CiteSpace knowledge map analysis of Angong Niuhuang Pills in recent twenty years / 中国中药杂志

Angong Niuhuang Pills, a classical formula in traditional Chinese medicine, are lauded as one of the "three treasures of febrile diseases" and have been widely used in the treatment of diverse disorders with definite efficacy. However, there is still a lack of bibliometric analysis of research progress and development trend regarding Angong Niuhuang Pills. Research articles on Angong Niuhuang Pills in China and abroad(2000-2022) were retrieved from CNKI and Web of Science. CiteSpace 6.1 was used to visualize the key contents of the research articles. In addition, the research status of Angong Niuhuang Pills was analyzed by information extraction to allow insight into the research trends and hotspots about Angong Niuhuang Pills. A total of 460 Chinese articles and 41 English articles were included. Beijing University of Chinese Medicine and Sun Yat-Sen University were the research institutions that have published the largest amount of research articles in Chinese and English. The keyword analysis showed that the Chinese articles focused on cerebral hemorrhage, stroke, neurological function, coma, cerebral infarction, craniocerebral injury, and clinical application, while the English articles focused on the mechanisms of cerebral ischemia, stroke, heavy metal, blood-brain barrier, and oxidative stress. Stroke, blood-brain barrier, and oxidative stress were presumably the research hotspots in the future. At present, the research on Angong Niuhuang Pills is still in the developing stage. It is necessary to highlight the in-depth research on the active components and mechanism of action and carry out large-scale randomized controlled clinical trials to provide references for the further development and application of Angong Niuhuang Pills.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Systematic review of efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage. CNKI, VIP, Wanfang, CBM, PubMed, EMbase, Cochrane Library were retrieved to collect the randomized controlled trial(RCT) from the time of database establishment to November 2020. Two researchers screened out the literatures and extracted the data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. A total of 13 RCTs were included, involving 1 196 patients with cerebral hemorrhage, with 599 in the treatment group and 597 in the control group, and all of them were treated with internal medicine. The results of Meta-analysis showed that compared with conventional therapy, the combined administration with Angong Niuhuang Pills could improve the effective rate in patients with cerebral hemorrhage(RR=1.25, 95%CI[1.18, 1.34], P<0.000 01), the National Institutes of Health stroke scale(NIHSS)score(MD=-5.18, 95%CI[-8.12,-2.23], P=0.000 6) and Glasgow coma scale(GCS) score(MD=1.12, 95%CI[0.46, 1.78], P=0.000 9), activity of daily living(ADL)(MD=15.70, 95%CI[14.05, 17.36 ], P<0.000 01), reduce the malondialdehyde(MDA)(MD=-1.73,95%CI[-2.81,-0.64],P=0.002), but with no statistically significant difference in hematoma volume changes between the two groups. In terms of safety, the combined administration with Angong Niuhuang Pills reduced the incidence of adverse reactions compared with the single administration of conventional therapy(RR=0.40, 95%CI[0.28, 0.57], P<0.000 01), with no serious adverse events. The existing clinical study evidences show that Angong Niuhuang Pills had a good effect in adjuvant treatment of cerebral hemorrhage, and can improve the treatment efficacy, activity of daily living and symptoms of neurological deficits, and reduce oxidative stress, with a higher safety. However, the methodological quality of the included studies is not high, so the above conclusions still need to be verified with more high-quality studies.

UPLC characteristic fingerprint and chemical pattern recognition of Angong Niuhuang Pills / 中国中药杂志

To establish the UPLC fingerprint of Zhongyi Angong Niuhuang Pills, in order to evaluate its quality by chemical pattern recognition. The method was developed on a column of Poroshell 120 EC-C_(18), with methanol-0.1% formic acid solution as the mobile phase for gradient elution at a flow rate of 0.4 mL·min~(-1). The column temperature was 30 ℃,and the detective wavelength was 254 nm. The similarity of 24 batches of Angong Niuhuang Pills was compared by using Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2004 A). Hydrophobic cluster analysis,principal components analysis and partial least squares discriminant analysis were conducted by using SIMCA 13.0 software to investigate different components among these products. The UPLC characteristic fingerprint was established in this study. And 17 common peaks were identified by standard reference and UPLC-MS. The similarity of 24 batches samples were above 0.980,which can be classified into three categories for pattern recognition. Baicalin,berberine,jatrorrhizine,wogonin and wogonoside were identified as the main markers that cause differences of various batches. The method is simple,rapid,accurate and reproducible,and can provide scientific basis for improving the quality standard of Zhongyi Angong Niuhuang Pills.

Quality characterization of Angong Niuhuang Pills based on characteristic spectrum of natural musk/bezoar and four herbal medicines / 中草药

Objective: To establish an Angong Niuhuang Pills (ANP) characteristic spectrum analysis method, and to comprehensively characterize the quality properties and characteristics of ANP, and then to apply it to the quality detection and analysis of 10 batches of ANP, and to find out the specificity of the quality characterization of ANP. Methods: The UPLC-PDA multi-wavelength was used in the method, and a Waters Cortecs shields RP18 Column (100 mm × 2.1 mm, 1.6 μm) was used, the mobile phase was acetonitrile and 0.3% phosphoric acid solution, the detection wavelength was set at 240, 262, 330, 360, 274, and 440 nm, the column temperature was kept at 38 ℃, and the flow rate was 0.2 mL/min. Results: The results showed that the established analytical method can simultaneously determine 13 index components (including geniposide, genipin1-gentiobioside, crocin I, crocin II, berberine hydrochloride, coptis hydrochloride, palmatine chloride, epiberberine, baicalin, wogonoside, baicalein, wogonin and curcumin) in ANP, and a total of 35 characterstic peaks were identified in ANP. It included natural musk characteristic peak and natural bovis calculus characteristic peak which can identify the natural properties of raw materials. The mean values of the 13 index components in 10 batches of ANP were 2.87, 1.14, 0.40, 0.03, 3.17, 0.94, 0.74, 0.58, 10.01, 1.62, 0.34, 0.17, 0.05 mg/g, respectively. The RSD values ranged from 4.19% to 20.81%. All the 10 batches of ANP could be detected with 35 characteristic peaks, the average area values of natural musk and natural bovis calculus characteristic peaks were 0.031 and 0.003, and the RSD values ranged from 1.5% to 26.79%. Conclusion: According to the analysis of characteristic spectrum, the quality of finished products of 10 batches of ANP was relatively stable, and all showed the specific quality characterization of raw materials of natural musk, natural bovis calculus and Curcumae Radix; According to the analysis of the content of index components, the large fluctuation of the index components in 10 batches of samples mainly comes from Scutellaria baicalensis and Curcumae Radix, while the content of crocin I in Gardeniae Fructus and four alkaloids in Coptidis Rhizoma were relatively stable.

HPLC fingerprint and multi-components determination combined with chemical pattern recognition of Angong Niuhuang Pills / 中草药

Objective: To establish the HPLC fingerprint of Angong Niuhuang Pills (ANP) and determine the contents of six compounds with analysis of their quality by chemical pattern recognition. Methods: The separation was performed with acetonitrile-0.1% phosphoric acid aqueous solution as the mobile phase, and the detection wavelength was set at 230 nm. Twelve batches of samples were collected from four different companies and analyzed using the evaluation system of traditional Chinese medicine chromatographic fingerprint similarity, and chemometric Methods:. The content of the main effective components of geniposidic acid, geniposide, berberine hydrochloride, baicalin, wogonosidc, and wogonin were determined. The samples of different companies were analyzed by chemical pattern recognition. Results: The similarity of fingerprints was above 0.9, the content of six kinds of main effective components showed that there were some differences in the 12 batches of products, especially the composition of Scutellaria baicalensis. The results indicated that the quality of S. baicalensis was not stable. Among them, the contents of baicalin, wogonosidc and wogonin of company were more stable than other companies, and even higher than other companies. The samples can be sorted according to their quality through the F score of the PCA. The results showed that the samples of C company in the comprehensive ranking ranked more forward, which were consistent with the quantitative results. Conclusion: Fingerprints combined with chemical pattern recognition can comprehensively response the quality of ANP, providing the experiments basis of reasonable controlling the quality of preparation.

Study on the GC Fingerprint of Angong Niuhuang Pills / 中国药师

Objective:To establish the GC fingerprint chromatography of Angong Niuhuang pills. Methods: An HP-50 quartz capillary column was used,and the temperature injector and detector was 300℃. The column temperature was programmed raised,and the flow rate was 1.0 ml·min-1. Totally 10 batches of samples were analyzed and the GC fingerprint of Angong Niuhuang pills was es-tablished. Results:Totally 9 common peaks were marked in the fingerprint and the similarity of Angong Niuhuang pills was above 0.9. Conclusion:The method is simple,accurate and fast, which provides experimental basis for the quality control of Angong Niuhuang pills.

Therapeutic effects of Angong Niuhuang Pills on cerebrovascular diseases in Zebrafish models / 药物评价研究

Objective To investigate preventive and therapeutic effects ofAngong Niuhuang Pills (ANP) on cerebrovascular diseases in Zebrafish models.Methods Zebrafish cerebral hemorrhage was induced by treatment with simvastatin,thrombosis by arachidonic acid,blood vessel loss by simvastatin,and Alzheimer's disease (AD) by A1C13.Zebrafish models were treated with ANP by direct drug soaking at various concentrations.Results ANP had a significantly preventive effect on Zebrafish cerebral hemorrhage with an efficacy of 11％,41％,and 48％ at concentrations of 27.8,83.3,and 250 μg/mL,respectively,and the incidence of cerebral hemorrhage in 83.3 and 250 g/mL groups decreased significantly compared with model group (P ＜ 0.001).Compared with model group,the red cell staining intensity of Zebrafish in 333 and 1 000 g/mL groups increased significantly (P ＜ 0.001),and the thrombus prevention rates of 111,333,and 1000 g/mL groups were 5％,33％,and 64％ respectively.Compared with model group,the intestinal vascular area of Zebrafish in ANP 11.1,33.3,and 100.0 μg/mL groups increased significantly (P ＜ 0.001),and the rate of angiogenesis was 21％,25％ and 26％ respectively.ANP promoted dyskinesia recovery by 48％,88％,and 78％,and improved response efficiency by 15％,82％ and 75％,respectively in AD zebrafish at concentrations of 111,333,and 1000 μg/mL.Conclusions Our results in this study support ANP as a preventive and therapeutic medicine for cerebral hemorrhage,cerebral ischemia,thrombosis and AD.

Therapeutic effects of Angong Niuhuang Pills on cerebrovascular diseases in Zebrafish models / 药物评价研究

Objective To investigate preventive and therapeutic effects ofAngong Niuhuang Pills (ANP) on cerebrovascular diseases in Zebrafish models.Methods Zebrafish cerebral hemorrhage was induced by treatment with simvastatin,thrombosis by arachidonic acid,blood vessel loss by simvastatin,and Alzheimer's disease (AD) by A1C13.Zebrafish models were treated with ANP by direct drug soaking at various concentrations.Results ANP had a significantly preventive effect on Zebrafish cerebral hemorrhage with an efficacy of 11％,41％,and 48％ at concentrations of 27.8,83.3,and 250 μg/mL,respectively,and the incidence of cerebral hemorrhage in 83.3 and 250 g/mL groups decreased significantly compared with model group (P ＜ 0.001).Compared with model group,the red cell staining intensity of Zebrafish in 333 and 1 000 g/mL groups increased significantly (P ＜ 0.001),and the thrombus prevention rates of 111,333,and 1000 g/mL groups were 5％,33％,and 64％ respectively.Compared with model group,the intestinal vascular area of Zebrafish in ANP 11.1,33.3,and 100.0 μg/mL groups increased significantly (P ＜ 0.001),and the rate of angiogenesis was 21％,25％ and 26％ respectively.ANP promoted dyskinesia recovery by 48％,88％,and 78％,and improved response efficiency by 15％,82％ and 75％,respectively in AD zebrafish at concentrations of 111,333,and 1000 μg/mL.Conclusions Our results in this study support ANP as a preventive and therapeutic medicine for cerebral hemorrhage,cerebral ischemia,thrombosis and AD.

Effects of Angong-niuhuang pill on expression of eNOSmRNA in spontaneously hypertensive rats after intracerebral hemorrhage / 国际中医中药杂志

Objective To study the effect of Angong-niuhuang pill on expression of eNOSmRNA in spontaneously hypertensive rats after intracerebral hemorrhage and to explore it's protective mechanism.Methods 120 spontaneously hypertensive rats were randomly divided into four groups: model group, western medicine treated group. Angong-niuhuang pill treated group, combining traditional Chinese medicine western medicine group, expression of eNOSmRNA in rat brain tissue was detected by RT-PCR. Results Expression of BCL-2mRNA in combining traditional Chinese medicine western medicine group was significantly higer than other goups(P＜0.01), Compared with model group, the expression of BCL-2mRNA in western medicine treated group and Angong-niuhuang pill treated group was markedly increased (P＜0.01), the differences between Angong-niuhuang pill treated group and Western medicine treated group were not obvious (P＞0.05).Conclusion Protective effect of Angong-niuhuang pill on spontaneously hypertensive rats after intracerebral hemorrhage is related to the the inducement of eNOS expression.