Function-oriented mechanism discovery of coumarins from Psoralea corylifolia L. in the treatment of ovariectomy-induced osteoporosis based on multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.

Creatine supplementation combined with blood flow restriction training enhances muscle thickness and performance: a randomized, placebo-controlled, and double-blind study.

This study aimed to compare the effects of an 8-week creatine (CR) or placebo (PL) supplementation on muscle strength, thickness, endurance, and body composition employing different training paradigms with blood flow restriction (BFR) vs. traditional resistance training (TRAD). Seventeen healthy males were randomized between the PL (n = 9) and CR (n = 8) groups. Participants were trained unilaterally utilizing a within-between subject bicep curl exercise where each arm was allocated to TRAD or BFR for 8 weeks. Muscular strength, thickness, endurance, and body composition were evaluated. Creatine supplementation promoted increases in muscle thickness in TRAD and BFR compared with their placebo counterparts, however, without a significant difference between treatments (p = 0.349). TRAD training increased maximum strength (1 repetition maximum (1RM)) compared with BFR after 8 weeks of training (p = 0.021). Repetitions to failure at 30% of 1RM were increased in the BFR-CR group compared with the TRAD-CR group (p = 0.004). Repetitions to failure at 70% 1RM were increased from weeks 0-4 (p < 0.05) and 4-8 (p < 0.05) in all groups. Creatine supplementation exerted a hypertrophic effect when utilized with TRAD and BFR paradigms and increased muscle performance at 30% 1RM when utilized in conjunction with BFR. Therefore, creatine supplementation seems to amplify muscle adaptation following a BFR program. Registered in the Brazilian Registry of Clinical Trials (ReBEC), under the registration number: RBR-3vh8zgj.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Cognitive Function in Senior Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical (VATS). METHODS: From January to December 2020, 97 participants were randomly assigned to the TEAS group (49 cases) and the control group (48 cases) by a random number table. The patients in the TEAS group received TEAS, at the bilateral Neiguan (PC 6) and Zusanli (ST 36) acupoints. The control group received sham TEAS. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the incidence of pstoperative cognitive dysfunction (POCD), diagnosed based on the changes in the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes were plasma levels of S100ß protein and neuron-specific enolase (NSE). RESULTS: The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group [day 1 after surgery: 28.3% (13/46) vs. 52.3% (23/44), P=0.028; day 3 after surgery: 21.7% (10/46) vs. 40.9% (18/44), P=0.043]. Compared with baseline, the MMSE and MoCA scores decreased to various extents in both groups. The MMSE scores on day 1, 3, and 5 after surgery and MoCA scores on day 1, 3, 5, and 7 after surgery in the TEAS group were higher than those in the control group (all P<0.05) in both groups. Compared with baseline, the plasma levels of S100ß and NSE were significantly increased at 4, 8, 12, 24 h after surgery (all P<0.05). Compared with the control group, the plasma levels of S100ß and NSE were lower in the TEAS group at 4, 8, 12, and 24 h after surgery (all P<0.05). No obvious adverse events were found during the trial. CONCLUSION: Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.

Efficacy of traditional Chinese exercise for sarcopenia: A systematic review and meta-analysis of randomized controlled trials.

Objective: To conduct a systematic review and meta-analysis to evaluate the effectiveness of Traditional Chinese Exercise (TCE) for sarcopenia. Methods: A literature search was conducted in eight online databases from inception until September 2022. Based on the Cochrane risk of bias tool, randomized controlled trials (RCTs) with RoB score ≥ 4 were included for further analyses. The primary outcome was muscle strength and physical function, and the secondary outcomes were adverse events. Data collection and analyses were conducted by RevMan 5.4 Software. GRADE system was used to evaluate the certainty of evidence. Results: A total of 13 eligible RCTs with 718 subjects were identified and included in this study. Among them, 10 RCTs involved Yijinjing; 2 involved Tai Chi; and 1 involved Baduanjin. Meta-analyses showed that TCE had better clinical effects than control measures in the chair stand test (P < 0.00001, I2 = 38%; Certainty of evidence: Moderate), squatting-to-standing test (P < 0.00001, I2 = 0%; Certainty of evidence: Moderate), 6-m gait speed (P < 0.00001, I2 = 13%; Certainty of evidence: Moderate), Time Up and Go Test (P = 0.03, I2 = 81%; Certainty of evidence: Low), peak torque of the extensors (P = 0.03, I2 = 0%; Certainty of evidence: Moderate), total work of the extensors (P = 0.03, I2 = 35%; Certainty of evidence: Moderate), peak torque of the flexors (P = 0.03, I2 = 47%; Certainty of evidence: Low), total work of the flexors (P = 0.02, I2 = 42%; Certainty of evidence: Low), the average power of the flexors (P = 0.03, I2 = 30%; Certainty of evidence: Moderate), and balance function (P < 0.00001, I2 = 53%; Certainty of evidence: Low). In additional, no adverse events were reported in participants who receive TCE. Conclusion: The findings of the present systematic review, at least to a certain extent, provided supporting evidence for the routine use of TCE for sarcopenia.

The complete chloroplast genome of Chinese medicinal herb Belamcanda chinensis (L.) Redouté (Iridaceae).

The species of Belamcanda chinensis (L.) Redouté. is one of the Chinese traditional medicinal herb. In this study, we first report the complete chloroplast (cp) genome of B. chinensis. The chloroplast (cp) genome was determined to be 153,735 bp and the GC contents was 37.9%. The sequence includes a large single-copy (LSC) region of 83, 199 bp, a small single-copy (SSC) region of 18,168 bp, and two separated inverted regions of 26,184 bp each. It contains 132 genes, including 86 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Based on 10 chloroplast genomes data, the maximum likelihood phylogenetic analysis revealed that B. chinensis was sister to Iris (Bootstrap = 100%) within Iridaceae. This result will be helpful for the conservation and breeding programs of the B. chinensis.

Combination of Huanglian Jiedu Decoction and erlotinib delays growth and improves sensitivity of EGFR­mutated NSCLC cells in vitro and in vivo via STAT3/Bcl­2 signaling.

Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in the treatment of non­small cell lung cancer (NSCLC). However, erlotinib resistance leads to high mortality in patients with NSCLC, while the activation of STAT3 is closely related to erlotinib resistance. Studies have shown that the main components of Huanglian Jiedu Decoction (HJD) have antitumor effects. Therefore, the anticancer effect of HJD combined with erlotinib on NSCLC cells was investigated. The NSCLC HCC827, HCC827ER, and H1975 cell lines as well as xenograft nude mice were selected as models to study the effects of HJD. The proapoptotic effects of HJD were examined by CCK­8 and apoptosis assays. ELISA, immunostaining, and western blot analysis were also performed. HJD considerably enhanced the anticancer effect of erlotinib in both EGFR­TKI­resistant and ­sensitive NSCLC cells. HJD promoted erlotinib­induced apoptosis and caspase 3 activity. The co­treatment also inhibited the expression of Bcl­XL, Bcl­2, and p­STAT3. In addition, siSTAT3 had similar functions with HJD. In particular, the apoptotic rates of erlotinib­stimulated HCC827, HCC827ER, and H1975 cells were enhanced by transfecting siSTAT3. Furthermore, overexpression of STAT3 significantly inhibited HJD­mediated erlotinib sensitization. The combined use of HJD with erlotinib significantly reduced tumor growth in erlotinib­resistant HCC827ER and H1975 xenografts, induced caspase 3, and inhibited Ki67, STAT3, and Bcl­2 expression. HJD significantly alleviated erlotinib resistance by regulating the STAT3/Bcl­2 signaling pathway, which is a promising method to overcome the EGFR­TKI resistance of NSCLC.

Rectoseminal vesicle fistula after radical surgery for rectal cancer: Four case reports and a literature review.

BACKGROUND: A rectoseminal vesicle fistula (RSVF) is a rare complication after anterior or low anterior proctectomy for rectal cancer mainly due to anastomotic leakage (AL). Limited literature documenting this rare complication is available. We report four such cases and review the literature to investigate the etiology, clinical manifestations, and the diagnostic and treatment methods of RSVF in order to provide greater insight into this disorder. CASE SUMMARY: Four cases of RSVF were presented and summarized, and a further 12 cases selected from the literature were discussed. The main clinical symptoms in these patients were pneumaturia, fever, scrotal swelling and pain, anal pain, orchitis, diarrhea, dysuria, epididymitis and fecaluria. Imaging methods such as pelvic X-ray, computed tomography (CT), sinus radiography, barium enema and other techniques confirmed the diagnosis. CT was the imaging modality of choice. In cases presenting with reduced levels of AL, minimal surrounding inflammation, and controlled infection, the RSVF was conservatively treated by urethral catheterization, antibiotics administration and parenteral nutrition. In cases of severe RSVF, incision and drainage of the abscess or fistula and urinary or fecal diversion surgery successfully resolved the fistula. CONCLUSION: This study provides an extensive analysis of RSVF, and outlines, summarizes and examines the causes, clinical manifestations, diagnostic procedures and treatment options, in order to prevent misdiagnosis and treatment errors.

[Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice].

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 µmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

[Effect of lupeol on invasion and metastasis of human hepatoma HepG2 and SK-HEP-1 cells and its mechanism].

Epithelial-mesenchymal transformation(EMT) exists in embryonic development and is closely related to cell migration and invasion. The increased EMT level in tumors showed that E-cadherin was replaced by N-cadherin, and the expression of interstitial markers such as α-SMA and vimentin was up-regulated. It has been reported that lupeol can reduce the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9) and N-cadherin to inhibit the metastasis of osteoma cells. However lupeol has been less studied in liver cancer. Therefore, this paper investigated the effect of lupanol on invasion and metastasis of human hepatoma cell line HepG2 and SK-HEP-1 and its possible mechanism. MTT assay and Annexin V/PI double staining were used to investigate the effect of lupeol on activity and apoptosis of HepG2 cells and SK-HEP-1 cells. Moreover, the effect of lupeol on the invasion of HepG2 cells and SK-HEP-1 cells were evaluated by Transwell assay. The expressions of E-cadherin, N-cadherin, α-SMA, vimentin and MMP-9 were measured by Western blot. The model of subcutaneous transplantation of nude mice and the lung metastasis model of H22 hepatocellular carcinoma cells were established to evaluate the efficacy of lupeol in vivo on tumor growth and lung metastasis by HE staining combined with immunohistochemical assay. The results showed that lupeol inhibited the activity and invasion of HepG2 cells and SK-HEP-1 cells in a dose-dependent manner and induced apoptosis. Western blot showed that the expression of E-cadherin, a landmark protein for EMT, was induced by lupeol, and the expressions of N-cadherin, α-SMA, vimentin and MMP-9 were decreased. In vivo experiments showed that lupeol inhibited tumor growth in mice bearing xenograft. In addition, immunohistochemical experiments confirmed that lupeol could up-regulate the expression of E-cadherin in tumor tissues of nude mice, reduce the expression of N-cadherin, and inhibit the metastasis of liver cancer H22 cells in the lungs of mice. The above results indicated that the mechanism of lupeol inhibiting the invasion and metastasis of HCC cells may be related to the regulation of EMT process.

The Toxicity and Metabolism Properties of Herba Epimedii Flavonoids on Laval and Adult Zebrafish.

Zebrafish is being increasingly used for metabolism and toxicity assessment. The drugs consumed in zebrafish metabolism studies are far less than those used in rat studies. In our study, zebrafish embryos were exposed to icariin, Baohuoside I (BI), Epimedin A (EA), Epimedin B (EB), Epimedin C (EC), Sagittatoside A (SA), Sagittatoside B (SB), and 2''-O-rhamnosylicariside II (SC), respectively, to examine the toxicity and metabolic profiles of these flavonoids. The order of toxicity was SC, SB > EC, SA > BI, icariin, EA, EB. After 24 h exposure to SB and SC, the mortality of zebrafish larvae reached 100% and yolk sac swollen was obvious. Both SC and SB caused severe hepatocellular vacuolization and liver cells degeneration in adult zebrafish after 15 consecutive days' treatment. The metabolic profiles of these flavonoids with trace amount were also monitored in larvae. BI was the common metabolite shared by icariin, EA, EB, SA, and SB, via deglycosylation. Both BI and SC remained as the prototype in the medium, suggesting that it is hard for BI and SC to cleave the rhamnose residue. EC was metabolized into SC and BI in zebrafish, inferring that SC might be responsible for the toxicity observed in EC group. The metabolites of icariin, EA, EB, EC, and BI in zebrafish larvae coincided with results from rats and intestinal flora. These data support the use of this system as a surrogate in predicting metabolites and hepatotoxicity risk, especially for TCM compound with trace amount.

In vitro anti-platelet aggregation effects of fourteen fruits and vegetables.

In the present study, the anti-platelet aggregation activity of 14 vegetables and fruits was tested in vitro. The aqueous, 90% ethanol and ethyl acetate extracts, as well as concentrated juices of 14 foods (fruits and vegetables) were prepared, and the anti-platelet aggregation activity of those extracts was analyzed on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate (ADP), bovine thrombin (THR) and arachidonic acid (AA) as aggregation inducers, respectively. Aspirin (ASP) was used as the positive control. A number of the tested foods had inhibitory effects in concentration-dependent manner on platelet aggregations induced by various agonists. Especially, some foods such as lemon, leek, garlic, scallion, ginger, tomato and grapefruit showed good anti-platelet aggregation effect similar or higher than that of positive control group i.e. aspirin (ASP). The results of present study provide scientific reference for reasonable selection of daily dietary with supplementary curative effects or prevention of cardiovascular diseases (CVD).

Evaluation of thrombin inhibitory activity of catechins by online capillary electrophoresis-based immobilized enzyme microreactor and molecular docking.

An online capillary electrophoresis (CE)-based thrombin (THR) immobilized enzyme microreactor (IMER) method was established to screen THR inhibitors in this study. S-2366 was used as chromogenic substrate for determination of THR activity and other kinetic constants. After continuously run for 50 times, the prepared IMER could still remain 89% of the initial immobilized enzyme activity. The Michaelis-Menten constant (Km) of immobilized THR was measured as 0.514 mmol/L and the half-maximal inhibitory concentration (IC50) and inhibition constant (Ki) of argatroban on THR were determined as 78.07 and 26.53 nmol/L, respectively, which indicated that CE-based THR IMER was successfully established and could be applied to screen THR inhibitors. Then the prepared IMER was used to investigate the inhibitory potency on THR of four main catechins in green tea including epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG). The results showed that ECG and EGCG had good THR inhibition activity and their inhibition rates at concentration of 200 µmol/L were 53.2 ±â€¯3.8% and 55.8 ±â€¯2.6%, respectively, which was in consistent with the results of microplate reader assay. Additionally, molecular docking results showed that the benzopyran groups of ECG and EGCG were inserted into the THR active pocket and interacted with residues LYS60F, TRP60D, TRY60A, IEU99, GLY216, HIS57 and SER195, but EC and EGC did not. Therefore, the developed CE-based THR IMER is reliable method for measuring THR inhibitory activity of natural inhibitors.

Adsorbed hollow fiber-based biological fingerprinting for the discovery of platelet aggregation inhibitors from Danshen-Honghua decoction.

For lead compound discovery from natural products, hollow fiber cell fishing with chromatographic analysis is a newly developed method. In this study, an adsorbed hollow fiber-based biological fingerprinting method was firstly developed to discover potential platelet aggregation inhibitors from Danshen-Honghua decoction. Platelets were seeded on the fiber and their survival rate was tested. Results indicated that more than 92% platelets survived during the whole operation process. Ranitidine and tirofiban were used as positive and negative control respectively to verify the reliability of the presented approach. The main variables such as amount of extract and stirring time that affect the adsorbed hollow fiber-based biological fingerprinting process were optimized, and the repeatability of this method was also investigated. Finally, 12 potential active compounds in Danshen-Honghua decoction were successfully detected using the established approach and structures for nine of them were tentatively identified by liquid chromatography with mass spectrometry analysis. In addition, the in vitro platelet aggregation inhibition test was carried out for five of the nine hit compounds, and three active components, namely, lithospermic acid, salvianolic acid A, and salvianolic acid B were confirmed. These results proved that the proposed method could be an effective approach for screening platelet inhibitors from plant extracts.

Comparing coagulation activity of Selaginella tamariscina before and after stir-frying process and determining the possible active constituents based on compositional variation.

CONTEXT: Selaginella tamariscina (P. Beauv.) Spring (Selaginellaceae) (ST) has been widely used in China as a medicine for improving blood circulation. However, its processed product, S. tamariscina carbonisatus (STC), possesses opposite haemostatic activity. OBJECTIVE: To comprehensively evaluate the activity of ST and STC on physiological coagulation system of rats, and seek potential active substances accounting for the activity transformation of ST during processing. MATERIALS AND METHODS: The 75% methanol extracts of the whole grass (fine powder) of ST and STC were prepared, respectively. Male Sprague-Dawley rats were randomly divided into five groups: control group, model group, model + ST group, model + STC group and positive control group (model + Yunnanbaiyao). The duration of intragastric administration was 72 h at 12 h intervals. Haemorheology parameters were measured using an LB-2 A cone-plate viscometer and the existed classic methods, respectively. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of ST and STC extracts. RESULTS: STC shortened tail-bleeding time, increased whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR), reduced activated partial thromboplastin time (APTT) and increased the fibrinogen (FIB) content in the plasma of bleeding model rats. Although ST could shorten APTT and TT, the FIB content was significantly decreased by ST. Dihydrocaffeic acid with increased content in STC vs. ST showed haemostatic activity for promoting the platelet aggregation induced by collagen and trap-6, and reducing APTT and PT significantly with a concentration of 171.7 µM in vitro. Amentoflavone with reduced content in STC vs. ST inhibited ADP and AA-induced platelet aggregation significantly with a concentration of 40.7 µM. DISCUSSION AND CONCLUSIONS: As the processed product of ST, STC showed strong haemostatic activity on bleeding rat through regulating the parameters involved in haemorheology and plasma coagulation system. Two active compounds, dihydrocaffeic acid and amentoflavone, might be partially responsible for the haemostatic and anticoagulant activity of STC and ST, respectively.

Clinical study on TCM enema combined with continuous renal replacement therapy on the treatment of severe acute renal injury / 国际中医中药杂志

Objective To evaluate the clinical efficacy of TCM enema combined with continuous renal replacement therapy on the treatment of severe acute renal injury. Methods A total of 100 patients of severe AKI patients were divided into 2 groups by random digital table, each of which was 50 cases. The control group was treated with CRRT, and the observation group cooperated with the traditional Chinese medicine enema on the basis of the control group. The 2 groups were treated continuously for 14 d. The renal function and urine volume recovery time were observed; 24 h urinary protein and 24 h urinary albumin excretion rate were determined by automatic biochemical analyzer.The blood urea nitrogen (BUN), serum creatinine (SCr), serum cystatin C (Cys C) were detected. And theclinical efficacy was compared between the two groups. Results The total effective rate of the observation group was 70.0％ (35/50) and the control group was 50.0％ (25/50). The difference between the 2 groups was statistically significant. After treatment, the levels of serum BUN (6.51 ± 1.07 mol/L vs. 8.22 ± 2.31 mol/L, t=4.750), SCr (91.29 ± 21.05 μmol/L vs. 108.67 ± 19.34 μmol/L, t=4.299) and Cys C (0.85 ± 0.33 mg/L vs. 1.03 ± 0.45 mg/L, t=2.281) in the observation group were significantly lower than those of the control group (P<0.01 or P<0.05). The urinary albumin excretion rate of 24 h urine protein (115.37 ± 26.15 mg/24 h vs. 167.55 ± 38.66 mg/24 h, t=7.905) and 24 h urine (198.41 ± 33.24 μg/min vs. 226.19 ± 38.35 μg/min, t=3.871) was significantly lower than that of the control group (P<0.01). Conclusions TCM enema combined with CRRT can promote the recovery of renal function in patients with severe AKI, can effectively delay the progression of renal injury.

[Research and application of hepatotoxicity evaluation technique of traditional Chinese medicine].

The safety of traditional Chinese medicine (TCM) has received the widespread attention in recent years. Hepatotoxicity of TCM is one of the key problems of the safety of TCM. This article summarized research progress and application prospect in the mechanism of TCM hepatotoxicity, biomarkers, toxic omics database, prevention of hepatotoxicity of the liver cell lines, subcellular fraction, three-dimensional cultivation models, the model animals, aiming to provide theoretical basis for TCM toxicity evaluation and technical guidelines, thus promoting the development of TCM toxicity studies. Hope for Chinese medicine liver toxicity evaluation method provides the theoretical foundation and technical guidelines, promote the development and improvement of TCM liver toxicity research system.

An ultrafiltration and high performance liquid chromatography coupled with diode array detector and mass spectrometry approach for screening and characterizing thrombin inhibitors from Rhizoma Chuanxiong.

Thrombin (THR) plays a significant role in thromboembolic diseases, direct THR inhibitors are a class of important clinical anticoagulant drugs. This study established a THR in-solution based biospecific extraction combined with ultrafiltration and high performance liquid chromatography coupled with diode array detector and mass spectrometry analysis (TUA) method to screen and identify ligands for THR in Rhizoma Chuanxiong. After evaluating the reliability of the present TUA method using positive (argatroban) and negative (adenosine, tirofiban, ticagrelor) control drugs, this method was successfully applied to detect eight potential active compounds in Rhizoma Chuanxiong. Two new THR-targeted compounds isochlorogenic acid C and senkyunolide I with high THR inhibitory activity (IC50 206.48 and 197.23µM, respectively) were identified by liquid chromatography/mass spectrometry and enzyme inhibitory activity test finally. They were reported with direct THR inhibition activity for the first time and their ligand-THR interactions were explored by in silico molecular docking research. In addition, based on the TUA screening result, four compounds gained similar structure with the two hit compounds were also investigated as promising candidates targeting THR with high binding energy (>5.0kcal/mol). These results may prove that the proposed method could effectively screen THR inhibitors in complex mixtures.

The potential of Epimedium koreanum Nakai for herb-drug interaction.

OBJECTIVES: This study aims to investigate potential herb-drug interactions (HDI) of Epimedium koreanum Nakai. METHODS: Human liver microsomes (HLMs) were used to determine the enzyme kinetics of the major human cytochrome P450s (CYPs). Inducible potential of E. koreanum on CYP1A2, 2B6, 2C19 and 3A4 activities of human primary hepatocytes was also examined. KEY FINDINGS: Ethanol extract of E. koreanum showed direct inhibitory potency for CYP1A2 (IC50  = 121.8 µg/ml, Ki  = 110.7 ± 36.8 µg/ml) and CYP2B6 (IC50  = 59.5 µg/ml, Ki  = 18.1 ± 2.9 µg/ml). For CYP2C9, 2C19, 2D6, 2E1 and 3A4, only negligible effect was observed. Time-dependent (irreversible) inhibition by E. koreanum was observed for CYP1A2 (KI  = 32.9 ± 18.4 µg/ml, kinact  = 0.031 ± 0.006 min-1 ). However, ethanol extract of E. koreanum (1.5-150 µg/ml) did not change the activity or mRNA expressions for CYP3A4, 1A2, 2C19 and 2B6. CONCLUSIONS: The ethanol extract of E. koreanum is not likely to cause HDI via inducing the major human CYPs. But the potential for interactions between E. koreanum extract and substrates of CYP1A2 or 2B6 cannot be overlooked.

Molecularly imprinted polymers for the selective extraction of tiliroside from the flowers of Edgeworthia gardneri (wall.) Meisn.

Nano-sized molecularly imprinted polymers for tiliroside were successfully prepared by a precipitation polymerization method. Acrylamide, ethylene glycol dimethacrylate, azobisisobutyronitrile, and acetonitrile/dimethyl sulfoxide were used as functional monomer, cross-linker, initiator, and porogen, respectively. The structural features and morphological characterization of tiliroside-imprinted polymers were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. The adsorption experiments indicated that the tiliroside-imprinted polymers exhibited high selective recognition property to tiliroside. Scatchard analysis indicated that the homogeneous-binding sites were formed in the polymers. The selectivity test revealed that the adsorption capacity and selectivity of polymers to tiliroside was significantly higher than that of rutin, astragalin, and kaempferol. Finally, the tiliroside-imprinted polymers were employed as adsorbents in solid-phase extraction for the extraction of tiliroside from the ethyl acetate extract of the flowers of Edgeworthia gardneri (wall.) Meisn. The results demonstrated that the extraction recoveries of tiliroside ranged from 69.3 to 73.5% by using tiliroside-imprinted polymers coupled with solid-phase extraction method. These results indicated that the tiliroside-based molecularly imprinted solid-phase extraction method was proven to be an effective technique for the separation and enrichment of tiliroside from natural medicines.

Components of Goutengsan in Rat Plasma by Microdialysis Sampling and Its Protection on Aß1-42-Induced PC12 Cells Injury.

Goutengsan, a Chinese herbal formula, potential protection on Alzheimer's disease (AD) has been less reported. In current study, we investigated the protection of Goutengsan on Aß1-42-induced pheochromocytoma-derived cells (PC12). Furthermore, the components from Goutengsan in rat plasma were identified by microdialysis (MD) for in vivo sampling. Meanwhile, the protection of components identified was also verified. At last, we found that Goutengsan has a potential protective effect on Aß1-42-induced PC12 cells via reducing cells damage and increasing cells vitality as well as six components (pachymic acid, liquiritin, rhynchophylline, isorhynchophylline, corynoxeine, and isocorynoxeine) which may be effective components. This study helps to understand the treatment of Goutengsan for AD and would facilitate the clinical and further studies for this formula.