Fructus Xanthii and Magnolia liliiflora Volatile Oils Liposomes-Loaded Thermosensitive in situ Gel for Allergic Rhinitis Management.

Purpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration. Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed. Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects. Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.

Effects of Wuzhi Capsule on Whole-Blood Tacrolimus Concentration Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: Wuzhi Capsule (WZC) is a traditional Chinese medicinal herb widely used to treat drug-induced hepatitis or liver dysfunction and is usually prescribed in China to increase tacrolimus concentration. Several studies with small sample sizes have shown that WZC can increase tacrolimus concentration levels in clinical practice. This study aimed to evaluate the effect of WZC on whole-blood tacrolimus concentration levels and safety. METHODS: We searched 7 databases for randomized clinical trials (RCTs) and observational studies (OSs) comparing whole-blood tacrolimus concentration levels between WZC and non-WZC treatments. Data analysis was performed using Review Manager version 5.3. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. RESULTS: Eleven studies involving 6 RCTs and 5 OSs were included. The meta-analysis indicated that whole-blood tacrolimus concentration levels in the WZC group was significantly higher than that of the non-WZC group [weighted mean difference = 1.38, 95% CI (confidence interval), 1.21-1.56, P < 0.001], and similar results were shown in all the subgroups of follow-up time, different primary disease, and different WZC doses. In the self-control OSs, the whole-blood tacrolimus concentration levels in the WZC group was significantly higher than the non-WZC group (weighted mean difference = 1.17, 95% CI, 0.71-1.64, P < 0.001). WZC was generally well tolerated and there was no significant difference in the incidence of adverse reactions between the 2 groups. CONCLUSIONS: WZC can increase whole-blood tacrolimus concentration levels. This may be an economical and practical treatment choice for patients, especially those with poor oral tacrolimus absorption capabilities. Nevertheless, RCTs and OSs with large sample sizes and high quality are needed in the future to confirm these positive results.

Efficacy and safety of standardized Ginkgo biloba L. leaves extract as an adjuvant therapy for sudden sensorineural hearing loss: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. has been used for medical purposes in China for centuries. Standardized Ginkgo biloba L. leaves extract (GBE) is a widely used botanical drug which displays a variety of pharmacological effects against sudden sensorineural hearing loss (SSNHL). AIM OF THE STUDY: To evaluate the efficacy and safety of GBE as an adjuvant therapy, administered with corticosteroids, for the initial management of patients with SSNHL. MATERIALS AND METHODS: We searched seven databases for randomized clinical trials (RCTs) comparing GBE plus corticosteroids with corticosteroids alone for SSNHL treatment. Data analysis was carried out by Review Manager 5.4 and Stata 16.0 software. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. We subsequently evaluated the certainty of evidence using the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: A total of 11 RCTs involving 1069 patients were included. Meta-analysis indicated that the clinical cure rate (RR = 1.33, 95% CI = 1.12 to 1.58, P = 0.001) and total effective rate (RR = 1.24, 95%CI = 1.17 to 1.31, P < 0.001) in SSNHL patients receiving GBE plus corticosteroids was superior to patients receiving corticosteroids alone. After treatment, pure tone average (PTA) improvement of observation group was better than that in the control group (WMD = 10.33, 95%CI = 6.46 to 14.21, P < 0.001). The levels of whole blood high shear viscosity (WMD = 0.93, 95%CI = 0.28 to 1.59, P = 0.005), whole blood medium shear viscosity (WMD = 0.53, 95%CI = 0.11 to 0.95, P = 0.01), whole blood low shear viscosity (WMD = 1.26, 95%CI = 0.80 to 1.72, P < 0.001), plasma viscosity (WMD = 0.19, 95%CI = 0.09 to 0.30, P < 0.001) and fibrinogen (WMD = 0.80, 95%CI = 0.25 to 1.35, P = 0.004) were lower than those in the control group. There was no significant difference in the change of hematokrit between two groups (WMD = 4.23, 95%CI = -0.54 to 8.99, P = 0.08). GBE was generally well tolerated, and there was no significant difference in the incidence of adverse reactions between two groups (RR = 1.01, 95%CI = 0.57 to 1.79, P = 0.97). CONCLUSION: The results of the current study suggested that GBE might be effective and promising as an adjuvant to corticosteroids in the initial treatment of moderate to profound SSNHL. However, the GRADE assessment indicated that the overall strength of evidence was not high. Further studies with high methodological quality and low risk of bias are needed to confirm the positive results. PROSPERO registration No. CRD 42020190113.

Therapeutic Drug Monitoring and Pharmacogenetic Testing in Northern China.

Background: Therapeutic drug monitoring (TDM) and pharmacogenetic (PGx) testing are widely used as approaches to improve individualized (personalized) pharmacotherapy. Little is known about TDM and PGx testing services in China. This study is aimed to describe the TDM and PGx testing services in northern China, and to lay the foundation for improving these services. Methods: We developed an electronic survey using online software and disseminated it to 32 public hospitals in northern China from May to July 2019. The data were analyzed using the Statistical Package for Social Sciences (SPSS) program (Ver.27.0). Results: We collected 29 of the 32 questionnaires (90.6% response rate) from public hospitals in seven provinces of northern China. Twenty-two public hospitals (76%) utilized TDM; immune suppressants, antiepileptic drugs and anti-infective drugs were the main drugs monitored. The hospitals that did not provide TDM service were traditional Chinese medicine hospitals and hospitals with a smaller number of hospital beds. Seventeen public hospitals (58.6%) had PGx testing programs. The hospitals that did not offer PGx testing service had a smaller number of hospital beds and had fewer daily outpatients. Conclusion: TDM is available in the vast majority of public hospitals in northern China, although mainly in tertiary hospitals. PGx testing, a newer approach, is less widely available. We recommend that more hospitals be encouraged to provide TDM and PGx testing services and more efforts be directed toward quality control, delivery of results and counseling of patients based on those results.

Anaphylaxis effect and substance basis of honeysuckle extract.

Objective: To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle. Methods: Rat peritoneal mast cells (PMC) were separated and purified, the cells were incubated with compound 48/80 (0.02 g/L), physiological saline and honeysuckle extract (120 g/L) at 37 °C for 0, 15, 30, 45 and 60 min. Degranulation were observed by optical microscope and transmission electron microscope. Annexin V positive cell rate was detected by flow cytometry to reflect the degranulation rate of PMC. SD rats were supplied with honeysuckle extract by intravenous injection at a dose of 2.25 g/L. After administration, different parameters were analyzed, including the symptoms, histamine (HIS) and tryptase (MCT) levels, which were determined to explore the effect of anaphylaxis. Regression analysis was used to calculate the relationships between the peaks and the pharmacological effects to explore potentially anaphylactoid components. Results: The percentage of Annxin V positive cells and the degranulation ratio were markedly elevated in PMC treated with honeysuckle extract for more than 15 min (P < 0.05). HIS and MCT level were significantly elevated after injection of honeysuckle extract for more than 15 min. Morphology of PMC and systemic symptoms were also changed compared with the controlled group (P < 0.05). Regression analysis was used to calculate the relationship between peaks and pharmacological effects, and to determine peaks 7, 10 and 13 as possible anaphylactoid ingredients. Conclusion: This study established a prospective method to clarify the anaphylactoid components of honeysuckle extract, which would provide guidance for screening anaphylactoid components in traditional Chinese medicine injections containing honeysuckle in the prescription.

Using Spectrum-Effect Relationships Coupled with LC-TOF-MS to Screen Anti-arrhythmic Components of the Total Flavonoids in Hypericum attenuatum Extracts.

This research explored the HPLC fingerprints of Hypericum attenuatum Choisy, which has anti-arrhythmic activity. HPLC was adopted to perform a determination of chemical fingerprints of H. attenuatum specimens acquired through seven distinct sources. The anti-arrhythmic activity of each H. attenuatum sample was obtained through pharmacodynamics experiments in animals. A regression analysis and correlation analysis were utilized to calculate the relationship of the peak and pharmacological effectiveness with the identified peak. Peaks numbered 5, 7, 13 and 14 in the fingerprint were regarded as the likely anti-arrhythmic agents. The fingerprint was compared with reference standards for identification of the correlative peaks. Liquid chromatography-time-of-flight-mass spectrometry was applied to identify its structure. As a consequence, a universal model was established for the utilization of HPLC to investigate anti-arrhythmic activity and the spectrum-effect relationship among H. attenuatum. This model is available for the discovery of the major bioactive constituents of Hypericum.

Screening anaphylactoid components of Shuang Huang Lian Injection by analyzing spectrum-effect relationships coupled with UPLC-TOF-MS.

Shuang Huang Lian Injection (SHLI) has been used in China for over 30 years as an effective and widely used Chinese herbal prescription to treat acute respiratory infectious. SHLI has, however, caused many severe anaphylactoid reactions. It is important to identify the potential anaphylactoid components of SHLI. Spectrum-effect relationships were used to explore potentially anaphylactoid components. Based on the original herbal formula, honeysuckle, Fructus Forsythiae and Radix Scutellariae extracts were prepared and combined in appropriate proportions. The preparations were then injected into the caudal vein of rats to obtain in vivo serum samples for pharmacological evaluation and fingerprint analysis. The release rate of ß-hexosaminidase from RBL-2H3 cells and plasma histamine level was used as the pharmacological index. Chromatographic fingerprint analysis identified 22 common peaks. Regression analysis and correlation analysis were used to calculate the relationships between the peaks and the pharmacological effects and identified peaks 5, 6, 11, 12 and 17 as likely anaphylactoid agents. The correlated peaks were identified by comparing the fingerprints with in vitro samples and reference standard samples and the structure was identified by UPLC-TOF-MS. This study established a prospective method to clarify the anaphylactoid components in SHLI, which would provide guidances for screening anaphylactoid components in other traditional Chinese medicine injections.

Meta-analysis of the efficacy and safety of structured triglyceride lipid emulsions in parenteral nutrition therapy in China.

BACKGROUND & AIMS: We performed a meta-analysis of data from recent studies to evaluate the safety and efficacy of parenteral nutrition (PN) with structured triglyceride (STG) lipid emulsions compared to medium-chain triglyceride (MCT)/long-chain triglyceride (LCT) lipid emulsions in Chinese patients. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Internet, Wanfang, and VIP were searched for randomized controlled trials comparing STGs with MCTs/LCTs published in English or Chinese between January 1987 and October 2017. Two independent investigators screened and selected studies according to prespecified selection criteria. Data were pooled and analysed using RevMan® version 5.3. RESULTS: Thirty-two studies comprising 1944 patients were included in the meta-analysis. Compared with MCT/LCT emulsions, STGs resulted in a shorter hospital length of stay (LOS) (weighted mean difference [WMD], -1.65 days; 95% confidence interval [CI]: -2.63, -0.67; P = 0.001) and lower adverse event rates (relative risk, 0.64; 95% CI: 0.48, 0.85; P = 0.002). STGs were associated with a significantly better cumulative nitrogen balance (WMD, 4.04 g/24 h; 95% CI: 3.10, 4.97; P < 0.0001) as well as higher concentrations of pre-albumin (WMD 35.20 mg/L; 95% CI: 26.59, 43.81; P < 0.0001) and albumin (WMD, 1.64 g/L; 95% CI: 1.17, 2.10; P < 0.0001) compared with MCTs/LCTs. In contrast, significantly lower concentrations of plasma triglycerides (WMD, -0.21 mmol/L; 95% CI: -0.30, -0.12; P < 0.0001), total cholesterol (WMD, -0.45 mmol/L; 95% CI: -0.60, -0.29; P < 0.0001), alanine aminotransferase (WMD, -7.68 IU/L; 95% CI: -9.68, -5.68; P < 0.0001) and aspartate aminotransferase (WMD, -10.27 IU/L; 95% CI: -16.05, -4.49; P = 0.0005) were observed in patients receiving STGs compared with MCT/LCTs. STGs were also associated with reduced inflammation and improved immunological function, as reflected by significantly lower C-reactive protein concentrations (WMD, -2.67 mg/L; 95% CI: -4.55, -0.79; P = 0.005) and increased concentrations of IgG (WMD, 2.11 g/L; 95% CI: 0.23, 3.99; P = 0.03), IgA (WMD, 0.21 g/L; 95% CI: 0.14, 0.28; P < 0.0001), CD3+ (WMD, 5.81%; 95% CI: 0.92, 10.70; P = 0.02), and CD4+/CD8+ (WMD, 0.12; 95% CI: 0.00, 0.24; P = 0.04) compared with MCT/LCTs. CONCLUSIONS: Administration of STGs was shown to improve hepatic function, nutrition status, and immunological function and reduce inflammation, LOS, and adverse events compared with MCT/LCTs in Chinese patients receiving PN.

Hippocampus and serum metabolomic studies to explore the regulation of Chaihu-Shu-Gan-San on metabolic network disturbances of rats exposed to chronic variable stress.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine formula, has been effectively used for the treatment of depression. However, studies of its anti-depressive mechanism are challenging, due to the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different receptors. In the present work, metabolomic studies of biochemical changes in the hippocampus and serum of chronic variable stress (CVS)-induced depression rats after treatment with CSGS were performed using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Partial least squares-discriminate analysis indicated that the metabolic perturbation induced by CVS was reduced by treatment with CSGS. A total of twenty-six metabolites (16 from the hippocampus and 10 from serum) were considered as potential biomarkers involved in the development of depression. Among them, 11 were first reported to have potential relevance in the pathogenesis of depression, and 25 may correlate to the regulation of CSGS treatment on depression. The results combined with a previous study indicated that CSGS mediated synergistically abnormalities of the metabolic network, composed of energy metabolism, synthesis of neurotransmitters, tryptophan, phospholipids, fatty acid and bile acid metabolism, bone loss and liver detoxification, which may be helpful for understanding its mechanism of action. Furthermore, the extracellular signal-regulated kinase (ERK) signal pathway, involved in the neuronal protective mechanism of depression related to energy metabolism, was investigated by western blot analysis. The results showed that CSGS reversed disruptions of BDNF, ERK1/2 and pERK1/2 in CVS rats, which provides the first evidence that the ERK signal system may be one of the targets related to the antidepressant action of CSGS.

Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.

Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1)H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS) treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36) were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36) involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC) and indoleamine 2, 3-dioxygenase (IDO) in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1)H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify the comprehensive potential depression-related biomarkers and helpful in further understanding the underlying molecular mechanisms of depression through the disturbance of metabolic pathways.

[Application and advance of artificial antigens in studies on allergic reaction of traditional Chinese medicine injections].

There are some small molecules with potential allergenicity in traditional Chinese medicine injections. They are lack of immunogenicity due to their small molecular weight, but they can lead to allergic reactions when they were coupled with appropriate vectors. Therefore, how to couple small molecule semi-antigens with vectors to prepare complete antigens with immunogenicity and reactogenicity is the key for screening small molecular allergenic substances out of traditional Chinese medicine injections. In terms of semi-antigen characteristics of traditional Chinese medicine injections, vector selection and application, coupling method and complete antigen purification and identification, the author introduces the latest research situations of artificial antigen and antibody preparation technology, the advance in experimental studies on screening of allergenic substances in traditional Chinese medicine injections, as well as the application prospect of immuno-chip technology in studies on allergenic substances in traditional Chinese medicine injections, with the aim of providing new experimental thoughts and methods for safety control of traditional Chinese medicine injections.

Metabonomics Combined with UPLC-MS Chemical Profile for Discovery of Antidepressant Ingredients of a Traditional Chinese Medicines Formula, Chaihu-Shu-Gan-San.

This study proposed a new strategy for uncovering the active chemical constituents of a traditional Chinese medicines (TCMs) formula, Chaihu-Shu-Gan-San (CSGS). Metabonomics and chemical profile were integrated in combination with the multivariate statistical analysis (MVA) to discover the chemical constituents which contribute to the antidepressant effect of CSGS. Based upon the difference between CSGS and QZ (CSGS without Zhi-Qiao) extracts in the chemical profiles and the regulations of metabolic disturbances induced by CUMS, synephrine, naringin, hesperidin, and neohesperidin were recognized as the active constituents of CSGS from Zhi-qiao responsible for those missing regulations of CSGS when Zhi-Qiao was subtracted from the whole formula. They participated in the regulations of the deviated metabolites 2-4, 10-14, and 22-25, involved in metabolic pathways of ketone bodies synthesis, phenylalanine, tyrosine and tryptophan biosynthesis, valine, aspartate, glutamate metabolism, and glycolysis/gluconeogenesis. Furthermore, the assay of MAO-A activity confirmed the potential antidepressant effect of naringin and its active sites on the MAO-A was inferred by molecular docking study. The integration of metabonomics and chemical profile was proved to be a useful strategy for uncovering what the active chemical constituents in TCM formula are and how they make contributions for the efficacy of the formula.