The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.
Animals ; Mice ; Caspase 1/genetics* ; Colitis, Ulcerative/genetics* ; Colon ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Mesalamine/pharmacology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Scutellaria baicalensis/chemistry* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.
Drugs, Chinese Herbal ; adverse effects ; Epimedium ; chemistry ; Humans ; Medicine, Chinese Traditional ; Plant Leaves ; chemistry ; Retrospective Studies

In this paper,immune fingerprint was used to screen the allergenic components of Shuanghuanglian Injection(SHLI) by enzyme-linked immuno sorbent assay(ELISA) combined with HPLC/MS method. ELISA-embedded anti-IgE antibody could successfully adsorb allergens in SHLI and its plasma samples containing drugs through different routes of administration,suggesting that SHLI can induce type I hypersensitivity in rats. HPLC fingerprints and MS map of SHLI and drug-containing plasma samples from different routes of administration before and after anti-IgE antibody adsorption were established. According to the similarity evaluation of HPLC fingerprints and analysis results MS map,the sensitization of traditional Chinese medicine injections can be changed by different administration methods. There were 22 kinds of components that can be adsorbed by specific anti-Ig E antibodies in Shuanghuanglian Injection and its drug-containing plasma,most of them were acids and nitrogen compounds. Based on supramolecular theory,it was inferred that these compounds came from SHLI or body,and may form supramolecular hapten,which results in immunotoxicity and allergic reaction when being used as injection instead of oral liquid. Immune fingerprint is not only used to screen out single component allergen,but also more comprehensive,sensitive and easy to operate. It can provide reference for the future research methods of allergic reaction of traditional Chinese medicine injections.
Allergens ; analysis ; Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; Enzyme-Linked Immunosorbent Assay ; Hypersensitivity ; Injections ; Medicine, Chinese Traditional ; Rats

Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.
Chemical and Drug Induced Liver Injury ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; adverse effects ; Fallopia multiflora ; chemistry ; Humans ; Medicine, Chinese Traditional ; Phytochemicals ; adverse effects

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ 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 Ⅲ 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.
Chemical and Drug Induced Liver Injury ; epidemiology ; China ; Dictamnus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Liver ; Retrospective Studies ; Risk Factors

OBJECTIVEThe main objective of this study was to preliminarily determine the optimum formulation of a Chinese herbal formula that may have neuroprotective effects against rotenone-induced Parkinson's disease (PD).

METHODSSeven recipes were made from Dihuang (DH, Rehmannia glutinosa Libosch), Roucongrong (RCR, Cistanche deserticola Y.C.Ma), Niuxi (NX, Achyranthes bidentata Bl.) and Shanzhuyu (SZY, Cornus officinalis Sieb. et Zucc) in different proportions, according to the principles of uniform design (4 factors 7 levels). Tyrosine hydroxylase (TH)-positive neurons in substantia nigra pars compacta (SNpc) were detected by immunohistochemistry and rotenone-exposure days necessary to induce PD symptoms were recorded. To probe one likely mechanism of the formulas, echinacoside (ECH) concentrations of all seven recipes were determined by high-performance liquid chromatography and related to number of TH-positive neurons.

RESULTSThe data showed that recipe 4 (DH:RCR:SZY:NX = 1:1:1:1) and recipe 7 (DH:RCR:SZY:NX = 7:5:3:1) partially reversed rotenone-induced death of TH-positive neurons in the SNpc and significantly increased rotenone-exposed days compared with model group. Pharmacologically, there was not a strong correlation between ECH concentration and TH-positive neurons.

CONCLUSIONThe investigated formulations of Chinese herbs had neuroprotective effects against PD models, and the neuroprotective effects were weakly related to the proportion of key herbs. However the neuroprotective effects of the formula may not result from a single active constituent.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Male ; Neuroprotective Agents ; administration & dosage ; chemistry ; Parkinson Disease ; drug therapy ; etiology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Rotenone ; adverse effects

To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang. Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect relevant information. The papers were then screened according to inclusion and exclusion criteria. A total of 234 papers were included in this study, including 164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non-randomized controls, 56 case series, and 1 cohort study. The patients were only treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99% in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing no severe adverse reactions. Gastrointestinal system damage was most common in mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling Jiaonang was acceptable. The direct evidences of the drug's safety case reports were systematically analyzed in this study, but the mechanism study on the safety of the drug after marketing or the prospective long-term clinical observation study was not sufficient, so the further studies on the safety of drug use should be conducted in order to provide better guidance for clinical medication.
Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Product Surveillance, Postmarketing ; Randomized Controlled Trials as Topic ; Wolfiporia ; chemistry

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
Animals ; C-Reactive Protein ; genetics ; immunology ; Cecum ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Heart ; drug effects ; physiopathology ; Humans ; Interleukin-6 ; genetics ; immunology ; Ligation ; adverse effects ; Male ; Myocardium ; immunology ; Phenanthrenes ; administration & dosage ; chemistry ; Punctures ; adverse effects ; Rats ; Salvia miltiorrhiza ; chemistry ; Sepsis ; drug therapy ; etiology ; immunology ; physiopathology ; Troponin T ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.
Acetaminophen ; adverse effects ; Alanine Transaminase ; metabolism ; Animals ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; metabolism ; Caspase 3 ; genetics ; metabolism ; Chemical and Drug Induced Liver Injury ; genetics ; metabolism ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Glutathione ; metabolism ; Humans ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Mitogen-Activated Protein Kinases ; chemistry ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Schisandra ; chemistry ; Signal Transduction ; drug effects

Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; immunology ; Chemokine CCL2 ; genetics ; immunology ; Diterpenes ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Epoxy Compounds ; adverse effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Intracellular Signaling Peptides and Proteins ; genetics ; immunology ; Liver ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; immunology ; Phenanthrenes ; adverse effects ; Tripterygium ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology