Project description: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.
Project description:BackgroundQingfei Paidu decoction (QFPDD) showed to be beneficial for the treatment of coronavirus disease 2019 (COVID-19) in China.PurposeThis study aimed to systematically assemble the evidence on the efficacy and safety of QFPDD combined with Western medicine treatments (WMT) for COVID-19.Study designSystematic review and meta-analysis.MethodsA 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.ResultsA 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)].ConclusionQFPDD 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.
Project description:Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.
Project description:Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.
Project description:Since the sudden epidemic of coronavirus disease 2019 (COVID-19), the State Administration of Traditional Chinese Medicine immediately organized experts to formulate and screen the effective prescriptions of traditional Chinese medicine according to the characteristics of the novel coronavirus infection. Qingfei Paidu decoction (QFPDD) has been proven to be effective in multi-provincial clinical trials, and has been selected as a general prescription for the treatment of COVID-19 in different stages that was later promoted to be used nationwide. This review highlights the latest advances of QFPDD, focusing on the TCM theory, mechanism analysis, clinical application of QFPDD and its future perspectives. Moreover, an in-depth discussion of some valuable issues and possible development for future research on QFPDD is also discussed, aiming to provide a novel guide to combat the global epidemic COVID-19.
Project description:ObjectiveTo explore the target, signaling pathways and their biological functions of Qingfei Paidu Decoction in the treatment of COVID-19 based on network pharmacology and molecular docking technology.MethodsThe active components and target proteins in 21 drugs such as Ephedrae Herba and Pinelliae Rhizoma in Qingfei Paidu decoction were analyzed, and the signaling pathways and biological functions of the target proteins common with COVID-19 were screened by using TCMSP, Swiss Target Prediction, CooLGeN, GeneCards, DAVID and other databases. The network diagram of Qingfei Paidu decoction was constructed using Gephi software.ResultsWe identified 163 active ingredients, including MOL004798, MOL000519, MOL004824, MOL000554, MOL010428, and MOL013443, from 18 drugs in Qingfei Paidu decoction (such as Ephedrae Herba, Pinelliae Rhizoma, Glycyrrhizae Radix Et Rhiizoma, Farfarae Flos, Asteris Radix Et Rhizoma and Aurantii Fructus Immaturus). These ingredients activate renin-angiotensin system signaling pathway and apoptosis signaling pathway by regulating 10 protein targets (ACE, ACE2, AGTR1, FURIN, TNF, CASP3, CASP6, DPP4, MCL1 and POLD1) to execute 42 biological functions such as renin-angiotensin regulation of blood volume and systemic arterial blood pressure to treat COVID-19. The results of preliminary molecular docking showed that MOL000519 (from Pinelliae Rhizoma), MOL000554 (from Farfarae Flos), MOL004798 (from Ephedrae Herba), MOL004824 (from Glycyrrhizae Radix Et Rhiizoma), MOL010428 (from Asteris Radix Et Rhizoma), and MOL013443 (from Aurantii Fructus Immaturus) had good affinity with SARS-CoV-2 3CL hydrolase to form complexes with stable conformations and high binding activity (binding energy ≤- 5 kJ/mol).ConclusionsQingfei Paidu decoction can treat COVID-19 through its multiple medicinal ingredients that have multiple targets and involve multiple signaling pathways for different biological functions. Our finding provides reference for further investigation into the pharmacological mechanism of Qingfei Paidu decoction in treating COVID-19.
Project description:Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, has spread globally, affecting people's lives worldwide and hindering global development. Traditional Chinese Medicine (TCM) plays a unique role in preventing and treating COVID-19. Representative prescriptions for the COVID-19 treatment, Lianhua Qingwen (LHQW) and Qingfei Paidu Decoction (QFPD), effectively alleviate COVID-19 symptoms, delaying its progression and preventing its occurrence. Despite the extensive similarity in their therapeutic effects, the mechanisms and advantages of LHQW and QFPD in in treating mild-to-moderate COVID-19 remain elusive. To characterize the mechanisms of LHQW and QFPD in treating COVID-19, we used integrated network pharmacology and system biology to compare the LHQW and QFPD components, active compounds and their targets in Homo sapiens. LHQW and QFPD comprise 196 and 310 active compounds, some of which have identical targets. These targets are enriched in pathways associated with inflammation, immunity, apoptosis, oxidative stress, etc. However, the two TCM formulas also have specific active compounds and targets. In LHQW, arctiin, corymbosin, and aloe-emodin target neurological disease-related genes (GRM1 and GRM5), whereas in QFPD, isofucosterol, baicalein, nobiletin, oroxylin A, epiberberine, and piperlonguminine target immunity- and inflammation-related genes (mTOR and PLA2G4A). Our findings indicate that LHQW may be suitable for treating mild-to-moderate COVID-19 with nervous system symptoms. Moreover, QFPD may effectively regulate oxidative stress damage and inflammatory symptoms induced by SARS-CoV-2. These findings may provide references for the clinical application of LHQW and QFPD.
Project description: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.
Project description: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.
Project description: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-β, 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.