSP70 in Brain Tissue of VD Model Rats].

OBJECTIVE: To study the effect of Guiqicongzhi Decoction on expression of HSP27 and HSP70 in brain tissue of VD model rats. METHODS: The method of "repeatedly clip carotid artery join with injection of sodium nitroprusside and with permanent unilateral carotid artery ligation" was used to prepare the vascular dementia model. And then the effect of Guiqicongzhi Decoction on the model rats from rats praxiology, histopathological and the molecules expression of heat shock protein (HSP) were observed. RESULTS: Compared with control group, the navigation incubation period extended and space search ability became worse in model group; cell number was less, contour fuzzy shrivel, cytoplasm deep stain and nuclear was not clear in hippocampus pathological section; as well as an increase in the expression of HSP27 and HSP70. The above indexes changed significantly in middle dose group and high dose group. The curative effect of middle dose group was better than piracetam. CONCLUSION: Guiqicongzhi Decoction can protect brain tissue and improve the pathological damage and memory functions of VD rats, the mechanism maybe related to the regulation of HSP27 and HSP70 expression.

[Effect of Xiaoyao Powder on the ethology, morphology, and activities of neurotransmitters of Alzheimer's disease model mice].

OBJECTIVE: To investigate the effect of Xiaoyao Powder (XP) and its compatible prescriptions on the ethology, morphology, and activities of neurotransmitters, thus exploring their effects and mechanism in preventing and treating D-galactose induced Alzheimer's disease (AD) model mice, and clarifying the compatibility mechanism for soothing Gan, nourishing blood, and invigorating Pi. METHODS: Sixty SPF mice were randomly divided into the blank control group, the model group, and the XP group, Shugan Jianpi group (SJ), Shugan Yangxue group (SY), and Jianpi Yangxue group (JY), 10 in each group.The AD mouse model was prepared by peritoneal injecting D-galactose. Meanwhile, mice in the blank control group and the model group were administered with physiological saline (at the daily dose of 24 mL/kg) by gastrogavage. Mice in the XP group (2.485 g/kg), the SY group (1.136 g/kg), the SJ group (1.775 g/kg), and the JY group (2.059 g/kg) were administered with corresponding medicated decoction by gastrogavage, with the gastric volume of 24 mL/kg. On the 41st day the training of capability for learning and memory was started. On the 42nd day capability for learning and memory was tested. The brain tissue was cut. One half was used to determine the contents of homogenate acetyl cholinesterase (AchE), choline acetyltransferase (ChAT), and monoamine oxidase (MAO).Another half was used to carry out morphological observations. RESULTS: The capability for learning and memory could be improved and the latency time could be lowered in all the treatment groups. Besides, the homogenate AchE and MAO could also be elevated, ChAT could be lowered; the morphology, number, and distribution of neurons could be improved. But the improvement of ethology, morphology, and activities of neurotransmitters were most obviously seen in the XP group. CONCLUSIONS: XP could improve the ethology, morphology, and activities of neurotransmitters, and showed better effects on prevention and treatment of AD. The rationality of compatibility methods and combination thinking ways of soothing Gan, nourishing blood, and invigorating Pi were clarified.