Lianhua Qingwen(Forsythiae fructus 225 mg, Lonicerae japonicae flos 225 mg, Ephedrae herba (processed w/ honey) 85 mg, Armeniacae semen amarum (stir-baked) . Methods and analysis : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the . doi:10.11954/ytctyy.201608076, Chan, K. W., Wong, V. T., and Tang, S. C. W. (2020). Though the quality of the included literature was mixed, the lung protection effects of LHQW was demonstrated. Clinical Drug Safety of Lianhuaqingwen Preparation: a Systematic Evaluation. Li H.R., Chang L.P., Wei C., Jia Z.H. Avoid alcohol and tobacco and spicy,cold, greasy food during taking this product. Lv R.B., Wang W.J., Li X. These in vitro studies indicate that LHQW shows a wide range of antiviral activities including its anti-SARS-CoV-2 role. 14 (2), 6772. Therefore, it is essential to perform a systematic review and meta-analysis to assess the effect of Lianhua Qingwen combined with conventional antiviral Western Medicine in clinical treatment of COVID-19 or asymptomatic infection. aDepartment of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, PR China, bShanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, PR China, cShanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai, 200082, PR China, dDepartment of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310018, PR China, eDepartment of Pharmacy, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310018, PR China, fState Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing, 210023, PR China. It is not registered as a COVID-19 medication, and a doctor's prescription is required for its use. Trim and Fill: a Simple Funnel-Plot-Based Method of Testing and Adjusting for Publication Bias in Meta-Analysis. We examined 54 studies on treatment of influenza, 42 of which reported adverse reactions. A study by Lei (2020) on childhood influenza treatment revealed no statistical difference of adverse effects between LHQW group and conventional drug group (p = 0.751), inconsistent with our meta-analysis. Hsieh C.F., Lo C.W., Liu C.H., Lin S., Yen H.R., Lin T.Y., Horng J.T. Chin. Wang C., Horby P.W., Hayden F.G., Gao G.F. A novel coronavirus outbreak of global health concern. The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. Results of publication bias and sensitivity analysis. Lian-Di Kan, Ye-Cheng Jin and Hong-Mei Fang were responsible for the conception and design of the review. Inclusion in an NLM database does not imply endorsement of, or agreement with, LHQW is recommended by the National Health Commission of the Peoples Republic of China as a traditional Chinese medicine appropriate for COVID-19 pneumonia (trial version from Fourth to the Eighth Edition). doi:10.1371/journal.pmed.100009710.1136/bmj.b2535, Peng, L. L., Li, L., Shen, L., and Li, X. X. Vahl (Lianqiao); Lonicera japonica Thunb. 7 (3), 177188. 28 (1), 1332. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. The outcome measures included the alleviation of fever and other symptoms including nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills or sweats in subjects with acute uncomplicated influenza. Royal Botanic Gardens, Kew science (2021). doi:10.1142/S0192415X20500378. 2017ZYY07). There was no statistically significant difference in the incidence of adverse reactions during treatment of other diseases between the LHQW group and the conventional drug group (RR = 0.95, 95% CI = 0.651.39, p = 0.780). The LHQW group has a reduced incidence of gastrointestinal system damage than the conventional drug group (RR = 0.83, 95% CI = 0.740.93, p = 0.002). Prof. Zhenhua Jia formulates the prescription of Lianhua Qingwen based on the theory of collateral disease, and participates in the research projects of Lianhua Qingwen against H 1 N 1 and COVID-19. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2022.764774/full#supplementary-material, Ahsan, W., Javed, S., Bratty, M. A., Alhazmi, H. A., and Najmi, A. There was a reduced risk of skin and its appendage damage in the LHQW group compared to the conventional drug group (RR = 0.63, 95% CI = 0.440.92, p = 0.015). Analysis of the molecular mechanism of Pudilan (PDL) treatment for COVID-19 by network pharmacology tools. doi:10.1111/j.1365-2796.1990.tb00199.x, Higgins, J. P., Altman, D. G., Gtzsche, P. C., Jni, P., Moher, D., Oxman, A. D., et al. Wang L., Yang Z.H., Zhang H.R., Yu H.X., Yang K., Fu B.H., Yang H.T. 17 studies focused on the treatment of Influenza A (H1N1), 12 of which reported adverse reactions. (2021). doi:10.14009/j.issn.1672-2124.2013.08.001, Wang, Y. (Gancao) with a herbal ratio of 170 g: 170 g: 57g: 57g: 170 g: 170 g: 170 g: 170 g: 57g: 34 g: 57g: 5 g: 57g, which is recorded in Chinese Pharmacopeia (2015 Edition). (2020). Zhao P., Yang H.Z., Lv H.Y., Wei Z.M. This review has introduced the advances of LHQW in anti-viral treatment, intending to provide ideas for the timely treatment of COVID-19 patients. Systematic Review Registration: https://clinicaltrials.gov/, CRD-42020224180. Li Q., Yin J., Ran Q.S., Yang Q., Liu L., Zhao Z., Li Y.J., Chen Y., Sun L.D., Wang Y.J., Weng X.G., Cai W.Y., Zhu X.X. The most common adverse reactions in our analysis were gastrointestinal system damage, skin and its appendage damage. Electronic retrieval was performed using following databases, which were searched from outset to February 18, 2021: Embase, PubMed, the Cochrane Library, CNKI (a Chinese database), VIP (a Chinese database), and Wanfang (a Chinese database). The basic clinical treatments for COVID-19 include anti-infectious, anti-proinflammatory cytokines, nonspecific antiviral as well as life support therapies [[6], [7], [8]]. Res. Nevertheless, there are also potential limitations that need to be improved for future challenges. While LHQW has recently been approved for marketing by CFDA, its safety is yet to be conclusively established. Pharmacopoeia of Peoples Republic of China. We would like to express our appreciation to all authors of eligible studies which were included in the current meta-analysis. showed that the usual treatment in combination with LHQW capsules (4 capsules thrice daily for 14 days) had significantly higher recovery rate, and shorter median time to symptom recovery, as compared with control group [43]. Dong L., Xia J.W., Gong Y., Chen Z., Yang H.H., Zhang J., He J., Chen X.D. doi:10.11816/cn.ni.2015-134443. doi:10.1136/bmj.d5928, Higgins, J. P., Thompson, S. G., Deeks, J. J., and Altman, D. G. (2003). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement. J. Chin. Tradit. Six studies reported the adverse reactions of abnormal white blood cells and reticuloendothelial system. Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial. Shi, M., Peng, B., Li, A., Li, Z., Song, P., Li, J., et al. Careers, Unable to load your collection due to an error. 37 studies reported adverse reactions of skin and its appendage damage. An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. 8600 Rockville Pike Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., Niu P., Zhan F., Ma X., Wang D. A novel coronavirus from patients with pneumonia in China, 2019. The following information was collected from each qualifying study: first authors name, year, treating disease, sample size, number of male and female, age, adverse reactions, dispose or outcome of adverse reactions. Jia and colleagues established a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS) to analyze the major constituents of LHQW capsule, and the results demonstrated that 12 representative compounds were quantified as chemical marker, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid [17]. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings. Med. (2021) investigated the efficacy and security of LHQW in the treatment of mild or moderate COVID-2019 pneumonia, reported no statistical difference in the incidence of adverse reactions between LHQW and conventional treatment groups from two studies (RR = 0.43, 95%CI = 0.121.54, p = 0.19). A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components. The results are expected to enhance its effectiveness against viruses. 1 Vahl [Oleaceae; Forsythiae Fructus] (255g), Lonicera japonica Thunb. LHQW capsules also showed a multi-access effects on anti-human influenza A virus H3N2, including the prevention effect on virus adsorption, inhibition on virus proliferation after adsorption and direct killing of the virus [25]. Efficacy of Huoxiang Zhengqi Dropping Pills and Lianhua Qingwen Granules in Treatment of Covid-19: a Randomized Controlled Trial. Clinical efficacy and mechanism of Lianhua Qingwen Granule on COVID-19 based on network pharmacology research. Statistical analysis was performed with Stata 14 software (Stata Corporation, College Station, TX, USA). Our findings support the adverse reactions recorded by Yiling Pharmaceutical, and compare the incidence risk of gastrointestinal system damage and rash with the control group. Liu, X. Y. A multi-center, randomized, double-blind, and placebo-controlled phase II clinical study, sponsored by Yiling Pharmaceutical Inc., was conducted to investigate the safety and efficacy of two doses of LHQW capsule compared to placebo in subjects with acute uncomplicated influenza in the U.S.A (https://www.clinicaltrials.gov/ct2/show/study/{"type":"clinical-trial","attrs":{"text":"NCT02867358","term_id":"NCT02867358"}}NCT02867358). Chakraborty C., Sharma A.R., Sharma G., Bhattacharya M., Lee S.S. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Dr. Tan says that LianHua QingWen is not advisable for COVID patients who are experiencing a chilling sensation due to the infection. Otherwise, the fixed-effects model was used (DerSimonian and Laird, 1986; Higgins et al., 2003). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Lianhua-qingwen Displays Antiviral and Anti-inflammatory Activity and Synergistic Effects with Oseltamivir against Influenza B Virus Infection in the Mouse Model. The discovery of potential effective drugs on the market becomes one of the principal means to develop antiviral drugs for COVID-19. Meta-Analysis of Efficacy of Oseltamivir and Substitution Therapy for Anti- H1n1 Infection. Keywords: Pharmacol. doi:10.5582/ddt.2020.03008, PubMed Abstract | CrossRef Full Text | Google Scholar, Cao, B., Zhang, D., and Wang, C. (2020). [13], A 2020 "randomized controlled trial" of LHQW involving Zhong was also found in April 2022 to have undisclosed funding from Yiling Pharmaceuticals, forcing an erratum. Subgroup analysis further showed the incidence of disease recurrence was lower in the LHQW group than the conventional drug group (RR = 0.33, 95% CI = 0.170.65, p = 0.001), no statistical difference was detected for secondary infection. Jie Chen, Qin Chen and Hua-Qian Jin analyzed literatures. Alternat Med. Research progress in use of traditional Chinese medicine for treatment of spinal cord injury. Methods: Comprehensive document retrieval was performed from both English and Chinese databases. Zhou X.P. Assoc. Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model. doi:10.26434/chemrxiv.12016236.v1. Besides, the collected clinical trials involving TCM in the treatment of COVID-19 were mainly from China and published in Chinese, and thus further well-designed multicenter RCTs from different countries will be more attractive before a definitive conclusion can be drawn. Some notable dangerous reactions include heart attacks, strokes, seizures, and sudden deaths. Literature analysis of Chinese patent medicine treatment in the observation period of Clinical Management of Corona Virus Disease 2019 (trial 6th edition). Tian S., Song X., Wang Y., Wang X., Mou Y., Chen Q., Zhao H., Ma K., Wu Z., Yu H., Han X., Wang H., Wang S., Ji X., Zhang Y. Chinese herbal medicine Baoyuan Jiedu decoction inhibits the accumulation of myeloid derived suppressor cells in pre-metastatic niche of lung via TGF-/CCL9 pathway. All authors approved the final version of this manuscript. The Cochrane Collaboration risk of bias tool comprising seven items was applied to assess the risk of bias of each eligible study (Higgins et al., 2011). Efficacy of Lianhua Qingwen Compared With Conventional Drugs in the Treatment of Common Pneumonia and Covid-19 Pneumonia: a Meta-Analysis. Lianhua Qingwen Prescription is approved for the treatment of fever, cough, and fatigue caused by light and common type of COVID-19 . In cases of I2 > 50%, obvious heterogeneity was defined and the random-effects model selected. 13:764774. doi: 10.3389/fphar.2022.764774. Analysis of Clinical Application and Adverse Reactions of Houttuynia Cordata Injection. recently published a clinical study on the treatment of mild COVID-19 with LHQW granules (6g, tid) combined with abidor (0.2g, tid) [44]. The participants, interventions, comparison, outcome and study design (PICOS) criteria were used to identify articles: 1) participants: patients treated with LHQW, 2) interventions: LHQW or LHQW combined with conventional drug (LHQW capsule: Shijiazhuang Yiling Pharmaceutical Co., Ltd., National medicine approval Z20040063; LHQW granule: Shijiazhuang Yiling Pharmaceutical Co., Ltd., National medicine approval Z20100040), 3) comparison: conventional drugs, including antiviral drugs, conventional antibiotics or symptomatic treatment, 4) outcome: relevant data on adverse reactions, and 5) study design: experimental study. The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. The following terms were searched using the title, abstract or keywords in the English databases: Lianhuaqinwen granule, Lianhuaqinwen capsule, Lianhua Qingwen capsule/granule. For the Chinese databases, the search terms used were: , , /.. Lianhua Qingwen Capsules of Yiling Pharmaceutical Approved in mauritius. Skin rashes, allergic dermatitis and other skin allergic reactions are also reported to be associated with LHQW treatment, and may be related to Houttuynia cordata Thunb. However, since subgroup and sensitivity analyses did not explore the source of heterogeneity, we utilized meta-regression to determine the potential underlying factors. With gradual improvement of the adverse drug reaction monitoring system of China, reports of adverse reactions or events have increased. A total of 2,511 citations were identified, among which 1,796 irrelevant, animal studies or duplicate studies were excluded, for screen of titles and abstracts. These data indicate that LHQW prescription protects against the virus attack, and it has been recommended in the treatment of COVID-19 in China [47]. (2021). Subgroup, sensitivity and meta-regression analyses were conducted to explore the possible sources of heterogeneity across eligible studies. (2016). In conclusion, this review has summarized the benefits of LHQW for treating virus infection, especially its anti-SARS-CoV-2 role as an alternative candidate and complementary strategy. Use Overdosage Contraindications Special Precautions Adverse Reactions Storage MIMS Class ATC . Identification of a pharmacological biomarker for the bioassay-based quality control of a thirteen-component TCM formula (Lianhua Qingwen) used in treating influenza A virus (H1N1) infection. The incidence of adverse reactions during treatment of influenza A (H1N1) was lower in the LHQW group compared to the conventional drug group (RR = 0.21, 95% CI = 0.130.36, p < 0.001). In another prospective multicenter randomized controlled trial in confirmed COVID-19 cases, Hu et al. N. Engl. The latest meta-analysis by Fan et al. 6 (01), 6364. 3.2.2. Clinical Practice Guideline on Treating Influenza in Adult Patients with Chinese Patent Medicines. In vitro, LHQW capsules could inhibit the proliferation of influenza viruses of various strain with the 50 % inhibitory concentration ranging from 0.35 to 2mg/mL [24]. Conclusion: The current study provides potential a reference for the security of LHQW. Traditional Chinese medicine has accumulated substantial clinical experience over thousands of years. (1990). 132 studies documented gastrointestinal system damage. [9], During the COVID-19 pandemic, the government of the People's Republic of China (PRC) approved the use of Lianhua Qingwen for mild to moderate COVID-19 cases in January 2020, and promotes the use of the medicine abroad. Potential publication bias was assessed using Funnel plot, Beggs and Eggers test. Cheng D.Z., Li Y. Now, there are no study results posted on ClinicalTrials.gov for this study yet. The inconsistent use of conventional drugs in individual studies, along with individual differences in drug absorption, may be factors underlying high heterogeneity. Efficacy and safety of Lianhua Qingwen capsule for influenza: a systematic review. Available at: http://www.theplantlist.org/(Accessed December 18, 2021). The official monograph of LHQW states that the adverse effects are "unclear". Role of LHQW in the treatment of COVID-19. 13 (08), 676681. 26 (11), 812. No proven effective antiviral treatments for COVID-19 pneumonia are available at present (Ahsan et al., 2020; Cao et al., 2020; Chan et al., 2020; Khan et al., 2020; Kupferschmidt and Cohen, 2020). COVID-19 pandemic has caused a serious threat to public health and become the greatest challenge facing the world. A number of advantages of our study should additionally be mentioned. "This medicine has a cooling effect so if you take this, lalo kang magchi -chill," he cautions. School of Pharmacy, Faculty of Life Sciences, University College London, United Kingdom. [Saururaceae; Houttuyniae Botanical drug] (255g), Pogostemon cablin (Blanco) Benth. Available at: https://chemrxiv.org/engage/chemrxiv/article-details/60c74908ee301c485bc799cf (Accessed July 23, 2021). (2011). Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. LHQW is composed of 11 herbs including Forsythia suspensa (Thunb.) Front. Chen J., Wang Y.K., Gao Y., Hu L.S., Yang J.W., Wang J.R., Sun W.J., Liang Z.Q., Cao Y.M., Cao Y.B. Multiple clinical observations of Lianhua Qingwen combined with conventional treatment can increase the disappearance rate of major symptoms of NCP (fever, cough, fatigue) and other symptoms (chest tightness, dyspnea, and loss of appetite), and reduce the proportion of severe symptoms. Meta-analysis in Clinical Trials. (Hongjingtian), Mentha haplocalyx Briq. "It's the first time in the world that we have enough evidence to prove Lianhua Qingwen capsule is effective and can help . These results were different from our findings, which may be attributed to the limited number of adverse reactions reported in the previous study. In the evaluation of security indexes, our meta-analysis revealed that LHQW group having a lower level of adverse reactions compared to the conventional drug group, such as respiratory system damage, skin and its appendage damage, nervous system damage, gastrointestinal system damage and other adverse reactions. Advances in Pharmacology and Clinical Research of Lianhua Qingwen Capsules. 81503129, No. Asia-Pacific Traditional Med. Efficacy and Safety of Lianhuaqingwen for Mild or Moderate Coronavirus Disease 2019. Subgroup analysis additionally revealed a reduced incidence of some adverse reactions in the LHQW group compared to the conventional drug group (Rash of skin and its appendage damage, dizziness or headache owing to nervous system damage, nausea or vomiting from gastrointestinal system damage and resurgence of disease from other adverse reactions). doi:10.13260/j.cnki.jfjtcm.012210, Jia, W., Wang, C., Wang, Y., Pan, G., Jiang, M., Li, Z., et al. (2021). Wang Z., Chen X., Lu Y., Chen F., Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and western medicine treatment. Chin. The COVID-19 pneumonia epidemic has spread across the globe poses a significant challenge to public health worldwide. [Caprifoliaceae; Lonicerae Japonicae Flos] (255g), Ephedra sinica Stapf [Ephedraceae; Ephedrae Botanical drug] (85g), Prunus armeniaca L. [Rosaceae; Armeniacae Semen Amarum] (85g), Gypsum Fibrosum (255g), Isatis indigotica Fort. Similar results were obtained in subgroup analysis of hepatic function abnormal and transaminase increased. Systematic review of efficacy and safety of Lianhua Qingwen capsules in treatment of viral influenza. Sensitivity analysis was performed by assessing the stability of the results after removal of individual studies. A Trial of Lopinavir-Ritonavir in Covid-19. Contraindications . Results were reported as risk ratio (RR) with 95% confidence interval (CI). doi:10.3969/j.issn.1672-2809.2020.13.020, Liu, C. Y., Li, X. Q., and Cai, S. Q. Percentage of risk of bias for all qualified studies. Based on analysis of 40 cases of RCT, the clinical safety of LHQW was comprehensively examined, 163 adverse reactions were reported from 24 studies (Wang et al., 2013). Efficacy of Lianhuaqingwen capsule compared with oseltamivir for influenza A virus infection: a meta-analysis of randomized, controlled trials.