Use of Network Pharmacology and Molecular Docking to Investigate the Mechanism by Which Ginseng Ameliorates Hypoxia

Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the

Protective effect of fu-qi granule on carbon tetrachloride-induced liver fibrosis in rats

AIM： To investigate the effcacy of fu-qi granule （FQG） on carbon tetrachloride （CCl4） induced liver fbrosis in rats and the underlying mechanisms. METHODS： Sixty rats were randomly divided into six groups： normal control group, CCl4 induced liver fbrosis group, AnluoHuaxianWan group and three treatment groups of FQG. Treatment of rats with intraperitoneal injection of carbon tetrachloride solution at 0.3 mL per 100 g body weigh twice a week for 8 wk. The normal control group the rats were given the media （olive oil） at the same time. In the frst 2 wk, rats were raised with feedstuff （80% corn meal, 20% lard, 0.5% cholesterol）. Serum samples were collected for alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein assay and typical histopathological changes was observed in Hematoxylin-eosin staining sections. Smooth muscle alpha actin （α-SMA） was analyzed with immunohistochemistry. Mammalian target of rapamycin （mTOR） and hypoxia-inducible factor-1 （HIF-1α） expressions were detected by Western blot-ting. Tissue inhibitor of matrix metalloproteinases-1 （TIMP-1） and matrix metalloproteinases-9 （MMP-9） were measured with semi-quantitative reverse transcriptase-polymerase chain reaction.RESULTS： FQG significantly reduced the serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and increased the serum contents of albumin, total protein in rats with liver fibrosis. Moreover, FQG promoted extracellular matrix degradation by increasing MMP-9 and inhibiting TIMP-1 and α-SMA. mTOR and HIF-1α expression in liver significantly decreased in the rats treated with FQG. CONCLUSION： The results indicated that FQG signi-fcantly reverse fbrosis induced by CCl4, which should be developed as a new and promising preparation for the prevention of liver fbrosis.

Exploring an Integrative Therapy for Treating COVID-19:A Randomized Controlled Trial

Objectives:To develop a new Chinese medicine(CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome(ARDS)in COVID-19 patients.Methods:A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized,controlled two-arm trial.The two arms of the trial consist of a control therapy(alpha interferon inhalation,50(x g twice daily;and lopinavir/ritonavir,400 and 100 mg twice daily,respectively)and a testing therapy(control therapy plus Keguan-119.4 g twice daily)by random number table at 1:1 ratio with 24 cases each group.After 2-week treatment,adverse events,time to fever resolution,ARDS development,and lung injury on newly diagnosed COVID-19 patients were assessed.Results:An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events.Based on this result,the study was expanded to include a total of 48 participants(24 cases each arm).The results show that compared with the control arm,the testing arm exhibited a significant improvement in time to fever resolution(P=0.035),and a significant reduction in the development of ARDS(P=0.048).Conclusions:Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients.(Trial registration No.NCT 04251871 at www.clinicaltrials.gov).

Guidelines for the Diagnosis and Management of Herb-Induced Liver Injury

Herb-induced liver injury （HILl） is a type of adverse drug reactions related to using Chinese medicine （CM） or herbal medicine （HM）, and is now a growing segment of drug-induced liver injury （DILl） worldwide. Owing to the complicated compositions and miscellaneous risk factors associated with the clinical usage of CM or HM, it is more challenging to diagnose and manage HILl than DILl. In the present guideline issued by the China Association of Chinese Medicine （CACM）, the authors present an evidence chain-based workflow with 9 structured judgment criteria for diagnosing HILl. The 3 diagnostic ending points--suspected diagnosis, clinical diagnosis, and confirmed diagnosis--could be reached according to the length of the evidence chain acquired in the structured diagnostic workflow. Either identifying the species of CM or HM or excluding adulterations and toxin contaminants was strongly recommended to improve the level of evidence for a clinical diagnosis of HILl. In addition, the authors report that the improper use of CM, which violates the general law of CM theory, is one of the most important factors that contributes to HILl and should be avoided. By contrast, based on syndrome differentiation, some CM can also be used to treat HILl if used in accordance with the general law of CM theory. Therefore, 9 recommendations are put forward in this guideline.

Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury

Heshouwu is a traditional non-toxic Chinese medicine commonly used in the clinical setting;however,clinical cases of Heshouwu-induced hepatotoxicity have been frequently reported^([1]).Pharmacoepidemiological studies have found that Heshouwu-induced liver injury occurs only in a small fraction of individuals taking the drug;these patients presented with the typ-

T cell–associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Although oxymatrine(OMT) has been shown to directly inhibit the replication of hepatitis B virus(HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection.The infection was achieved by tail vein injection of a large volume of DNA solution. OMT(2.2, 6.7 and20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag)and hepatitis B core antigen(HBc Ag). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir(ETV) in the elimination of serum HBs Ag and intrahepatic HBc Ag. Inaddition, OMT accelerated the production of interferon-γ(IFN-γ) in a dose-dependent manner in CD4^+T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum

The main constituents of a typical medicinal herb, Polygonum multiflorum （Heshouwu in Chinese）, that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide （LPS） and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent ＂knock-out＂ and ＂knock-in＂ strategy, we found that the ethyl acetate （EA） extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4＇-tetrahydroxy trans-stilbene-2-O-p-glucoside （trans-SG） and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization oftrans- SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

Evidence chain-based causality identification in herb-induced liver injury： exemplification of a well-known liver-restorative herb Polygonum multiflorum

Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury （DILI） in the United States. However, reliable methods to identify the DILl causality of some herbs, such as Heshouwu （dried root ofPolygonum multiflorum）, remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% （9/40） and 30.6% （45/147） of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% （19/20） of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin （heavy metals, pesticides, and mycotoxins） contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.

Icariside Ⅱ, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation

Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.

Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug-induced Liver Injury

Cases of suspected herb-induced liver injury(HILI)caused by herbal Traditional Chinese Medicines(TCMs)and of druginduced liver injury(DILI)are commonly published in the scientific literature worldwide.As opposed to the multiplicity of botanical chemicals in herbal TCM products,which are often mixtures of several herbs,conventional Western drugs contain only a single synthetic chemical.It is therefore of interest to study how HILI by TCM and DILI compare with each other,and to what extent results from each liver injury type can be transferred to the other.China is among the few countries with a large population using synthetic Western drugs as well as herbal TCM.Therefore,China is well suited to studies of liver injury comparing drugs with TCM herbs.Despite some concordance,recent analyses of liver injury cases with verified causality,using the Roussel Uclaf Causality Assessment Method,revealed major differences in HILI caused by TCMs as compared to DILI with respect to the following features:HILI cases are less frequently observed as compared to DILI,have a smaller proportion of females and less unintentional rechallenge events,and present a higher rate of hepatocellular injury features.Since many results were obtained among Chinese residents who had access to and had used Western drugs and TCM herbs,such ethnic homogeneity supports the contention that the observed differences of HILI and DILI in the assessed population are well founded.

Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

Study of the anti-MRSA activity of Rhizoma coptidis by chemical fingerprinting and broth microdilution methods

AIM： Methicillin-resistant Staphylococcus aureus （MRSA） is a pathogenic bacterium that causes both hospital- and community-acquired infections, and for which single-drug treatments are becoming less efficient. Rhizoma coptidis has been used for more than two thousand years in China to treat diarrhea, fever, and jaundice. In this study, the anti-MRSA activity of Rhizoma coptidis is examined and its effective components sought. METHODS： The mecA and norA genes were determined by PCR amplification and sequencing. Drug susceptibility of Staphylococcus aureus ATCC43300 was performed using the VITEK2 compact system. The chemical fingerprint of Rhizoma coptidis was investigated using HPLC and preparative liquid chromatography, and the anti-MRSA activity was determined using an improved broth microdilution method. RESULTS： The drug susceptibility test revealed that the penicillin-binding protein phenotype of the strain changed in comparison to penicillin-sensitive Staphylococcus aureus. Ten batches of Rhizoma coptidis showed anti-MRSA activity on the norA-negative Staphylococcus aureus strain, as well as the strain that contained a norA gene. The spectrum-effect relationship revealed that the berberine alkaloids were the effective components, within which berberine, coptisine, palmatine, epiberberine,, and jatrorrhizine were the major components. CONCLUSION： This study lays a foundation for in vivo studies of Rhizoma eoptidis and for the development of multi-component drugs.

Establishment of one-step approach to detoxification of hypertoxic aconite based on the evaluation of alkaloids contents and quality

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.

Toxicity of Five Herbs in Aconitum L. on Tetrahymena thermophila Based on Spectrum-effect Relationship

Objective To explore the active components with toxic effects in five Aconitum L. herbal medicines on Tetrahymena thermophila. Methods The fingerprints of five Aconitum L. herbal medicines were established by ultra-high performance liquid chromatography （UPLC） and the toxicity was evaluated by using a TAM Air Isothermal Calorimeter on Tetrahymena thermophila SB1 10. Results By analyzing the spectrum- effect relationships between UPLC fingerprints and toxic effects, the active components which had the toxic effects were obtained. Conclusion This work provides a general model of the combination of UPLC and microcalorimetry to study the spectrum-effect relationships of the five Aconitum L. herbal medicines, which could be used to evaluate the toxic effects and analyze the principal toxic components of the five Aconitum L. herbal medicines. On the whole, this result provides the experimental basis for the safe use of the five Aconitum L. herbal medicines in clinic.

San-Cao Granule (三草颗粒) Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway

Objective： To investigate the possible mechanism of San-Cao Granule（SCG, 三草颗粒） mediating antiliver fibrosis. Methods： A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid（UDCA, 60 mg/kg）, SCG（3.6 g/kg） group, SCG（1.8 g/kg） group and SCG（0.9 g/kg） group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase（ALT）, aspartate transaminase（AST）, albumin（ALB）, total bilirubin（TBIL）, hyaluronic acid（HA）, laminin（LN）, and type Ⅳcollagen（ⅣC） were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein（HMGB1）, transforming growth factor β1（TGF-β1）, phosphorylated mothers against decapentaplegic homolog 3（p-Smad3）, Smad7, toll-like receptor 4（TLR4）, myeloid differentiation factor 88（My D88）, nuclear factor-kappa B（NF-κB） and α-smooth muscle actin（α-SMA） were determined by western blot, immunohistochemistry and real time quantitativereverse transcription polymerase. Results： Both SCG（3.6 and 1.8 g/kg） and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and ⅣC and preventing the serum level reducing of ALB compared with the model group（all P〈0.01）. Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, My D88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group（all P〈0.01）. Conclusion： SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）

Acupuncture-moxibustion Theories of Ge Hong

Ge Hong （261-341）, courtesy name Zhichuan, also known as Baopuzi or Ge Ximlweng, born in Jurong of Danyang （present-day Jurong ofJimlgsu Pronce）, was a famous Taoist and physician during the Eastern Jin Dynasty. He had a reputation for broad reading, mad was enthusiastic over Huamg Di Nei Jl＇ng （Yellow Emperor＇s Classic of InternM Mediclhe） and A^J J？hg （Classic of Ditticult Issues）, esoteric arts, mid alchemy. He was once ma official of theEastern Jin Dynasty, but later lived as a recluse on Luofu Mount of Guangdong Province. His one hundred scrolls of Yu Hail FaJlg （PrescripKons Hidden 111 Golden Chambe was supplemented later by Tao Hong-jing and Yang Yong-dao, and became Fu GuaJlg Zhou Hou BeiJi Fang （Supplement Handbook of Prescripgons for Emergenc [Zhou Hou Bei Ji Fang （Handbook of Prescripgons for Emergencies） for short] nowadays, in which, convenient, low-price, and effective treatment methods were included.

Comprehensive Evaluation of Powdered Chinese Herbal Medicines-An Exemplification of Isatidis Radix

Objective Currently, powdered Chinese herbal medicines （CHMs） were mainly evaluated through physical property, chemical dissolution, and bioactivity independently. It could not reflect the quality comprehensively. This paper was to explore and establish a comprehensive evaluation method for powdered CHMs. Methods Isatidis Radixwas chosen as an exemple. Firstly, powdered Isatidis Radixin different particle size was prepared. Then, their physical properties were characterized. The dissolution of index component epigoitrin was determined, and their antiviral activities were evaluated by neuraminidase-based bioassay. Results As the particle size decreased, powder distribution tended to be uniform, and the dissolution of epigoitrin increased, antiviral activity enhanced. According to cluster analysis of above results, the sequence of evaluation consequence was ultrafine powder S2 （D90：32.80± 0.29） 〉 ultrafine powder S1 （D90：52.08 ± 0.53） 〉 fine powder SO （D90：118.16± 0.76） （from the superior to the inferior）. Conclusion Overall, the comprehensive evaluation for powdered CHMs based on the physical characterization, chemical dissolution, and bioassay could not only be used to evaluate powdered herbs, but also guide the screening and optimization of the particle size of powder.

Disease-based Toxicology on Safety Assessment Strategy and Application for Herbal and Traditional Medicines

The safety issue on herbal and traditional medicines(H&TM) is one of the most challenging problems and serious concern worldwide. With scientific endeavor and further exploration, we came to realize that there are great differences between H&TM and synthetic drugs in many aspects, such as medical theory, medication experience, compatibility, processing, toxicological characteristics, and safety evaluating requirements. In the current preclinical models for synthetic drugs, the safety assessment results of some conventional deemed 'nontoxic' H&TM were not well consistent with clinical situations, which resulted in major difficulties to understand the mechanisms and guide the safe and rational uses of these H&TM. Thus, based on the traditional Chinese medicine toxicity theory called You Gu Wu Yun, this paper introduces a novel safety assessment strategy for H&TM, named as disease-based toxicology. It aims to cognize the relativity and susceptibility of the toxicity of H&TM, and then to enhance controllability in new drug development and clinical applications. It also provides a theoretical practice for the traditional Chinese medicine toxicity theory and a methodological promotion for the future development of the precision toxicology for H&TM.

Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb,Polygonum multiflorum

Erratum to Frontiers of Medicine 201711(2):253–265 https://doi.org/10.1007/s11684-017-0508-9 The original version of this article unfortunately contained some mistakes.The panel of“LPS–/drug–”in Fig.3B(Page 259),the panels of“LPS–/EtoAc+”and“LPS–/Residue+”in Supplementary Fig.3(Page 7 in the online supplementary materials)should be corrected.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.