In addition, LHQW treatment efficiently impaired the nuclear export of the viral RNPl [24]. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: a multicenter, prospective, randomized controlled trial. Sensitivity analysis was performed by assessing the stability of the results after removal of individual studies. The Trim and Fill method was further applied to assess the impact of publication bias. These results were different from our findings, which may be attributed to the limited number of adverse reactions reported in the previous study. As the Financial Times report showed, these appeared to be serious conflicts of interest as the investments benefited from the PRC and HK governments' rapid approval and then widespread national & international promotion of Lianhua Qingwen and other suspect treatments for purportedly helping COVID-19 sufferers. 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). doi:10.1111/j.0006-341x.2000.00455.x, Fan, Z., Guo, G., Che, X., Yang, Y., Liu, Y., Li, L., et al. From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment. 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. (2015). Pharmacokinetics-based identification of pseudoaldosterogenic compounds [8], Lianhua Qingwen has also been promoted and distributed by the government in Hong Kong (HK). Due to the inclusion of Ephedra people with high blood pressure, anxiety, history of seizures, irregular heart beats, or other heart heart conditions, should avoid taking Linhua Quingwen. The risk ratio (RR) and 95% confidence interval (CI) were calculated for categorical variables. Percentage of risk of bias for all qualified studies. LHQW, an innovative proprietary traditional Chinese medicine used to treat influenza, was approved by the Food and Drug Administration of the United States for Phase II of clinical trial in 2015 (Ye et al., 2020). Emerging data have also shown its beneficial effects in treating diverse diseases such as acute respiratory infection, influenza, pneumonia, hand-foot-mouth disease, chronic obstructive pulmonary disease (COPD), as well as COVID-19 [[20], [21], [22], [23]]. System-Organ Code Retrieval Involved. Available at: http://www.plantsoftheworldonline.org (Accessed December 18, 2021). Fig. Eval. ADVERSE REACTION Uncertainty. (2002). Lianhua-qingwen Displays Antiviral and Anti-inflammatory Activity and Synergistic Effects with Oseltamivir against Influenza B Virus Infection in the Mouse Model. doi:10.14009/j.issn.1672-2124.2013.08.001, Wang, Y. [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. Yang C., Wang Y., He J., Yan W., Jiang H., Chen Q., Li L., Yang Z. Lianhua-Qingwen displays antiviral and anti-inflammatory activity and synergistic effects with oseltamivir against influenza B virus infection in the mouse model. All authors approved the final version of this manuscript. This review has introduced the advances of LHQW in anti-viral treatment, intending to provide ideas for the timely treatment of COVID-19 patients. Shi, M., Peng, B., Li, A., Li, Z., Song, P., Li, J., et al. Conclusion: The current study provides potential a reference for the security of LHQW. Pharmacol. Case reports, unrelated studies, those with duplicate data, reviews, commentaries and animal-based studies were excluded from the current meta-analysis. 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 clinical application experience of LHQW has improved over the years, the clinical considers the patients condition, physical quality, and age, controls the amount of LHQW prescribed accordingly and thereby, reduced the likelihood of adverse reactions. 339 (7), b2535. 152 (3), 393402. Literature Analysis of Clinical Application and Adverse Drug Reaction/Event of Lianhua Qingwen Capsule. Subgroup, sensitivity and meta-regression analyses were conducted to determine the potential sources of heterogeneity. A Trial of Lopinavir-Ritonavir in Covid-19. Efficacy of Lianhua Qingwen Compared with Conventional Drugs - Hindawi Lian-Di Kan, Ye-Cheng Jin and Hong-Mei Fang were responsible for the conception and design of the review. Ma Y., Zhang Z., Wei L., He S., Deng X., Ji A., Zhou B., Jiang D., Li M., Wang Y. Efficacy and safety of Reduqing granules in the treatment of common cold with wind-heat syndrome: a randomized, double-blind, double-dummy, positive-controlled trial. [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. Tradit. Retrospective clinical analysis on treatment of coronavirus disease 2019 with traditional Chinese medicine Lianhua Qingwen. The post-marketing monitoring data incorporated information on the following gastrointestinal adverse reactions: nausea, diarrhea, vomiting, abdominal pain, abdominal distension, dry mouth; as well as skin rash, itching, dizziness (Yiling Pharmaceutical, 2021). Based Complement. [Systematic review of efficacy and safety of Lianhua Qingwen - PubMed (2015). Twenty-three studies on other diseases were included, with 12 reporting adverse reactions. Cheng D.Z., Wang W.J., Li Y., Wu X.D., Zhou B., Song Q.Y. Med. Lianhua Qingwen capsule/granule (LHQW) is obtained by combining Ma Xing Shigan Decoction with Yinqiao Powder and widely used in the clinical treatment of respiratory disorders (Liu et al., 2010). COVID-19: TCM Lianhua Qingwen speeds up recovery but no effect in (2020). Kunming: Kunming University of technology. [Efficacy and safety of Lianhua Qingwen capsule for influenza a Frontiers | Lian Hua Qing Wen Capsules, a Potent Epithelial Protector It was found that the total effective rate of LHQW granules combined with abidor treatment (LHQW group) was significantly higher than that of abidor group (80.95 % vs 64.86 %), while the rate of severe illness was markedly lower (14.29 % vs 23.65 %) [44]. Lianhua Qingwen Dosage & Drug Information | MIMS Philippines Results were reported as risk ratio (RR) with 95% confidence interval (CI). Reply. We examined 54 studies on treatment of influenza, 42 of which reported adverse reactions. Jia W., Wang C., Wang Y., Pan G., Jiang M., Li Z., Zhu Y. Qualitative and quantitative analysis of the major constituents in Chinese medical preparation Lianhua-Qingwen capsule by UPLC-DAD-QTOF-MS. Wang C.H., Zhong Y., Zhang Y., Liu J.P., Wang Y.F., Jia W.N., Wang G.C., Li Z., Zhu Y., Gao X.M. Analysis of Clinical Application and Adverse Reactions of Houttuynia Cordata Injection. [14] Retraction Watch also notes that author Jia Zheng-hua is the son-in-law of Wu Yi-ling, the founder of the company in question. Warning 1. Lianhua Qingwen (LHQW) is a classical Chinese medical preparation, while one of its prescription compositions Maxingshigan Decoction has a history of more than thousand years to treat plague, and exhibits antiviral and lung protection actions [15,16]. (2020). A Working List of All Plant Species. The COVID-19 pneumonia epidemic has spread across the globe poses a significant challenge to public health worldwide. Keywords: Pharmacological Action, Clinical Application and Adverse Reactions of Houttuynia Cordata. 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. High-quality randomized controlled trials conducted over the long-term from multiple countries are warranted to further validate the efficacy and safety of LHQW. [15], In the Philippines, its Food and Drug Administration approved Lianhua Qingwen on 7 August 2020 as a traditional herbal product that helps remove "heat-toxin invasion of the lungs, including symptoms such as fever, aversion to cold, muscle soreness, stuffy and runny nose". The authors report no declarations of interest. The quantitative analysis of all eligible studies. The cochrane Collaboration's Tool for Assessing Risk of Bias in Randomised Trials. Vahl [Oleaceae; Forsythiae Fructus] (255g), Lonicera japonica Thunb. The majority of studies lacked sufficient description of allocation concealment and therefore, the project was predominantly evaluated as unclear risk of bias. Although the blinding method was not reported, since some symptom indicators needed measurement with instruments, assessment of symptom indicators was unlikely to be affected by the lack of blinding. Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. 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]. *Correspondence: Guoliang Zhang, zhangguoliang61@sina.com, These authors have contributed equally to this work, https://doi.org/10.3389/fphar.2022.764774, World Health Organization Adverse Drug Reaction Terminology (2009), https://www.frontiersin.org/articles/10.3389/fphar.2022.764774/full#supplementary-material, http://m.news.cctv.com/2020/03/17/ARTIEYQ2aws8fPYWQxjnynzo200317.shtml?from=singlemessage, https://mpns.science.kew.org/mpns-portal/, https://chemrxiv.org/engage/chemrxiv/article-details/60c74908ee301c485bc799cf, http://www.yiling.cn/contents/75/132.html. Med. Lu Z.J., Wu L.Y., Mou Y.Y., Duan H.M., Chen R.C., Xiao Y., Zheng W.J. We observed no significant alteration in the security evaluation indexes of treatment among different diseases. Experimental study on prevention and treatment of influenza virus FM1 infection in mice by Lianhua Qingwen capsule. Adverse Drug Reactions to Antibiotics Observed in Two Pulmonology Divisions of Catanzaro, Italy: a Six-Year Retrospective Study. 20 studies documented other adverse reactions. The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. Lianhua Qingwen combined with conventional treatment obviously improved COVID-19. Lv R.B., Wang W.J., Li X. MANILA, Philippines The Makati Medical Center's therapeutics and medication safety committee (TMSC) has said that the Chinese drug, Lianhua Qingwen (LQ), should not be taken without a doctor's prescription to ease new coronavirus disease (COVID-19) symptoms, warning that it may do more harm than good. After 7 days of treatment, the main TCM syndrome scores (fever, fatigue, cough, dry throat, chest tightness), C-reactive protein and procalcitonin levels in the LHQW group were significantly lower, and the white blood cell and lymphocyte counts were obviously higher than those in abidor group [44]. [Fabaceae; Glycyrrhizae Radix et Rhizoma] (85g) (Rivera et al., 2014; Royal Botanic Gardens, Kew, 2021; Royal Botanic Gardens, Kew science, 2021; The Plant List, 2021; Yiling Pharmaceutical, 2021). A network analysis of the Chinese medicine Lianhua-Qingwen formula to identify its main effective components. 161, 105126. doi:10.1016/j.phrs.2020.105126, Yang, C., Wang, Y., He, J., Yan, W., Jiang, H., Chen, Q., et al. Chin. These above ingredients are decocted, distilled, filtered, refrigerated, mixed well with powdered sugar, dextrin or starch, dried and finally made into LHQW (Chinese Pharmacopoeia, 2020). Liu, X. Y. Hence, the researches on specific active components of LHQW are still important and the reduction of irrelevant ingredients may be related to less adverse reactions. 48 (3), 737762. (Guanghuoxiang), Rheum palmatum L. (Dahuang), Rhodiola rosea Linn. (2013). The recent meta analysis reported 22 studies with a total of 2,007 patients, showing that the adjuvant therapy of LHQW with western medicine could improve the clinical efficiency and C-reactive protein index, shorten the time of antifebrile, cough time, rhondros duration and imaging time, as well as speed up the recovery of pneumonia patients [39]. 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). Ni L., Zhou L., Zhou M., Zhao J., Wang D.W. COVID-19 has led to a great case fatality. Res. 37 studies reported adverse reactions of skin and its appendage damage. Future related studies will provide accumulated evidence to clarify it. The basic clinical treatments for COVID-19 include anti-infectious, anti-proinflammatory cytokines, nonspecific antiviral as well as life support therapies [[6], [7], [8]]. On March 27, 2019, Yiling Pharmaceutical Co. Ltd. amended the LHQW drug manual to include adverse reactions related to its clinical application. doi:10.1136/bmj.327.7414.557, Hu, C., Liang, M., Gong, F., He, B., Zhao, D., and Zhang, G. (2020). In the evaluation of treating disease, significant reduced incidence of adverse reactions during treatment of influenza A (H1N1) and influenza were detected in the LHQW group. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Frontiers | The Adverse Reactions of Lianhua Qingwen Capsule/Granule Declaration of competing interest. 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. A total of 420 participants with influenza (ages from 18 years to 65 years) were randomly divided into three groups: high dose LHQW capsule treatment (6 capsules each time, bid), low dose LHQW capsule treatment (4 capsules of LHQW+2 capsules of placebo each time, bid) and placebo intervention (6 capsules of placebo each time, bid). Here, we performed a meta-analysis of 217 Chinese experimental studies to evaluate the safety of LHQW. [Saururaceae; Houttuyniae Botanical drug] (255g), Pogostemon cablin (Blanco) Benth. [citation needed]. Medicinal Plant Names Services. J. Intern. As Chinese Pharmacopoeia records, LHQW consists of 13 ingredients: Forsythia suspensa (Thunb.) Role of LHQW in the treatment of COVID-19. J. Nosocomiology. Further investigation confirmed that the combination treatment of LHQW capsules (200mg/kg/day) with oseltamivir (2mg/kg/day) markedly reduced IBV infection over the individual administration of either alone in vivo, proving that LHQW capsules could be used as an assistant drug to enhance the effect of oseltamivir against IBV infection [26]. (2020). The results are expected to enhance its effectiveness against viruses. doi:10.11954/ytctyy.201608076, Chan, K. W., Wong, V. T., and Tang, S. C. W. (2020). The different incidence of these adverse reactions may be related to the metabolic level, which varies greatly among the different age groups. LHQW had been proven to accelerate the improvement of acute exacerbation of COPD (AECOPD) patients, especially for the high-risk subgroup, due to the decreased release of inflammatory mediators including IL-8, TNF- , IL-17, and IL-23 [38]. 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). 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). (2015). The inconsistent use of conventional drugs in individual studies, along with individual differences in drug absorption, may be factors underlying high heterogeneity. 28 (1), 1332. 81503129, No. Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus. 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. Till August 8, 2020, over 19,000,000 people have been confirmed infected and more than 700,000 people have died during this severe viral prevalence. (Bohe), Glycyrrhiza uralensis Fisch. Individuals w/ cold deficiencies in spleen & stomach or w/ qi. Are there any known contraindications? While LHQW has recently been approved for marketing by CFDA, its safety is yet to be conclusively established. Besides, on April 14, 2020, the National Medical Products Administration of China approved modifying the specification of LHQW (Yiling Pharmaceutical Inc.) by adding a new indication for COVID-19 treatment in mild and normal cases. The documents were filtered and summarized for final evaluation. Received 2020 Jul 3; Revised 2020 Aug 9; Accepted 2020 Aug 16. Bras (1992). Efficacy and mechanism of Lianhua Qingwen Capsules(LHQW) on chemotaxis of macrophages in acute lung injury (ALI) animal model. 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.