[Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats].

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.

Transdermal Administration of Ibuprofen-Loaded Gel: Preparation, Pharmacokinetic Profile, and Tissue Distribution.

The purpose of this study was to compare the pharmacokinetics and tissue distribution of ibuprofen (IBU) gel in female rats after transdermal administration through the skin of the abdomen and back. IBU was used as the model drug to prepare carbomer gel. After the abdominal and back administration, the concentration of IBU in rat plasma was detected by high-performance liquid chromatography (HPLC). Besides, the contents of IBU in the uterus, heart, liver, spleen, lung, and kidney were detected, respectively, to clarify the distribution characteristics in vivo. Through abdominal route, the AUC0- ∞ (area under the concentration-time curve from time zero to infinity) of uterus was 424.75 µg/g h, which is 3.60 times higher than that of plasma, and was significantly higher than that of other tissues (P < 0.0001). Tmax (peak time) of uterus and plasma was 4 h and 2 h, respectively. Upon transdermal application of IBU to the back, the AUC0-∞ of uterus was 75.47 µg/g h, which is 12.63 times lower than that of plasma, while Tmax of uterus and plasma was not lower than 20 h. These results indicated that IBU entered the blood circulation through abdominal administration in a small amount and mainly of the drug entered the uterus, while IBU entered the blood circulation and redistributed to tissues after absorption through the dorsal skin slowly. IBU could effectively reach the uterus and have a certain targeting through abdominal administration, which provides a prospect for clinical transdermal administration in the treatment of dysmenorrhea.

[Evolution of commercial specification and experimental identification terms of Gastrodiae Rhizoma].

Gastrodia Rhizoma, as a precious Chinese materia medica, has attracted the attention of Chinese materia medica experts in the past dynasties for the commercial specification and experimental identification, and has gradually formed a wealth of terms concerning commercial specification and experimental identification. Through combing the literatures of successive dynasties, this paper discussed the change of the commercial specification of the Gastrodiae Rhizoma and formation of its identifying terms. It has found that the Gastrodiae Rhizoma mainly came from the dried rhizomes of the Gastrodia elata f.elata before the Qing Dynasty. Since the Qing Dynasty, G. elata in Yunnan and Guizhou gradually arose and become one of sources of mainstream commodities. After that, G. elata f. glauca and G. elata f. elata were becoming the main sources of Gastrodiae Rhizoma. Before the large-scale cultivation of G. elata in the 1970 s, there is only wild G. elata over the country. In terms of commercial specification, they were often classified into Chunma and Dongma according to their harvest time. With the successful promotion of cultivation technology and the endangered wild resources of G. elata, the Dongma became the mainstream in the market. The adulterants of G. elata increased significantly in the 1960 s and 1970 s, in this period, the terms of experimental identification for G. elata also increased obviously. Experimental identification is distinctive in different times, therefore, studying experimental identification of medicinal materials helps to promote the development of the Chinese materia medica.

[Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent].

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the in vitro evaluation and practical application of the product.

[Evolution and transition of quality evaluation of Platycodon grandiflorum].

Platycodon grandiflorum, a traditional Chinese medicine commonly used for coughing and eliminating phlegm to relieve asthma, has gained great attention to its quality evaluation in ancient and modern herbal books. This paper investigated the methods of quality evaluation in the ancient herbal books systematically, and the results showed that there were bitter and sweet P. grandiflorum, south and north P. grandiflorum. Those distributed in east China were called south P. grandiflorum, with bitter taste; and those distributed in north China, northeast China were called north P. grandiflorum, with sweet taste. There was a common sense that P. grandiflorum with a bitter taste had good quality in the ancient herbal books, namely those produced in east China. P. grandiflorum of better quality were characterized by thicker and longer root, white color, solid texture and bitter taste in properties. In addition, the quality of P. grandiflorum was also affected by its germplasm, collecting and processing. This paper summarized the formation and development of the "assessing the quality by distinguishing features of traditional Chinese medicinal materials" views of P. grandiflorum, providing the herbalism basis for its present quality evaluation.

[Preparation and evaluation of intra-articular injectable sinomenine hydrochloride-loaded in situ liquid crystals].

Phytantriol (PT), ethanol (ET) and water were used to prepare in situ cubic liquid crystal (ISV2). The pseudo-ternary phase diagram of PT-ET-water was constructed and isotropic solution formulations were chosen for further optimization. The physicochemical properties of isotropic solution formulations were evaluated to optimize the composition of ISV2. In situ hexagonal liquid crystals (ISH2) were prepared based on the composition of ISV2 with the addition of vitamin E acetate (VitEA) and the amount of VitEA was optimized by in vitro release behavior. The phase structures of liquid crystalline gels formed by ISV2 and ISH2 in excess water were confirmed by crossed polarized light microscopy and small angle X-ray scattering, respectively. Rheological properties of ISV2 and ISH2 were studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using a dialysis membrane diffusion method. Pharmacokinetics was investigated by determination of sinomenine hydrochloride (SMH) concentration in synovial membrane after intra-articular injection of SMH-loaded ISH2 in adjuvant-induced arthritis rats. The optimal ISV2 (PT/ET/water, 64 : 16 : 20, w/w/w) loaded with 6 mg x g(-1) of SMH showed a suitable pH, injectable and formed a cubic liquid crystalline gel in situ with minimum water absorption in the shortest time. The optimal ISV2 was able to sustain the drug release for 144 h. The optimal ISH2 system was prepared by addition of 5% VitEA into PT in the optimal ISV2 system. This ISH2 (PT/VitEA/ET/water, 60.8 : 3.2 : 16 : 20, w/w/w/w) was an injectable isotropic solution with suitable pH. The new ISH2 was able to sustain the drug release for more than 240 h. Local pharmacokinetics study indicated that the retention time and AUC(0-∞) of ISH2 group were increased significantly compared with that of SMH solution group and the AUC(0-∞) of ISH2 group was 6.01 times higher than that of SMH solution group. The developed ISH2 was suitable for intra-articular injection that may apply to patients in the treatment of rheumatoid arthritis.

[Formation mechanism of Pickering emulsions induced by self-assembly of medium chain triglycerides and α-cyclodextrin].

In this study, the Pickering emulsions were prepared using medium chain triglycerides(MCT) and α-cyclodextrin(α-CD) and the formation mechanism was studied by means of several physicochemical techniques. The MCT/α-CD microparticles, which stabilized the emulsions, were characterized by the measurement of interfacial tension and the contact angle(θ(ow)), powder X ray diffraction(XRD), scanning electron microscope(SEM), high performance liquid chromatography(HPLC), differential interference microscope(DIM), Cryo-scanning electron microscopy(Cryo-SEM). The physical stability of emulsions with different α-CD content in the continuous aqueous phase was investigated by determination of the droplet size and sedimentation rate, combined with the observation of droplet morphologies by the inverted phase contrast microscope. As a result, it was observed that the amphiphilic supramolecule of MCT and α-CD were indeed formed. Furthermore, MCT/α-CD microparticles formed by the aggregation of MCT/α-CD supramolecule absorbed at the oil/water interface, and then forming a membrane structure to stabilize emulsion. In addition, the average θ(ow) for the MCT/α-CD microparticles was(46.1 ± 3.4)° which stabilized O/W emulsion. When the content of α-CD was increased in the continuous phase, there were more microparticles formed at the oil/water interface and in the continuous aqueous phase, which resulted in smaller particle size of droplet and higher viscosity of the continuous phase. In summary, the study suggest that α-CD/MCT/water emulsions were of O/W Pickering emulsions and the physical stability was better for emulsions with higher content of α-CD in the continuous phase.

Assembly of polysaccharide-based polymer brush for supramolecular hydrogel dressing.

Extracted from Platycodon grandiflorum, platycodon grandiflorum polysaccharides (PGPs) with diverse biological functions have been extensively employed for modification and fabrication of hydrogels for biomedical applications, such as wound dressings. However, since the lack of effective structural design, the reported polysaccharide-based hydrogel dressings are still suffered from structural failures and limited bio-functionality. Herein, we demonstrate a facile and general strategy to fabricate a supramolecular hydrogel composed of PGP-based polymer brush as building blocks combined with a Ca2+-mediated self-assembly process. The specific polymer brush with high branch functionality was achieved with polyacrylamide arms evenly grown on the PGP (grafting efficiency as high as 80 %) with series of chemical modifications. With above structural merits, the resulting hydrogel with densely crosslinked polymer brush featured enhanced mechanical strength as well as self-healing, and shear-thinning behaviors. Further biocompatible investigation indicated the as-prepared hydrogels with admirable performances in self-adhesion (adhesive strength of 16.7-79.5 kPa), a pH-responsive swelling ratio as high as 44 at pH 5.4, and pH-responsive degradation. They also showed antioxidant capacity by scavenging DPPH activity of nearly 80 % in 20 min, hemocompatibility, cell viability and cell migration. Impressively, the PGP-based polymer brush hydrogel served as a wound dressing revealed significant acceleration on wound closure.

Two new N-containing heterocyclic compounds from the roots of Platycodon grandiflorus.

Two unusual N-containing heterocyclic compounds, Plagranlines B-C, were isolated from the roots of Platycodon grandiflorus. Plagranline B (1) was consisted of neolignane and monomeric quinoline constituent units and plagranline C (2) possessed pyridinone ring that was not commonly discovered in natural product. Their planar structures were elucidated based on analysis of NMR and HRESIMS spectroscopy data, and their absolute configurations were determined by quantum chemical calculations, including GIAO 13C NMR (DP4+) calculation and ECD calculation. In addition, extensive activity screening including glycosidases, oestrogen-like, and NO inhibitory assays were performed, compounds 1 and 2 possessed the weak activities.

Study of the therapeutic effects of Painong powder on ulcerative colitis and the role of Platycodonis Radix in the prescription based on pharmacodynamic, pharmacokinetic, and tissue distribution analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulas have unique efficacy and are of great significance to the theory and practice of Chinese medicine and are therefore gaining increasing attention in research. Painong powder (PNS), composed of Aurantii fructus immaturus (Zhishi in Chinese, ZS), Paeoniae Radix Alba (Baishao in Chinese, BS), and Platycodonis Radix (Jiegeng in Chinese, JG), has remarkable effects on the detoxification and discharge of pus. JG is traditionally used to treat pulmonary carbuncles and is considered a 'medicinal guide'. According to the composition theory of prescriptions, JG is an 'assistant and guide' medicine. The role of JG as an adjuvant has gained increasing attention. AIM OF THE STUDY: The study was designed to prove the efficacy of PNS in ulcerative colitis (UC) and to study the role of JG in PNS via pharmacodynamic, pharmacokinetic, and tissue distribution analyses. MATERIALS AND METHODS: For the pharmacodynamic study, the UC rat model was induced using 5% trinitrobenzene sulfonic acid (TNBS). The results of the macroscopic characterization, histological analysis, and cytokine levels, including those of tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB), were integrated to evaluate the treatment of UC with PNS. In addition, an LC-MS/MS method was established and validated to analyze the blood pharmacokinetic parameters and tissue distribution of naringin and paeoniflorin. RESULTS: After the administration of high-dose PNS, the UC rats showed amelioration of macroscopic damage at the lesion site. The cytokine levels in the plasma, colon, and lung tissues were also decreased. The pharmacokinetic parameters showed that compared with UC rats administered with PNS-JG, those administered with PNS showed an increase in the AUC, MRT, and Tmax of naringin and paeoniflorin, and a decrease in their clearance rate. Furthermore, naringin and paeoniflorin had higher concentrations in the colon and lung tissues in the normal and model groups administered with PNS than in those administered with PNS-JG. CONCLUSIONS: PNS was shown to have marked therapeutic efficacy against TNBS-induced UC in rats. The effect of JG in PNS was reflected by the differences in the pharmacokinetic parameters and tissue distribution of the active components, providing valuable information for the clinical application of PNS in the treatment of UC. However, knowledge about how JG works as an adjuvant medicine in PNS is still lacking.

Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide.

The purpose of this study was to develop and evaluate triptolide-loaded cubic and hexagonal liquid crystals for transdermal drug delivery systems (TDDSs). We prepared and characterized triptolide-loaded lyotropic liquid crystals and evaluated for their percutaneous permeation properties in vitro and in vivo. We then used the adjuvant arthritic rat model and HaCaT cells to analyze the pharmacodynamics and conduct cell-stimulating studies of these liquid crystals. The optimized preparations were identified as cubic and hexagonal phase structures, respectively. Moreover, the in vitro percutaneous penetration studies demonstrated that compared to the homemade triptolide gel, cubic and hexagonal liquid crystals could significantly increase the percutaneous cumulative penetration of drugs within 48 h. Besides, the results of skin-blood synchronous microdialysis showed that the triptolide concentration in skin was higher than that in blood, and the cubic and hexagonal liquid crystals significantly increased the bioavailability of triptolide. Triptolide-loaded cubic and hexagonal liquid crystals presented excellent anti-arthritic effects, alleviating paw swelling and inhibiting inflammation by downregulating the levels of TNF-α and IL-1ß. In vitro cell-stimulating studies displayed that triptolide-loaded cubic and hexagonal liquid crystals exhibited no obvious toxicity, which exhibited that triptolide-loaded cubic and hexagonal liquid crystals were remarkable biocompatibility. Collectively, triptolide-loaded cubic and hexagonal liquid crystals represented a promising candidate for rheumatoid arthritis therapy.

The Effect of Prescription on the Framework of Lipid Matrix and In Vitro Properties.

PURPOSE: To clarify the inner framework and relative properties in vitro of Lyotropic liquid crystal (LLC) based on various prescriptions by using hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) as model drugs. METHODS: Phase structures were checked by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological studies and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) analysis were carried out to reveal their molecular interactions. In vitro release and skin permeation were conducted by Franz diffusion cell. RESULTS: PLM and SAXS showed double diamond cubic crystal. All the samples displayed characteristics of non-Newtonian fluid, and the molecular interactions increased with the reducing water. ATRFTIR showed that the strongest strength of hydrogen bond emerged in the formulation with 32% water. Released SH of S2 and S3 arrived over 80%, while S1 only reached 45%, and that of CA was about 23%. Water-rich prescription gave higher percutaneous penetration for hydrophilic drugs, whereas no significant difference existed in CA permeation. CONCLUSION: Proportion of Phytantriol to water determined the LLC assembling and affected the dissolving status of hydrophilic substance, thereby impacting on the location sites of guest molecular interactions among the substances, rheology properties, and finally the release and penetration behavior in vitro. Adjusting the basic prescription was the key to obtain satisfactory percutaneous delivery and stability for LLC carrying multi-therapeutic agents.

On the Structure and Transdermal Profile of Liquid Crystals Based on Phytantriol.

BACKGROUND: There has been a growing concern in transdermal drug technology over the past several decades. As a novel transdermal delivery system, Lyotropic liquid crystals (LLC) still face challenges such as drug loading, limited drug permeation and instability of systems. LLC system is so sensitive that a very subtle change in composition may induce a phase transformation or conversion of spatial configuration, and result in a diverse percutaneous delivery subsequently. OBJECTIVE: To find out the effects of hydrophilic and lipophilic components on the structure and transdermal properties of LLCs, hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a model drug and a skin permeation enhancer, respectively, several formulations were prepared and compared. METHOD: The structure of LLC was evaluated by visual observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin penetration of SH across the rat skins. Fourier transform infrared spectroscopy (FTIR) was recorded to evaluate the intermolecular interaction between the LC samples and stratum corneum (SC). CONCLUSION: The results showed that a controlled transdermal process might be obtained by adjusting the ratios of different drugs or loading doses when LLCs with dual-components were applied.

Phytantriol-based lyotropic liquid crystal as a transdermal delivery system.

The purpose of this study was examined the feasibility of using phytantriol-based cubic and hexagonal liquid crystal preparation for the percutaneous administration of trans­cinnamaldehyde (TCA). TCA-loaded lyotropic liquid crystal formulations were prepared and characterized, their skin permeability in vitro and in vivo was evaluated. Preliminary pharmacodynamics were also investigated in adjuvant arthritics (AA) rats. The formulations were identified respectively as cubic and hexagonal structure. The in vitro permeability study exhibited that both cubic and hexagonal liquid crystal improved the cumulative permeation quantity and permeation rates of TCA compared with home-made gel. The results of an in vivo transdermal permeability experiment showed that the area under the curve [AUC(0-∞)] of the hexagonal and cubic liquid crystal was 1.62 and 1.53 times higher than that of the gel group, respectively. Preliminary pharmacodynamics studies indicated that the group of high-dose TCA-loaded (200 mg·kg-1) hexagonal liquid crystal was shown to inhibit the paw swelling of AA rats, improve synovial hyperplasia and inflammatory cell infiltration, and down-regulate the levels of serum interleukin (IL)­1ß and tumor necrosis factor (TNF)­α. Furthermore, there was no significant difference in the anti-inflammatory effects of TCA-loaded hexagonal liquid crystal and the commercially available product Voltaren® emulgel®. Thus, hexagonal liquid crystal was considered as an effective delivery system for TCA.

Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on liver fibrosis induced by carbon tetrachloride in rats.

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated more excellent hepato-protective activity than the single herbs used individually as indicated in our preliminary studies. The present study was carried out to investigate the effects of PAE on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its possible mechanisms. Liver fibrosis was induced in male Sprague-Dawley rats by injection with 50% CCl(4) subcutaneously twice a week for 8 weeks. At the same time, PAE (40, 80 and 160 mg/kg) was administered intragastrically. Upon pathological examination, the PAE-treated rats significantly reduced the liver damage and the symptoms of liver fibrosis. Administration of PAE decreased CCl(4)-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissue by approximately 30-60%. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl(4) treatment. Moreover, PAE (80, 160 mg/kg, ig) decreased the elevation of TGF-beta1 by 47.7% and 53.1%, respectively. In the primary cultured hepatic stellate cells (HSCs), PAE also significantly decreased [(3)H] thymidine incorporation in cells stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB) and suppressed [(3)H] proline incorporation. These results suggested that PAE significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to scavenge free radicals, decrease the level of TGF-beta1 and inhibit collagen synthesis and proliferation in HSCs.

HII mesophase as a drug delivery system for topical application of methyl salicylate.

The main objective of this study was to develop reversed hexagonal (HII) mesophase for transdermal delivery of methyl salicylate. The formulation was prepared, characterized and evaluated for its skin penetration in vitro and skin retention in vivo. Preliminary pharmacodynamics and skin irritation were also investigated. The formulation was identified as hexagonal structure. In vitro study exhibited that HII mesophase enhanced the skin permeation by delivering 2.61 times more methyl salicylate than the commercially available cream. Meanwhile, HII mesophase presented higher bioavailability as AUC(0-24) and AUC(0-∞) were 32.894µg·mL-1 and 32.935µg·mL-1 respectively, while the cream were 12.791µg·mL-1 and 12.970µg·mL-1. Preliminary pharmacodynamics studies demonstrated that HII mesophase possessed anti-inflammatory and analgesic effects for inhibiting paw edema, granuloma and pain. MeSa HII mesophase showed no skin irritation on the normal rat skin. Thus, HII mesophase was considered as an effective delivery system for MeSa.

Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats.

Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.

[Effects and mechanisms of shaoqiduogan on mice with chemical liver injury].

OBJECTIVE: To study the therapeutic effects and mechanisms of SQDG on carbon tetrachloride-induced chemical liver injury in mice as well as its possible mechanisms. At the same time the pharmacodynamics of SQDG was compared with TGP or ASTs of effective dose. METHOD: The model of carbon tetrachloride-induced chemical liver injury in mice was prepared. The levels of ALT, AST, MDA content, SOD and GSH-Px activities in liver homogenate were assayed by spectrophotometry; Meanwhile, hepatic pathological examination was observed. RESULT: Protective effect of SQDG on carbon tetrachloride-induced chemical liver injury: SQDG was able to significantly decrease serum transaminase levels of chemical liver injury's mice induced by carbon tetrachloride, decreased MDA content and improved the reduced SOD and GSH-px levels in liver homogenate. Furthermore, SQDG also attenuate the area and extent of necrosis and reduce the infiltration of inflammatory cell. Compared with TGP or ASTs of effective dose, SQDG has a better effect on carbon tetrachloride-induced chemical liver injury in mice. CONCLUSION: SQDG can protect mice injured by carbon tetrachloride-induced chemical.

Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting.

The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-µCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-µCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.

Protective effect of fufanghuangqiduogan against acute liver injury in mice.

AIM: To study the effects and possible mechanisms of fufanghuangqiduogan (FFHQ) in mice with acute liver injury (ALI). METHODS: ALI was successfully induced by injecting carbon tetrachloride (CCl4) intraperitoneally and by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice, respectively. Each of the two model groups was divided into normal group, model group, FFHQ (60, 120 and 240 mg/kg) treatment groups, and bifendate treatment group. At the end of the experiment, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in liver homogenate were measured by biochemical methods. The activities of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were determined by radio-immunoassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS: In the two models of ALI, FFHQ (60, 120, 240 mg/kg) was found to significantly decrease the serum transaminase (ALT, AST) activities. Meanwhile, FFHQ decreased MDA contents and upregulated the lower SOD and GSH-px levels in liver homogenate. Furthermore, in immunologic liver injury model, FFHQ decreased levels of TNF-alpha and IL-1 in serum. Histologic examination showed that FFHQ could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. CONCLUSION: FFHQ had protective effect on liver injury induced by either CCl4 or BCG+LPS in mice, and its mechanisms were related to free radical scavenging, increasing SOD and GSH-px activities and inhibiting the production of proinflammatory mediators.