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The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, β-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.
Subject(s)
Humans , COVID-19 , Pandemics , Drugs, Chinese Herbal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Drug TreatmentABSTRACT
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide. Currently, there is no accepted specific drug for COVID-19 treatment. Therefore, it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19. According to several reliable reports from China, traditional Chinese medicine (TCM), especially for three Chinese patent medicines and three Chinese medicine formulas, has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines. In this review, we systematically summarized and analyzed the pathogenesis of COVID-19, the detailed clinical practice, active ingredients investigation, network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat. Additionally, we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism, which provides guidance for the development of new drugs against COVID-19. Collectively, by addressing critical challenges, for example, unclear targets and complicated active ingredients of these medicines and formulas, we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.
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Objective To evaluate the efficacy and safety of Llianhua Qingwen capsule versus oseltamivir in the treatment of influenza. Methods Data from PubMed, Cochrane Library, Embase, VIP, CNKI and CBM, RCTs about Lianhua Qingwen capsule or Lianhua Qingwen capsule combined with other drugs (trial group) versus oseltamivir (control group) in the influenza were collected. The outcome indicators such as the effective rate of extraction, the time for viral nucleic acid to become negative, the time for fever and the time for symptom resolution, etc., were used for Meta analysis with RevMan 5.3 statistical software. Results Totally 14 studies were included, involving 1459 patients. The Meta analysis results showed that there was no significant difference in the therapeutic effect, the time of virus turning negative and defervescence, and fever reduction time in the experimental group compared with the control group. In terms of symptom relief, the effect of cough and headache resolution in the experimental group was better than that in the control group, and the difference was statistically significant. There was no significant difference in the time to subside of general muscle soreness and pharyngeal pain in the test group and the control group. In terms of safety, there was no statistically significant difference in the incidence of adverse reactions between the experimental group and the control group. Conclusion Lianhua Qingwen capsule is similar to oseltamivir phosphate in curative effect and adverse reaction rate in the treatment of influenza, and is superior to oseltamivir in relieving cough and headache symptoms.
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The outbreak of COVID-19 posed a huge threat to human health and social stability. With the rapid spread of the virus around the world, the drug development and related research of novel coronavirus (SARS-CoV-2) have become an urgent issue in the medical field. COVID-19 fails into the category of epidemics in the theory of TCM. LHQW capsule has repeatedly played an important role in many major epidemics. Previous studies have shown that LHQW capsule can inhibit the biological activity of varied viruses including MERS-CoV and SARS-CoV. The paper summarizes the relevant research data and achievements of LHQW capsule in the past few years, reviews the chemical constituents, clinical efficacy and pharmacological effects of LHQW capsule, and provides scientific basis for the anti-virus mechanism of LHQW capsule and clinical treatment of COVID-19.
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The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases.In particular,it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However,due to its complex composi-tion,little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule.This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry(GC-MS).An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds.A total of 104 compounds,consisting of alkaloids,flavonoids,phenols,phenolic acids,phenylpropanoids,quinones,terpenoids,and other phytochemicals,were suc-cessfully characterized.In addition,the fragmentation pathways and characteristic fragments of some representative compounds were elucidated.GC-MS analysis was conducted to characterize the volatile compounds present in LHQW.In total,17 compounds were putatively characterized by comparing the acquired data with that from the NIST library.The major constituent was menthol,and all the other compounds were terpenoids.This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS,coupled with GC-MS,and the results of this study can be used for the quality control and standardization of LHQW capsules.
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Objective: To study the chemical constituents of Lianhua Qingwen Capsule and illuminate its substance foundation. Methods: The compounds were isolated and purified by LPLC and preparative HPLC from the 30% ethanol fraction of Lianhua Qingwen Capsule macroporous resin column chromatography. Their chemical structures were elucidated by the spectral analyses. Results: 18 compounds were isolated and identified as forsythoside A (1), forsythoside I (2), forsythoside H (3), lugrandoside (4), isolugrandoside (5), ferruginoside A (6), lianqiaoxinoside C (7), calceolarioside C (8), forsythoside E (9), ferruginoside B (10), D-amygdaloside (11), L-amygdaloside (12), sambunigrin (13), cornoside (14), 4-hydroxy-4-methylenecarbomethoxy-cyclohexa- 2,5-dienone (15), liriodendrin (16), liquiritigenin-7-O-β-D-glucopyranoside (17), and 3,4-dihydroxy benzaldehyde (18). Conclusion: Compounds 2-8, 10, and 13-18 are isolated from Lianhua Qingwen Capsule for the first time, and compounds 4-6, 10, 15, and 16 are isolated from single herb in Lianhua Qingwen Capsule compound for the first time. The spectral data in DMSO-d6 solution of compound 8 are reported firstly with 2D NMR spectral data. The above results show the high polar chemical constitutions of Lianhua Qingwen Capsule, which provides more chemical information of Lianhua Qingwen Capsule.
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Objective To study the chemical constituents of Lianhua Qingwen Capsule (LQC). Methods The compounds were isolated and purified by column chromatography over silica gel and sephadex LH-20, and preparative RP-HPLC. Their structures were elucidated by physicochemical properties and spectral analyses. Results Twenty compounds were isolated and identified as aloe-emodin (1), phillygenol (2), cepharanone B (3), pinoresinol (4), epipinoresinol (5), pinoresinol monomethyl ether (6), piperolactam A (7), (E)-ethyl 3-(4-hydroxyphenyl) acrylate (8), formononetin (9), isoliquiritigenin (10), naringenin (11), kaempferol (12), citreorosein (13), rhein (14), physcion-8-O-β-D-glucopyranoside (15), 4,5-dioxodehydroasimilobine (16), kaempferol-3-O-α- L-ramnopyranosyl-4″-O-E-(4-hydroxy)-cinnamoyl (17), chrysophanol-1-O-β-D-glucopyranoside (18), chrysophanol-8-O-β-D- glucopyranoside (19), and emodin-8- O-β-D-glucopyranoside (20). Conclusion Compounds 2, 3, 5-17, 19, and 20 are isolated from LQC for the first time. This study establishes the foundation for explaining the efficient substance of LQC.
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To evaluate the efficacy and safety of Lianhua Qingwen capsule for influenza. All reports of the randomized controlled trials (RCTs) on Lianhua Qingwen capsule treating influenza were retrieved from database of CNKI, WANFANG DATA, VIP, PubMed, the Cochrane Library by February 2017. The studies were screened according to the inclusion and exclusion criteria, the data were extracted by 2 authors, the quality of the included RCTs was assessed, and meta-analysis was performed using Revman5.3 software. A total of 1 525 patients and 10 studies were included. The results of meta analysis showed that compared with oseltamivir, Lianhua Qingwen capsule was more effective in alleviating flu symptoms, including the time of headaches disappeared [SMD=-0.25,95% CI(-0.48, -0.01)], the time of sore throat disappeared [SMD=-0.53,95% CI（-0.72, -0.34）], the time of cough disappeared [SMD=-0.39,95%CI（-0.57, -0.21）], whole body aches disappeared [ SMD=-0.49, 95% CI (-0.78, -0.21)], the time of weak disappeared [SMD=-0.56,95%CI (-0.82, -0.29)], and the time of abatement of fever [SMD=-3.47,95%CI（-6.27, -0.67）]. Also, there were some statistical significant differences between the two groups except nasal congestion and the time of virus turning negative. Compared with Ribavirin, Lianhua Qingwen capsule was more effective in terms of the rate of temperature effect, [RR=1.53, 95% CI (1.24, 1.90)], the difference between the two groups was statistically significant. Compared with Ankahuangmin capsules, significant differences were found in terms of the he rate temperature effect [RR=1.37, 95%CI (1.19,1.57)]. Current evidence shows that Lianhua Qingwen capsule is more effective and safer than Oseltamivir, Ribavirin and Ankahuangmin capsules. Due to the low quality of the clinical research, the accuracy of this conclusion needs to be conducted to verify.
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Objective: To develop a new method based on dispersive solid phase extraction-high performance liquid chromatography (DSPE-HPLC) for the rapid extraction, cleansing, and determination of iridoid glycosides (loganic acid, morroniside, loganin, sweroside, secoxyloganin, and secologain dimethyl acetal) in Lonicerae Japonicae Flos (LJF) and the related traditional Chinese patent medicine (TCPM) Lianhua Qingwen Capsule (LQC). Methods: Ultrasonic extraction was used for the extraction, different purification material was investigated for the rapid purification, and HPLC method was used for the determination of the content of iridoid glycosides. Results: The purification effect of LJF extract was much better by using diatomite as the purification material; The purification of LQC extract was much better by using diatomite-active carbon 80∶20. This method was simple and rapid, and has high efficiency. It could be used for the extraction, cleaning, and determination of iridoid glycosides in LJF and related prescription combined with HPLC. Conclusion: This study expands the application of DSPE in the extraction and purification of complex matrix traditional Chinese material medicine (TCMM) and TCPM, and supplies the new method and data support for the extraction and purification of bioactive compounds from complex matrix TCMM and TCPM.
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OBJECTIVE:To establish a method for the content determination of amygdalin in Lianhua qingwen capsule. METH-ODS:HPLC was performed on the column of Phenomenex Kinetex XB-C18 with mobile phase of acetonitrile-0.2%Phosphoric acid so-lution(6∶94,V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 207 nm,column temperature was 30℃,and the injec-tion volume was 10μl. RESULTS:The linear range of amygdalin was 43.16-215.80 μg/ml(r=0.999 7);the limit of detection was 0.431 6μg/ml,the limit of quantitation was 1.294 8μg/ml;RSDs of precision,stability and reproducibility tests no more than 0.69%;recovery was 95.16%-100.49%(RSD=1.67%,n=9). CONCLUSIONS:The method is simple and rapid with high accuracy and well reproducibility,and can be used for the content determination of amygdalin in Lianhua qingwen capsule.
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Objective To study the application of dynamic ultrasound countercurrent extraction technology in industrialization of Lianhua Qingwen Capsule by multi-index optimization. Methods Ultrasonic temperature and ultrasonic time were investigated by using single factor design. The three factors of dry extract yield, the active ingredient content, and fingerprints were selected as the optimization indexes to investigate the solvent consumption and extraction time between the dynamic ultrasound countercurrent extraction process and the original reflux extraction process under the fixed conditions of process parameters. Results Compared with traditional reflux extraction technology, dynamic ultrasound countercurrent extraction technology effectively reduced the alcohol consumption and saved extraction time on the basis of guarantee of the active ingredient content. Conclusion Dynamic ultrasound countercurrent extraction process, with simple and fast advantages, can be used to Lianhua Qingwen Capsule production, which can significantly reduce production costs and increase productivity.
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OBJECTIVE:To observe the clinical efficacy of Lianhua qingwen capsules in treatment of influenza.METHODS:A total of 160 patients with influenza were randomly divided into control group and trial group:80 patients in trial group were assigned to receive Lianhua qingwen capsules(4 granules/time) tid per os for one week,and another 80 in control group to receive Kugan granules(8 g/time)tid per os for one week.RESULTS:The total effective rate in clinical syndrome,temperature,and symptoms in the trial group was significantly higher than in the control group(P
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Objective To study the anti-viral effects of Lianhua Qingwen Capsule against influenza A virus in vitro.Methods Under different administration modes,the inhibitory effect of Lianhua Qingwen Capsule on human influenza A virus(H3N2)in vitro and its time-effect relationship were assayed by crystal violet staining assay with ribavirin as positive reference drug.Results Lianhua Qingwen Capsule showed a multi-access effect on anti-human influenza A virus,such as comprehensive inhibition effect,prevention effect on virus adsorption,inhibition on virus proliferation after adsorption and direct killing the virus effect,and the median effective concentrations(EC50)in above-mentioned effects were 0.042,0.031,0.051 and 0.050 mg/mL respectively.Among them,the prevention effect on virus adsorption was the strongest.With the expanding actuation duration of the drug,the inhibitory effect of Lianhua Qingwen Capsule against influenza A virus weakened at low concentration,but no change at high concentration(≥0.031 g/mL).Meanwhile,Lianhua Qingwen Capsule can remarkably decrease the infectivity of influenza A virus.Conclusion Lianhua Qingwen Capsule has an obvious effect against human influenza A virus in vitro.
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Objective To evaluate the therapeutic effect and safety of Lianhua Qingwen Capsules (LHQC) in the treatment of influenza. Methods A multi- center, randomized, double- blind, positive- controlled, parallel group trial was designed. A total of 240 cases, which were diagnosed with influenza and classified as the syndrome of toxic heat invading lung, aged from 18 to 50 years old, with body temperature over 38.0 ℃ and disease course with 48 hours, was recruited. The intent- to- treat infected (ITTI) population was 152 cases , among which 76 were treated with LHQC (4 capsules thrice daily for 3 days) and other 76 with Lingyang Ganmao Capsules (2 capsules thrice daily for 3 days). Results In the ITTI population, the effective rate for subsiding fever was 71.1 % and 53.9 % (P=0.029), and that for relieving TCM symptoms was 73.7 % and 55.3 % (P=0.018) in LHQC group and Lingyang Ganmao Capsules group, respectively. A safety analysis was conducted in 233 cases. No adverse action was found in LHQC group while two adverse events (allergic dermatitis and diarrhea) in Lingyang Ganmao Capsules group. Conclusion Early application of LHQC is effective and safe in treating infuenza.