The new crown virus quickly swept the world, with more than 4 million confirmed cases. To date, there is no vaccine or specific drug to prevent covid-19 infection. The new use of old drugs is a major idea at present, and the scientific research team from China has found that pudilan anti-inflammatory oral liquid has a curative effect on new crown pneumonia. In the fight against the new crown, traditional Chinese medicine has been widely used, and even Huaqing plague has been recommended by many experts, including Academician Zhong Nanshan. The researchers say that existing drugs have advantages over developing new drugs in terms of pharmacokinetics, known side effects, safety and dosing regimens. Pudilix anti-inflammatory oral liquid is a traditional Chinese medicine preparation, the main ingredients are is islan root (Isatis Indigotica), corydalis Bungeana, dandelion (Taraxacum Mongolicum), skullcap (Scutellaria Baicalensis). The study (Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid) for COVID-19 in vitro and in vivo was published on May 8 in Signal Transduction and, an English-language academic journal jointly organized by West China Hospital/State Key Laboratory of Biotherapy of Sichuan University and Springer Nature Publishing Group Targeted Therapy (STTT). The research team comes from the National Health Commission's Key Laboratory of Comparative Medicine of Human Diseases, the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences, the Center for Comparative Medicine of Peking Union Medical College, and the Beijing Key Laboratory of Animal Model Research on Emerging Recurrent Infectious Diseases. The corresponding author of the study is Linlin Bao, a researcher at the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences and the Center for Comparative Medicine of Peking Union Medical College. Pauline mainly focuses on laboratory zoology, mainly engaged in the development of animal models of infectious diseases of influenza and MERS infection through the respiratory system. Its research group quickly established animal models of mouse and ferret infection during the outbreak of influenza A in 2009, and developed a multi-species transmission early warning system and an aerosol transmission early warning model to provide a realistic basis for the formulation and updating of risk assessments for new influenza viruses. Puddylan anti-inflammatory oral solution is believed to have the functions of clearing heat, detoxification, cooling blood and dissolving stasis. Researchers said that it also has a strong antiviral and antibacterial effect, has been widely used in mumps, pharyngitis, children's acute tonsillitis, acute bronchitis and so on. In this study, the researchers evaluated the efficacy of pudilan anti-inflammatory oral solution against SARS-CoV-2 through in vitro and in vivo studies, and believed that it could provide a reference for the treatment of COVID-19. The researchers first compared the differences in viral replication between the use of pudilan anti-inflammatory oral solution in SARS-CoV-2-infected Vero E6 cells with the control group.
As shown in the figure above, the semi-maximum effector concentration (EC50, concentration for 50% of maximal effect) = 1.078 mg/mL, the hemi-cytotoxic concentration (CC50) = 8.914 mg/mL, and the targeted index = 8.27 (Editor's Note: used to evaluate the safety of an extract or compound) indicate that pudilane anti-inflammatory oral solution may be effective in inhibiting viral replication and preventing viral infection. The researchers treated hACE2 transgenic mice infected with SARS-CoV-2 with pudilan anti-inflammatory oral solution to show its potential efficacy. Twelve SARS-CoV-2-infected hACE2 mice were randomly divided into two groups, namely the pudilan anti-inflammatory oral liquid treatment group and the model control group. Starting from 1 h after virus inoculation, mice are administered by the intragastric route with pudilane anti-inflammatory oral solution, the dose is in accordance with pudillan anti-inflammatory oral solution (4 μmL/kg), and then once a day for 5 days. Compared with the weight loss of the model control group, at 1 day after infection (dpi, p=0.0120), 3 dpi (p = 0.0020) and 5 dpi (p = 0.0006), the weight of mice treated with pudilan anti-inflammatory oral solution had a significant increase compared with the control group after SARS-CoV-2 infection. As shown in the following figure:
Subsequently, compared with the model control group, the viral RNA copy in the lungs of SARS-CoV-2-infected hACE2 mice treated with pudillin anti-inflammatory oral solution was significantly reduced at 3 dpi (**** p<0.0001, t = 27.94, df = 4) and 5 dpi (p = 0.0021).
These data show that pudilan anti-inflammatory oral solution has an inhibitory effect on SARS-CoV-2 in vitro and in vivo, and improves the weight loss caused by viral replication in mice. To evaluate the efficacy of pudilan anti-inflammatory oral solution against SARS-CoV-2 pneumonia, researchers observed histopathological changes in mice treated with pudilan anti-inflammatory oral solution and mice in the control group. In SARS-CoV-2-infected hACE2 mice, diffuse moderate pneumonia with interstitial hyperplasia appeared in lung tissue at 5 dpi. In addition, the alveolar interstitium is thickened by inflammatory cells and infiltration of inflammatory cells is found around the blood vessels. In contrast, the lung tissue of mice treated with pudilane anti-inflammatory oral solution showed mild interstitial pneumonia and a small amount of inflammatory cell infiltration, as shown in the following figure:
A semi-quantitative comparison of the degree of lung inflammation in the two groups showed that mice treated with pudilan anti-inflammatory oral solution had a reduced inflammation (p = 0.0034) compared with untreated control mice, as shown in the following figure:
The researchers said that these data show that pneumonia in hACE2 mice infected with SARS-CoV-2 was relieved after treatment with pudillin anti-inflammatory oral solution. Puddylan Anti-Inflammatory Oral Solution contains four herbs consisting of 181 ingredients. According to the disease enrichment analysis of the gene-targeted genes of the components of the pudilan anti-inflammatory oral solution in the therapeutic target database (TTD), the pudilan anti-inflammatory oral solution has a potential effect on asthma (p = 2.41E-03), chronic obstructive pulmonary disease (p = 2.45E-03). The researchers say these are closely related to COVID-19. Since Jinhua Qinggan Granules, Lianhua Qingyi and Wind Detoxification Capsules entered the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Seventh Edition)", the researchers excavated 84 SARS-related genes and 16 co-targeting genes (ACE, IL10, ACE2, IL6, ADAM17, GOT1, MIP, AGT, NFKB1, CCL5, RNase2, FcεR2, TNF, GPT, TPO, IFN-γ) through DisGeNET, By Venn diagram, pudilan anti-inflammatory oral solution, Jinhua Qinggan granules, Lianhua Qing plague and wind detoxification capsules were analyzed. For STRING analysis, protein-protein interaction enrichment between pudilan anti-inflammatory oral solution and SARS indicates that a highly specific physical contact was established between these 16 proteins (p = 3.82E14). The researchers analyzed the active ingredients in these 16 protein-related pudilan anti-inflammatory oral liquid compounds, as shown in the following figure:
Previous studies have reported that pudilan anti-inflammatory oral solution can alleviate pathological damage to the lungs and reduce pro-inflammatory cytokines in the serum through protein-metabolite networks, such as IL-10 and TNF-α. In the study, IL-10 and TNF-α were included in 16 targeted proteins. However, further experimental data is needed on whether these proteins are involved in immune-mediated anti-inflammatory and antiviral processes. Therefore, the researchers said that the results combined with bioinformatics and network pharmacological analysis showed that pudilane anti-inflammatory oral solution showed effective anti-SARS-CoV-2 activity in vitro and in vivo, and had better outcomes for patients, which can be used clinically alone for treatment or in combination with other effective antiviral drugs.
Source: The Paper
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