Establishment of an anti-inflammation-based bioassay for the quality control of the 13-component TCM formula (Lianhua Qingwen).
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ABSTRACT: Context
Owing to the complexity of chemical ingredients in traditional Chinese medicine (TCM), it is difficult to maintain quality and efficacy by relying only on chemical markers.Objective
Lianhua Qingwen capsule (LHQW) was selected as an example to discuss the feasibility of a bioassay for quality control.Materials and methods
Network pharmacology was used to screen potential targets in LHQW with respect to its anti-inflammatory effects. An in vitro cell model was used to validate the prediction. An anti-inflammatory bioassay was established for the quality evaluation of LHQW in 40 batches of marketed products and three batches of destructed samples.Results
The tumor necrosis factor/interleukin-6 (TNF/IL-6) pathway via macrophage was selected as the potential target of LHQW. The IC50 value of LHQW on RAW 264.7 was 799.8 μg/mL. LHQW had significant inhibitory effects on the expression of IL-6 in a dose-dependent manner (p < 0.05). The anti-inflammatory biopotency of LHQW was calculated based on the inhibitory bioactivity on IL-6. The biopotency of 40 marketed samples ranged from 404 U/μg to 2171 U/μg, with a coefficient of variation (CV) of 37.91%. By contrast, the contents of forsythin indicated lower CV (28.05%) than the value of biopotency. Moreover, the biopotencies of destructed samples declined approximate 50%, while the contents of forsythin did not change. This newly established bioassay revealed a better ability to discriminate the quality variations of LHQW as compared to the routine chemical determination.Conclusions
A well-established bioassay may have promising ability to reveal the variance in quality of TCM.
SUBMITTER: Chen S
PROVIDER: S-EPMC8110188 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F2α and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by in vivo gene expression and in vitro enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.
| S-EPMC7261828 | biostudies-literature
Project description:Influenza is a common respiratory infectious disease. In China, Lianhua Qingwen capsule (LHQWC), a drug with significant clinical efficacy and few side effects, is commonly used to treat influenza. However, the composition of LHQWC is complicated, and currently used quality control methods cannot ensure its consistency. In this study, combined with its clinical efficacy, the targets of LHQWC were screened using network pharmacology. Then, anti-inflammation quality markers of LHQWC were screened and judged by combined chemical with biological evaluation. Cyclooxygenase-2 (COX-2) was identified as one of the main targets of the anti-inflammatory activity of LHQWC. The rate of inhibition of COX-2 by different batches of LHQWC was determined. Furthermore, seven components of LHQWC were identified. The potential quality markers were screened by spectral-effect relationship. As a result, chlorogenic acid, isochlorogenic acid B, and isochlorogenic acid C were identified and confirmed as anti-inflammatory quality markers of LHQWC. We hope that these findings provide a scientific basis for the accurate quality control of LHQWC and serve as a reference for the quality control of other drugs.
| S-EPMC8226139 | biostudies-literature
Project description:BackgroundLianhua Qingwen Capsules (LHQW) is a traditional Chinese medicine prescription commonly used to treat viral influenza in China. There has been sufficient evidence that LHQW could effectively treat COVID-19. Nevertheless, the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds in LHQW are still vague.MethodsThe compounds of LHQW and targets were collected from TCMSP, TCMID, Shanghai Institute of Organic Chemistry of CAS database, and relevant literature. Autodock Vina was used to carry out molecular docking. The pkCSM platform to predict the relevant parameters of compound absorption in vivo. The protein-protein interaction (PPI) network was constructed by the STRING database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out by Database for Annotation, Visualization, and Integrated Discovery (DAVID). The anti-(mutant) SARS-CoV-2 and anti-inflammation networks were constructed on the Cytoscape platform.Results280 compounds, 16 targets related to SARS-CoV-2, and 54 targets related to cytokine storm were obtained by screening. The key pathways Toll-like receptor signaling, NOD-like receptor signal pathway, and Jak-STAT signaling pathway, and the core targets IL6 were obtained by PPI network and KEGG pathway enrichment analysis. The network analysis predicted and discussed the 16 main anti-SARS-CoV-2 active compounds and 12 main anti-inflammation active compounds. Ochnaflavone and Hypericin are potential anti-mutant virus compounds in LHQW.ConclusionsIn summary, this study explored the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of LHQW against COVID-19, which can provide new ideas and valuable references for discovering active compounds in the treatment of COVID-19.
| S-EPMC9261255 | biostudies-literature
Project description:BackgroundAn outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002-2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment.PurposeThis review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19.Study design and methodThe research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were "virus", "COVID-19", or "SARS-CoV-2", and "Lianhua Qingwen". The documents were filtered and summarized for final evaluation.ResultsThe collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function.ConclusionAlthough the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.
| S-EPMC7437484 | biostudies-literature
Project description:BackgroundTraditional Chinese medicine (TCM) has been proven to played a great important role on the treatment of COVID-19. As one of the drugs recommended in Chinese guidelines, Lianhua Qingwen Granules or Capsules (LQ) are widely used.This systematic review and meta-analysis amis to evaluate the clinical efficacy of LQ on the treatment of COVID-19.MethodsSeven databases (PubMed, EMBASE, CENTRAL, CNKI, VIP, CBM and Wanfang) were searched to include all appropriate clinical trials that explore the efficacy of LQ on the treatment of COVID-19.ResultA total of 3 trials including 245 COVID-19 patients were eventually enrolled.Compared with the control group,the LQ group showed great significant difference on reducing the rate of clinical change to severe or critical condition[RR = 0.38, 95 %CI (0.17,0.85), P < 0.05]and the fever time (SMD =-0.57,95 %CI (-0.96,-0.17), P<0.05),as well as the significant improvement on the disappearance rate of the clinical symptoms: fever [RR = 1.36,95 %CI (1.14,1.61), P < 0.05],cough[RR = 1.99,95 %CI (1.39,2.86), P < 0.05],fatigue[RR = 1.52,95 %CI (1.15,2.01), P < 0.05] and anhelation [RR = 4.18,95 %CI (1.99,8.81), P < 0.05], but no significance on expectoration[RR = 2.46,95 %CI (0.81,7.51), P < 0.05].ConclusionThe clinical application of LQ on the treatment of COVID-19 has significant efficacy in improving clinical symptoms and reducing the rate of clinical change to severe or critical condition. Nevertheless, due to the limited quantity and quality of the included studies, more and higher quality trials with more observational indicators are expected to be published.
| S-EPMC8213518 | biostudies-literature
Project description:The traditional Chinese medicine formula Lianhua Qingwen (LQ) combined with western medicine therapy is beneficial to coronavirus disease-19 (COVID-19), but there is still a lack of strong evidence-based. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LQ combined with western medicine for patients with COVID-19. Seven databases (Chinese and English) were searched by two independent reviewers. Search for relevant keywords such as “Chinese medicine,” “Chinese herbal medicine,” and “Lianhua Qingwen” in the titles and abstracts of articles retrieved in the databases. Randomized controlled trials or case-control studies that reported sufficient data of participants before and after the intervention were included. Two researchers independently reviewed the studies and extracted the data. Fixed-or random-effect model was used to calculate the overall pooled risk estimates. Forest plots were generated to show pooled results. Seven studies involving 916 participants were included in the meta-analysis. Overall, compared with the control group, the total efficacy (OR = 2.23, 95% CI 1.56, 3.18), adverse events (OR = 0.42, 95% CI 0.18, 0.97), chest computed tomography manifestations (OR = 1.74, 95% CI 1.12, 2.72), and aggravation rate of conversion to severe cases (OR = 0.47, 95% CI 0.30, 0.75) of the intervention group were better. Moreover, the intervention group has an advantage over the control group in improving clinical symptoms (fever, cough, fatigue, chest tightness, shortness of breath, and expectoration) and shortening the fever duration (p < 0.05). Our findings indicate that LQ combined with western medicine may be more effective in treating COVID-19. However, due to the urgency of SARS-CoV-2 outbreaks leading to low methodological quality and not rigorous designs. This meta-analysis cannot draw clear conclusions. PROSPERO registration number: CRD42020190757
| S-EPMC9204491 | biostudies-literature
Project description:Background and Purpose: Sepsis is a life-threatening condition associated with secondary multiple organ injury. Acute lung injury (ALI) caused by sepsis has high morbidity and mortality in critical care units. Lianhua Qingwen (LHQW) is a traditional Chinese medicine composing of 11 herbs and 2 medicinal minerals. LHQW exhibits anti-inflammatory activity and is effective in treating pneumonia. Our study aimed to evaluate the effect of LHQW on sepsis-induced ALI and its underlying mechanism. Materials and Methods: A network pharmacology approach was used to predict the bioactive components and effective targets of LHQW in treating ALI. We established ALI model C57/BL6 mice via an intraperitoneal injection of LPS and inhibited p53 expression by pifithrin-α, in order to validate the mechanism by which LHQW exerted protective role in ALI. Hematoxylin-eosin staining was conducted to assess the severity of lung injury. The severity of inflammation was evaluated based on MPO (myeloperoxidase) activity. TUNEL assay was employed to detect apoptotic cells. The levels of p53 and caspase-3 were tested by immunohistochemical staining and Western blotting. The expression levels of Bcl-2, Bax, cytochrome C and caspase-9 were detected by Western blotting. Results: A total of 80 genes were associated with LHQW in the treatment of ALI. After PPI network construction, four active components (quercetin, luteolin, kaempferol and wogonin) and 10 target genes (AKT1, TP53, IL6, VEGFA, TNF, JUN, STAT3, MAPK8, MAPK1, and EGF) were found to be essential for ALI treatment. GO and KEGG analyses indicated that apoptosis pathway was mainly involved in the LHQW-ALI network. Animal experiments showed that LHQW was able to attenuate LPS-induced ALI, and medium-dose LHQW exhibited the most prominent effect. LHQW could inhibit the overexpression of p53 induced by LPS and suppress p53-mediated intrinsic apoptotic pathways by decreasing the levels of Bax, caspase-3 and caspase-9, increasing the expression of Bcl-2, and attenuating the release of cytochrome C in ALI mice. Conclusion: This study reveals that LHQW may alleviate LPS-induced ALI via inhibiting p53-mediated intrinsic apoptosis pathways.
| S-EPMC8551812 | biostudies-literature
Project description:BackgroundCorona virus disease 2019 (COVID-19) has spread around the world since its outbreak, and there is no ascertained effective drug up to now. Lianhua Qingwen (LHQW) has been widely used in China and overseas Chinese, which had some advantages in the treatment of COVID-19.ObjectiveTo evaluate the efficacy and safety of LHQW for COVID-19 by conducting a systematic review with meta-analysis.MethodsA comprehensive literature search was conducted in 12 electronic databases from their establishment to October 30, 2021. Note Express 3.2.0 was used for screening of trials, and the data was independently extracted in duplicate by 2 researchers. The risk of bias of randomized controlled trials (RCTs) and retrospective studies were assessed by using the Cochrane collaboration tool and Newcastle Ottawa Scale, respectively, followed by data analysis using RevMan 5.3. The RCTs or retrospective studies to treat COVID-19 using LHQW were included. The intervention measures in the experimental group were LHQW alone or combined with chemical drugs (LCWC), and that in the control group were chemical drugs (CDs). Outcome measures included computed tomography (CT) recovery rate, disappearance rates of primary (fever, cough, fatigue), respiratory, gastrointestinal and other symptoms, exacerbation rate and adverse reaction. Subgroup analysis was conducted according to whether LHQW was combined with CDs and the different treatment methods in the control group.ResultsNine trials with 1,152 participants with COVID-19 were included. The CT recovery rates of LHQW and LCWC were 1.36 and 1.32 times of CDs, respectively (P<0.05). Compared with CDs, LCWC remarkably increased the disappearance rates of fever, cough, fatigue, expectoration, shortness of breath, and muscle soreness (P<0.05). LHQW also obviously decreased the exacerbation rate, which was 0.45 times of CDs alone (P<0.05). There was no obvious difference between LCWC and CDs in adverse reaction (P>0.05).ConclusionsLHQW was more suitable for treating COVID-19 patients with obvious expectoration, shortness of breath and muscle soreness. LHQW had advantages in treating COVID-19 with no obvious exacerbation. (PROSPERO No. CRD42021235937).
| S-EPMC9247911 | biostudies-literature
Project description:Objectives: Lianhua Qingwen capsule/granule (LHQW) is an innovative patented traditional Chinese medicine with potential curative effects on respiratory diseases. However, no consensus has been reached on the security of LHQW to date. The current meta-analysis was performed to evaluate the safety profile of LHQW in relation to conventional drugs (PROSPERO CRD-42020224180). Methods: Comprehensive document retrieval was performed from both English and Chinese databases. Results were reported as risk ratio (RR) with 95% confidence interval (CI). Subgroup, sensitivity and meta-regression analyses were conducted to explore the possible sources of heterogeneity across eligible studies. Results: In total, 217 experimental studies were included. For pooled studies, the incidence of adverse reactions was lower in the LHQW group than the conventional drug group (RR = 0.63, 95% CI = 0.58-0.69, p < 0.001). In the evaluation of treating disease, significant reduced incidence of adverse reactions during treatment of influenza A (H1N1) and influenza were detected in the LHQW group. 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. Subgroup analysis additionally revealed a reduced incidence of some adverse reactions in the LHQW group compared to the conventional drug group (Rash of skin and its appendage damage, dizziness or headache owing to nervous system damage, nausea or vomiting from gastrointestinal system damage and resurgence of disease from other adverse reactions). Conclusion: The current study provides potential a reference for the security of LHQW. Further long-term high-quality studies are essential to validate our conclusions. Systematic Review Registration: https://clinicaltrials.gov/, CRD-42020224180.
| S-EPMC8830515 | biostudies-literature
Project description:IntroductionAs the global epidemic continues to spread, countries have tapped effective drugs to treat new coronavirus pneumonia. The therapeutic effect of the traditional Chinese medicine Lianhua Qingwen in this new coronary pneumonia epidemic has attracted attention from all walks of life, and relevant research reports continue to appear. Therefore, we conducted a systematic review of the clinical efficacy and safety of the traditional Chinese medicine Lianhua Qingwen in the treatment of new coronavirus pneumonia (COVID-19) (referred to as "new coronary pneumonia"), and evaluated the overall level of research quality.MethodsWe searched seven databases and retrieved the Chinese Journal Full-text Database (CNKI), Vip Database (VIP), China Biomedicine (SinoMed), Wanfang Database and PubMed, Cochrane Central, EMBASE from October 2019 to May 2020 Literature references. We included randomized controlled trials (RCTs) that tested the efficacy of the traditional Chinese medicine lotus clearing plague in the treatment of new coronavirus pneumonia. The authors extracted data and independently assessed quality. We used Stata15.1 software to analyze the data of randomized trials.ResultsA total of 2 articles were identified, including 154 patients. All the participating patients were diagnosed with new coronavirus pneumonia (COVID-19). The meta-analysis results showed that the disappearance rate of the main clinical symptoms of Chinese medicine Lianhua Qingwen in the treatment of new coronavirus pneumonia was significantly higher than that of the control group [OR = 3.34, 95% CI (2.06, 5.44), P <0.001]; the disappearance rate of other clinical secondary symptoms is significantly higher than the control group [OR = 6.54, 95% CI (3.59, 11.90), P <0.001]. The duration of fever was significantly lower than that of the control group [OR = -1.04, 95% CI (-1.60, -0.49), P <0.001]. It is confirmed that the traditional Chinese medicine Lianhua Qingwen treatment improves the clinical effectiveness, and also has certain advantages in relieving cough and fever.ConclusionThe treatment of new pneumonia with traditional Chinese medicine lotus clearing plague can be used as an effective therapy to improve the clinical symptoms of new coronary pneumonia. More rigorous design, multi-center, and prospective RCTs are necessary to further determine the effectiveness and safety of the traditional Chinese medicine lotus decoction in the treatment of new pneumonia.
| S-EPMC7485773 | biostudies-literature