Introduction: The new crown epidemic in Shanghai is still not over, the shortage of materials still exists, many Shanghai citizens reported receiving lianhua qing plague capsules distributed, but the antiviral ability of the drug is doubtful. Rao Yi, a professor at Peking University and a researcher at the Beijing Institute of Life Sciences, said: "If Lianhua Qingpeng has never been strictly proven to be effective, forcibly delivering this drug will harm the people waiting for necessary supplies and medicines." Wang Sicong, known as the "Discipline Inspection Commission of the Entertainment Industry", posted on Weibo that "the CSRC should strictly investigate Yiling Pharmaceutical." It is really difficult to see a media in China that is rigorous, dares to seek verification, has a conscience, and dares to tell the truth. "So is there a scientific basis for the antiviral of Lianhua Qing plague capsules? This article has been combed through.
Lianhua Qing plague capsules
Birth background and theoretical basis
Lianhua Qing plague granules (capsules) were developed by the Chinese Academy of Military Medical Sciences for anti-novel coronavirus SARS during the SARS period in 2003, and were developed from two classic Chinese medicine formulas with a long history in the clinical treatment of influenza, Ma Xing Shi Gan Tang and Silver Warp, which inhibited half of the effective concentration (IC50) of the SARS-CoV virus was 0.09 mg/mL. The therapeutic index of 40.33 significantly inhibits the replication of THE SARS virus and is one of the few traditional Chinese medicines with evidence of anti-SARS-CoV effects [1]. It is rumored on the Internet that 14 days of research and development of Lianhua Qing plague, but it is just empty.
By consulting the instructions of Lianhua Qing plague capsules, it was found that the drug is composed of 13 herbs of forsythia, honeysuckle, ephedra, bitter almond, gypsum, plate blue root, cotton horse guanzhongzhong, houttuynia cordata, herb, rhubarb, rhodiola rosea, menthol, licorice, and its function is indications: detoxification of plague, catharsis and heat dissipation. It is used for the treatment of influenza fever attack lung evidence, fever or high fever, chills, muscle soreness, nasal congestion, runny nose, cough, headache, dry throat, red tongue, moss yellow or yellow greasy, etc. (Figure 1).
Figure 1 Instruction manual of Lianhua Qing plague capsule (Source: Sina Weibo)
From the perspective of traditional Chinese medicine, Lianhua Qing plague capsules aim at the pathogenesis characteristics of COVID-19 "epidemic poison invasion, heat poison attacking the lungs", can exert its effect of suppressing lung qi, clearing phlegm fever, detoxifying and activating blood, alleviating the initial fever and respiratory symptoms of COVID-19 patients, and achieving the therapeutic effect of wei qi co-treatment, double solution in the surface and in the whole adjustment, which helps to block patients from entering the "inflammatory storm" quickly.
In vitro studies
Lianhua Qing plague has the ability to resist the new crown virus
In March 2022, a research team from the Chinese Center for Disease Control and Prevention conducted a study on the in vitro anti-novel coronavirus activity and cytotoxicity of eight traditional Chinese medicines, including Lianhua Qing plague granules[2].
In vitro cell model experimental findings
1. There are 6 kinds of drugs that are less toxic to cells, while Liushen Pill and Huoxiang Zhengqi Water are more toxic to cells;
2. In addition to lianhua qing plague has a certain inhibitory effect on the new coronavirus, other drugs have no inhibitory effect on the new coronavirus at this concentration;
3. Lianhua Qingpeng has good antiviral activity in vitro, its EC50 is 0.43 mg/mL, and the SI is greater than 4.65 (Table 1);
4. Under the microscope, it was found that Lianhua Qing plague can significantly improve the cell state and inhibit the cytopathy caused by the virus.
Table 1 Cytotoxic and antiviral effects of 8 chinese medicines
Source: [2] | Tabulation: Bio Exploration Editorial Team
In January 2022, a research team from Gansu University of Traditional Chinese Medicine explored the network pharmacological basis of Lianhua Qingyi capsules for the treatment of NEW Crown Pneumonia [3].
The results were found
1. Apigenin, orange peel, locustin, norphedrine, licorice chalcone, emodyl methyl ether, serotonin and SARS-CoV-2 S protein in Lianhua Qingxiao granules have a high affinity, and 10 kinds of medicinal materials are attributed to the lung meridian;
2. The "medicinal materials-compounds-targets" network model contains 12 kinds of medicinal materials, 184 compounds, and 145 targets of action. Cluster analysis obtained 51 key components, mainly flavonoids, flavonoids, sterols, anthraquinones. GO function enrichment analysis yielded 554 entries, and KEGG channel enrichment analysis obtained 33 signal paths.
A variety of flavonoids such as apigenin, orange peel, and locustin in Lianhuaqing plague granules can bind to the S protein of SARS-CoV-2 to prevent the invasion of viruses, and combine with HARS, PIK3R1, AKT1, ESR2, PTGS2, HSP90AA1 to regulate immunity, inflammation and other signaling pathways to reduce inflammatory responses.
In December 2021, research teams from the National Clinical Research Center for Respiratory Diseases and Guangzhou Medical University published an article titled "Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2)" at Phantom Research (Figure 2) [ 1]。 The researchers assessed the antiviral activity of Lianhua Qingxiao on SARS-CoV-2 in Vero E6 cells by CPE (Cytopathic Effect) and plaque reduction assay; observed the effect of Lianhua Qingpeng on virion morphology under transmission electron microscopy; and measured pro-inflammatory cytokine expression levels after SARS-CoV-2 infection in Huh-7 cells by real-time quantitative PCR assay.
Figure 2 Research results (Source: [1])
The results were found
1. Lianhua Qingpeng significantly inhibited the replication of SARS-CoV-2 in Vero E6 cells;
2. Lianhua Qingpeng significantly reduced the production of pro-inflammatory cytokines (TNF-α, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) at mRNA levels.
3. The treatment of Lianhua Qing plague leads to the abnormal particle morphology of virions in cells.
Clinical studies
Lianhua Qing plague reduces the rate of new crown infection
In November 2021, the Department of Medical Imaging of Hebei Provincial Corps Hospital and the Research Team of the Department of Respiratory and Critical Care Medicine of the Second Hospital of Hebei Medical University published a paper entitled "Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A" at Evid Based Complement Alternat Med Prospective Open-Label Controlled Trial". The results showed that Lianhua Qing plague played little role in reducing close infection, but could effectively reduce secondary close infection.
Figure 3 Research results (Source: [4])
The study enrolled 1976 close contacts of COVID-19 (including second-degree close contacts) to be given to the treatment group (n=1101) lianhua qing plague capsules at a dose of 4 capsules 3 times a day for 14 days. The control group (n=875) was not medicated and was normally isolated for observation. The general treatment of both groups of patients was based on the covid-19 protocol (trial version 8). Nasopharyngeal swab to detect the nucleic acid of the new crown virus, the positive rate is statistically calculated.
The results were found
1. The positive rate of nucleic acid test in the treatment group was significantly lower than that in the control group (0.27% and 1.14% respectively; mean difference: -0.87%; 95% CI: -1.83~-0.13;);
2. For subjects with different close contact states, among close contacts, there was no statistical significance in the positive rate of nucleic acid tests in the treatment group and the control group (6.45% and 11.43% respectively;). Among the secondary close contacts, the positive rate of nucleic acid tests in the treatment group was significantly lower than that in the control group (0.09% and 0.71% ;), respectively;
3. No serious adverse events were reported.
In May 2021, Academician Zhong Nanshan's team and the research team of Yiling Hospital of Hebei Medical University jointly published a paper entitled "Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, Prospective, randomized controlled trial". The results showed that compared with the conventional treatment group, the clinical symptom disappearance rate of patients taking Lianhua Qing plague capsules was higher within 14 days, and the CT improvement rate was significantly higher than that of viral nucleic acid detection.
Figure 4 Research results (Source: Ptytomedicine)
The study enrolled 284 people infected with COVID-19 and were divided into two groups (Lianhua Qing plague treatment group and control group).
The results were found
1. The rehabilitation rate of the Lianhua Qing plague treatment group was significantly higher than that of the control group (91.5% vs 82.4%, P=0.022);
2. The median time for symptom recovery in the Lianhua Qing plague treatment group was significantly shortened (median: 7 days vs 10 days, P
3. The recovery time of fever (2 days vs 3 days), fatigue (3 days vs 6 days) and cough (7 days vs 10 days) in the Lianhua Qing plague treatment group was significantly shortened (all P
4. The improvement rate of chest CT performance in the treatment group of Lianhua Qing plague was higher (83.8% vs. 64.1%, PP=0.017);
5. There was no difference in the rate of conversion to severe cases or the results of viral tests (both P>0.05);
6. No serious adverse events were reported.
From SARS to influenza to new crown pneumonia, lianhua qing plague capsules are everywhere. People's doubts about Lianhua Qingpeng have also fluctuated, all due to the unexplained pharmacology of Chinese medicine and the unexplained "panacea oil" effect. During the new crown pneumonia period, the anti-epidemic effect of traditional Chinese medicine is obvious to all, but the actual efficacy of Lianhua Qingpeng has not been strictly proven, coupled with the commercial attributes of Yiling Pharmaceutical, which will naturally cause the public to have doubts.
The theory of Western medicine is full of obstacles when adapting to the study of Chinese medicine, compared with the immediate results of Western medicine, the treatment of Chinese medicine is "slow work and meticulous work", and the inexplicable chemical composition and adverse reactions of Chinese medicine also make many people who are accustomed to Western medicine have doubts. Science can't answer all the questions, but it will tell us part of the truth. Recent scientific research data have reported that Lianhua Qingpeng does have the ability to fight the new crown virus, but further scientific research is still needed to confirm it in the treatment of new crown.
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End
Resources:
[1] Runfeng L, Yunlong H, Jicheng H, et al. Corrigendum to: Lianhuaqingwen exerts anti-viral andanti-inflammatory activity against novel coronavirus (SARS-CoV-2) [Pharmacol.Res. 156 (2020) 104761]. Pharmacol Res. 2021 Dec;174:105907. doi:10.1016/j.phrs.2021.105907. Epub 2021 Nov 19. Erratum for: Pharmacol Res. 2020Jun;156:104761. PMID: 34802883; PMCID: PMC8603740.
[2] Ye Fei, Huang Baoying, Zhao Li, et al. Study on the in vitro anti-novel coronavirus activity and cytotoxicity of 8 kinds of traditional Chinese medicines such as Lianhua Qing plague granules[J].Acta Virica sinica,2022,38(02):284-289.DOI:10.13242/j.cnki.bingduxuebao.004083.
Wang Yu, Jin Xiaojie, Zhao Lei, et al. Discussion on the material basis of Lianhua Qingpeng granules in the treatment of COVID-19 based on network pharmacology[J/OL].Proprietary Chinese Medicine:1-5[2022-04-19].http://kns.cnki.net/kcms/detail/31.1368.R.20220118.1505.005.html
[4] Gong X, Yuan B, Yuan Y, et al. Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A Prospective Open-Label Controlled Trial. Evid Based Complement AlternatMed. 2021 Nov 23;2021:7962630. doi: 10.1155/2021/7962630. PMID: 34858512; PMCID: PMC8632393.
[5] Hu K, Guan WJ, Bi Y, et al. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlledtrial. Phytomedicine. 2021 May;85:153242. doi: 10.1016/j.phymed.2020.153242.Epub 2020 May 16. Erratum in: Phytomedicine. 2022 Jan;94:153800. PMID:33867046; PMCID: PMC7229744.
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