Development and application of the physiologically-based toxicokinetic (PBTK) model for ochratoxin A (OTA) in rats and humans.

Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (Fup) of OTA in plasma of rat and human was 0.02-0.04% and 0.13-4.21%, respectively. In vitro experiments, the maximum enzyme velocity (Vmax) and Michaelis-Menten constant (Km) of OTA in rat and human liver microsomes were 3.86 and 78.17 µg/g min-1, 0.46 and 4.108 µg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.

Systematic characterization of the chemical constituents in vitro and in vivo of Qianghuo by UPLC-Q-TOF-MS/MS.

The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.

Lipidomics reveals the lipid metabolism disorders in Fructus Psoraleae-induced hepatotoxicity in rats with kidney-yin deficiency syndrome.

Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes.

BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.

Vacuum sealing drainage to treat Fournier's gangrene.

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

The Evolution of Single-Cell RNA Sequencing Technology and Application: Progress and Perspectives.

As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for describing cell subpopulation classification and cell heterogeneity by achieving high-throughput and multidimensional analysis of individual cells and circumventing the shortcomings of traditional sequencing for detecting the average transcript level of cell populations. It has been applied to life science and medicine research fields such as tracking dynamic cell differentiation, revealing sensitive effector cells, and key molecular events of diseases. This review focuses on the recent technological innovations in scRNA-Seq, highlighting the latest research results with scRNA-Seq as the core technology in frontier research areas such as embryology, histology, oncology, and immunology. In addition, this review outlines the prospects for its innovative application in traditional Chinese medicine (TCM) research and discusses the key issues currently being addressed by scRNA-Seq and its great potential for exploring disease diagnostic targets and uncovering drug therapeutic targets in combination with multiomics technologies.

A review of the current research on in vivo and in vitro detection for alpha-synuclein: a biomarker of Parkinson's disease.

Parkinson's disease is a health-threatening neurodegenerative disease of the elderly with clinical manifestations of motor and non-motor deficits such as tremor palsy and loss of smell. Alpha-synuclein (α-Syn) is the pathological basis of PD, it can abnormally aggregate into insoluble forms such as oligomers, fibrils, and plaques, causing degeneration of nigrostriatal dopaminergic neurons in the substantia nigra in the patient's brain and the formation of Lewy bodies (LBs) and Lewy neuritis (LN) inclusions. As a result, achieving α-Syn aggregate detection in the early stages of PD can effectively stop or delay the progression of the disease. In this paper, we provide a brief overview and analysis of the molecular structures and α-Syn in vivo and in vitro detection methods, such as mass spectrometry, antigen-antibody recognition, electrochemical sensors, and imaging techniques, intending to provide more technological support for detecting α-Syn early in the disease and intervening in the progression of Parkinson's disease.

Transanal Opening of Intersphincteric Space for Fistula-in-Ano.

BACKGROUND: The role of the intersphincteric space in the pathogenesis of fistula-in-ano is being increasingly recognized. Submucosal and intersphincteric rectal abscesses have been surgically managed by laying open and draining the intersphincteric space as well as by the modified ligation of intersphincteric fistula tract (LIFT) procedure. In 2017, the transanal opening of intersphincteric space (TROPIS) technique was reported for the treatment of high, complex anal fistulae. AIM: We aim to investigate the advantages of performing the TROPIS procedure in patients with fistula-in-ano. METHODS: This was a prospective cohort study investigating the outcomes in patients who had undergone a procedure using the TROPIS technique for the treatment of fistula-in-ano. Preoperative magnetic resonance imaging scans and electronic colonoscopies were performed on all patients. A clinical database evaluating the following variables was constructed: age, gender, body mass index (BMI), previous fistula surgery, type of fistula, postoperative complications, duration of follow-up, success rate, and incontinence scores pre- and postoperatively. RESULTS: The TROPIS procedure was performed on 41 patients with fistula-in-ano with a follow-up time of 6-23 months. The characteristics of the patients were as follows: 36 males, 6 females, mean age 38.6±13.2 years, and mean BMI 23.5±3.9 kg·m-2. All patients (41) had transsphincteric fistulae, and 90.2% (37) had high fistula. Of the 41 patients, 22% (9) had recurrent fistulae, 29.27% (12) had horseshoe fistulae, 7.3% (3) had supralevator fistulae, and 14.6% (6) had an associated abscess. The fistula healed completely in 85.3% (35) of patients and failed to heal in 14.7% (6) of patients, and the healing of high fistula was 86.5% (32). Of those patients who had not healed completely, 2 were found to have contracted iatrogenic infections due to foreign residues and underwent surgery with the passing of a loose seton. The additional 4 patients who had not healed underwent a fistulotomy and healed completely thereafter. There were no significant changes in incontinence scores. The incontinence scores were .15 ± .36 preoperatively and .22 ± .47 3 months postoperatively (t = -1.438, P = .16). CONCLUSIONS: The TROPIS technique is a novel sphincter-preserving procedure, which can be effectively used in treating fistula-in-ano.

Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer's disease.

Introduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE. Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aß) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids. Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.

The Meridian Tropism and Classification of Red Yeast Rice Investigated by Monitoring Dermal Electrical Potential.

Red yeast rice is a traditional Chinese medicine and food that has been purported to color food, ferment, and lower cholesterol. In order to study the antioxidative capacity of red yeast rice and the effects on electrical potential difference (EPD) of 12 acupuncture meridians, the pH value, oxidation reduction potential (ORP), ABTS, FRAP, T-SOD, and particle size distribution of red yeast rice were analyzed. 20 volunteers were recruited and randomly divided into two groups, the red yeast rice group (10 g red yeast rice and 40 g water) and control CK group (50 g water). The left 12 acupuncture meridians' EPD was real-time monitored. Samples were taken at the 10th minutes. The whole procedure continued for 70 minutes. It is shown that the pH value of the red yeast rice was 4.22, the ORP was 359.63 mV, the ABTS was 0.48 mmol Trolox, the FRAP was 0.08 mmol FeSO4, the T-SOD was 4.71 U, and the average particle size was 108 nm (7.1%) and 398.1 nm (92.9%). The results of 12 acupuncture meridians' EPD showed that the red yeast rice can significantly affect the EPD of stomach, heart, small intestine, and liver meridians.

ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.

[Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of compatibility].

ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters in vivo, and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.

Looking for agonists of ß2 adrenergic receptor from Fuzi and Chuanwu by virtual screening and dual-luciferase reporter assay.

More and more studies demonstrated that ß2 adrenergic receptor (ß2-AR) plays a crucial role for the treatment of heart failure. Chuanwu and Fuzi have been used over thousands of years in China for the treatment of heart failure. Considering the effects of these herbs are very similar to ß2-AR agonists, we presume whether ß2-AR agonists can be found from Fuzi and Chuanwu. Fuzi and Chuanwu decoction were used to receive the luciferase reporter activity assay to verify the hypothesis, and the result is positive and encouraging. For it is very difficult to get all of the monomer compounds of Fuzi and Chuanwu, virtual screening was used to find potential ß2-AR agonists and a cell-based ß2-AR agonist functional evaluation model, combined with a luciferase reporter assay system, was used to confirm the final result. In this research, 45 compounds were identified as ß2-AR agonists, and four compounds were verified and the rest need further experiment.

Resveratrol via activation of AMPK lowers blood pressure in DOCA-salt hypertensive mice.

OBJECTIVE: Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. Activation of AMPK induces vasorelaxation to lower blood pressure (BP). Whether resveratrol via activation of AMPK decreases, BP remains unknown. METHODS: Male wild-type (WT) mice and mice deficient in AMPKα2 (AMPKα2(-/-)) were fed with resveratrol (400 mg/kg). After 7 d, mice were implanted with deoxycorticosterone acetate (DOCA)-salt (150 mg/kg) for 35 d. BP was detected by the radiotelemetry method. Vessel contraction was determined by organ chamber. Active RhoA, Rho-associated kinase (ROCK) activity, phosphorylations of myosin light chain (MLC), and myosin phosphatase targeting subunit 1 (MYPT1) were assayed by western blot. RESULTS: Implantation of DOCA-salt dramatically increased systemic BPs (systolic BP and diastolic BP) in WT and AMPKα2(-/-) mice. However, treatment of resveratrol significantly decreased systemic BP in WT mice but not in AMPKα2(-/-) mice. In the organ chamber study, resveratrol inhibited agonist-induced vessel relaxation in WT mice aortas. Loss of AMPKα2 or AMPK inhibition by compound C reversed resveratrol-suppressed vasoconstriction in isolated mice aortas. In cultured vascular smooth muscle cells (VSMCs), activation of AMPK by resveratrol inhibited phenylephrine-enhanced MLC phosphorylation in a dose-dependent manner. CONCLUSIONS: Resveratrol via activation of AMPK lowers BP in DOCA-hypertensive mice through an AMPK/RhoA/ROCK2/MLCMLC pathway.

[Effects of acupotomy, electroacupuncture or round-sharp acupuncture needle interventions on expression of Bcl-2, Bax, Caspase-3 proteins of rectus femoris in rabbits with knee ostarthritis].

OBJECTIVE: To observe the effect of acupotomy, electroacupuncture (EA) or round-sharp acupuncture needle intervention on the expression of Bcl-2,Bax and Caspase-3 proteins in the rectus femoris in rabbits with knee ostarthritis (KOA), so as to explore their mechanisms underlying improvement of braking-induced joint damage from the cellular apoptosis. METHODS: Forty-five New Zealand rabbits were equally and randomized into control group, model group, acupotomy (AP) group, EA group and round-sharp acupuncture needle (RSAN) group (n = 9 in each group). The knee-joint injury model was established by fixing the left knee joint in extention position with plaster bandage. EA (2 Hz/100 Hz, 3 mA, 20 min each time) was applied to the left "Yanglingquan" (GB 34)- "Yinlingquan" (SP 9) and left "Neixiyan" (EX-LE 4)- "Waixiyan"(ST 35) for rabbits in the EA group. The EA treatment was given once daily, 3 times a week, 3 weeks in total. For rabbits of the AP group, a needle-knife was held to insert into the front edge of the midpoint, the starting point and the stopping point of the left medial collateral ligamen, lateral collateral ligament and the patellar ligament of the knee to make a loosening manipulation for 5 times in a session of treatment, once a week, 3 times altogether. For rabbits of the RSAN group, a round-sharp needle was performed in the same way to the needle-knife including the stimulation point, the manipulation method and treatment sessions. At the end of the experiment, the left rectus femoris was taken out for detecting the expression of Bcl-2, Bax and Caspase-3 proteins with Western blot. RESULTS: In comparison with the control group, the passive range of motion (PROM) level was significantly decreased 4, 8 and 12 weeks after modeling (P < 0.01), and the expression levels of Bax and Caspase-3 proteins in the rectus femoris were considerably upregulated in the model group (P < 0.05), while the ratio of Bcl-2/Bax was notably down-regulated (P < 0.05) in the model group. Compared with the model group, the PROM level at week 12 after modeling in the AP, EA and RSAN groups were significantly increased (P < 0.01); while Bax and Caspase-3 expression levels in both AP and RSAN groups were considerably downregulated (P < 0.05). No significant differences were found among the five groups in Bcl-2 expression levels (P > 0.05), and between the EA and model groups in Bax and Caspase-3 expression levels and the ratio of Bcl-2/Bax (P > 0.05). CONCLUSION: AP, RSAN and EA interventions are effective in improving the knee-joint motion range in KOA rabbits, and this effect of both AP and RSAN is closely associated with their actions in lowering the expression of Bax and Caspase-3 proteins of the rectus femoris and in raising ratio of Bcl-2/Bax protein (reducing muscular cellular apoptosis). The mechanism of EA intervention in improving PROM may be different.

Effect of jingqian zhitong fang on serum sex hormone levels in women with primary dysmenorrhea.

Primary dysmenorrhea is a common gynecological disease garnering increasing attention and research. To investigate the clinical therapeutic effects of Jingqian Zhitong Fang (JQF) and the differences in serum sex hormone levels during the treatment of primary dysmenorrhea, we selected 30 healthy volunteers and 60 individuals with primary dysmenorrhea. On the third day of the menstrual cycle, we used ELISA to determine the levels of serum prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TEST), progesterone (PROG), and estradiol (E2) compared with normal levels and levels in the JQF group, the Western medicine group receiving continuous treatment during the first and third menstrual cycles, and the group followed up after the drug was stopped. We observed that after JQF treatment, the levels of the following hormones changed significantly: PRL, LH, TEST, and E2 levels decreased significantly and the PROG level increased significantly after treatment. After treatment with Western medicine, the serum levels of FSH, LH, PROG, and E2 showed no significant change. We conclude that the long-term effect of JQF treatment was better than that of Western medicine. JQF treatment of primary dysmenorrhea is related to adjustment of PRL, LH, TEST, and E2 hormone levels in the human body.

Effect of two Chinese medicinal compounds, blood-activating and water-draining medicine, on tumor necrosis factor α and nuclear factor κ B expressions in rats with intracerebral hemorrhage.

OBJECTIVE: To investigate the effect of blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds on tumor necrosis factor alpha (TNF-α) and nuclear factor kappaB (NF-κ B) expressions in rats with intracerebral hemorrhage (ICH) at the acute stage, and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema. METHODS: A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus. A total of 168 rats were randomly divided into 4 groups: blood-activating medicine group (n=42), water-draining medicine group (n=42), sham operated group (n=42), and the model group (n=42). A series of brain samples were obtained at days 1, 3 and 5 after ICH from rats in all groups. Protein expression levels of TNF-α and NF-κ B were measured by immunohistochemical staining and gene expression levels of TNF-α and NF-κ B were measured by real-time fluorescent PCR. RESULTS: Compared to the sham operated group, protein expression levels of TNF-α and NF-κ B in the model group significantly increased (P<0.01). Protein and gene expressions of TNF-α from the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group P<0.05). Meanwhile, compared to the model group, the expression of NF-κ B in the blood-activating medicine group significantly decreased (P<0.05), while expression of NF-κ B in the water-draining medicine group did not differ (P>0.05). CONCLUSIONS: Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema. However, the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds. The possible effective mechanism may be by means of inhibiting the activation of NF-κ B so as to suppress the transcription of target genes including gene expression of TNF-α.

[Study on the constituents of essential oil of Shunaoxin dropping pills by GC-MS].

OBJECTIVE: To study the constituents of essential oil from Shunaoxin dropping pills by GC-MS. METHODS: The essential oil from Shunaoxin dropping pills were extracted by absolute alcohol and analyzed by GC-MS. RESULTS: 15 components from the essential oil of Shunaoxin dropping pills were identified. CONCLUSION: The main components in the essential oil of Shunaoxin dropping pills are lactones such as Z-ligustilide, senkyunolide A,3-butylphthalide and 3-butylidenephthalide, other components are organic acids such as ethyl linoleate, 9,12-octadecadienoic acid and ethyl palmitate.