[Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS].

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 µm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Chemical profiling of Qingfei Paidu Decoction by triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Qingfei Paidu Decoction is a Chinese medicine formula that has been proved effective in the treatment of coronavirus disease 2019. However, the comprehensive separation and characterization of Qingfei Paidu Decoction are of a great challenge due to the diversity of chemical components in a wide range of polarity. In this study, a triplex off-line two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is developed for the analysis of Qingfei Paidu Decoction. One reversed-phase liquid chromatography×hydrophilic interaction liquid chromatography system and two reversed-phase liquid chromatography×reversed phase liquid chromatography systems were constructed to separate polar components and weak-polar components in Qingfei Paidu Decoction, respectively. Benefiting from the good orthogonality of two-dimensional liquid chromatography and high sensitivity of quadrupole time-of-flight MS, chemical components with different polarities and content were discovered. A total of 749 peaks were detected in positive and negative ionization mode and presented as a four-dimensional data plot. Meanwhile, 498 compounds belonging to 14 categories were tentatively identified. These results provide good supplementary to elucidate the material basis of Qingfei Paidu Decoction. The triplex off-line two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry strategy can be a powerful and efficient tool for the separation and characterization of chemical substances in traditional Chinese medicine formulas.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In silico and experimental study.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.

[Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats].

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

[Rationality of Asari Radix et Rhizoma in Qingfei Paidu Decoction based on literature analysis].

Qingfei Paidu Decoction is a traditional Chinese medicine compound recommended by National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine for clinical therapies of coronavirus disease 2019(COVID-19). Qingfei Paidu Decoction consists of 21 traditional Chinese medicines, such as Asari Radix et Rhizoma. However, the dosage of Asari Radix et Rhizoma has been questioned by some people, because of one ancient proverb. To explore the rationality of the dosage of Asari Radix et Rhizoma in Qingfei Paidu Decoction, this study systematically examined the ancient and modern physicians' understanding of the toxicity of Asari Radix et Rhizoma, and collated the application and dosage of Asari Radix et Rhizoma in ancient prescriptions and modern clinics based on literature analysis. As a result, we found that ancient and modern physicians have different understanding on the toxicity of Asari Radix et Rhizoma and that the theory about the dosage of Asari Radix et Rhizoma is flawed. We also found that the dose of Asari Radix et Rhizoma in ancient and modern clinical applications was not constrained by ancient experience. Physicians usually increase the dosage of Asari Radix et Rhizoma in clinical therapy according to the actual conditions, and there were no adverse reactions. Additionally, according to laws and regulations concerning medical affairs, physician could increase or decrease the dosage of the drug under special circumstances. Based on the analysis of safety and effectiveness of Asari Radix et Rhizoma in Qingfei Paidu Decoction, we conclude that the dose of Asari Radix et Rhizoma in Qingfei Paidu Decoction is safe, effective and reasonable.

[Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology].

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 µm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.

Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. AIM OF THE STUDY: This study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. MATERIALS AND METHODS: The coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. RESULTS: The administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1ß, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. CONCLUSIONS: To sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.

Status and hotspot analysis of Qingfei Paidu Decoction for the prevention and treatment of COVID-19 based on bibliometric analysis.

Background: Qingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases. Methods: Six databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace. Results: A total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of "Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences" and "Shanghai University of Chinese Medicine Cross Academy of Science" have been formed, and two core teams with "Wang Yanping" and "Zhang Weidong" have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research. Conclusion: QFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD.

Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses.

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-ß, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.

Construction of a multi-tissue compound-target interaction network of Qingfei Paidu decoction in COVID-19 treatment based on deep learning and transcriptomic analysis.

The Qingfei Paidu decoction (QFPDD) is a widely acclaimed therapeutic formula employed nationwide for the clinical management of coronavirus disease 2019 (COVID-19). QFPDD exerts a synergistic therapeutic effect, characterized by its multi-component, multi-target, and multi-pathway action. However, the intricate interactions among the ingredients and targets within QFPDD and their systematic effects in multiple tissues remain undetermined. To address this, we qualitatively characterized the chemical components of QFPDD. We integrated multi-tissue transcriptomic analysis with GraphDTA, a deep learning model, to screen for potential compound-target interactions of QFPDD in multiple tissues. We predicted 13 key active compounds, 127 potential targets and 27 pathways associated with QFPDD across six different tissues. Notably, oleanolic acid-AXL exhibited leading affinity in the heart, blood, and liver. Molecular docking and molecular dynamics simulation confirmed their strong binding affinity. The robust interaction between oleanolic acid and the AXL receptor suggests that AXL is a promising target for developing clinical intervention strategies. Through the construction of a multi-tissue compound-target interaction network, our study further elucidated the mechanisms through which QFPDD effectively combats COVID-19 in multiple tissues. Our work also establishes a framework for future investigations into the systemic effects of other Traditional Chinese Medicine (TCM) formulas in disease treatment.

What can traditional plant therapy do in the face of Covid-19? Examples from traditional Chinese medicine.

Background: Until June 2022, more than 540.9 million people had been diagnosed with COVID-19, and the pandemic had claimed more than six million lives worldwide. Two years after fighting the virus, we faced a more uncertain position. SARS-CoV-2 is constantly mutating and reappears regularly, particularly with Omicron variants showing high genetic variation and immune escape mechanisms. The efficacy and duration of protection of existing vaccines against new variants of SARS-CoV-2 remains uncertain. The world needs time to develop new variant-specific drugs, including monoclonal topics, vaccines, and other antiviral drugs, to fight the epidemic. Objective: The aim of this study was to illustrate the scientific, effective and systematic nature of three classical prescriptions of traditional Chinese medicine (TCM) for the treatment of COVID-19 through comparison of disease symptoms, diagnostic process, and treatment methods and evidence-based and pharmacological studies. Methods: We analysed the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (Version 9) made by China, "WHO-2019-nCoV-therapeutics", "Therapeutic Guidelines" published by Australian Therapeutic Guidelines Limited, "Shanghan Lun (Treatise on Febrile Diseases)", "Jinkui Yaolue (Golden Chamber Synopsis), and "Wenyi Lun (The Epidemic Febrile Disease)". We manually retrieved the dictionary of traditional Chinese medicine (Version II). In addition, we searched the Wiley online library, National Center for Biotechnology Information (NCBI), VIP, WHO website, and China National Knowledge Infrastructure (CNKI) for relevant literature from 2001 to 2022. We searched the original plants, ingredients, pharmacology, functions and indications, usage and dosage, drug efficacy, literature sources, and conduct an evidence-based studies. We quantified the strength of pharmacological action to show the pertinence of disease development. Results: We found that the diagnosis and treatment of pulmonary infection caused by epidemic disease in TCM classics is consistent with the diagnostic process of modern medical therapeutic guidelines. The three classic prescriptions have significant symptomatic therapeutic effects on the respiratory, gastrointestinal, urinary and hematological symptoms of the clinical manifestations of COVID-19. It was found that the herbal functional group of Houpo (Cortex Magnoliae Officinalis), Chaihu (Radix Bupleuri), Cangzhu (Rhizoma Atractylodis), Qianghuo (Notopterygii Rhizoma et Radix), etc showed strong anti-inflammatory activity and had a positive effect on treating and preventing the outbreaks of systemic inflammatory factors. Conclusion: TCM can obtain obvious curative effect in symptomatic treatment, has strong anti-inflammatory effect, and can effectively reduce symptoms and patients' pain.

Long-term effects of Qingfei Paidu decoction in patients with coronavirus disease 2019 acute pneumonia after treatment: a protocol for systematic review and Meta-analysis.

This study aims to provide evidence regarding whether Qingufei paidu decoction (, QFPD) treatment in the acute phase shows long-term benefits for coronavirus disease 2019-associated sequelae. The 10 databases will be retrieved. Every reference list of related trials and gray literature will be searched as well. Study screening, data extraction, and risk of bias evaluation will be performed by two reviewers (CUI Hanjin and FAN Rong). Data analysis will be conducted by using STATA (version 14). Statistical heterogeneity will be explored by a standard χ2 test with a significance level of P < 0.10. Funnel plots, Egger's & Begg's test, and Trim and Fill analysis will be used for publication bias assessment. The results of the present Meta-analysis and systematic review will be disseminated via peer-review journal publication. Ethical approval is not required, as this Meta-analysis will not contain any individual patient data. This systematic review has been registered on PROSPERO (registration number: CRD42021246937) on 15 April 2021.

An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PURPOSE: An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. METHODS: Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). RESULTS: According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. CONCLUSION: In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.

New insights for infection mechanism and potential targets of COVID-19: Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide. Currently, there is no accepted specific drug for COVID-19 treatment. Therefore, it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19. According to several reliable reports from China, traditional Chinese medicine (TCM), especially for three Chinese patent medicines and three Chinese medicine formulas, has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines. In this review, we systematically summarized and analyzed the pathogenesis of COVID-19, the detailed clinical practice, active ingredients investigation, network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat. Additionally, we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism, which provides guidance for the development of new drugs against COVID-19. Collectively, by addressing critical challenges, for example, unclear targets and complicated active ingredients of these medicines and formulas, we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.

Treatment Effect of Qingfei Paidu Decoction Combined With Conventional Treatment on COVID-19 Patients and Other Respiratory Diseases: A Multi-Center Retrospective Case Series.

Background: Qingfei Paidu decoction (QFPDD) has been widely used in treating coronavirus disease 2019 (COVID-19) in China. However, studies on the treatment effect of COVID-19 patients and other respiratory diseases have not been well demonstrated. Our study aims to determine the treatment effect of QFPDD in combination with conventional treatment on COVID-19 patients and other respiratory diseases. Methods: This retrospective study recruited COVID-19 patients who were treated with QFPDD for at least two courses (6 days) from seven hospitals in five provinces from January 21 to March 18 2020. Demographic, epidemiological, clinical, laboratory, computed tomography characteristics, treatment, and outcome data were collected and analyzed. The improvements in clinical symptoms before and after QFPDD treatment were compared. Results: Eight COVID-19 patients were included in this study. Of them, six were males (75.0%). The median age of the patients was 66 (60-82) years. Four patients were classified as mild and moderate cases (50.0%); there were two severe cases (25.0%) and critical cases (25.0%). The most common symptom was cough (7 [87.5%]), followed by fever (6 [75.0%]), fatigue (4 [50.0%]), asthma (4 [50.0%]), and anorexia (3 [37.5%]). Abnormal findings included decrease in neutrophils (3 [37.5%]), lymphocytes (2 [25.0%]), alkaline phosphatase (3 [37.5%]), lactic dehydrogenase (4 [50.0%]), erythrocyte sedimentation rate (2 [25.0%]), and C-reactive protein (5 [83.3%]) at admission. After one course (3 days) of QFPDD, nasal obstruction and sore throat completely disappeared, and fever (5 [83.3%]), fatigue (2 [50.0%]), and cough (2 [28.6%]) were improved. After two courses (6 days), the fever disappeared completely in all patients, and the other symptoms showed a tendency to improve. In non-severe patients, 87.5% baseline symptoms completely disappeared. In severe patients, 61.1% of the baseline symptoms completely disappeared after patients were administered QFPDD for two courses. Of the abnormal indicators, 55.6% returned to normal levels. The median duration to complete fever recovery was 1.0 day. The median durations of viral shedding and hospitalization were 10.5 and 21.5 days, respectively. None of the patients worsened and died, and no serious adverse events occurred related to QFPDD during hospitalization. Conclusion: QFPDD combined with conventional treatment improved clinical symptoms in COVID-19 patients with other respiratory diseases, and no serious adverse reactions associated with QFPDD were observed. Larger sample studies confirm our findings in the future.

Effect and Mechanism of Qingfei Paidu Decoction in the Management of Pulmonary Fibrosis and COVID-19.

Qingfei Paidu decoction (QFPD) has been repeatedly recommended for the clinical treatment of novel coronavirus disease 2019 (COVID-19) in multiple provinces throughout China. A possible complication of COVID-19 lung involvement is pulmonary fibrosis, which causes chronic breathing difficulties and affects the patient's quality of life. Therefore, there is an important question regarding whether QFPD can alleviate the process of pulmonary fibrosis and its potential mechanisms. To explore this issue, this study demonstrated the anti-pulmonary fibrosis activity and mode of action of QFPD in vivo and in vitro pulmonary fibrosis models and network pharmacology. The results showed that QFPD effectively ameliorated the bleomycin-induced inflammation and collagen deposition in mice and significantly improved the epithelial-mesenchymal transition in pulmonary fibrosis in mice. In addition, QFPD inhibited bleomycin-induced M2 polarization of macrophages in pulmonary tissues. An in-depth study of the mechanism of QFPD in the treatment of pulmonary fibrosis based on network pharmacology and molecular simulation revealed that SRC was the main target of QFPD and sitosterol (a key compound in QFPD). QFPD and sitosterol regulate the EMT process and M2 polarization of macrophages by inhibiting the activation of SRC, thereby alleviating pulmonary fibrosis in mice. COVID-19 infection might produce severe fibrosis, and antifibrotic therapy with QFPD may be valuable in preventing severe neocoronavirus disease in patients with IPF, which could be a key factor explaining the role of QFPD in the treatment of COVID-19.

Effect of Qingfei Paidu decoction combined with Western medicine treatments for COVID-19: A systematic review and meta-analysis.

BACKGROUND: Qingfei Paidu decoction (QFPDD) showed to be beneficial for the treatment of coronavirus disease 2019 (COVID-19) in China. PURPOSE: This study aimed to systematically assemble the evidence on the efficacy and safety of QFPDD combined with Western medicine treatments (WMT) for COVID-19. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, CSTJ, CBM, Wanfang Data for clinical trials with a control arm until January 13, 2022. Studies matched the selection criteria were included. Data extraction and quality assessment of the included studies were independently conducted by two reviewers. Review Manager 5.4 was used for meta-analysis. RESULTS: A total of 9 trials including 1108 COVID-19 patients met the selection criteria. Meta-analysis demonstrated that QFPDD combined with WMT reduced aggravation rate (AR) by 71% [risk ratio (RR) = 0.29, 95% confidence intervals (CI) (0.17, 0.51)], increased effective rate (ER) by 13% [RR = 1.13, 95%CI (1.04, 1.22)], shortened 4.78 days of viral shedding [95%CI (-5.79, -3.77)] and 4.45 days of hospital stay [95%CI (-6.05, -2.86)], also decreased the incidence of adverse events (AE) by 56% [RR = 0.44, 95%CI (0.22, 0.89)]. CONCLUSION: QFPDD combined with WMT might reduce the proportion of severe cases and the incidence of AE, shorten the duration of viral shedding and length of hospital stay. More randomized controlled trials (RCTs) are required to confirm our findings in the future.

Identification of phytochemicals in Qingfei Paidu decoction for the treatment of coronavirus disease 2019 by targeting the virus-host interactome.

Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of COVID-19. The antiviral activity of the active components was determined by a live virus infection assay, and possible mechanisms were analysed by pseudotyped virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of IL-6, IL-1ß and CXCL-10 were detected by ELISA. Three components of QFPDD, oroxylin A, hesperetin and scutellarin, exhibited potent antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC50 values ranging from 18.68 to 63.27 µM. Oroxylin A inhibited the entry of SARS-CoV-2 pseudovirus into target cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion by binding with the ACE2 receptor. The active components of QFPDD obviously inhibited the IL-6, IL-1ß and CXCL-10 release induced by the SARS-CoV-2 S protein. This study supports the clinical application of QFPDD and provides an effective analysis method for the in-depth study of the mechanisms of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19.

Efficacy and Safety of Qingfei Paidu Decoction for Treating COVID-19: A Systematic Review and Meta-Analysis.

Background: Qingfei Paidu decoction (QFPD) has been widely used in treating COVID-19 in China. However, there is still a lack of comprehensive and systematic evidence to demonstrate the effectiveness and safety of QFPD. This study aims to evaluate the efficacy and safety of QFPD in patients with COVID-19. Methods: We searched seven databases up to 5 March 2021. Two reviewers independently screened studies, extracted data of interest, and assessed risk of bias. The Cochrane risk of bias tool was used to assess the risk of bias of randomized controlled trials. The Newcastle-Ottawa scale was used to assess the risk of bias of cohort and non-randomized trials. The "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" was adopted for controlled pre-post studies. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of evidence. We carried out a random effect meta-analysis using RevMan 5.3. For outcomes that could not be meta-analyzed, we performed a descriptive analysis. Results: We identified 16 studies with 11,237 patients, including one RCT, six non-randomized trials, two cohort studies, and seven pre-post studies. The certainty of evidence was low to very low because of the observational study design. QFPD combined with conventional treatment might decrease the time for nucleic acid conversion (MD = -4.78 days, 95% CI: -5.79 to -3.77), shorten the length of hospital stay (MD = -7.95 days, 95% CI: -14.66 to -1.24), shorten the duration of symptoms recovery of fever (MD = -1.51 days, 95% CI: -1.92 to -1.09), cough (MD = -1.64 days, 95% CI: -1.91 to -1.36) and chest CT (MD = -2.23 days, 95% CI: -2.46 to -2.00), improve the overall traditional Chinese medicine symptom scores (MD = 41.58 scores, 95% CI: 32.67 to 50.49), and change the laboratory indexes, such as WBC, AST, and CRP. Conclusion: QFPD combined with conventional treatment might be effective for patients with COVID-19. No serious adverse reactions related to QFPD were observed. Further high-quality studies are still needed in the future.