Pathogenesis and Drug Intervention of Diabetic Cardiomyopathy： A Review / 中国实验方剂学杂志

Diabetic cardiomyopathy， one of the cardiovascular complications of diabetes， is characterized by cardiac systolic and diastolic dysfunction at the early stage， which can later develop into heart failure. Due to the high incidence and mortality， it has been a hot topic in recent years. The pathogenesis of diabetic cardiomyopathy is complicated. It has been proved related to abnormal glucose and lipid metabolism， cardiac insulin resistance， mitochondrial dysfunction， abnormal calcium homeostasis， activation of renin-angiotensin-aldosterone system， increased oxidative stress， endoplasmic reticulum stress， inflammation， autophagy， and so on. The specific pathogenesis remains unclear. Currently， the diabetic cardiomyopathy is mainly tackled with both western medicine and traditional Chinese medicine （TCM）. Traditional western medicine has no specific remedy for diabetic cardiomyopathy， and the resulting side effect cannot be neglected. In order to improve the efficacy and reduce the side effects， researchers have tried some potential medical treatments， such as vaspin， melatonin， Coenzyme Q10， and non-coding RNA， which still need further clinical trials. Diabetic cardiomyopathy is not recorded in ancient TCM books. According to the symptoms and signs， modern physicians often consider it as a "consumptive disease"， whose main therapeutic principles lie in benefiting Qi， tonifying Yin， activating blood， and removing stasis. The individual Chinese herbs such as Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma and Chinese herbal compounds like Huotan Jiedu Tongluoyin are effective in protecting the heart. But there are few studies exploring the pharmacodynamic mechanisms of TCM. With the continuous emergence of new drugs， the integration of TCM with western medicine may be a more promising treatment in the future. In conclusion， the pathogenesis of diabetic cardiomyopathy is unclear， and there is a lack of effective prevention and treatment. This paper reviewed the latest findings in pathogenesis and treatment of diabetic cardiomyopathy， in order to provide reference for further research.

Anti-tumor Effect and Mechanisms of Triterpenoids and Polysaccharides in Ganoderma lucidum： A Review / 中国实验方剂学杂志

With the population aging， the morbidity and mortality of cancer patients continue to rise. At present， the treatment methods for tumors include surgery， chemotherapy， radiotherapy， targeted therapy， and immunotherapy. However， most chemotherapeutic drugs can cause severe side effects and drug resistance. Therefore， as an alternative therapy， traditional Chinese medicine （TCM） treatment can effectively relieve the clinical symptoms of tumor patients， improve the quality of life， inhibit or stabilize the development of tumors， and prolong the survival period of patients. Due to the good safety of Chinese medicine， its potential anti-cancer activity has attracted increasing attention. Ganoderma lucidum， a treasure of Chinese medicinal material， is a medicinal fungus with a history of more than 2 000 years in China. So far， many studies have proposed the anti-cancer properties of G. lucidum. G. lucidum has extensive pharmacological activities， such as anti-tumor， anti-atherosclerosis， and anti-aging. It can also regulate immunity， protect the liver and the heart， and reduce blood glucose and lipid. The chemical composition of G. lucidum is complex. At present， it is proved to contain polysaccharides， triterpenoids， alkaloids， nucleosides， amino acids， and various trace elements. The anti-tumor mechanisms of polysaccharides and triterpenoids in G. lucidum are mainly achieved by apoptosis induction， immune regulation， anti-angiogenesis， and induction of cell cycle arrest. Currently， it has been widely used in the adjuvant treatment of complex tumors such as lung cancer， liver cancer， cervical cancer， prostate cancer， breast cancer， and colon cancer. The present study reviewed the bioactivities and mechanisms of triterpenoids and polysaccharides in G. lucidum in recent years and highlighted the anti-tumor effects and mechanisms to provide references for the further development and utilization of G. lucidum.

Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions" / 中国中药杂志

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Effect of moxibustion on clinical symptoms, peripheral inflammatory indexes and T lymphocyte subsets in COVID-19 patients / 中国针灸

OBJECTIVE@#To explore the therapeutic effect and the mechanism of the adjuvant treatment with moxibustion on coronavirus disease 2019 (COVID-19).@*METHODS@#A total of 95 patients with COVID-19 were randomly divided into a moxibustion group (45 cases) and a basic treatment group (50 cases). The routine treatment of western medicine was applied in the patients of both groups. In the moxibustion group, on the base of the treatment of western medicine, moxibustion was applied to Dazhui (GV 14), Feishu (BL 13), Qihai (CV 6) and Zusanli (ST 36), once daily and consecutively for 14 days. At the end of treatment courses, clinical symptom scores for cough, asthmatic breathing, chest oppression and short breath, as well as their remission rates were compared between the two groups before and after treatment. Before and after treatment, the white blood cell (WBC) count, the levels of c-reactive protein (CRP) and interleukin-6 (IL-6) and the absolute number of T lymphocyte subsets, i.e. , and of the peripheral blood were compared in the patients between the two groups. The principal component analysis was adopted to analyze the common data extracted from the above 10 clinical indexes variables and comprehensively evaluate the differences in the therapeutic effect of two regimens.@*RESULTS@#The clinical symptom scores were all decreased after treatment in both of the moxibustion group and the basic treatment group as compared with those before treatment (@*CONCLUSION@#On the base of the routine treatment with western medicine, moxibustion therapy supplemented relieves the clinical symptoms, reduces the levels of inflammatory indexes, i.e. IL-6 and CRP as well as improves the absolute number of peripheral T lymphocyte subsets. The clinical therapeutic effect of such regimen with moxibustion supplemented is significantly better than the simple routine treatment of western medicine.

Effect of Guanxin Danshen Formulation on diabetic kidney disease in db/db mice through regulation of Nrf2 pathway / 中国中药杂志

Diabetic kidney disease(DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formulation(GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into 4 groups: control group, model group, metformin group, and GXDSF group. After 8 weeks' treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for the further analysis. Compared with the model group, TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement-membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated GSH-PX levels, while reduced LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated protein levels of ERα and p-Akt, and subsequently promoted HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERα and Nrf2-mediated HO-1 expression.

Protective Effect of Salvianolic Acid B on Arsenic Trioxide-induced HepaRG Human Hepatocyte Injury / 中国实验方剂学杂志

Objective::To investigate the protective effect of salvianolic acid B on HepaRG hepatocyte injury induced by arsenic trioxide (As2O3 ) and its mechanism. Method::HepaRG cells were incubated with 5μmol·L-1 As2O3 for 24 h to induce hepatocyte injury. The cells were divided into control group, model group, salvianolic acid B 10 μmol·L-1 group, salvianolic acid B 10 μmol·L-1+ As2O3 group, salvianolic acid B 5 μmol·L-1+ As2O3 group, and salvianolic acid B 2.5 μmol·L-1+ As2O3 group. HepaRG cells were preincubated with salvianolic acid B for 2 h and then incubated with As2O3 for 24 h. At the end of the incubation, cell viability was detected by thiazolyl blue tetrazolium bromide assay, apoptosis was observed by Hoechst33342 fluorescence staining, apoptosis rate was detected by annexin V-FITC/propidium iodide double staining flow cytometry, and mitochondrial membrane was observed by JC-1 fluorescence staining. Western blot was used to detect the protective effect of expressions of relevant proteins Bcl-2, Bax, Akt, p-Akt on salvianolic acid B in the liver. Result::As2O3 concentration-dependently reduced the survival rate of HepaRG cells(P<0.01), salvianolic acid B had no effect on normal cell viability for 2 h, pre-incubation with salvianolic acid B(5, 10 μmol·L-1) for 2 h significantly increased the decreased cell survival rate caused by As2O3 (P<0.01). As2O3 significantly increased hepatocytes apoptosis rate(P<0.01), while pre-incubation with salvianolic acid B(10 μmol·L-1) deceased apoptosis rate(P<0.01). Incubation with As2O3 for 24 h caused decrease of mitochondrial membrane potential, pre-incubation with salvianolic acid B maintained mitochondrial membrane potential, indicating that the anti-apoptotic effect of salvianolic acid B were related to the mitochondrial pathway modulation. Western blot analysis showed that salvianolic acid B promoted the ratio of Bcl-2/Bax and promoted p-Akt/Akt compared with As2O3 group(P<0.01). Conclusion::Salvianolic acid B has a protective effect on hepatocyte injury induced by As2O3, and its mechanism is related to maintenance of mitochondrial function and inhibition of hepatocyte apoptosis.

Research Progress on Pharmacological Mechanisms of Scutellarin / 中国实验方剂学杂志

Scutellarin is a flavonoid extracted from breviscapus， a traditional Chinese medicine. Pharmacological studies have shown that scutellarin has anti-inflammatory， antioxidant， anti-fibrosis， anti-tumor， improving cardiac and cerebral ischemia. In recent years， with the deepening of research on scutellarin， it was found that it could inhibit the tumor through multi-target and multi-pathway， and the anti-human colorectal cancer was related to the regulation of p53 pathway， Hedgelog pathway and erythropoietin generates liver cancer interactivator B2（EphrinB2）.The anti-esophageal squamous cell carcinoma is related to protein kinaseB1 /protein kinaseB2（ Akt1/Akt2）.Anti-renal carcinoma and melanoma are associated with phosphatase and tension protein homologues（PTEN） and phosphatidylinositol 3-kinase（PI3K）/Akt/mammalian target of rapamycin（mTOR） pathway. Anti-lung cancer is related to Akt/mTOR/4E binding protein1（4EBP1） and signal transduction and transcriptional activator（STAT3 ）signaling pathway. Anti-cervical cancer is related to pyruvate kinase 2（PKM2）.Anti-breast cancer is associated with Hippo/YAP pathway. At the same time， scutellarin was found to prevent diabetic microangiopathy， atherosclerosis and non-alcoholic fatty liver disease by regulating glucose and lipid metabolism， but the mechanism of action was not well studied. A review of the literature found that scutellarin anti-tumor， atherosclerosis， diabetic microangiopathy， non-alcoholic fatty liver disease， osteoarthritis， osteoporosis mechanism of action lack of detailed summary. In this paper， the research progress of pharmacological action and mechanism of scutellarin in recent 5 years is reviewed， and Suggestions on its current research status and future direction are put forward， in order to speed up the discovery of pharmacological mechanism of scutellarin and provide scientific basis for its further development and utilization.

Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice / 中国实验方剂学杂志

<b>Objective::To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice. <b>Method::Ninety male ICR mice were randomly divided into normal group, model(DOX) group, DOX+ Qidong Yixin oral liquid group (9.55, 23.88, 47.75 g·kg^-1) and high dose group (47.75 g·kg^-1) with 15 mice in each group. The normal group and model group were given pure water by gavage, and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days. On the seventh day, normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid. Doxorubicin was injected into the abdominal cavity of the other groups (15 mg·kg^-1). After 21 days, the weight and heart weight of mice were weighed and cardiac index was calculated. Serum was taken for the detection of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST). Heart was taken for hematoxylin-eosin (HE) staining, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) in myocardial tissue were detected. The expression of nuclear factor NF-E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot. <b>Result::Compared with normal group, adriamycin could significantly reduce the body weight of mice (<italic>P</italic><0.01), increase the activities of LDH, CK and AST in serum(<italic>P</italic><0.01), and decrease the activities of antioxidant enzymes (<italic>P</italic><0.01). Compared with DOX group, high dose Qidong Yixin oral liquid could significantly increase the weight of mice (<italic>P</italic><0.05, <italic>P</italic><0.01), decrease the level of myocardial three enzymes(<italic>P</italic><0.01), increase the activity of antioxidant enzymes(<italic>P</italic><0.05, <italic>P</italic><0.01), and increase the expression of Nrf2 and HO-1(<italic>P</italic><0.01). <b>Conclusion::Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity. Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.

Progress in Prevention and Treatment of Diabetic Complications with Breviscapine / 中国实验方剂学杂志

Erigeron breviscapus, a species within the genus of Erigeron, is mainly distributed in Southwest China. It is cold in property, slightly bitter in taste, and has the effect of dispersing cold table, removing wind and dehumidification, promoting blood circulation and removing blood stasis, relieving pain and inflammation. Breviscapine is the extract of E. breviscapus. It is mainly consisted of flavonoids, lignans, coumarins, terpenes, phytosterols, etc. As the major components of breviscapine, the content of breviscapine b (4′-hydroxybaicalin-7-O-glucuronide) and breviscapine a (apigenin-7-O-glucuronide) is greater than 90%. Modern pharmacological studies have shown that breviscapine has a wide range of pharmacological effects, including anti-oxidation, anti-fibrosis, anti-inflammation, anti-aging, anti-platelet aggregation, lowering blood lipid, increasing blood flow, improving microcirculation, preventing and treating tumors, and resisting brain injury. In clinical, breviscapine has been widely used in the treatment of diabetes, cerebral insufficiency, sequelae caused by cerebral hemorrhage, hypermucolipemia, cerebral thrombosis, kidney disease, liver disease, Alzheimer's disease, and some other complex diseases. Specially, in the treatment of diabetes and its chronic complications, such as diabetic nephropathy, diabetic cardiomyopathy, diabetic foot, diabetic retinopathy, breviscapine has showed significant efficacy. In addition, studies have demonstrated that the combined application of breviscapine, mecobalamine, and micopol can improve the therapeutic effect. In this work, the application of breviscapine in the treatment of chronic complications of diabetes mellitus and its related combination drugs were reviewed, by which we attempted to provide some valuable clues for the clinical application of breviscapine in the treatment of diabetes mellitus and its chronic complications.

Preventive and therapeutic effects of Keluoxin Capsules on early diabetic retinopathy in db/db mice / 中国中药杂志

The aim of this paper was to investigate the preventive effects of Keluoxin Capsules(KLX) on diabetic retinopathy in db/db mice. One hundred male db/db diabetic mice(45-55 g, 8 weeks) were randomly divided into 5 groups(model, KLX low dose, KLX middle dose, KLX high dose, Dobesilate) and 20 male C57 BL/KsJdb~(+/+) were taken as control group. Body weight and fasting blood-glucose were detected every week. Mice were administrated with saline(control and model group), KLX(780, 1 560, 3 120 mg·kg~(-1)·d~(-1), ig), Dobesilate(195 mg·kg~(-1)·d~(-1), ig) for 20 weeks, respectively. At the end of the administration, optical coherence tomography, fundus fluorescein angiography and electroretinogram of the retina were measured. The eyeball was extirpated and retina was isolated to make paraffin section, followed by HE staining and glial fibrillary acidic protein(GFAP) immunohistochemistry. The results indicated that KLX has no obvious effect on body weight and fasting blood level in db/db mice. However, KLX could significantly regulate the thickness of retinal ganglion layer and inner plexiform layer. KLX was able to remarkably reduce the quantity of diabetic microvessel. Meanwhile, KLX could notably improve retinal function. Moreover, KLX could observably modulate the cell arrangement and edema in each layer. There was no markable difference in retina according to the immunochemistry assay. In the present study, KLX exert marked preventive effects on diabetic retinopathy in db/db mice, which provided an experimental evidence for clinical use.

Nitrogenous Chemical Constituents from Brassica campestris Seeds / 中国实验方剂学杂志

Objective:To study nitrogenous chemical constituents from the seeds of Brassica campestris. Method:The aerial parts of nonfat seeds were extracted with 75% ethanol heat refluxing method,then suspended in H2O and separated with ligarine and ethyl acetate to obtain respective fractions.Chemical constituents were isolated and purified by various chromatographic methods and identified by physicochemical characters and spectroscopic analysis or comparison with standard compounds. Result:Thirteen nitrogenous chemical compounds were isolated and identified as coixspirolactam C (1),indole-3-acetonitrile (2),2-β-D-glucopyranosylsulfanyl-1H-indole-3-acetonitrile (3),nicotinic acid (4),adenosine (5), 1H-indole-3-carbaldehyde (6),4-hydroxy-1H-indole-3-carbaldehyde (7),6-hydroxy-1H-indole-3-carboxylic acid (8),ethyl 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylate (9),5-hydroxy-4(1H)-quinazolinone (10),4-hydroxy-2-quinazolinone (11),5-hydroxy-quinazoline-2(1H),4(3H)-dione (12),5-allyloxazolidin-2-one (13). Conclusion:All of the compounds were isolated from this plant for the first time, and compounds 1,3 and 13 were isolated from Brassica for the first time.

Protective effects of scutellarin on diabetic cardiomyopathy in mice / 药学学报

To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg∙kg-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen III in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.

Quality evaluation of Magnoliae Officinalis Cortex based on combinative method of fingerprint,quantitative analysis of multicomponents and chemometrics / 中国中药杂志

This study aims to establish a combinative method based on fingerprint,assay of multi-component and chemometrics for quality evaluation of Magnoliae Officinalis Cortex. Twenty batches of samples were determined by UPLC and a common mode of fingerprint was established. The similarities between fingerprints of 20 batches of samples were over 0. 90 and the common mode were evaluated. Eight components were identified as syringing, magnocurarine, magnoflorine, magnoloside B, magnoloside A, honokiol,magnolol,and piperitylmagnolol by comparison with reference substances and their content in samples were simultaneously determined.Based on the results,the fingerprint had good consistency between the same origin and minor diversity between the different sources.Piperitylmagnolol and peak 13 could be used as a distinction with the different sources. According to content of 8 components,Fisher discriminant analysis model was established and different source sample was classified pursuant to the discriminant fraction. It is indicated that simultaneous quantification of multi components coupled with chemometrics analysis could be a well-acceptable strategy to identify and evaluate the quality of Magnoliae Officinalis Cortex.

Total saponins of Aralia elata(Miq)Seem protect tumor necrosis factor-α-induced human umbilical vein endothelial cells via PI3K/Akt and NF-κB signal pathways / 中国药理学与毒理学杂志

It is now thought that atherosclerosis,although due to enhanced lipid deposition,is mainly the result of a series inflammatory process.Total saponins of Aralia elata (Miq)Seem(TASAES)from the Chinese traditional herb Longya Araliachinensis L.,a folk medicine used for treating various diseases, increasing energy and improving the body′s ability to prevent hypoxia in Asian countries has attracted widespread attention. However, the ability of TASAES on inflammation-triggered vascular endothelial cell injury, a key early event in the pathogenesis of atherosclerosis, and its potential mechanisms of this protection have never been demonstrated. The present study determined the anti-inflammatory and anti-apoptoticactivities and protective mechanisms of the total aralosides of Araliaelata(Miq)Seem (TASAES) ameliorate tumor necrosis factor-α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury. Our results indicate that TASAES pretreatment provided cytoprotective effects by suppressing TNF-α-induced HUVECs apoptosis, mitochondrial membrane depolarization, caspase-3 activation, and modulation of inflammatory factors (IL-6, MCP-1 and VCAM-1), meanwhile inhibiting NF- κB transcription. Furthermore, the effect was correlated with the activation of the PI3K/Akt signal pathway. Blocking Akt activation with the PI3K inhibitor LY294002 effectively reversed the protective effect of TASAES against TNF-α-induced cell apoptosis.Moreover,the PI3K inhibitor partially blocked the effects of TASAES on the increasing of Bcl-2 and Bcl-xl protein expression,and inactivation of Bax protein expression. In conclusion, the results showed that TASAES decreased the inflammation and apoptosis of HUVECs caused by TNF-α treatment,and PI3K played a crucial role in enhancing cell sur-vival during this process.

Research advance of A20 on atherosclerosis / 中国药理学通报

Atherosclerosis, as a chronic inflammatory disease, is the most common one among cardiovascular system disorders. Inflammation is crucial in the development of atherosclerosis, which participates in the entire process of atherosclerosis. NF-κB can target to most inflammatory factors, and excessive NF-κB activation aggravates atherosclerosis development. Previous stud- ies have shown that the zinc finger protein A20 plays a key role in the anti-inflammatory and anti-apoptotic response. Research advances on A20 in protection of atherosclerosis are thus summa-rized in this review.

Study on mechanism of HepaRG cell injury induced by bavachinin / 中国药理学通报

Aim To probe into the bavachinin toxic mechanisms in HepaRG cells. Methods MTT assay was used to determine toxicity and dose. After treated with 6.25,12.5 and 25 μmol·L-1bavachinin for 24 h,the cell death was investigated by Hoechst 33342/PI,LDH,caspase-3 activity,and Bax,Bcl-2 expression levels. Mitochondrial damage was detected by mito-chondrial membrane potential,ATP content,openness of mitochondrial permeability transition pore and cyto-chrome C level. Results Bavachinin administration up-regulated Bax/Bcl-2 ratio and caspase-3 activity with increase of drug concentration after 24 h. Apop-totic rate increased in a dose-dependent manner be-tween 6.25 and 25 μmol·L-1,but when reached to 25 μmol·L-1,cells showed more necrosis. Mitochon-drial injury indicators significantly increased after 24h. Conclusion Bavachinin induces HepaRG cell apopto-sis and necrosis through mitochondria injury.

Pathogenesis of diabetic cognitive dysfunction and intervention by traditional Chinese medicine / 中国药理学通报

Diabetic cognitive dysfunction (DCD) is a common chronic complication of diabetes mellitus with sophisticated path-ogenesis which has not yet been fully elucidated. In this review paper, the mechanisms of metabolic abnormalities, insulin re-sistance,endoplasmic reticulum stress,neuronal calcium dysho-meostasis, in ammation, blood brain barrier impairment, and mitochondrial injury associated with DCD are reviewed. In addi-tion,the prevention and treatment of DCD by traditional Chinese medicines (TCMs) and the effective compounds are comprehen-sively summarized, in order to provide an updated overview on the DCD pathogenesis,as well as the scientific evidence under-pinning the use of TCM interventions for the treatment and pre-vention of DCD.

Lesions Caused by Intracerebral Injection of Aquaporin-4 Immunoglobulin G / 中山大学学报(医学科学版)

[Objective]To investigate the pathological damage caused by aquaporin-4 antibody extracted from patients with neuromyelitis optica spectrum disorders(NMOSD)and the influence of systemic immune status on the local disease focus.[Methods]The C57BL/6 mice were chose for establishing experimental autoimmune encephalomyelitis (EAE).During the peak at onset,serum-derived immunoglobulin G(IgG)from aquaporin-4(AQP4)IgG positive patients and healthy human complement(hC)were injected in the brain parenchyma(EAE+AQP4-IgG+hC group,n=5).The EAE induced mice injected with normal saline(EAE+NS group,n=5)and mice without EAE injected with AQP4-IgG and hC from healthy volunteers(AQP4-IgG + hC group,n=5)were served as control groups. The dramatic loss of AQP4,astrocyte glial fibrillary acidic protein(GFAP),oligodendrocyte myelin basic protein(MBP)and the infiltration of inflammatory cells(T lymphocytes,neutrophils and macrophages)were compared with each group by using immunoflu-orescence,in order to find abnormal changes.[Results]Intracerebral injection of AQP4-IgG together with hC can cause NMO-like lesions,including astrocyte injury,demyelination and inflammatory cell infiltration.However,EAE mice model with intracerebral injection of AQP4-IgG and hC represented more significant loss of AQP4 and GFAP(P=0.008 and P=0.016,respectively)compared with mice without EAE induced.The area of MBP loss was also increased,while there′s no statistical difference.No statistical difference was also found in the number of vessels infiltrated with CD3+T cell,neu-trophils and the area infiltrated with macrophage. Astrocyte proliferation existed in all groups,but no loss of AQP4, GFAP and MBP was found in EAE mice injected with NS.[Conclusion]Intracerebral injection of AQP4-IgG and hC can cause distinct pathological damage and the pathology can be promoted by immune system activated by EAE.Intracerebral injection of AQP4-IgG and hC can mimic the pathogenesis of NMOSD better in EAE mice model.

Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix / 中国中药杂志

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Safety evaluation and risk control measures of Psoralea corylifolia / 中国中药杂志

Through a systematic and comprehensive study of domestic and foreign literatures and information, this study aims to trace the herbal origin and the toxicity recorded in ancient and current documents, analyze the safety case reports of Psoralea corylifolia and experimental studies on toxicity in recent years, and make a preliminary summary about the clinical characteristics and potential risk factors of cases related to the safety of P. corylifolia and its preparations. The study involved 84 patients in the safety case reports of P. corylifolia. The adverse events were mainly liver damage (55.95%) and light toxic contact dermatitis (38.10%), sugguesting that P. corylifolia may lead to liver damage and photo toxicity. However, reproductive toxicity and renal damage were only reported in animal studies, but not in clinical reports. Because of its complicated ingredients, the toxic components and mechanisms of P. corylifolia have not been clear at present. Therefore, the authors proposed to strictly apply P. corylifolia in clinic, use it rationally and combine it with other medications. Besides, efforts shall be made to strength the guidance for doctors, the safety monitoring of P. corylifolia and relevant preparations, and actively carry out safety-related basic and clinical studies, so as to give a better guidance to safe medication, full exert the efficacy and avoid the medication risk.