[Synergistic effect of Coptidis Rhizoma processed with Euodiae Fructus on ulcerative colitis through energy metabolism].

Based on the differences in targeted energy metabolomics, intestinal barrier protein expression, and glucose transport,the synergistic mechanism of Coptidis Rhizoma(CR) processed with Euodiae Fructus(ECR) on ulcerative colitis(UC) was explored.Mice were administered 4% dextran sulfate sodium to induce UC model, and then randomly divided into a model group, a CR group,and an ECR group. After 14 days of treatment, the therapeutic effect of processing on UC was assessed through histopathology of colon tissue and inflammatory indexes. Targeted energy metabolomics analysis was performed to evaluate the effect of processing on colon tissue energy metabolism. Molecular docking was carried out to predict the binding affinity of energy metabolites with intestinal barrier tight junction protein Claudin and glucose transporter 2(GLUT2). In vivo unidirectional intestinal perfusion experiments in rats were conducted to evaluate the effect of processing on intestinal glucose transport. The results showed that both CR and ECR could repair colon tissue damage in UC mice, downregulate tissue inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)levels, with the efficacy of ECR being superior to CR. Processed products significantly upregulated levels of multiple metabolites in colon tissue glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation, among which the upregulated levels of 1,6-diphosphate fructose and acetyl coenzyme A could bind well with Claudin and GLUT2. Additionally, the processed product also increased the expression of GLUT2 and enhanced glucose transport activity. This study suggests that ECR may enhance glucose transport to improve colon energy metabolism, promote barrier repair, and exert synergistic effects through processing.

[Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats].

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Comparative pharmacokinetics, intestinal absorption and urinary excretion of six alkaloids from herb pair Phellodendri Chinensis cortex-Atractylodis Rhizoma.

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

[Comparative analysis of pharmacokinetics and intestinal absorption of six alkaloids between Sanmiao Pills and Simiao Pills in rats].

The present study investigated the differences in pharmacokinetics and intestinal absorption of six alkaloids in Sanmiao Pills and Simiao Pills in rats and explored the different efficacies of the two formulae. After oral administration of Sanmiao Pills and Simiao Pills in rats, blood samples were collected at different time points. Samples were prepared for the determination of six alkaloids in plasma by UPLC-MS/MS. The chromatography was performed on an ACE Excel 3 C_(18 )column with acetonitrile-0.1% formic acid in water as the mobile phase for gradient elution. Analytes were detected in the positive ion mode. Plasma concentrations and pharmacokinetic parameters were calculated. Intestinal absorption of alkaloids was investigated by single-pass intestinal perfusion and absorption parameters of ingredients were calculated. The results showed that the UPLC-MS/MS method for simultaneous determination of concentrations of six alkaloids in plasma was developed and validated by methodological investigations, such as specificity, calibration curves, precision, accuracy, recovery, matrix effect, and stability. The results of the pharmacokinetic assay revealed that C_(max) and AUC values of phellodendrine, berberine, magnoflorine, berberrubine, and jatrorrhizine in Simiao Pills were significantly increased, and CL/F values were reduced as compared with those in Sanmiao Pills, which indicated the increase in plasma concentrations of alkaloids. The intestinal absorption parameters K_(a )and P_(eff) values of phellodendrine, berberine, and jatrorrhizine in Simiao Pills were higher than those in Sanmiao Pills. The intestinal absorption and plasma concentrations of alkaloids in Simiao Pills were significantly higher than those in Sanmiao Pills, suggesting that the composition of Simiao Pills was more conducive to the alkaloids into the blood to resist inflammation and lower uric acid.

Comparative metabolism of the eight main bioactive ingredients of gegen qinlian decoction by the intestinal flora of diarrhoeal and healthy piglets.

Diarrhoeal diseases alter the composition of intestinal flora, thereby affecting the efficacy of herbal medicinal formulations. Gegen Qinlian decoction (GQD), a Chinese traditional herbal formulation, is widely used to treat infectious diarrhoea. However, little is known about the microbial disposition of GQD in the diarrhoeal state. In this study, the comparative metabolism of components of GQD by diarrhoeal and normal intestinal flora was investigated in vitro. UPLC-MS/MS was performed for simultaneous analysis of eight ingredients of GQD in bacterial solution. The type, activities, and sources of microbial enzymes were also investigated. Microbial metabolism of daidzin, genistin and liquiritin (metabolized by ß-glucosidase); baicalin, wogonoside and glycyrrhizin (metabolized by ß-glucuronidase); and berberine and coptisine (metabolized via nitroreductase) was faster in the diarrhoeal group than in the normal group. Moreover, the activities of these enzymes in the diarrhoeal group were higher than those in the normal group. This difference might be associated with the increase in Escherichia spp. Thus, a change in the metabolism of components by diarrhoeal intestinal flora is associated with a preponderance of Escherichia spp., which might improve the efficacy of GQD. These findings have implications for understanding the action mechanism of GQD for diarrhoea treatment in terms of the microbial milieu.

Evaluation of Clinical Outcome and Risk Factors for Recurrence after Pelvic Reconstruction of Pelvic Organ Prolapse with Implanted Mesh or Biological Grafts: A Single-Blind Randomized Trial.

BACKGROUND: There are few studies on the relative factors related to postoperative recurrence. OBJECTIVES: To compare the outcomes of pelvic floor reconstruction involving Herniamesh mesh and biological grafts and to investigate the correlative factors of postoperative recurrence. METHOD: Two hundred and thirty-two patients were randomly divided into 2 groups: Herniamesh mesh group (117) and biological graft group (115). Follow-ups for 6 months and 1 year after the surgery. The primary outcomes were recurrence, perioperative complications. Secondary outcome was a questionnaire about the life habits associated with relapse. RESULTS: The recurrence rate at 6 months or 1 year did not differ substantially between the 2 groups (p = 0.787 and 0.968, respectively). Adverse events occurred with significantly different frequencies over 1 year (p = 0.005). Twelve factors were investigated and analyzed by logistic regression analysis. It showed that recurrence had a strong association with a long-term vegetarian diet (OR 0.283, 95% CI 0.117-0.683), long-term soybean product diet (OR 8.010, 95% CI 2.514-25.523), and vaginal intercourse (OR 5.154, 95% CI 1.461-18.184). CONCLUSIONS: The surgical recurrence rate for the mesh was similar to biological grafts at short-term follow-up. Eating soy products often and vaginal intercourse after surgery can reduce recurrence.

[Pharmacokinetic characteristics of fourteen main components of Gegen Qinlian Decoction in rats].

A specific and selective UPLC-MS/MS method was developed and validated for the simultaneous determination of isoflavonoids(3'-hydroxy puerarin, puerarin, daidzin, daidzein, genistin, genistein), flavonoids (baicalin, baicalein, wogonoside, wogonin, liquiritin)and alkaloids(berberine, jatrorrhizine, palmatine)(14 bioactive compounds) of Gegen Qinlian Decoction(GQD) in plasma. The pharmacokinetics characteristics of 14 bioactive compounds were study after oral administration of GQD at a single dose to rats. Prednisolone was used as the internal standard of liquiritin, and naringin was used as the internal standard of the other thirteen analytes. After the plasma samples were processed by precipitation protein method, the constituents and internal standards were gradient eluted by using a Zorbax SB-18 column with a mobile phase of acetonitrile(A) and 0.1% formic acid aqueous solution(B) using a gradient elution of 0-2.5 min, 15%-30% A; 2.5-3.5 min, 30%-35% A; 3.5-5.0 min, 35%-40% A; 5.0-9.0 min, 40%-60% A; 9.0-11.0 min, 60%-15% A, and the flow rate was 0.4 mL·min⁻¹. The auto sampler was conditioned at 25 °C and the sample injection volume was 5 µL. A mass spectrometry was applied with electrospray ionization (ESI) ion source in the positive and negative ion multiple reaction monitoring(MRM) mode. All pharmacokinetic parameters were processed by non-compartmental analysis with DAS 3.2.2 software. The results showed that the linear correlation coefficient of the 14 components were all greater than 0.99, indicating that the method had good linearity in their respective concentration ranges. Post-preparative stability (25 °C, 24 h), short-term stability(25 °C, 12 h), long-term stability (-20 °C, 7 d), and freeze and thaw stability (3-cycles) of the fourteen constituents were examined to evaluate the stability of methodology. The results of the inner and inter-day relative standard deviations were both less than 10%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of the fourteen analytes. The kinetic parameters of the related drugs were calculated according to the blood concentration of the 14 components. The results showed that the MRT0-t of the isoflavones and flavonoids was 7.5-11.8 h, T1/2z were mainly in 11.0-29.7 h, and the AUC0-t flavonoids were larger than the isoflavones. The MRT0-t of alkaloids were between 4.3-7.2 h, T1/2z were 1.0-5.0 h, AUC0-t were less than flavonoids and isoflavones. The results suggest that flavonoids and isoflavones have a high concentration of blood and long time of action, which are beneficial to the anti-inflammatory and antipyretic effects. The concentration of alkaloids in the body is low and the time of action is short, and it may play its bacteriostasis in the intestinal tract.

Tunable and switchable dual-waveband ultrafast fiber laser with 100 GHz repetition-rate.

We demonstrate a tunable and switchable dual-waveband 100 GHz high-repetition-rate (HRR) ultrafast fiber laser based on dissipative four-wave-mixing (DFWM) mode-locked technique. Each waveband maintains HRR operation. The DFWM effect was realized by combining a Fabry-Perot (F-P) filter and a piece of highly nonlinear fiber (HNLF). The tunable and switchable operations were achieved by nonlinear polarization rotation (NPR) technique. Through appropriately controlling the filtering effect induced by NPR, the laser could operate at two kinds of tunable regimes. One is that the spacing between these two wavebands could be tuned while keeping their center at 1559 nm. The other is that the central position of the entire dual-waveband is tunable while with the same separation between these two wavebands of 13.2 nm. Moreover, the laser could switch between these two wavebands. Correspondingly, the center of the single-waveband has a tuning range of 15.2 nm. This versatile ultrafast fiber laser may find applications in fields of optical frequency combs, high speed optical communications, where HRR pulses are necessary.

Dissipative soliton resonance in Bismuth-doped fiber laser.

We experimentally demonstrate the generation of dissipative soliton resonance (DSR) in a passively mode-locked Bi-doped fiber ring laser based on nonlinear polarization rotation (NPR) technique. The DSR with the central wavelength of 1169.5 nm has a repetition rate of 343.7 kHz. By purely increasing the pump power, the DSR evolves from Gaussian shape to rectangular shape with the duration extending from 2.1 ns to 13.1 ns, while keeping the pulse amplitude and the 3-dB spectrum bandwidth almost constant. The single-pulse energy reaches 24.82 nJ. Furthermore, we construct a lumped model to reproduce the mode-locking process and the traits of the DSR pulse. The obtained results indicate that it could achieve higher pulse energy in mode-locked Bi-doped fiber laser by generating DSR.

[Study on material basis of Mahuang Fuzi Xixin decoction for anti-inflammation and immune suppression based on combined method of serum pharmacochemistry and serum pharmacology].

To investigate me material basis of Mahuang Fuzi Xixin decoction (MFXD) for anti-inflammation and immune-suppression based on the combined method of serum chemical and serum pharmacological. The LC-MS/MS fingerprints of MFXD, drug-containing serum and blank serum were compared to define the components in plasma. Histamine, ß-hexosaminidase released from RBL-2H3 cell infulenced by drug-containing serum at different time points were measured by ELISA. The effect of drug-containing serum on lipopolysaccharide-induced splenocyte proliferation at different time points were determined by MTT. A correlation analysis was made on components of MFXD and pharmacological indexes based the stepwise regression method. After the intragastrical administration with MFXD, 32 components were discovered in rat serum, including 27 prototype components (10 from Mahuang, 13 from Fuzi and four from Xixin) and five unknown components. Compared with blank serum, drug-containing serum could reduce the release of histamine from RBL-2H3 induced by antigen at different time points (P < 0.05); except the 4-hour drug-containing serum, all of the remaining drug-containing serums could inhibit the RBL-2H3 mastocyte degranulation induced by antigen at different time points (P < 0.05). Drug-containing serum could significantly lipopolysaccharide-induced mouse splenocyte proliferation at 15 and 30 min (P < 0.05). A regression analysis was made on the chemical data of components absorbed into blood and pharmacological indexes, i. e. release rate of histamine, release rate of ß-hexosaminidase and inhibition rate of splenocyte. This suggested the close correlations among methyl pseudo-ephedrine, pseudoephedrine and histamine released from RBL-2H3 induced by antigen; pseudoephedrine, hypaconine, methyl pseudoephedrine and ß-hexosaminidase released from RBL-2H3 induced by antigen; as well as benzoyl hypaconine, benzoylaconine, 14-benzoyl-10-OH-mesaconine, mesaconine and lipopolysaccharide-induced mouse splenocyte proliferation. Methylpseudoephedrine, pseudoephedrine, benzoyl hypaconine, benzoylaconine and mesaconine may be part of material basis of MFXD on anti-inflammation and immune suppression.

[Simultaneous determination of formononetin, calycosin and isorhamnetin from Astragalus mongholicus in rat plasma by LC-MS/MS and application to pharmacokinetic study].

OBJECTIVE: To establish a method to determine the concentration of formononetin, calycosin and isorhamnetin from Astragalus mongholicus in rats' plasma using LC-MS/MS and calculate their pharmacokinetic parameters. METHODS: The contents of formononetin, calycosin and isorhamnetin in plasma were detected before and 24 h after 10 rats were treated with 10 g/kg Astragalus mongholicus. Rutin was used as internal standard. Agilent 1 200 HPLC system with Alltima C18 (150 mm x 2.1 mm, 5 microm) was used. Mobile phase was methanol-water solution with gradient elute at a flow rate of 0.3 mL/min. The column temperature was 40 degrees C. The LC-MS/ MS system was operated using an electrospray ionization probe in negative ion mode; Scan mode: multiple reaction ion monitoring (MRM) mode. The ion of monitor: m/z 267.0 --> 251.9 for formononetin, m/z 283.1 --> 268.2 for calycosin, m/z 315.4 --> 300.1 for isorhamnetin and m/z 609.4 --> 300.1 for rutin (internal standard), respectively. RESULTS: The linear range of formononetin, calycosin and isorhamnetin was 5 - 1 000 (r = 0.9996), 3.91 - 500 (r = 0.9989) and 0.5 - 100 ng/mL (r = 0.9992), respectively. The lowest limit of quantification (LLOQ) of formononetin, calycosin and isorhamnetin was 0.625, 0.5 and 0.1 ng/mL, respectively. The pharmacokinetic parameter, t(1/2beta), of formononetin, calycosin and isorhamnetin was (10.43 +/- 2.94), (6.91 +/- 1.33) and (5.07 +/- 1.21) h, respectively. The C(max) of formononetin, calycosin and isorhamnetin was (398.5 +/- 103.7), (138.7 +/- 32.8) and (58.3 +/- 14.5) ng/mL, respectively. The AUC(0 -> 12h), of formononetin, calycosin and isorhamnetin was (1238.8 +/- 311.3), (669.5 +/- 159.7) and (274.1 +/- 83.9)ng x h/mL, respectively. CONCLUSION: A sensitive, accuracy and suitable LC-MS/MS method for determination of formononetin, calycosin and isorhamnetin is developed and successfully applied to the pharmacokinetic study of 10 g/kg Astragalus mongholicus after oral administration in rats.

Viscoelasticity in trapezius myofascial pain syndrome: quantitative assessment using Real-Time Shear-Wave Elastography.

OBJECTIVE: To investigate the differences in the viscoelastic properties between normal trapezius muscles and those in patients with trapezius myofascial pain syndrome (MPS) using real-time shear-wave elastography (SWE). MATERIALS AND METHODS: This study included 31 patients with trapezius MPS and 31 volunteers. Sixty-one trapezius muscles (41 and 20 on the affected and non-affected side, respectively) of patients with MPS and 62 normal trapezius muscles in volunteers were assessed. Conventional ultrasonic parameters, including skeletal muscle thickness, resistance index (RI), and mean shear wave velocity (SWVmean) of trapezius muscles, were obtained in the seated position with the shoulders and neck relaxed. The daily neck leaning time (unit:hours) of all participants was obtained using a questionnaire. RESULTS: Ultrasound showed no statistically significant differences in thickness or RI of the trapezius muscles of the affected and non-affected sides in MPS patients versus normal trapezius muscles (p = 0.976 and 0.106, respectively). In contrast, the SWVmean of trapezius muscles in patients with MPS was significantly higher than that of normal trapezius muscles in both the affected and non-affected sides (4.41 ± 1.02 m/s vs. 3.35 ± 0.79 m/s, p < 0.001; 4.05 ± 0.63 m/s vs. 3.35 ± 0.79 m/s, p = 0.002). There was no significant difference between the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (4.41 ± 1.02 m/s vs. 4.05 ± 0.63 m/s, p = 0.225). Correlation analysis showed that daily neck forward time was positively correlated with the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (r = 0.635, p < 0.001; r = 0.576, p = 0.008). CONCLUSION: SWE can quantitatively evaluate stiffness of trapezius muscles in patients with trapezius MPS. The stiffness of both affected and non-affected trapezius muscles increased in patients with trapezius MPS, and the degree of increase positively correlated with the time of cervical forward leaning.

[Research on TLC identification and anti-coagulant activity quantitatively methods of Scolopendra subspinipes mutilans].

OBJECTIVE: To improve the quality standard of Scolopendra subspinipes mutilans by researching the methods of the TLC identification and anti-coagulant activity quantitatively. METHODS: Identified the free arginine (Arg) and serine (Ser) in scolopendra by TLC, screened the samples preparation process and developed solvent systems; Determined the anti-coagulant activity by method of titration with thrombin and screened the pretreatment methods. RESULTS: When medicinal materials was extracted by formic acid and 95% ethanol (1:1) with ultrasonic method and developed by n-butanol-acetic acid-water (12:5:4), the spots of Arg and Ser were well separated. Ultrasonic method was suitable for preparation of the anti-coagulant components in Scolopendra subspinipes mutilans and their anti-coagulant activity was determined by method of titration with thrombin could get a well reproducibility, the anti-thrombin activity of testing sample was (14.00 +/- 1.53) U/g and those of three different batch were (13.00 +/- 0.58) U/g, (17.00 +/- 1.15) U/g, (15.67 +/- 1.53) U/g respectively. CONCLUSION: The methods of TLC identification and anti-coagulant activity quantitatively could be used as a basis for improving the quality standard of Scolopendra subspinipes mutilans.

Network Pharmacology Integrated with Transcriptomics Analysis Reveals Ermiao Wan Alleviates Atopic Dermatitis via Suppressing MAPK and Activating the EGFR/AKT Signaling.

Background: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear. Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD. Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics. Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group. Conclusion: EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear. Objective: To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI). Study design and methods: The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman's correlation. Results: Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2. Conclusion: SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

[Comparative analysis of volatile oils of Mahuang Fuzi Xixin decoction and its major constituted herbs by GC-MS].

OBJECTIVE: To evaluate the correlativity between volatile oils of Mahuang Fuzi Xixin decoction and its major constituted herbs in composition and proportion. METHODS: The chemical compositions of volatile oils obtained by wet distillation from Mahuang Fuzi Xixin decoction and its major constituted herbs (Herba Ephedrae, processed Radix Aconiti Lateralis, Herba Asari) were analyzed by GC-MS. RESULTS: 44 volatile components of Mahuang Fuzi Xixin decoction were identified, which mainly derived from its constituted herbs Mahuang and Xixin. 68, 8, 39 volatile components were respectively identified from volatile oils of Herba Epherae, processd Radix Aconiti Lateralis and Herba Asari. There were apparent changes in composition and proportion between volatile oils of Mahuang Fuzi Xixin decoction and its major constituted herbs. CONCLUSION: There are apparent changes not only in quantity but also in quality between decoction and its major constituted herbs. Meanwhile any changes in composition may lead to a change in efficacy.

Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1/PI3K/AKT signaling.

Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman's analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC-MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.

Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with high morbidity, which leads to poor quality of life. The Xianglian pill (XLP) is a classical Chinese patent medicine and has been clinically proven to be an effective treatment for UC. PURPOSE: The pharmacological mechanism of the key bioactive ingredients of XLP for the treatment of UC was investigated by a network pharmacology and pharmacokinetics integrated strategy. STUDY DESIGN AND METHODS: Network pharmacology was used to analyze the treatment effect of nine quantified XLP ingredients on UC. Key pathways were enriched and analyzed by protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses. The effect of XLP on Th17 cell differentiation was validated using a mouse model of UC. The binding of nine compounds with JAk2, STAT3, HIF-1α, and HSP90AB1 was assessed using molecular docking. A simple and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of nine ingredients from XLP in plasma and applied to a pharmacokinetic study following oral administration. RESULTS: Nine compounds of XLP, including coptisine, berberine, magnoflorine,berberrubine, jatrorrhizine, palmatine, evodiamine, rutaecarpine, and dehydrocostus lactone, were detected. Network pharmacology revealed 50 crossover genes between the nine compoundsand UC. XLP treats UC mainly by regulating key pathways of the immune system, including Th17 cell differentiation, Jak-Stat, and PI3K-Akt signaling pathways. An in vivo validation in mice found that XLP inhibits Th17 cell differentiation by suppressing the Jak2-Stat3 pathway, which alleviates mucosal inflammation in UC. Molecular docking confirmed that eight compounds are capable of binding with JAk2, HIF-1α, and HSP90AB1, further confirming the inhibitory effect of XLP on the Jak2-Stat3 pathway. Moreover, apharmacokinetic study revealed that the nine ingredients of XLP are exposed in the plasma and colon tissue, which demonstrates its pharmacological effect on UC. CONCLUSION: This study evaluates the clinical treatment efficacy of XLP for UC. The network pharmacology and pharmacokinetics integrated strategy evaluation paradigm is efficient in discovering the key pharmacological mechanism of herbal formulae.

[Analysis on the HPLC chromatographic fingerprint of gegen qinlian decoction].

OBJECTIVE: To investigate the multiple bioactive constituents in Gegen Qinlian decoction and evaluate its bioactivity and quality control. METHODS: A high performance liquid chromatography with diode array detection (HPLC-DAD) method for the simultaneous qualitative determination of multiple components was developed. The separation was performed on a Kromasil C18 column by gradient elution with acetonitrile and ammonium acetate (containing 0.3% triethylamine, and adjusted pH 4. 3 using 1% glacial acetic acid) as the mobile phase at a flow-rate of 0.7 mL/min, the column temperature was maintained at 30 degrees C, HPLC chromatographic comparison between Gegen Qinlian decoction, four medicinal material and 14 components were carried out to investigate components in the composite formula. RESULTS: 23 characteristic peaks were identified and could be dated back to four medicinal materials from Gegen Qinlian decoction, in which 12 peaks were identifed by standards. CONCLUSION: This readily available, low-cost and reliable HPLC-DAD method can be used for simultaneous analysis of multiple bioactive constituents of Gegen Qinlian decoction and will improve the quality control of Gegen Qinlian decoction.

Identification of Active Compounds of Mahuang Fuzi Xixin Decoction and Their Mechanisms of Action by LC-MS/MS and Network Pharmacology.

The decoction is an important dosage form of traditional Chinese medicine (TCM) administration. The Mahuang Fuzi Xixin decoction (MFXD) is widely used to treat allergic rhinitis (AR) in China. However, its active compounds and therapeutic mechanisms are unclear. The aim of this study was to establish an integrative method to identify the bioactive compounds and reveal the mechanisms of action of MFXD. LC-MS/MS was used to identify the compounds in MFXD, followed by screening for oral bioavailability. TCMSP, BindingDB, STRING, DAVID, and KEGG databases and algorithms were used to gather information. Cytoscape was used to visualize the networks. Twenty-four bioactive compounds were identified, and thirty-seven predicted targets of these compounds were associated with AR. DAVID analysis suggested that these compounds exert their therapeutic effects by modulating the Fc epsilon RI, B-cell receptor, Toll-like receptor, TNF, NF-κB, and T-cell receptor signaling pathways. The PI3K/AKT and cAMP signaling pathways were also implicated. Ten of the identified compounds, quercetin, pseudoephedrine, ephedrine, ß-asarone, methylephedrine, α-linolenic acid, cathine, ferulic acid, nardosinone, and higenamine, seemed to account for most of the beneficial effects of MFXD in AR. This study showed that LC-MS/MS followed by network pharmacology analysis is useful to elucidate the complex mechanisms of action of TCM formulas.