Statistical analysis was performed with Stata 14 software (Stata Corporation, College Station, TX, USA). 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. 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]. LHQW prescription (capsules type, or granules type) consists of 11 herbs, gypsum and menthol [18]. It may benefit the treatment of COVID-19 by the signaling pathways such as advanced glycation end products (AGE)-receptor of AGE (RAGE), TNF, sarcoma-associated herpesvirus infection, IL-17 and human cytomegalovirus infection [41]. Case reports, unrelated studies, those with duplicate data, reviews, commentaries and animal-based studies were excluded from the current meta-analysis. Study on the network pharmacology and evidences of Lianhua Qingwen in the treatment of Novel Coronavirus (2019 nCoV) Pneumonia. Materia Med. It is not registered as a COVID-19 medication, and a doctor's prescription is required for its use. Lianhuaqingwencaps.com - 608667 - 07/06/2020 | FDA Salvi R., Patankar P. Emerging pharmacotherapies for COVID-19. Chin. doi:10.1136/bmj.d5928, Higgins, J. P., Thompson, S. G., Deeks, J. J., and Altman, D. G. (2003). Methods: Comprehensive document retrieval was performed from both English and Chinese databases. [Lamiaceae; 1-Menthol] (7.5g), Glycyrrhiza uralensis Fisch. Clin. 161, 105126. doi:10.1016/j.phrs.2020.105126, Yang, C., Wang, Y., He, J., Yan, W., Jiang, H., Chen, Q., et al. J. Med. Wang L., Yang Z.H., Zhang H.R., Yu H.X., Yang K., Fu B.H., Yang H.T. ). School of Pharmacy, Faculty of Life Sciences, University College London, United Kingdom. Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial. Despite the ban, Lianhua Qingwen has been sold illegally in Australia as a COVID-19 treatment.[21]. 28 (1), 1332. In a lipopolysaccharide (LPS)-induced acute lung injury animal model, LHQW could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, and thus blocked the disease development by down-regulating MCP-1 expression [33]. During the study, no serious adverse events were reported. In treating fine particulates PM2.5 (7.5mg/kg)-exposed model rats, LHQW significantly relieved the pathological changes of thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole [34]. Eval. 81703740), the Zhejiang Provincial Natural Science Foundation of China (No. Other Symptoms Sputum.Four studies reported the effects of Lianhua Qingwen and those of conventional drugs on the duration of sputum. In our meta-analysis, information on adverse reactions was clearly reported in 12 of the 17 studies while the remaining five studies provided no specific evidence of adverse reaction specifically, and the incidence of adverse reactions was lower in LHQW group than that in the conventional drug group. 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). First, the quality of qualified studies was generally medium, randomization procedures and blinding information were lacking in most studies. The inconsistent use of conventional drugs in individual studies, along with individual differences in drug absorption, may be factors underlying high heterogeneity. No adverse treatment-related effects were reported in all the included publications (from 2009 to 2011). Broad Anti-viral Capacities of Lian-Hua-Qing-Wen Capsule and Jin-Hua-Qing-gan Granule and Rational Use against Covid-19 Based on Literature Mining. Declaration of competing interest. COPD is characterized by a chronic inflammatory response and can be worsened by acute exacerbations. From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment. Clinical applications and pharmacological research progress of Lianhua Received 2020 Jul 3; Revised 2020 Aug 9; Accepted 2020 Aug 16. Assoc. Medicine (Baltimore). Secondly, separate evaluations were further performed for different diseases and types of adverse reactions. conducted another single center clinical trial which was showed that seven days after treatment with LHQW granules (6g, tid) in conjunction with conventional treatment for COVID-19 patients had a total effective rate of 92.73 % accompanied by significantly reduced major symptoms including fever, cough, fatigue and chest tightness [41]. (2021). A multicenter retrospective study showed similar results, which revealed that combined application of LHQW granules (6g, tid) could notably improve the clinical symptoms of fever, fatigue, cough, expectoration, chest tightness, and anorexia, and reduce the proportion of common to severe cases in COVID-19 patients with common type [20]. Available at: http://www.theplantlist.org/(Accessed December 18, 2021). [2] In the practice of TCM, LHQW is considered to have the effects of clearing excessive heat, removing toxins, improving lung ventilation, and discharging heat. 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. 12 (08), 140141. Progress on the efficacy and clinical application of Lianhua Qingwen capsule (LHQW). Wang X., Ding Y.Q. (2020). There was no statistically significant difference in the incidence of adverse reactions during treatment of rheum between the LHQW group and the conventional drug group (RR = 0.46, 95% CI = 0.121.83, p = 0.270). Clinical efficacy and mechanism of Lianhua Qingwen Granule on COVID-19 based on network pharmacology research. In total, 95 studies reported randomization data while 93 did not provide information on randomization, and the remaining 29 were grouped according to order of intervention or hospitalization. FIGURE 1. Otherwise, the fixed-effects model was used (DerSimonian and Laird, 1986; Higgins et al., 2003). Inhibitory effects of three prescriptions of traditional Chinese medicine on SARS-associated coronavirus, http://kns.cnki.net/kcms/detail/11.2162.R.20200422.1429.002.html. However, the efficacy and safety of which shall be confirmed by more high-quality clinical trials. vahl (weeping forsythia) fruit 27.41 mg, Lonicera japonica Thunb. The China National Medical Products Administration agency has officially approved LHQW for the treatment of mild or ordinary COVID-19 pneumonia (Ahsan et al., 2020; Cao et al., 2020; Chan et al., 2020; Khan et al., 2020; Kupferschmidt and Cohen, 2020). the Need for Accurate Scientific Nomenclature for Plants. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings. 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]. Homogeneity of baseline data was reported in most studies. Overall, 61 chemical compounds of LHQW (including iridoids, flavonoids, anthraquinones, phenylpropanoids, triterpenoids, and other types) have been unambiguously or tentatively identified via rapid ultra-performance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (Jia et al., 2015). Available at: https://chemrxiv.org/engage/chemrxiv/article-details/60c74908ee301c485bc799cf (Accessed July 23, 2021). 37 studies reported adverse reactions of skin and its appendage damage. Science. Lv R.B., Wang W.J., Li X. 6 (01), 6364. Comprehensive analysis of influenza may provide a significant advantage in generalization of the conclusions. Treatment of SARS-Cov-2: How Far Have We Reached? 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. 152 (3), 393402. Study on treatment of "cytokine storm" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway. Lianhua Qingwen Dosage & Drug Information | MIMS Thailand Med. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. (2021). Based Complement. Res. 2019ZYC-A85), and the Scientific Research Projects of Hospital Pharmacy of Zhejiang Pharmaceutical Association (No. 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]. J. Eval. Available at: https://mpns.science.kew.org/mpns-portal/(Accessed December 19, 2021). The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. In the evaluation of security indexes, LHQW group has a reduced incidence of respiratory system damage, skin and its appendages injury, nervous system damage and gastrointestinal system damage, along with other adverse reactions. 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. Clinical Practice Guideline on Treating Influenza in Adult Patients with Chinese Patent Medicines. Zhou X.P. [citation needed]. doi:10.1126/science.367.6485.1412, Lei, X. 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. In addition, it can also interact with other compounds and herbs. 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: , , /.. Due to the low quality of the clinical research, the accuracy of this conclusion needs to be conducted to verify. HHS Vulnerability Disclosure, Help Yang C.X., Qu J., Liu Y.T., Meng S.W., Wang B.L., Feng M.Q., Sun Y. Med. Lianhua Qingwen Dosage & Drug Information | MIMS Philippines Publication bias data are shown in Table 2 and the Funnel plot of pooled studies presented in Figure 3. J. Nanjing Univ. J. Nosocomiology. ChemRxiv. It cannot be taken as prophylaxis or as a health supplement. Dang Y., Xu J., Yang Y., Li C., Zhang Q., Zhou W., Zhang L., Ji G. Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine. 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]. Twenty-six studies focused on treatment of common pneumonia, of which 23 reported adverse reactions. Studies were classified as low risk of bias, high risk of bias or unclear risk of bias based on individual items. Individuals w/ cold deficiencies in spleen & stomach or w/ qi. 26 (11), 812. Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS. ScientificWorldJournal. The https:// ensures that you are connecting to the Ding Y., Zeng L., Li R., Chen Q., Zhou B., Chen Q., Cheng P.L., Yutao W., Zheng J., Yang Z., Zhang F. The Chinese prescription Lianhua Qingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. *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. Literature analysis of clinical application and adverse drug reaction/event of Lianhua Qingwen capsule. 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]. Chin. In mice after infected with the flu virus FM1, LHQW capsule obviously increased IFN- content in lung homogenate and significantly reduced the levels of TNF-, IL-1 and IL-6 in lung tissues, and had inhibiting effect on the marked decrease of CD4+ and CD4+/CD8+ [31,32]. There are multiple drug trials going on, but there are no specific anti-SARS-CoV-2 drugs or vaccines till now. Wang F.C., Shen B.X., He C.Y., Zhao W.C., Nie S.L. 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. Twelve representative compounds were further quantified as chemical markers, including amygdalin, forsythoside E, salidroside, glycyrrhizic acid, chlorogenic acid, hyperin, rutin, forsythoside A, cryptochlorogenic acid, sweroside, phillyrin, and rhein (Jia et al., 2015). Formulae. doi:10.1016/0197-2456(86)90046-2, Duval, S., and Tweedie, R. (2000). Lianhua Qingwen combined with conventional treatment obviously improved COVID-19. Sci.). Few reports of adverse reactions in the course of treating COVID-19 pneumonia with LHQW are available. Dong L., Xia J.W., Gong Y., Chen Z., Yang H.H., Zhang J., He J., Chen X.D. In this analysis, the incidence of adverse reactions during treatment of influenza was lower in the LHQW group compared to the conventional drug group (RR = 0.74, 95% CI = 0.630.87, p < 0.001). COVID-19 pandemic has caused a serious threat to public health and become the greatest challenge facing the world. We observed no significant alteration in the security evaluation indexes of treatment among different diseases. Lianhua Qingwen prescription for Coronavirus disease 2019 (COVID-19 [18], In Singapore, the Health Sciences Authority has issued an advisory to clarify that although it has been approved for sale as a Chinese proprietary medicine for the relief of cold and flu symptoms, Lianhua Qingwen is not approved to treat or alleviate symptoms of COVID-19. (japanese honeysuckle) flower 27.41 mg, gypsu . [Cruciferae; Isatudus Radix] (255g), Dryopteris crassirhizoma Nakai [Polypodiaceae; Dryopteris Crassirhizomatis Rhizoma] (255g), Houttuynia cordata Thunb. 46 (5), 395400. LHQW was initially approved by the China Food and Drug Administration (CFDA) in 2004 and represents the first traditional Chinese medicine that passed the rapid drug approval channel of CFDA for treatment of severe acute respiratory syndrome (SARS). 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. [Efficacy and safety of Lianhua Qingwen capsule for influenza a Ephedra increases heartbeat and blood pressure. Shi, M., Peng, B., Li, A., Li, Z., Song, P., Li, J., et al. Figure 1 provides a detailed flowchart of the screening process. [11] The pro-establishment DAB alliance was found to have distributed unregistered doses of LHQW, in breach of health regulations. Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19. ADVERSE REACTION Uncertainty. doi:10.19803/j.1672-8629.2015.12.011, Rivera, D., Allkin, R., Obn, C., Alcaraz, F., Verpoorte, R., and Heinrich, M. (2014). Medicinal Plant Names Services. The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. The Chinese herbal medicine that can help treat COVID, according to 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). Besides, the effective rate of chest CT in the LHQW group was 69.39 %, which was higher than 62.84 % in abidor group [44]. Kong Q., Wu Y., Gu Y., Lv Q., Qi F., Gong S., Chen X. Use Overdosage Contraindications Special Precautions Adverse Reactions Storage MIMS Class ATC . Lianhua Qingwen has antiviral, anti-inflammatory and immunoregulatory activities. [8], Lianhua Qingwen has also been promoted and distributed by the government in Hong Kong (HK). 160, 105101. doi:10.1016/j.phrs.2020.105101, Xiao, M., Tian, J., Zhou, Y., Xu, X., Min, X., Lv, Y., et al. Med. (2011). government site. The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Pharmacol. Lianhua Qingwen, the FDA-approved traditional Chinese med, only treats Avoid prolonged use. Both Lian-Hua-Qing-Wen Capsule (LHQWC) and Jin-Hua-Qing . Med. Second, the herbs in LHQW are mostly grown in specific areas, the varied origin of herbs are usually together with different content of bioactive ingredients, thus the quality standard control of the included crude drugs should be encouraged [12]. Advances in Pharmacology and Clinical Research of Lianhua Qingwen Capsules. Clin. Beggs test and Eggers test detected no visible publication bias for data from pooled studies and disease evaluation. Keywords: Lianhua Qingwen capsule; Meta-analysis; influenza; systematic review. [12], In April 2022, the Financial Times reported that the leading COVID-19 health official in the PRC, the famous epidemiologist and pulmonologist Zhong Nanshan - who has also been the most prominent scientific promoter of Lianhua Qingwen - had undisclosed prior investments in large stakeholdings in corporations producing Lianhua Qingwen and other treatments under question. Recent data indicated that orally administered LHQW capsules (100400mg/kg/day) could alleviate IBV-induced pathological change and decrease the abnormal increased inflammatory cells in lung tissues, but did not reduce the lung viral load and mortality in mice [26]. The sensitivity results are shown in Table 2. [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). Therefore, studies with blinded participants and personnel and blinded outcome assessments were classified as low risk of bias. In terms of incomplete outcome data and selective reporting, the majority of studies reported complete data on all symptom indicators with a low risk of attrition and reporting bias. LHQW has a reduced incidence of other adverse reactions compared to the conventional drug group (RR = 0.60, 95% CI = 0.430.84, p = 0.003). The search keywords for screening the literature information were virus, COVID-19, or SARS-CoV-2, and Lianhua Qingwen. Seven studies reporting treatment of chronic obstructive pulmonary disease were included, among which two described adverse reactions. Lianhua Qingwen combined with conventional antiviral Western Medicine may be a useful treatment for prediabetes. Based Complement. The serious attack of Coronavirus Disease 2019 (COVID-19), infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (SARS-CoV-2), has quickly spread around the globe [[1], [2], [3]]. "This medicine has a cooling effect so if you take this, lalo kang magchi -chill," he cautions. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. Cui L.F., Xu H.R., Li F.Z., Wang C.X. [Cruciferae; Isatudus Radix], Dryopteris crassirhizoma Nakai [Polypodiaceae; Dryopteris Crassirhizomatis Rhizoma], Houttuynia cordata Thunb. Exploring material basis and mechanism of Lianhua Qingwen prescription against coronavirus based on network pharmacology. Some notable dangerous reactions include heart attacks, strokes, seizures, and sudden deaths. Ping F., Li Z., Zhang F., Li D., Han S. Effects of Lianhua Qingwen on pulmonary oxidative lesions induced by fine particulates (PM2.5) in rats. Subgroup analysis showed a lower level of nausea or vomiting in LHQW group (RR = 0.60, 95% CI = 0.480.74, p < 0.001), no statistical difference was detected for other symptoms of gastrointestinal system damage. No meta-regression was performed for COVID-19 pneumonia due to the limited number of studies. With gradual improvement of the adverse drug reaction monitoring system of China, reports of adverse reactions or events have increased. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Pharmacol. Lianhua Qingwen (simplified Chinese: ; traditional Chinese: ; lit. The basic clinical treatments for COVID-19 include anti-infectious, anti-proinflammatory cytokines, nonspecific antiviral as well as life support therapies [[6], [7], [8]]. In addition to western medicine, the potential adverse drug reactions (ADRs) can not be ignored. Hu K., Guan W.J., Bi Y., Zhang W., Li L., Zhang B., Liu Q., Song Y., Li X., Duan Z., Zheng Q., Yang Z., Liang J., Han M., Ruan L., Wu C., Zhang Y., Jia Z.H., Zhong N.S. The Trim and Fill method was further applied to assess the impact of publication bias. Efficacy and Safety of Lianhuaqingwen for Mild or Moderate Coronavirus Disease 2019. 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. [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. Asia-Pacific Traditional Med. doi:10.1111/jep.13614, Wang, Y. X., Zhang, K. Y., Huang, J. H., Han, S. L., Zhao, J. H., and Xu, Z. J. Further evaluation revealed that LHQW significantly inhibited SARS-CoV-2 replication in Vero E6 cells, markedly reduced pro-inflammatory cytokines (TNF-, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production and resulted in abnormal particle morphology of virion in cells [30].

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