Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Establishment of HPLC fingerprint and content determination of multiple index components in Xiao’er resuqing oral liquid / 中国药房

OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid， and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution （gradient elution） at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， the column temperature was 30 ℃， the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to evaluate the similarity. The contents of 12 components were determined， including （R， S）-goitrin， 3，5-O-dicaffeoyl quinic acid， puerarin， forsythin， forsythoside A， chlorogenic acid， baicalin， saikosaponins d， wogonoside， baicalein， emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97， and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows： 0.078-0.172， 1.564-2.736， 1.338-2.578， 0.426-0.872， 1.477-2.628， 1.396-2.447， 4.052-9.146， 0.367- 0.692， 1.974-4.674， 1.274-2.969， 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity， which can be used for the quality evaluation of Xiao’er resuqing oral liquid.

Improvement on Quality Standard of Yuanhu Zhitong Oral Liquid / 中国实验方剂学杂志

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

Yunkang Oral Liquid Promotes Restoration of Mice from Postpartum Kidney Deficiency via TGF-β/Smads Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg-1）， medium-dose （9 mL·kg-1）， and high-dose （12 mL·kg-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E2）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E2 and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection / 中国中药杂志

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Mechanism of Simotang oral liquid in improving functional dyspepsia model rats / 中国药房

OBJECTIVE To explore the improvement effect and mechanism of Simotang oral liquid on functional dyspepsia （FD） model rats by regulating PTEN-induced putative kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin） axis. METHODS SD male rats were subjected to unpredictable chronic stress to establish an FD model， and were randomly grouped into the model group， positive control group （Domperidone tablets， 3.5 mg/kg）， Simo decoction group （Simotang oral liquid， 5.4 mL/kg）， with 20 rats in each group. The blank group without modeling was set up. Administration groups were given relevant medicine intragastrically， blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 14 d. After the last administration， the gastric emptying rate and small intestine propulsion rate of rats were detected. The contents of gastrointestinal hormones [motilin （MTL）， gastrin （GAS） and cholecystokinin （CCK）] in rats were determined； the mitochondrial structure of ICC in gastric antrum tissue of rats was observed； the immunofluorescence co-localization method was applied to observe the expression of cytochrome C oxidase Ⅳ （COX Ⅳ） and Parkin in gastric antrum tissue of rats； the protein expressions of LC3， p62， Pink1 and Parkin in gastric antrum tissue of rats were all detected. RESULTS Compared with the blank group， the gastric emptying rate， small intestinal propulsion rate， the serum contents of MTL and GAS， and protein expression of p62 in model group were all reduced significantly （P＜0.05）； the serum content of CCK， the co-localization expression of COX Ⅳ and Parkin in mitochondria， the protein expressions of LC3， Pink1 and Parkin were all increased significantly （P＜0.05）. The number of ICC mitochondria in gastric antrum tissue decreased， mitochondria became vacuolated， mitochondrial cristae were blurry， and there were more autophagic lysosomes. Compared with the model group， the above indexes of the positive control group and the Simo decoction group were reversed significantly （P＜0.05）； the mitochondrial structure of ICC gradually recovered， with clear mitochondrial cristae and reduced autophagic lysosomes. CONCLUSIONS Simotang oral liquid can improve gastrointestinal motility and gastrointestinal hormone levels in model rats， the mechanism of which may be related to inhibiting Pink1/Parkin axis and blocking autophagy.

Preparation of Baoyuan Chewable Tablets and Evaluation of Its Anti-fatigue Effect / 中国实验方剂学杂志

ObjectiveTo screen the preparation technology of Baoyuan chewable tablets and to preliminarily elucidate its anti-fatigue effect and mechanism. MethodTaking encapsulation rate of volatile oil， extract rate and extraction rate of active ingredients as indexes， single factor test and orthogonal test were used to optimize the volatile oil inclusion， aqueous decoction and formulation molding processes of Baoyuan chewable tablets. ICR rats were randomly divided into the blank group， model group， Gaoshan Hongjingtian oral liquids group（6.01 mL·kg-1） and and Baoyuan chewable tablets low， medium， and high dose groups（2.1， 4.2， 8.4 g·kg-1）， 8 mice in each group， and were administered by gastric gavage at the corresponding dose once a day， the blank and model groups were given equal volume of saline for 15 d. After the last administration for 30 min， the mice were loaded with 5% of the body mass of lead at the tail and swam until exhaustion to establish the fatigue model， and the weighted swimming time of the mice in each group was recorded， meanwhile， the muscle tissues of the mice were sliced， stained by hematoxylin-eosin（HE） and subjected to pathological observation， and the levels of blood urea nitrogen（BUN）， lactic acid（LA）， liver glycogen（LG）， activities of lactate dehydrogenase（LDH） and creatine kinase（CK） in the serum were determined. ResultThe optimal inclusion process of cinnamon oil in Baoyuan chewable tablets was 10∶1 for β-cyclodextrin-volatile oil， and inclusion at 50 ℃ for 2 h with saturated aqueous solution method. The optimal water extraction process was to extract twice， adding 10 times of water to extract for 50 min for the first time， and adding 9 times of water to extract for 40 min for the second time. The ratio of the extract of Baoyuan chewable tablets with microcrystalline cellulose， maltodextrin， mannitol， citric acid， magnesium stearate was 63∶13∶8∶17∶17∶1∶1， the tablets were pressed by wet granulation， the each tablet weight was 1.2 g， and the hardness was 60-80 N. Compared with the model group， Baoyuan chewable tablets low， medium， and high dose groups could significantly prolong the exhaustion time of mice in weight bearing swimming（P<0.05， P<0.01）， and improve the exercise endurance of the body， and the results of HE staining showed that all dose groups of Baoyuan chewable tablets could significantly improve the muscle tissue damage caused by exercise， significantly reduce the levels of BUN， LA and the activities of LDH and CK in serum（P<0.01）， and significantly increase the content of LG（P<0.05， P<0.01）. ConclusionThe optimized preparation process of Baoyuan chewable tablets is stable and feasible， and the preparation can improve exercise endurance by increasing the LG level in liver tissue， and relieve muscle soreness by accelerating the removal of LA from the body， and reduce CK and LDH activities to exert anti-fatigue effects.

Study on the mechanism of Kechuan'an Oral Liquid for the treatment of asthma / 国际中医中药杂志

Objective:To explore the mechanism of Kechuan'an Oral Liquid in treating asthma based on network pharmacology; To carry out experimental verification.Methods:The effective components and targets of Kechuan'an Oral Liquid were obtained through TCMSP and literature search. The related targets of asthma were screened by GEO database, and the intersection targets of drug and disease were selected. The PPI network was constructed by STRING database, and the GO function and KEGG pathway were enriched and analyzed for key targets by DAVID database. The rats were divided into blank control group, model group and Kechuan'an Oral Liquid group according to the method of random number table. Kechuan'an Oral Liquid group received Kechuan'an Oral Liquid 12.34 ml/kg for gavage, and blank control group and model group were perfused with distilled water of the same volume for gavage, once a day for 3 days. The asthma model of rats was prepared by atomizing the mixture of acetylcholine chloride and histamine phosphate, and HE staining was used to observe the pathological changes of lung tissue; Western blot was used to detect the protein expressions of IL-6, TLR4, MyD88 and TAK1, and the network pharmacological prediction results were verified.Results:A total of 153 active components, 1 896 targets and 2 982 differentially expressed genes of Kechuan'an Oral Liquid were screened out, and 25 intersection targets of drugs and diseases were obtained. The enrichment results showed that toll-like receptor signaling pathway, TNF signaling pathway and Nod-like receptor signaling pathway were the main mechanisms of immune inflammation. Compared with the control group, the lung tissue of rats in the model group showed morphological changes such as thickening of air duct wall and infiltration of inflammatory cells, which were significantly improved in the Kechuan'an Oral Liquid group. Compared with the control group, the expressions of IL-6, TLR4, MyD88 and TAK1 in the model group significantly increased ( P<0.01), and compared with model group, the expressions of IL-6, TLR4, MyD88 and TAK1 in Kechuan'an Oral Liquid group significantly decreased ( P<0.05 or P<0.01). Conclusion:Kechuan'an Oral Liquid can inhibit toll-like receptor signaling pathway and mediate anti-inflammatory effect to treat asthma.

Clinical Efficacy of Chonglian Oral Liquid on COVID-19 Patients / 中国实验方剂学杂志

ObjectiveTo observe the effect of Chonglian oral liquid on inflammatory and immune markers as well as the clinical outcomes of patients with mild-to-moderate corona virus disease 2019（COVID-19） and comprehensively evaluate its efficacy and safety. MethodA clinical randomized controlled trial （RCT） was conducted， involving 120 confirmed cases of mild-to-moderate COVID-19. The patients were randomly divided into two groups， with 55 cases in the observation group and 56 cases in the control group. According to the updated diagnosis and treatment protocol， the control group received standard western medical treatment， while the observation group received Chonglian oral liquid in addition to standard western medical treatment. Both groups were treated continuously for 10 days. The traditional Chinese medicine （TCM） syndrome scores， syndrome efficacy， fever abatement time， nucleic acid negative conversion time， inflammatory and immune markers， improvement in imaging findings， clinical outcomes， and occurrence of adverse events were compared between the two groups. ResultBoth groups showed a significant decrease in TCM syndrome scores after treatment （P<0.01）. Compared with the control group after treatment， the observation group exhibited a more significant improvement in cough， dry throat， sore throat， fatigue， and muscle pain （P<0.05）. The total effective rate in the observation group was 100% （55/55）， significantly higher than 98.21% （55/56） in the control group （Z=3.707， P<0.01）. The observation group also showed a significantly shorter duration of fever abatement and nucleic acid negative conversion compared with the control group after treatment （P<0.05）. Both groups had a significant increase in lymphocyte count （LYM）， lymphocyte percentage （LYM%）， mature T lymphocytes （CD3+）， and helper/inducer T lymphocytes （CD4+） after treatment （P<0.01）. Compared with the control group after treatment， the observation group showed greater improvement in these markers （P<0.05）. In terms of inflammatory markers， both groups had a significant decrease compared with those before treatment （P<0.01）. The observation group exhibited lower levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， and procalcitonin （PCT） than the control group after treatment （P<0.05）. There was no statistically significant difference in imaging efficacy evaluation and clinical outcomes between the two groups. No adverse events were reported in either group during the treatment period. ConclusionChonglian oral liquid combined with standard western medical treatment significantly improves clinical symptoms， shortens fever abatement and nucleic acid negative conversion time， regulates immune function， and inhibits inflammatory responses in patients with mild-to-moderate COVID-19， leading to improved clinical efficacy.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Diquafossol sodium combined with Qingrun Yangmu oral liquid for the treatment of dry eye after cataract operation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of diquafosol sodium(DQS)eye drops combined with Qingrun Yangmu oral liquid in the treatment of dry eye after phacoemulsification and intraocular lens implantation.METHODS:A total of 57 patients(65 eyes)with dry eye after cataract surgery, who were admitted to the ophthalmology department of our hospital from September 2020 to January 2021, were selected as the research objects. They were divided into a control group(28 cases, 32 eyes, treated with 3% DQS eye drops)and an observation group(29 cases, 33 eyes, treated with 3% DQS eye drops combined with the Qingrun Yangmu oral liquid)based on a random number table method. Indicators, such as ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), Schirmer I test(SIt), corneal fluorescein sodium staining(CFS), and TCM symptom score, were compared and analyzed between the two groups 1d before, 1wk after(before treatment), and 1mo after(after treatment)surgery.RESULTS:The total effective rates of the observation group and the control group after treatment were 88% and 75%, respectively. The OSDI, NIBUT and SIt of the two groups after treatment showed significant improvement compared to those before treatment(P&#x003C;0.05). The NIBUT, SIt, CFS, and TCM symptom scores of the observation group after treatment were better than those of the control group(P&#x003C;0.05). No adverse reactions were observed in both groups.CONCLUSION:Combined use of DQS eye drops and the Qingrun Yangmu oral liquid can improve symptoms and clinical indicators of dry eye after cataract surgery, providing a new treatment method for ocular surface management of dry eye during the perioperative period of cataract surgery.

Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Efficacy and safety of Tianmeng Oral Liquid in the treatment of hyperprolactinemia caused by antipsychotics in female patients with schizophrenia： a Meta-analysis / 四川精神卫生

ObjectiveTo systematically evaluate the efficacy and safety of Tianmeng Oral Liquid in the treatment of hyperprolactinemia caused by antipsychotics in female patients with schizophrenia， and to provide references for intervention of antipsychotic-induced hyperprolactinemia patients. MethodsEnglish databases （PubMed， Cochrane Library， PsycINFO and Embase） and Chinese databases （CNKI and Wanfang） were systematically searched， with a search time frame of the period from database creation to September 16， 2022. Randomized controlled studies （RCTs） on adjunctive Tianmeng Oral Liquid in the treatment of hyperprolactinemia caused by antipsychotics in female patients with schizophrenia were included. Three investigators independently screened the literatures and extracted data according to PICOS principles and evaluated the quality of including literatures， and the Meta-analysis was performed by using RevMan 5.3. ResultsA total of 3 articles including 256 female schizophrenic patients with hyperprolactinemia were included. Meta-analysis results showed that at the treatment endpoint， the improvement of hyperprolactinemia symptoms reported a significant superiority of the intervention group than the control group （RR=1.73， 95% CI： 1.07~2.79， P˂0.05）. Similarly， the significant superiority of the intervention group than the control group were also found in reducing serum prolactin levels （WMD=-55.17， 95% CI： -68.16~-42.18， P<0.01） and Positive and Negative Syndrome Scale （PANSS） total scores were lower in the intervention group than in the control group （WMD=-7.36， 95% CI： -8.94~-5.77， P<0.01）. ConclusionTianmeng Oral Liquid may help improve clinical efficacy and reduce serum prolactin levels in female schizophrenia patients with hyperprolactinemia. It may improve psychiatric symptoms in female patients with schizophrenia.

A Multicenter Clinical Trial of Pudilan Anti-inflammatory Oral Liquid of Different Doses in Treatment of Acute Pharyngitis/Tonsillitis Caused by Bacterial Infection in Adults / 中国实验方剂学杂志

ObjectiveThrough a randomized， double-blind， double-simulation， positive-control， multicenter design， this study aimed to analyze the relationship between the dosage， efficacy， and safety of Pudilan anti-inflammatory oral liquid in treating acute pharyngitis/tonsillitis in adults caused by bacterial infection and validate the regulatory effect of Pudilan anti-inflammatory oral liquid on inflammatory markers such as serum amyloid A （SAA）， C-reactive protein （CRP）， white blood cells （WBC）， neutrophil percentage （NE%）， and erythrocyte sedimentation rate （ESR）， thereby exploring the feasibility of using Pudilan anti-inflammatory oral liquid as a substitute for antibiotics in the treatment of infectious diseases and providing a basis for rational clinical medication. MethodUsing a stratified randomized， double-blind， double-simulation， positive-control， multicenter design， 220 participants were enrolled from nine centers. The participants were randomly divided into three groups at 1∶1∶1 — a Pudilan anti-inflammatory oral liquid 20 mL group （73 cases）， a Pudilan anti-inflammatory oral liquid 10 mL group （73 cases）， and a control group （amoxicillin group， 74 cases）. The treatment course was 7 days. The study observed parameters including the total effective rate of sore throat， onset and disappearance time of sore throat， health status score， treatment time， and inflammation markers. Result①Dataset division： The 211 cases were included in the full analysis dataset （FAS）， 208 cases were included in the per-protocol dataset （PPS）， and 218 cases were included in the safety dataset （SS）. ② Efficacy evaluation： There were statistically significant differences （P<0.05） in the comparison of the three groups regarding the total effective rate of sore throat， disappearance time of sore throat， and health status. Both the 20 mL and 10 mL groups were non-inferior to the control group， and there was a statistically significant difference between the 20 mL and 10 mL dosage groups （P<0.05）. There was no statistically significant difference in the comparison of onset time of sore throat among the groups. CRP， WBC， and NE% of patients in all three groups significantly decreased on the 7th day of treatment compared with those before treatment （P<0.01）. ③Safety evaluation： Adverse events mainly occurred in various examination indicators. There were no statistically significant differences in the comparison between groups， and no adverse reactions or serious adverse events occurred. ④Economic evaluation： The increased cost of the 10 mL and 20 mL dosage groups was entirely justified as compared with that in the control group. When comparing the 10 mL and 20 mL dosage groups， the 10 mL dosage group was deemed less advantageous. ConclusionPudilan anti-inflammatory oral liquid can be used alone as an alternative to antibiotics in the treatment of acute pharyngitis/tonsillitis caused by bacterial infection. It demonstrates good safety and can lower inflammation markers such as CRP， WBC， and NE%， suggesting its potential to reduce the body's inflammatory response. Its mechanism of action may be related to its multi-target regulatory mechanism.

Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults / 中国中药杂志

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Analysis of chemical components of Changtong oral liquid by UHPLC-Orbitrap HRMS / 中国药房

OBJECTIVE To identify the chemical components of Changtong oral liquid （CTOL），and to provide reference for the basic research and secondary development of its pharmacological substances. METHODS UHPLC-Orbitrap HRMS technique was adopted. CTOL sample was separated on a Hypersil Gold column with mobile phase consisted of 0.1% formic acid （containing 5 mmol/L ammonium formate）-acetonitrile （gradient elution）. The eluent was detected in positive and negative ion modes using an electrospray ionization source. The data was processed by Xcalibur 4.3 and Compound Discoverer 3.3 software. The primary and secondary mass spectra data of each compound were collected. The unknown compounds were identified according to the mass spectrometry library of the instrument and the network databases mzCloud，mzVault，etc. Through matching with the pharmacology database and analysis platform of the traditional Chinese medicine system，the chemical components could be attributed to the traditional Chinese medicine. RESULTS Fifty-three chemical components were identified and analyzed from CTOL，such as 24 flavonoids，8 quinones，5 phenylpropanoids，4 sugars and glycosides，5 organic acids，3 amino acids，1 alkaloid，1 phenolic and 2 other compounds. Among them，12 components were derived from Salvia miltiorrhiza，9 from Citrus aurantium，7 from Rheum palmatum，4 from Angelica sinensis，1 from Magnolia officinalis，16 from Glycyrrhiza uralensis，and 4 from many kinds of medicinal materials. CONCLUSIONS CTOL mainly contains flavonoids，quinones and phenylpropanoid compounds，and its chemical components mainly come from G. uralensis，S. miltiorrhiza and C. aurantium.

Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway / 中国天然药物

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency.@*METHODS@#This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded.@*RESULTS@#TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment.@*CONCLUSIONS@#The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.