Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial.

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

[Evaluation of implementation effect of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis].

The purpose of this article is to evaluate the clinical effect of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis. The applicability and application of the Guideline were evaluated based on the clinicians by using the electronic questionnaire. Questionnaires about 538 on application evaluation and 502 questionnaires on applicability evaluation were completed from April 28 to July 9, 2018. The subjects in the questionnaires include the clinicians with junior title, intermediate title, and senior title that have used this Guideline. The descriptive statistical analysis of the collected questionnaire was carried out. In the applicability evaluation, according to the classification of professional titles, the application rate was highest in intermediate title clinicians (26.77%), followed by junior (23.98%) and deputy senior (19.33%) professional title clinicians. In the quality evaluation, the rationality of application scope (98.61%) and the terminology accuracy (98.81%) scores were higher, and the rationality of differentiation and classification (96.05%) was the lowest. The applicability evaluation suggested that clinicians believed this Guideline had high safety (98.42%), reasonable content (98.03%), significant effect (99.6%), reduced use of antibiotics in Western medicine (93.89%), and a high applicability ratio (96.44%). In the application evaluation, Department of lung disease showed the highest application rate (44.24%); rationality of the Guideline was more than 97% in treatment rules and prophylaxis except the syndrome differentiation (92.75%); a high ratio of clinicians believed the recommended scheme was good: curative effect 97.4%, safety 97.59%, and economy 93.87%. The study shows that the clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for acute tonsillitis is of good quality, high clinical use and good effect. It can be used as a standardized treatment scheme for acute tonsillitis in traditional Chinese medicine. But there are some unsuitable contents and need to be further improved. The Guideline should strengthen the revision on differentiation of symptoms and signs as well as prophylaxis.

[Advantages and evidence of Chinese medicine in prevention and treatment of adult acute tonsillitis].

Though evaluation and analysis on the relevant literatures at home and abroad in recent years, the total number of retrieved literature was 2 664. According to the inclusion criteria and exclusion criteria,the literatures were screened out, and the results were as follows：374 literatures. To analyse the advantages and evidence of Chinese medicine in the prevention and treatment of adult acute tonsillitis. It is found to be effective, convenient and practical for the treatment of acute tonsillitis by traditional Chinese medicine (TCM) like treatment according to syndrome differentiation, Chinese patent drug, self Chinese medicine prescription and external treatment. TCM has obvious advantages in the prevention and treatment of acute tonsillitis, has the function of supplementing or substituting antibiotics, and has the function of regulating the defense function of organism.

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

AIM: Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. METHODS: Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 µmol/L) or high glucose (27 mmol/L). RESULTS: ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 µmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. CONCLUSION: Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes.

[Comparative study on decoction and dissolution of crude and processed corni fructus].

To compare and study the decoction and dissolution of active constituents in crude and processed Corni Fructus. HPLC, the traditional Chinese medicine (TCM) decoction method and the dissolution methods were adopted to compare and study the decoction yield and dissolution rate of loganin and morroniside, active constituents in crude and processed Corni Fructus. The results showed that the content of active constituents loganin and morroniside in crude and processed Corni Fructus did not change significantly; compared with crude Corni Fructus, processed Corni Fructus (decoction) contained much higher loganin, with no obvious change in morroniside; compared with crude Corni Fructus, processed Corni Fructus (extracts) showed no significant difference in loganin dissolution, but notable increase in morroniside dissolution in intestinal fluid; in gastric fluid, processed Corni Fructus showed significant increase in loganin and morroniside dissolutions. However, in comprehensive consideration of the decoction dose in clinical administration, and calculated on the basis of the formula of the decoction yield x dissolution rate = decoction-dissolution product, it showed increase in the decoction-dissolution products of both of the active constituents loganin and morroniside, with significant difference. This suggested that processed Corni Fructus is superior to crude Corni Fructus in clinical application. In this article, we proposed to compare the changes in decoction and dissolution of active constituents in crude and processed Corni Fructus, study the decoction-dissolution product, and then apply it in the quality evaluation of crude and processed Corni Fructus.

Novel software-based method to classify structurally similar compounds combined with high performance liquid chromatography-quadrupole time of flight mass spectrometry to identify complex components of herbal medicines.

The components of herbal medicines (HMs) are usually extremely complex, belonging to hundreds of compound classes with diverse chemical and physical properties. Full characterization of HMs is hugely important in order to identify the individual chemical constituents and provide a first step toward determining which components are responsible for the therapeutic effects of a particular medical plant. In this study, a novel software-based approach was developed to classify structurally similar compounds, and this was combined with high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) to identify the individual components in an extract of Mentha haplocalyx. A total of 33 compounds were tentatively identified in samples of M. haplocalyx extract, including 9 new minor constituents reported for the first time. Semi-quantitative analysis of the extract sample was also carried out. Software validation and robustness tests were performed. The results of this study demonstrate the enormous potential of this strategy, using classification based on structural similarity together with HPLC-QTOF-MS, for the identification and quantification of complex components in HMs and related products.

Application of Fourier transform near-infrared spectroscopy combined with high-performance liquid chromatography in rapid and simultaneous determination of essential components in crude Radix Scrophulariae.

A method is described using rapid and sensitive Fourier transform near-infrared spectroscopy combined with high-performance liquid chromatography-diode array detection for the simultaneous identification and determination of four bioactive compounds in crude Radix Scrophulariae samples. Partial least squares regression is selected as the analysis type and multiplicative scatter correction, second derivative, and Savitzky-Golay filter were adopted for the spectral pretreatment. The correlation coefficients (R) of the calibration models were above 0.96 and the root mean square error of predictions were under 0.028. The developed models were applied to unknown samples with satisfactory results. The established method was validated and can be applied to the intrinsic quality control of crude Radix Scrophulariae.

Activation of AQP4, p66Shc and endoplasmic reticulum stress is involved in inflammation by carrageenan and is suppressed by argirein, a derivative of rhein.

OBJECTIVES: We investigated the effect of argirein on acute inflammation edema and examined that aquaporin 4 (AQP4), p66Shc and activating transcription factor (ATF-6) might be involved in carrageenan-induced rat paw inflammation and be reversed by argirein, rhein and indometacin, but not L-arginine. METHODS: Inflammation was produced by carrageenan injected into rat paw and treated orally with argirein (100 mg/kg), rhein (100 mg/kg), L-arginine (100 mg/kg) or indometacin (5 mg/kg). Inflammatory oedema and biomarkers were examined. KEY FINDINGS: Swelling was reduced by argirein, rhein and indometacin; argirein was more effective than rhein at 1 h following medication. Activation of AQP4, p66Shc, ATF-6, NADPH oxidase subunits p22phox, gp91phox and matrix metalloproteinase 2 (P < 0.01) was significant and was suppressed by arginine, rhein and indometacin but not by l-arginine. CONCLUSIONS: Activated AQP4, endoplasmic reticulum stress and p66Shc were actively implicated in the inflammation and these were suppressed by argirein, and its activity is favorable due to synergism in combination with L-arginine.

Global detection and analysis of volatile components from sun-dried and sulfur-fumigated herbal medicine by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry.

The sulfur-fumigation process can induce changes in the contents of volatile compounds and the chemical transformation of herbal medicines. Although literature has reported many methods for analyzing volatile target compounds from herbal medicine, all of them are largely limited to target compounds and sun-dried samples. This study provides a comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC-TOF/MS) method based on a chemical profiling approach to identify non-target and target volatile compounds from sun-dried and sulfur-fumigated herbal medicine. Using Chrysanthemum morifolium as a model herbal medicine, the combined power of this approach is illustrated by the identification of 209 and 111 volatile compounds with match quality >80% from sun-dried and sulfur-fumigated Chrysanthemum morifolium, respectively. The study has also shown that sulfur-fumigated samples showed a significant loss of the main active compounds and a more destructive fingerprint profile compared to the sun-dried ones. 50 volatile compounds were lost in the sulfur-fumigated Chrysanthemum morifolium sample. The approach and methodology reported in this paper would be useful for identifying complicated target and non-target components from various complex mixtures such as herbal medicine and its preparations, biological and environmental samples. Furthermore, it can be applied for the intrinsic quality control of herbal medicine and its preparations.

Simultaneous determination of four bioactive compounds in Verbena officinalis L. by using high-performance liquid chromatography.

BACKGROUND: Verbena officinalis L., called mabiancao in Chinese, is derived from the aerial part of Herba Verbanae. It is a traditional Chinese medicine commonly used in China and northern Europe, which is widely used for clearing away heat and detoxicating, promoting blood circulation, and removing blood stasis. This paper describes a sensitive and specific assay for the determination of four bioactive compounds in V. officinalis L. MATERIALS AND METHODS: In this paper, the four components were separated on an Agilent Zorbax Extend C(18) column (250 mm × 4.6 mm × 5 µm) and detected by a diode array detector. The mobile phase was composed of (a) aqueous phosphoric acid (0.1%, v/v) and (b) acetonitrile using a gradient elution. Analytes were performed at 30°C with a flow rate of 1.0 ml/min and UV detection at 203, 238, and 331 nm. RESULTS: All calibration curves showed good linear regression (r(2) ≥ 0.9999) within tested ranges. Overall intra- and interday variations were less than 1.84%, and the average recoveries were 97.32-102.81% for analytes. DISCUSSION AND CONCLUSION: The proposed method would be sensitive enough and reliable for comprehensive quality control for clinical use and modernization of V. officinalis L.

Screening and identification of potential active components in crude Fructus Corni using solid-phase extraction and LC-LTQ-linear ion trap mass spectrometry.

CONTEXT: Fructus Corni is derived from the dry ripe sarcocarp of Cornus officinalis Sieb. et Zucc. (Cornaceae). It has attracted increasingly much attention as one of the most popular and valuable herbal medicine in clinic. This paper applied a rapid and validated method to the intrinsic quality control of Fructus Corni. MATERIALS AND METHODS: The components of crude Fructus Corni were investigated by means of solid-phase extraction (SPE) and LTQ-linear ion trap mass spectrometry (MS) technique in the negative ion mode. RESULTS: The 29 detected compounds were identified by comparing the retention time and mass spectrometry data and retrieving the reference literatures. DISCUSSION AND CONCLUSION: It was concluded that a rapid and validated method was successfully applied based on SPE-LC-DAD-LTQ-linear-MS(n) which showed high sensitivity and resolution that was more suitable for identifying main components in Traditional Chinese medicines (TCMs) and their prescriptions, which would be helpful to their quality control.

ER stress, p66shc, and p-Akt/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats.

We investigated the anti-inflammatory activities of argirein and rhein on inflammatory edema in rat paw which was caused by complete adjuvant, compared with ibuprofen. We hypothesized that the adjuvant-induced inflammation is attributed to upregulation of activating transcript factor 6 (ATF6; a chaperone for endoplasmic reticulum (ER) stress), p66Shc (an adaptive protein modulating oxidative stress), and NADPH oxidase subunits p22phox and gp91phox in the inflamed tissues. Biomarkers were measured in the rat paw in association with monitoring swellings. The primary inflammatory edema of the injected paw occurred rapidly and sustained over a couple of days, and the secondary inflammation developed 2 weeks later. The inflammatory edema was accompanied by upregulation of cytokines including ATF6, p66Shc, p22phox, gp91phox, and MMP-2 and an increase in ratio of p-Akt/Akt in the afflicted paw. These were suppressed by either argirein and rhein or ibuprofen. These findings indicate that ER stress, upregulated p66Shc, and phosphorylated Akt are actively implicated in the inflammatory zone caused by adjuvant injection. These biomarkers were causal factors responsible for inflammation of the afflicted paw and were suppressed by a supermolecule argirein and rhein, and the anti-inflammatory activities of the two compounds were comparable to that of ibuprofen.

Global detection and identification of components from crude and processed traditional Chinese medicine by liquid chromatography connected with hybrid ion trap and time-of-flight-mass spectrometry.

We herein present a chemical profiling method to efficiently process the information acquired by ultra fast liquid chromatography (UFLC)-electrospray ionization source in combination with hybrid ion trap and high-resolution time-of-flight mass spectrometry (UFLC-(ESI)-IT-TOF/MS), facilitating the structural determination of serial components contained in crude or processed traditional Chinese medicine (TCM). Under the optimized UFLC and IT-TOF-MS(n) conditions, over 39 compounds were separated and detected in crude or processed Fructus corni within 25 min. The components were identified by comparing the mass spectra and retention time with reference compounds, or tentatively assigned by elucidating low-energy collision-induced dissociation (CID) fragment ions and matching empirical molecular formula with that of the published compounds. Several factors in the processing procedure were examined. The experimental results demonstrate that the chemical reactions that occurred in the processing procedure can be used to elucidate the processed mechanism of F. corni, which is regularly affected by the processing conditions. This study provides a novel approach and methodology to identify the complicated components from various complex mixtures such as crude TCM, processed TCM, and biological samples. It can be used as a valid analytical method for further understanding the processing mechanism of TCM, along with the intrinsic quality control of TCM and its processed product.

Simultaneous chemical fingerprinting and quantitative analysis of crude and processed Radix Scrophulariae from different locations in China by HPLC.

A validated liquid chromatography method was first developed to evaluate the quality of crude and processed Radix Scrophulariae extracts through establishing chromatographic fingerprint and simultaneous determination of five bioactive compounds, namely 5-hydroxymethylfurfural (5-HMF), acteoside, angroside C, harpagoside and cinnamic acid. The chromatographic were separated on an Agilent Zorbax Extend C(18) column (250 mm × 4.6 mm, 5 µm) and detected by diode array detector (DAD). Mobile phase was composed of (A) aqueous phosphoric acid (0.03%, v/v) and (B) acetonitrile using a gradient elution. Analytes were performed at 30 °C with a flow rate of 1.0 mL/min and UV detection at 280 nm. All calibration curves showed good linear regression (r(2) ≥0.9996) within the tested ranges, and the recovery of the method was in the range of 98.12-103.38%, with RSD values ranging from 0.6 to 2.8%. In addition, the contents of those five bioactive compounds in crude and processed Radix Scrophulariae prepared by different locations of China were determined to establish the effectiveness of the method. The results demonstrate that the developed method is accurate and reproducible and could be readily utilized as a suitable quality control method for the quantification of Radix Scrophulariae.

Identification of metabolites of crude and processed Fructus Corni in rats by microdialysis sampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry.

A microdialysis (MD) sampling coupled with electrospray ionization linear quadrupole ion trap mass spectrometry (LTQ-MS(n)) method has been developed for rapid and sensitive analysis of rat microdialysate metabolite profile of Fructus Corni, a well-known Traditional Chinese Medicine (TCM). The purified samples were separated by a reversed-phase HPLC with C18 column under a gradient elution. Parent compounds and metabolites of crude and processed Fructus Corni of Jiu Zheng Pin (JZP, JZP is produced after steaming the crude drug pre-steeped in wine) were detected by the on-line MS(n) detector in negative scan model. The identification of the metabolites and their structural elucidation were performed by comparing the changes in molecular mass and defining sites of biotransformation based on the accurate MS(n) spectral information of diagnostic fragment ions. In this work, we used such strategies for the identification of the parent compounds and metabolites of crude and processed Fructus Corni in rats, and seven parent compounds and three new metabolites of Fructus Corni were found in rats for the first time. This study provides important structural information regarding to the metabolism of crude Fructus Corni and its JZP. Furthermore, this work also demonstrated the possibilities of using microdialysis sampling coupled with LC-MS(n) approach for identification of bioactive compounds from TCM in vivo.

Pharmacokinetic parameters of morroniside in iridoid glycosides of Fructus corni processing based on back-propagation neural network.

CONTEXT: Fructus Corni is derived from the dry ripe sarcocarp of Cornus officinalis Sieb. et Zucc. (Cornaceae). Morroniside is an active constituent of Fructus Corni used in many traditional Chinese medicines (TCMs). This article describes a sensitive and specific assay for the quantitation of morroniside in rat plasma after oral administration of iridoid glycosides from Fructus Corni. MATERIALS AND METHODS: In this article, back-propagation (BP) neural network method was fist developed for the prediction of pharmacokinetic (PK) parameters of morroniside in Fructus Corni. RESULTS: The results show that mean square error (MSE) of neural network model with 11 hidden neurons and 90% training data is 0.092. DISCUSSION AND CONCLUSION: This article provides a new method to calculate PK data, one do not need to figure out all the compartment parameters to acquire PK data of morroniside. Therefore, the BP neural network method would be useful for guiding the holistic PK study in consistence with the intrinsic theory and characteristics of TCM.