San-Cao Granule () Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.</p><p><b>METHODS</b>A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.</p><p><b>RESULTS</b>Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).</p><p><b>CONCLUSION</b>SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.</p>

Lignans-rich extract from Herpetospermum caudigerum alleviate physical fatigue in mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum.</p><p><b>METHODS</b>The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum (chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione (HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid (BLA), blood urea nitrogen (BUN), malondialdehyde (MDA), hepatic glycogen (HG), lactic dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) determined following the recommended procedures provided by the commercial kits.</p><p><b>RESULTS</b>Compared with the control group, the lignans extract (ethyl acetate fraction) of Herpetospermum caudigerum and HPE could signifificantly prolonged the exhaustive swimming time (P<0.05 or P<0.01), and also increased the HG levels (P<0.05 or P<0.01) and the activities of antioxidant enzymes (SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups (P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group (P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters.</p><p><b>CONCLUSIONS</b>The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.</p>

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method.

AIM: To improve the absorption and bioavailability of baicalin using a nanocrystal (or nanosuspension) drug delivery system. METHODS: A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. RESULTS: The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of -34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 µg·mL(-1), was much higher than the baicalin-microcrystals and the physical mixture (135 and 86.4 µg·mL(-1), respectively). In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability (with the AUC(0-t) value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L(-1)·h(-1), respectively). CONCLUSION: The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin.

Dynamic effect of curcumin on urine concentration of neuronal thread protein in AD mice / 中国中药杂志

<p><b>OBJECTIVE</b>Through the dynamic detection of the concentration change of the urine Alzheimer-associated neuronal thread protein (AD7C-NTP) in the curcumin treated Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice, the therapeutic effect of curcumin in AD was determined.</p><p><b>METHOD</b>Thirty three-month-old APP /PS1 double transgenic mice were randomly divided into 5 groups, 6 in each group, the model group, rosiglitazone group(10 mg . kg-1 . d-1) , high(400 mg . kg -1 . d-1) , medium(200 mg . kg-1. d-1) and low(100 mg . kg-1 . d-1) dose curcumin groups. Six C57BL/6J mice in the same age and genetic background were used as normal control group. All the 6 groups of mice were intragastrically administered for 6 months. Urine samples were collected on 4 month, 5 month and 6 month after intragastric administration, respectively. The changes of urinary AD7C-NTP concentration were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULT</b>The concentration of AD7C-NTP of each group was compared at the same time point, the concentration of model group is higher than normal control group (P <0.05) ; the concentration of other groups is lower than model group. The concentration of high curcumin dose group with 4 months treatment, has no statistical difference compared with model group. The AD7C-NTP concentration of each group was elevated with the age growth, and all concentrations of the treatment groups were lower than the model group at the same period. With the treatment of 4, 5 and 6 months, the concentration of the normal control group has significant difference with the treatment groups(P <0. 01). There have no statistical difference between all the groups with the treatment of 6 months compared with 5 months.</p><p><b>CONCLUSION</b>With the progression of the disease in AD mice, there are fluctuations in urinary AD7C-NTP concentration, the compound curcumin from traditional Chinese medicine can delay the progression of AD.</p>

Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction () treatment / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction (, YCHD) using an ultra pressure liquid chromatography (UPLC) method.</p><p><b>METHODS</b>Rats were divided into a normal group and a model group, after modeled by 4% ANIT (75 mg/kg) for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g/kg, and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL), direct bilirubin (DBIL)], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS2.1.1 software.</p><p><b>RESULTS</b>The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration (t(max)) were both 0.25 h, the maximum concentration (C(max)) were 4.533 μg/mL and 6.885 μg/mL, and their area under concentration-time curve (AUC)(0→24h) were 16.272 and 32.981, respectively. There was a 51.88% and 100.46% increase in C(max) and AUC(0-t) (P<0.05), but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution (P<0.05), respectively.</p><p><b>CONCLUSIONS</b>Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats, but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.</p>

Study on the complex prescription compatibility law of the cold and hot nature of Mahuang Decoction and its categorized formulae based on the cold-hot pad differentiating assay / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the complex prescription compatibility law of the cold and hot nature of Mahuang Decoction (, MHD) and Maxing Shigan Decoction (, MXSGD), both categorized both categorized MHD) and Maxing Shigan Decoction (both categorized MXSGD), both categorized formulas but with different hot/cold natures.</p><p><b>METHODS</b>Oxygen consumption of mice was determined among three groups: MHD, MXSGD and the control; a cold-hot pad differentiating assay was used to observe the variability of temperature tropism among the groups of mice which was treated with MHD, MXSGD, and their compositions. Meanwhile, the total anti-oxidant capability (T-AOC) activity were detected.</p><p><b>RESULTS</b>After administration of MHD, the mice showed increased oxygen consumption (P<0.01). Compared with MHD group, the remaining rate of MXSGD mice on the hot pad was found to be significantly increased with the cold-hot pad differentiating assay (P<0.05). There was no significant difference (P>0.05) among the remaining rates of MXSGD, MXSGD with high dose Gypsum Fibrosum (MXHGF) group, and MXSGD with low dose Gypsum Fibrosum (MXLGF) group mice. Compared with the MHD group, T-AOC activity of the mice in the Consensus Compositons group was significantly decreased (P=0.0494). Compared with the MXSGD group, T-AOC activity of Gypsum Fibrosum (GF) group was increased significantly (P=0.0013).</p><p><b>CONCLUSIONS</b>The differences in cold and hot nature could be represented objectively between MHD with a hot nature and MXSGD with a cold nature. The reason may be the Gypsum Fibrosum which decreased the efficacy of the consensus compositions. However, increasing or decreasing the dose of Gypsum Fibrosum will not change the cold and hot nature of MXSGD.</p>

COLD or HOT natural attribute of Zuojinwan and Fanzuojinwan based on temperature tropism of mice / 药学学报

This study is to investigate the authenticity between COLD and HOT natural attribute in the famous Chinese medicine formulas--Zuojinwan (Coptis-Evodia 6 : 1) and Fanzuojinwan (Coptis-Evodia 1 : 6) based on mice temperature tropism, and establish an objective method to estimate the difference of two natural attribute by using a cold/hot plate differentiating technology. The results indicated that the COLD nature Zuojinwan could decrease significantly the remaining rate of HOT-symptom rat on warm pad (P < 0.05). That was not notable to COLD-symptom rat. The interference result of COLD-HOT temperature tropism to COLD/HOT symptom rat in Fanzuojinwan was the reverse with the COLD nature Zuojinwan. Meanwhile, biochemical indicators which are relative to energy metabolism such as ATPase enzyme activity and total anti-oxidant capability (T-AOC), had corresponding change in the organism. In the study, the COLD and HOT natural tendency in Zuojinwan and Fanzuojinwan which were composed by the same herbs with different proportion could be expressed qualitatively, quantitatively, objectively and directly with applying animal temperature tropism, and be verified to philosophical idea of treating disease theory with "expelling heat with cold herbs and cryopathy requiring warm prescription", not "expelling heat with heat herbs and cryopathy requiring cold prescription" in ancient traditional Chinese medicine, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.