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Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

ABSTRACT: 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 F2? 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.

SUBMITTER: Gao D

PROVIDER: S-EPMC7261828 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

Gao Dan D Niu Ming M Wei Shi-Zhang SZ Zhang Cong-En CE Zhou Yong-Feng YF Yang Zheng-Wei ZW Li Lin L Wang Jia-Bo JB Zhang Hai-Zhu HZ Zhang Lan L Xiao Xiao-He XH

Frontiers in pharmacology 20200525

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. Initiall ...[more]

PMID: 32523531

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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.

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.

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.

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).

Dataset Information

Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

Publications

Identification of a Pharmacological Biomarker for the Bioassay-Based Quality Control of a Thirteen-Component TCM Formula (Lianhua Qingwen) Used in Treating Influenza A Virus (H1N1) Infection.

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