RESUMEN
Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Medicina Tradicional China/efectos adversos , Internacionalidad , Medicamentos Herbarios Chinos/efectos adversosRESUMEN
With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Consenso , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Factores de Riesgo , Suplementos Dietéticos/efectos adversosRESUMEN
BACKGROUND & AIMS: Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. METHODS: After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. RESULTS: A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. CONCLUSIONS: ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. LAY SUMMARY: Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Masculino , Adulto , Femenino , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Antivirales/uso terapéutico , China/epidemiologíaRESUMEN
Traditional Chinese medicine(TCM) has made outstanding contributions to disease prevention and treatment, survival, and reproduction of the Chinese nation. Currently, the inheritance and innovative development of TCM have become a national strategy. However, in recent years, adverse reactions/events of Chinese medicine frequently occurred. In particular, in terms of the safety problem of newly discovered "toxic" Chinese medicine, it is often difficult to answer the question scientifically and develop effective solutions. When facing international public opinions and public questioning, they are often "passively criticized". To solve the difficult problem about the safety of Chinese medicine, we urgently need to make breakthroughs in the cognition of toxicity of Chinese medicine and prevention and control of risks. This research team has been committed to the research on the safety of Chinese medicine for the long term. In particular, in terms of safety evaluation and risk prevention and control of newly discovered "toxic" Chinese medicine, they have made a series of original discoveries. On the basis of the discoveries, they innovated the cognition theory and methods of the toxicity of Chinese medicine, opened up a new field of research on the idiosyncratic toxicity and indirect toxicity of Chinese medicine, and proposed and established the disease-syndrome-based toxicology(DSBT), the model and method of safety evaluation of Chinese medicine related to diseases and syndromes. In light of the theory and methods of DSBT which have been applied to the objective eva-luation and analysis of the mechanism of the hepatotoxicity of Chinese medicine such as Polygoni Multiflori Radix, the mechanism hypothesis of "toxicity due to three causes" of idiosyncratic hepatotoxicity of Chinese medicine was proposed and confirmed. The findings revealed that the substances that induced idiosyncratic or indirect toxicity in Chinese medicine often did not possess definite direct toxi-city. Therefore, this research team proposed the concept of toxicity-related substances(TRS) in Chinese medicine. Based on the mo-dern scientific cognition of toxicity of Chinese medicine, the team proposed the strategy and method of Chinese medicine compatibility to reduce the toxicity based on the component-effect-target interaction to underpin the demonstration of the scientific connotation of toxicity and side effects of "toxic" Chinese medicine and establishment of scientific and effective risk prevention and control strategies. In light of the innovative development of toxicity cognition of Chinese medicine, this study is expected to provide important theoretical guidance and methodological support for scientific evaluation and precise prevention and control of the safety risk of "toxic" Chinese medicine.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicamentos Herbarios Chinos , Cognición , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Medicamentos Herbarios Chinos/toxicidad , Humanos , Medicina Tradicional ChinaRESUMEN
OBJECTIVE: To compare the risk of liver-related adverse drug reactions (ADRs) in children and adults. STUDY DESIGN: A case/non-case analysis on spontaneous reports based on the China National Adverse Drug Reactions Monitoring System database were conducted, focusing on events of liver-related ADRs in children younger than 14 years of age. Both the relative risk of liver-related ADRs in children vs entire population and the risk stratification in children were expressed as a measure of disproportionality using the reporting odds ratio (ROR). RESULTS: There were 1206 cases of pediatric liver-related ADRs identified from 2012 to 2016, accounting for 2.82% of the entire population. The greatest ROR values in children from 0 to 14 years vs the entire population were observed for analgesics (3.97, 95% CI 3.27-4.81), respiratory (2.60, 95% CI 1.04-6.43), antineoplastic (2.29, 95% CI 2.02-2.58), immunomodulatory (1.91, 95% CI 1.44-2.53), and antimicrobial agents (1.47, 95% CI 1.33-1.63). Notably, infants aged 0-1 years showed significantly greater risk (3.14, 95% CI 2.85-3.48) of liver-related ADRs than the other age groups of children. For infants, analgesics (3.21, 95% CI 2.20-4.66) and antimicrobials (3.15, 95% CI 2.50-3.97) agents were found to have the greatest adjusted RORs than other drug categories. The highest RORs were found for meropenem, amoxicillin, fluconazole, vancomycin, cefaclor, and ceftazidime in the antimicrobial agents for infants. CONCLUSIONS: Children are sensitive to liver-related ADRs caused by several specific drug categories, and infants are the most sensitive.
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Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Distribución por Edad , Analgésicos/efectos adversos , Antiinfecciosos/efectos adversos , Antineoplásicos/efectos adversos , Niño , Preescolar , China/epidemiología , Humanos , Lactante , Recién Nacido , Oportunidad RelativaRESUMEN
AIM: The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute-on-chronic liver failure (ACLF). METHODS: Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n = 57) and those with worse outcomes (n = 45), and controls (n = 15) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. RESULTS: Forty-one metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), L-metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC] = 0.859, 95% confidence interval [CI] = 0.787-0.931). Compared with Model for End-Stage Liver Disease (MELD) score (AUC = 0.639, 95% CI = 0.526-0.753) and MELD-sodium (MELD-Na) score (AUC = 0.692, 95% CI = 0.582-0.803), EBC-associated metabolite signature model could better predict worse outcomes in patients with ACLF (p < 0.05). Using the MELD-Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846-0.965). CONCLUSION: EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.
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Owing to the complexity of the composition of herbal and dietary supplements, it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) was selected as the subbject to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging, ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identify unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and the toxicity intensity verified by high-content imaging. The maximum nontoxic dose of processed samples with good detoxification effect reduced more than 9 times compared with unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone and neobavaisoflavone had high correlation with the hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with hepatotoxicity. This study verified the hepatotoxicity of these six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging of hepatocyte toxicity data, the potential toxic compound of herbal and dietary supplement products can be quickly and accurately screened.
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Suplementos Dietéticos/toxicidad , Medicamentos Herbarios Chinos/toxicidad , Hepatocitos/efectos de los fármacos , Psoralea/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ficusina/toxicidad , Flavonoides/toxicidad , Humanos , Isoflavonas/toxicidad , Espectrometría de Masas/métodos , Imagen Molecular/métodosRESUMEN
The output of high level innovative Chinese medicines(CM) is very rare for a few years, which is in sharp contrast to the reality that antibody drugs, small molecular targeted therapy, antibody-drug conjugate and other innovative drugs have heavy investment and high yield. Acceleration for the research and development of innovative CM drugs obviously relies on breakthrough of the modes of thinking and methodology. Deeply influenced by the thinking of allopathic medicine in Western science system, the mainstream of current basic researches on CM is to find the components and their molecular mechanisms that can directly inhibit or antagonize the target in disease focal. However, it is difficult to explain the mechanism of the reported " active" components in many CMs, since their steady-state concentrations in disease focal are usually significantly lower than the effective concentrations of those components. Therefore, based on the original methodology of CM-systemism and harmonizing medicine, this paper proposed that the mechanism of action of CMs may not be limited to the direct antagonistic effect on the target in disease focal. Instead, it may involve indirect action through the intermediate substances across different organs or systems with a long-distance action pattern.A fundamentally break may be achieved when exploring the mechanism of action of CM active components from the perspective of indirect action. It may also change the thinking of allopathic medicine in the researches of CM and start a new innovative road for the development of indirect-acting CMs.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , ChinaRESUMEN
Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.
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Medicamentos Herbarios Chinos , Antiinflamatorios/farmacología , Bioensayo , Medicamentos Herbarios Chinos/farmacología , Humanos , Medicina Tradicional China , Control de Calidad , RizomaRESUMEN
Uncontrolled activation of NLRP3 inflammasome initiates a series of human inflammatory diseases. Targeting NLRP3 inflammasome has attracted considerable attention in developing potential therapeutic interventions. Here, we reported that dehydrocostus lactone (DCL), a main component of Saussurea lappa from the traditional Chinese medicine, inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent interleukin (IL)-1ß production in primary mouse macrophages and human peripheral blood mononuclear cells and exerted an inhibitory effect on NLRP3-driven inflammation. Mechanistically, DCL significantly blocked the ASC oligomerization, which is essential for the assembly of activated inflammasome. Importantly, in vivo experiments showed that DCL reduced IL-1ß secretion and peritoneal neutrophils recruitment in LPS-mediated inflammation mouse model, which is demonstrated to be NLRP3 dependent. These results suggest that DCL is a potent pharmacological inhibitor of NLRP3 inflammasome and may be developed as a therapeutic drug for treating NLRP3-associated diseases.
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Quimiotaxis de Leucocito/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Inflamasomas/efectos de los fármacos , Inflamación/prevención & control , Lactonas/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Macrófagos/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Sesquiterpenos/farmacología , Adulto , Animales , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/fisiología , Proteínas Adaptadoras de Señalización CARD/antagonistas & inhibidores , Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas de Unión al Calcio/antagonistas & inhibidores , Proteínas de Unión al Calcio/fisiología , Caspasa 1/metabolismo , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/fisiología , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Interleucina-1beta/biosíntesis , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Nigericina/farmacología , Poli I-C/farmacología , Polimerizacion/efectos de los fármacos , Organismos Libres de Patógenos Específicos , Ácido Úrico/farmacologíaRESUMEN
Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case-control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography-mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion.
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Sangre/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Medicamentos Herbarios Chinos/efectos adversos , Fallopia multiflora , Adulto , Biomarcadores Farmacológicos/sangre , Sangre/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Citocinas/sangre , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Metabolómica/métodos , Curva ROCRESUMEN
A total of 1 392 reports on liver injury associated adverse drug reaction(LI-ADR) related to bone diseases were retrospectively analyzed based on national ADR monitoring system [18.75% of the patients used traditional Chinese medicine(TCM) alone and 68.68% used Western medicine alone]. This kind of cases accounted for 2.5% of all drug-related liver injury adverse reactions, ranking top ten of all drug categories. The number of reported cases and the proportion of serious cases showed an increasing trend from 2012 to 2016. The average age of the patients was(54.2±15.8) years old, and there was little difference in overall gender(male-female 1.04â¶1). However, the number of female patients with rheumatoid arthritis was significantly higher than that of male patients(male-female 1â¶2.6), while the number of male patients with gout was significantly higher than that of female patients(male-female 7.16â¶1). The overall prognosis was good, with the recovery and improvement rate of 85.27%. The time from medication to liver injury varied due to different medicines. The median time to liver injury was 27 days in TCM alone group, later than 11 days in Western me-dicine alone group(P<0.05). Drugs for bone diseases have been one of the important categories for clinical drug-induced liver injury, and the number of reported cases on liver injury caused by drugs for bone diseases is increasing, so we should pay close attention to the safe and rational use of them. The LI-ADRs of male and female were different due to their different diseases, and the latency of adverse reactions in TCM group was generally longer than that in Western medicine group. In clinical medication, liver function should be monitored according to different diseases and characteristics of drugs to prevent the risk of liver injury.
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Enfermedades Óseas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicamentos Herbarios Chinos , Adulto , Anciano , Femenino , Humanos , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.
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Infecciones por Coronavirus/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Neumonía Viral/tratamiento farmacológico , Enzima Convertidora de Angiotensina 2 , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Betacoronavirus , COVID-19 , China , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/química , Tratamiento Farmacológico de COVID-19RESUMEN
The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.
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Antiinflamatorios/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Glycyrrhiza/química , Tripterygium/química , Animales , Sulfato de Dextran , Ratones , Extractos Vegetales/farmacologíaRESUMEN
The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.
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Dermatitis Alérgica por Contacto/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Glycyrrhiza/química , Extractos Vegetales/farmacología , Tripterygium/química , Animales , Citocinas/sangreRESUMEN
In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.
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Medicamentos Herbarios Chinos/efectos adversos , Hepatopatías/sangre , Metabolómica , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Espectrometría de MasasRESUMEN
A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade â ¢ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade â ¢ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Dictamnus/química , Medicamentos Herbarios Chinos/efectos adversos , China , Humanos , Hígado , Estudios Retrospectivos , Factores de RiesgoRESUMEN
In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Medicamentos Herbarios Chinos , Adulto , Bases de Datos Factuales , Femenino , Humanos , MasculinoRESUMEN
The study aims to analyze the mechanisms of Hirudo in promoting blood circulation and removing blood stasis based on network pharmacology. A database of chemical components of Hirudo was established through literature retrieval. The targets were predicted by using the reverse pharmacophore matching method and screened according to the antithrombotic and anticoagulant drug targets approved by FDA in the DrugBank database. Then, the targets were analyzed by KEGG pathway analysis, the protein interactions were analyzed by using BioGrid database, and the active constituents-target-pathway network model of Hirudo was established to study the mechanisms of Hirudo in promoting blood circulation and removing blood stasis. This study collected 49 chemical components of Hirudo, including amino acid, polypeptide, fatty acid ester, alkaloid, glycosides, and steroid. Totally 376 targets were predicted, and 5 critical targets related to the effects of Hirudo in promoting blood circulation and removing blood stasis were screened, including fibrinogen gamma chain, plasminogen, prothrombin, Urokinase-type plasminogen activator and coagulation factor X. The potential regulatory pathways included complement and coagulation cascades, platelet activation, VEGF signaling pathway, focal adhesion. This study reflects the multi-component, multi-target and multi-pathway features of Hirudo, and provides a scientific basis for elucidating the mechanisms of action of Hirudo in promoting blood circulation and removing blood stasis, as well as a reference for the study of mechanisms of traditional Chinese medicine.
Asunto(s)
Circulación Sanguínea , Coagulación Sanguínea , Medicamentos Herbarios Chinos , Medicina Tradicional ChinaRESUMEN
To investigate the hepatoprotective effect of Schisandrae Chinensis Fructus (SCF) on CCl4-induced liver injury, observe its effect on serum metabolites, explore its scientific connotation in liver preservation and find the biomarkers for hepatoprotective effect of SCF. Liver injury model was established by using CCl4. The pathological sections of liver tissues were observed and the contents of alanine transaminase (ALT) and aspartate transaminase (AST) in serum were determined. The metabolic skills were adopted based on ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-Q-TOF-MS), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) for screening and identification of biomarkers related to liver injury. The results showed the metabolites in blank group, model group and administration group could be easily distinguished, 50 differential compounds were identified and 7 possible metabolic pathways of liver protection were enriched. In this experiment, the hepatoprotective effect of SCF was verified, and the related metabolic pathways such as amino acid metabolism, vitamin metabolism and glycerophospholipid metabolism were discussed.