Liver Injury Caused by Psoraleae Fructus： A Review / 中国实验方剂学杂志

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Chinese Medicine Regulates Intestinal Flora to Treat Ulcerative Colitis in Patients with Syndrome of Large Intestine Dampness-heat： A Review / 中国实验方剂学杂志

The clinical changes of ulcerative colitis （UC） with the main syndrome of large intestine dampness-heat and the alterations of intestinal flora in UC were summarized to reveal the underlying mechanism. After review of the treatment methods for UC with the syndrome of large intestine dampness-heat， we identified the representative traditional Chinese medicines and compound prescriptions and explored the treatment mechanisms. Furthermore， we probed into the associations of UC and the treatment methods with the intestinal flora. The related articles were retrieved from China National Knowledge Infrastructure （CNKI）. The available studies have shown that Akkermansia muciniphila， Escherichia coli， Enterococcus， and probiotics such as Bifidobacterium and Lactobacillus are closely associated with Chinese medicines in UC patients with the syndrome of large intestine dampness-heat. However， due to the shortcomings in clinical research and the susceptibility of intestinal flora to diverse factors， it is still challenging to accurately characterize the intestinal flora changes associated with diseases. Additionally， the research on the mechanisms of Chinese medicines in regulating intestinal flora in UC patients with the syndrome of large intestine dampness-heat remains to be improved. The feasibility of using Chinese medicines and compound prescriptions for precise regulation of intestinal flora in these patients is still debatable. In this regard， scientific issues such as the biological connotation of UC with the syndrome of large intestine dampness-heat and the correlation between syndrome and intestinal flora have become primary research tasks. Additionally， attention should also be paid to the interactions between the intestinal lumen exposure profile of Chinese medicines and intestinal flora. Finally， the thinking of traditional Chinese medicine （TCM） and the concepts of modern medicine should be combined for the research on the formulation of TCM regimens for regulating intestinal flora in treating UC.

Qualitative Analysis of Metabolites of Aristolochiae Fructus Aqueous Extract in Rats / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MSE） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg-1·d-1） or AAⅠ（5 mg·kg-1·d-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization（ESI+） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Chemical Constituents， Pharmacology， and Toxicology of Asari Radix et Rhizoma： A Review / 中国实验方剂学杂志

Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳa and aristolochic lactam Ⅰ. Aristolochic acid Ⅳa has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.

Serum Peroxiredoxin 3 in Early Pregnant Women / 医学研究杂志

Objective To investigate the role of peroxiredoxin 3 (PRX3) in early pregnancy.Methods We collected serum and villus tissues from ninety patients at first trimester.Enzyme-linked immunosorbent assay,real-time PCR,and Western Blotting were applied to examine the PRX3 level in above samples.Results The serum PRX3 in pregnant women was significantly higher than in non -pregnant controls.The expression of PRX3 in villus tissues was increased with gestational progression.Conclusion The oxidative stress was increased in pregnant women.PRX2 plays an active role in antioxidant defense of villus tissues.

Thought and method of reproductive toxicity research in traditional Chinese medicine / 药学学报

Reproductive toxicity research takes an important place in traditional Chinese medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment includes drug-related miscarriage, fetal death, teratism, and adverse effects on fertility, genital system, embryonic development and fetus, which is different from contraindicated in pregnancy in traditional Chinese medicine theory. Now the three-phases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. Besides that, alternative methods of whole embryos culture and embryonic stem cell test are also used in traditional Chinese medicine embryo toxicity evaluation. This article reviews research progress and pre-clinical evaluation on reproductive toxicity of traditional Chinese medicine.

Embryotoxicity of Senecionis Scandentis Hebra on in vitro cultured mouse embryos / 药学学报

The purpose of this study is to evaluate the embryotoxicity of alkaloids in Senecionis Scandentis Hebra on in vitro cultured mouse embryos. Mouse whole embryo culture (WEC) was applied in this study. Post-implantation (8.5 d) mouse embryos were isolated from their mothers, and cultured in medium of immediately centrifuged serum (ICS) with different concentrations of seneciphylline (target concentrations were 100, 50, 25 and 12.5 μg x mL(-1)) or senkirkine (target concentrations were 50, 25 and 12.5 μg x mL(-1)) for 48 h. After culturing completed, the development and organic morphodifferentiation of the cultured embryos were evaluated microscopically. Treatment with seneciphylline and senkirkine had adverse effects on the development and organic morphodifferentiation of embryos. The effect also had clear dose-response. Alkaloidals in Senecionis Scandentis Hebra had embryotoxicity on cultured embryos, which indicated that pregnant people exposed to Senecionis Scandentis Hebra may get potential risk on fetus.

Effect of Shaoyao Gancao Tang on function and expression of P-glycoprotein in Caco-2 cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shao Yao-Gan Cao-Tang on function and expression of P-glycoprotein (P-gp) in Caco-2 cells.</p><p><b>METHOD</b>3H-digoxin (Dig), a substrate of P-glycoprotein, was used as a probe to measure the P-gp-mediated drug efflux transport, which indicated the function of P-gp in Caco-2 cells, while Verapamil (Ver) was used as a positive P-gp inhibitor. P-gp expression in Caco-2 cells was tested by immunohistochemistry staining. Inhibition effect of SGT on P-gp-mediated drug efflux transport and P-gp expression were investigated.</p><p><b>RESULT</b>Dig was shown a positive absorption mode in Caco-2 cell monolayer, characterized as the ratio of apparent permeabilities (Papp) from basolateral side to apical side Papp (BL-->AP) and from apical side to basolateral side Papp (AP-->BL) of Dig was 27.07. Addition of Ver into Dig transport media significantly inhibited P-gp activity which was indicated by increasing the Papp (AP-->BL) of Dig by 3.82 times, whereas Ver had no significant effect on Papp (BL-->AP). SGT (at the concentrations of 1/25 IC5, 1/5 IC5, IC,) could promote Papp (AP-->BL) of Dig by 159.83%, 217.95% ,160.26%. Papp (AP-->BL) of Dig was mildly increased by 59.16%, 50.73% by SGT at 1/25 IC5, 1/5 IC, respectively. Immunohistochemistry staining showed that SGT inhibited the expression of P-gp of Caco-2 cells.</p><p><b>CONCLUSION</b>SGT showed the potential inhibition to the function and expression of P-gp, leading to the increase absorption of P-gp's substrates.</p>

Development of gastric precancerous lesion animal model / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a model of gastric precancerous lesion by using Aristolochic manshuriensis which contains aristolochic acids.</p><p><b>METHOD</b>The SD rats were randomly divided into four groups: control and three different doses of ethanol extractive of A. manshuriensis (EEA) (corresponding to aristolochic acid I 2.5, 5.0, 10.0 mg x kg(-1)), respectively. EEA was intragastrically given to rats every other day. At the end of the 10th, 15th, 20th week, part of the rats in each group was sacrificed and the stomachs were weighed. The gastric tumor was assessed by the weight and the relative stomach weight to the body weight. The stomachs were fixed in 4% neutral formalin, and the paraffin imbedding tissues were sliced and HE stained. Histomorphology was observed under the light microscope to determine gastric hyperplasia, mucosa precancerosis (atypical hyperplasia) and gastric cancer formation.</p><p><b>RESULT</b>The rats treated with different doses of EEA for 10 weeks induced mucosa papillary, epithelioma hyperplasia. Histological observation showed mucosa precancerosis lesions characterized as atypical hyperplasia at the dose levels corresponding to aristolochic acid I 5.0 and 10.0 mg x kg(-1) treated for 10 weeks. The incidence rate of gastric precancerosis in those two groups was 100% at the 15th week. Malignant tumors were observed in most of the animals in 10.0 mg x kg(-1) group. The animals in 5.0 mg x kg(-1) group were well tolerant compared to 10.0 mg x kg(-1) group during the course of experiment, so the dose of aristolochic acid I 5.0 mg x kg(-1) and 10-15 weeks treatment were considered to be optimum to establish the model of gastric precancerosis.</p><p><b>CONCLUSION</b>A rat model of gastric precancerosis can be induced within a short duration by giving an oral administration of the ethanol extract of A. manshuriensis which contains aristolochic acids.</p>

Methodology for preclinical assay of pseudoallergy of injectable drugs (I)--mouse model for assay of pseudoallergy induced by injections / 中国中药杂志

<p><b>OBJECTIVE</b>To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.</p><p><b>METHOD</b>Mouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue (EB). Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.</p><p><b>RESULT</b>Mouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation. Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy. Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing. The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.</p><p><b>CONCLUSION</b>Mice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.</p>

Methodology for preclinical assay of pseudoallergy of injectable drugs (II) rat model for assay of cutaneous pseudoallergy induced by injections / 中国中药杂志

<p><b>OBJECTIVE</b>To develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.</p><p><b>METHOD</b>Rats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed.</p><p><b>RESULT</b>Rat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine.</p><p><b>CONCLUSION</b>Rats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.</p>

Comparative study on pseudoanaphylactoid reactions induced by medicinal tween 80 and injectable tween 80 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the safety of different level of tween 80 by comparing the degree of pseudoanaphylactoid reactions (PR) induced by medicinal tween 80 and injectable tween 80.</p><p><b>METHOD</b>The analysis of vascular permeability of the mice ears: ICR mouse were divided into different test groups, the mice were intravenously injected with solutions of medicinal tween 80 and injectable tween 80 with 0.2%, 1% and 5% concentration, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The analysis of vascular permeability of the rat's skin: the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same substances were intradermal administrated into the back of rats. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leak out were measured 20 min after injection.</p><p><b>RESULT</b>Medicinal tween 80 and injectable tween 80 with 5% concentration caused obvious vascular hyper permeability in ICR mice, but the degree of vascular hyperpermeability caused by injectable tween 80 was lighter than by medicinal tween 80. Other tween 80 didn't cause obvious vascular hyper permeability in the ears of mouse. The solution of different concentration of tween 80 caused obvious locus ceruleus reaction in rat's back. As for the content Evans blue leak out, there was no statistical significance between each group except positive control Compound 48/80 group.</p><p><b>CONCLUSION</b>Tween 80 can cause obvious vascular hyper permeability and the effect is dose dependent, which indicated that tween 80 can cause PR. On the other hand, injectable tween 80 is more security than medicinal tween 80, the dosage of tween 80 should be still controlled strictly so that to decrease the incidence of PR.</p>

Relationship between specific immunocyte and pseudoanaphylactoid reactions induced by Shuanghuanglian injection / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the relationship between specific immunocyte and pseudoanaphylactoid reactions (PR) induced by Shuanghuanglian injection (SHLI).</p><p><b>METHOD</b>ICR mice, SCID mice and BALB/C athymic mouse were divided into different test groups, the mice were intravenously injected with solutions of different concentration of SHLI, positive control Compound 48/80 and normal sodium. All test substances were mixed with 0. 4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after SHLI injected.</p><p><b>RESULT</b>SHLI of 300, 600 mg x kg(-1) caused obvious vascular hyperpermeability in ICR mice, but the same dose of SHLI didn't cause vascular hyperpermeability in SCID mice and BALB/C athymic mouse.</p><p><b>CONCLUSION</b>SHLI in equivalent and 2 times the clinical dose can cause PR in ICR mice, but the same dose of SHLI can't cause PR in SCID mice and BALB/C athymic mouse, so specific immunocyte maybe take part in the SHLI-induced PR.</p>

Pathway analysis of the differential expression genes of oligonucleotide microarray of airway allergic diseases using GenMAPP / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To detected the mechanism of allergic rhinitis associated with asthma with bioinformatics methods.@*METHOD@#GenMAPP software was used to analyze the expression profile of nasal mucosa of seasonal allergic rhinitis(SAR) and SAR associated with asthma of oligonucleotide microarray (Affymetrix HG-U133-plus2). One the first step,of differentially expressed genes screening were done, then differential gene database retrieval was established, at last pathway analysis was performed.@*RESULT@#689 genes out of 47 000 analyzed transcripts of nasal mucosa of SAR associated with asthma were differentially expressed at least 4-fold, in which 233 genes were up regulated and 456 genes were down regulated. These differential expression genes participate in 69 bio-pathways, in which the interaction pathway between cytokine and cytokine receptor was most. Chemotactic factor CXCL12 and its receptor CXCR4 expressed in SAR associated with asthma patients were up-regulated predominantly, compared with that in SAR patients.@*CONCLUSION@#Multiple pathways were involved in the development of SAR and SAR complicated with asthma. The CXCL12/CXCR4 axis might play a main role in the allergic airway diseases.

Material and mechanisms for evaluation of Shuanghuanglian injection induced pseudoanaphylactoid reactions / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the substance basis and the mechanism of pseudoanaphylactoid reactions (PR) induced by Shuanghuanglian injection (SHLI).</p><p><b>METHOD</b>(1)The study of PR and the substance basis of PR of SHLI: ICR mice were divided into different test groups, the mice were intravenously injected with solutions of different concentration of SHLI, baicalin, forsythin, caffeotannic acid, positive control Compound 48/80 and normal sodium. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after SHLI injection. (2) The study of mechanisms: Mice were pretreated with an oral administration of Astemizol, intraperitoneal injection of cyclophosphamide 75 mg x kg(-1) or Compound 48/80 4 mg x kg(-1), then mice were intravenously injected with SHLI. At last, vascular permeability of the ears in pretreated groups was compared with SHLI treatment alone group.</p><p><b>RESULT</b>SHLI of 300 mg x kg(-1) and 600 mg x kg(-1) caused obvious vascular hyperpermeability, but baicalin, forsythin and caffeotannic didn't cause vascular hyperpermeability in the ears. The Astemizol can decrease the degree of SHLI-induced vascular hyperpermeability of the ears in the mice. After intraperitoneal injected with cyclophosphamide, there was a slight decrease in the degree of SHLI-induced vascular hyperpermeability, but there was no marked changes in the degree of the SHLI-induced vascular hyperpermeability after the mice were pretreated with Compound 48/80.</p><p><b>CONCLUSION</b>SHLI in clinic equivalent dose can cause vascular hyperpermeability. Baicalin, forsythin and caffeotannic may not result in the PR of SHLI. The mechanism of the PR maybe relate to that SHLI stimulates histamine release, the activation of leucocyte maybe take part in the SHLI-induced PR, too. Antihistamine drug can prevent the genesis of PR which induced by SHLI.</p>

Toxicity study of realgar / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the toxicity of realgar and provide the scientific basis for safety use of realgar in clinic.</p><p><b>METHOD</b>Acute toxicity was tested by single oral administration. Chronic toxicity of realgar was tested at different dose levels (5, 10, 20, 80, 160 mg x kg(-1) x d(-1)) which correspond to 1/2, 1, 2, 8, 16 times of human dose levels. The rats were treated with the test substances through oral administration once daily for successively 90 days. Urinary qualitative test, blood routine examination, serum chemistry measurement, and histomorphologic observation were conducted at day 30, 60 and 90. Toxic changes related to the treatment of realgar and no-observed adverse effect level (NOAEL) was evaluated.</p><p><b>RESULT</b>With the content of 90% total arsenic and 1.696 mg x g(-1) soluble asenic, LD50 of Realgar with oral administration was 20.5 g x kg(-1) (corresponding to 34.8 mg x kg(-1) soluble arsenic), equivalent to 12 812 times of clinical daily dose for an adult. Realgar can cause kidney toxicity or/and liver toxicity after administration for over 30, 60 or 90 days respectively. The kidney was more sensitive to realgar than liver. Based on repeated dose toxicity study, NOAELs were 160 mg x kg(-1) x d(-1) for 30 day's administration, 20 mg x kg(-1) x d(-1) for 60 day's administration, 10 mg x kg(-1) x d(-1) mg x kg(-1) x d(-1) for 90 day's administration respectively. Thus, for safety use of realgar, it is recommended that the daily doses of realgar (with soluble arsenic < or = 1.7 mg x g(-1)) for an adult of the body weight about 60 kg could be 10-160 mg depending on the variation of the treatment duration.</p><p><b>CONCLUSION</b>Long term use of realgar can cause kidney and liver pathological change, so the doses and administration duration should be limited. The suggestion is as follows: realgar which contains soluble arsenic < or = 1.7 mg x g(-1) should be used less than 2 weeks at daily dose 160 mg, less than 4 weeks at the dose of 20 mg and less than 6 weeks at the dose of 10 mg.</p>

Asenic accumulation following realgar administration in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic.</p><p><b>METHOD</b>The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing.</p><p><b>RESULT</b>Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain.</p><p><b>CONCLUSION</b>Asenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.</p>

Drug interactions on P-glycoprotein transport level and its application / 中国中药杂志

Potential drug interactions on P-glycoprotein transport level were discussed in this article. As an efflux transporter protein widely distributed in various tissues, P-glycoprotein plays an important role in many drugs interactions, via affecting the metabolic process to alter the concentration of drug in plasma and tissue. Interactions between herb and western drug may occur by inducing or inhibiting P-glycoprotein, resulting in either efficacy enhancement or adverse effects. So it is important for clinical drug use by rational utilization of the interaction between herb and western drug which medicated by P-glycoprotein.

Toxicity of monocrotaline on in vitro cultured mouse embryos / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the fetotoxicity of monocrotaline.</p><p><b>METHOD</b>Mouse whole embryo culture (WEC) was applied. Post-implantation (8.5 d) mouse embryos were isolated from their mothers and put into the medium of immediately centrifuged serum (ICS) prepared from rats. Different concentrations of monocrotaline (100, 50, 25, 12.5 mg x L(-1)) were added into the WEC. Development (yolk sac diameter, crown-rump length, head length, somite number) and organic morphodifferentiation (yolk sac circulation, allantois, embryonic flexion, heart, brain, optic-otic-olfactory organ, branchial arch, maxillary, mandible, bud) of embryos were observed at 48 h after treatment.</p><p><b>RESULT</b>Obvious fetotoxicity could be observed in various monocrotaline treatment groups in a dose-dependent manner. Development of embryos was delayed significantly at dose 12.5-100 mg x L(-1). Malformations were shown in all organic morphodifferentiation indice, especially in opti-otic organ, mandible and bud.</p><p><b>CONCLUSION</b>Monocrotaline had obvious fetotoxicity in vitro WEC, indicating that exposure of pregnant mice to monocrotaline may have potential risk on fetus.</p>

Development of animal model for anaphylactoid test of rodent / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a simple and feasible method of anaphylactoid test on awaked small animals for screening and assessing anaphylactoid reaction of traditional Chinese medicine (TCM) injection with different concentration of tween 80.</p><p><b>METHOD</b>Test substances containing 0.4% Evans blue were intravenously injected into mice at volume of 20 mL x kg(-1) or guinea pigs at a volume of 30 mL x kg(-1). The behaviors were observed and the vascular permeability of ears evaluated by the extent of ear blue staining and absorbance of Evans blue extraction of ears were tested at 30 min after injection.</p><p><b>RESULT</b>Tween 80 solution, Yuxingcao injection with tween 80, and Shuanghuanglian powder injection obviously increased vascular permeability of ears characterized as ear blue staining and increased absorbance of the Evans blue extract from ears extracted by acetone saline both in mice and in guinea pigs in a concentration-dependent (in the case of tween 80) or a dose-dependent (Shuanghuanglian) manner.</p><p><b>CONCLUSION</b>Ear vascular permeability test in mice and guinea pigs can be used as animal models to screen and test anaphylactoid reaction induced by injections.</p>