Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts / 药学学报

A quantitative analysis method for six principal active constituents (acubin, geniposidic acid, chlorogenic acid, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside) of crude Eucommiae Cortex (EC) and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo. UHPLC-QqQ-MS/MS technology was employed. Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion. The established method was fully validated by specificity, linearity, precision, accuracy, stability, recovery, and matrix effect, and the results of methodological investigation met the requirements of biological sample analysis. Then, a quick, sensitive, and accurate method was successfully established, which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma. After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts, the plasma concentration of each constituent at different time points was measured, the pharmacokinetic parameters were calculated and the concentration time curves were structured. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No. 202103A008). The results showed that compared to the crude Eucommiae Cortex group, the tmax of aucubin, pinoresinol di-O-glucopyranoside, geniposide, and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group (P < 0.05, P < 0.01); the Cmax and AUC0-48 h of chlorogenic acid, the Cmax, AUC0-48 h and AUC0-∞ of pinoresinol di-O-glucopyranoside, and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group (P < 0.05, P < 0.01). Our investigation found that compared to crude Eucommiae Cortex, a variety of active ingredients could play a role of quick effect with higher peak blood concentration and bioavailability after oral administration of salt-processed Eucommiae Cortex, which were consistent with the traditional Chinese medicine theory of "salt-processing enhancing drug into kidney meridian", providing an experimental basis for the selection of quality control indexes and the in-depth study of processing mechanisms and metabolic rules in vivo of Eucommiae Cortex and its salt-processed product.

Wuhutang Alleviates Respiratory Syncytial Virus-induced Asthma in Mice by Inhibiting STAT3 Protein and Regulating Dendritic Cell Autophagy / 中国实验方剂学杂志

Objective:To investigate the therapeutic mechanism of Wuhutang on respiratory syncytial virus （RSV）-induced asthma in mice and its influence on the expression of signal transducer and activator of transcription 3 （STAT3） in lung tissue. Method:One hundred female BALB/c mice of SPF grade were randomly divided into a normal group and an experimental group. After successful modeling via aerosol inhalation of RSV and ovalbumin （OAV）， the mice in the experimental group were further randomized into the following seven groups： model， positive control （dexamethasone， 1.82 mg·kg^-1）， STAT3 inhibitor （STATTIC， 3.75 mg·kg^-1）， STAT3 inducer （colivelin， 1.0 mg·kg^-1）， and low-， medium-， and high-dose （1.6， 3.2， and 6.4 g·kg^-1， respectively） Wuhutang groups. The corresponding drugs were administered for two weeks， followed by the detection of airway reactivity using a small animal ventilator， the pathological changes in lung tissue， mucus secretion by goblet cells and collagen deposition in airway were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS） and Masson staining， the serum levels of interleukin-6 （IL-6）， IL-10， and IL-17 were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA in lung tissue were detected by fluorescence-based real-time polymerase chain reaction （Real-time PCR）， autophagosomes present in lung tissue were examined by transmission electron microscopy， the protein expression levels of ATG5 and SQSTM1 in dendritic cells （DCs） and STAT3 and p-STAT3 in lung tissue were detected by Western blot. Result:The airway reactivity of the model group was enhanced in contrast to that in the model group （<italic>P<</italic>0.01）， manifested as inflammatory cell infiltration around the lung tissue， excessive metaplasia of goblet cells， and extensive deposition of airway collagen， the expression levels of serum IL-6 and IL-17 were increased （<italic>P<</italic>0.01）， while that of IL-10 declined （<italic>P<</italic>0.01）， the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA were elevated （<italic>P</italic><0.01）， the number of autophagosomes in the lung tissue increased. The protein expression levels of ATG5， STAT3， and p-STAT were up-regulated， while that of SQSTM1 was down-regulated （<italic>P<</italic>0.01）. Compared with the model group， Wuhutang and STATTIC significantly reduced the airway hyperresponsiveness of asthmatic mice （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， alleviated RSV-induced pathological changes in lung tissue， reduced the contents of serum IL-6 and IL-17 （<italic>P<</italic>0.01）， increased serum IL-10 and ATG5 in DCs （<italic>P<</italic>0.01）， down-regulated the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA as well as the protein expression levels of SQSTM1， STAT3 and p-STAT3 （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， and elevated the number of autophagosomes. Conclusion:Wuhutang relieves airway inflammation， improves airway remodeling and reduces airway hyperresponsiveness in RSV-induced asthmatic mice by inhibiting STAT3 protein and up-regulating DC autophagy in lung tissue.

Mechanism investigation on the enhanced anti-hepatic fibrosis effects in rats of Fructus Corni after wine-processing based on plasma metabonomics / 药学学报

Metabonomics technology was employed to investigate and identify the mechanisms and metabolic pathways of the crude and wine-processed Fructus Corni extracts on anti-hepatic fibrosis effects in rats, and to compare and analyze the potential mechanism of enhanced interference of the wine-processed Fructus Corni on hepatic fibrosis effects in rats. The rats were randomly divided into the blank control group, the model group, the colchicine group, the crude Fructus Corni groups with low, medium, and high-doses, and the wine-processed Fructus Corni groups with low, medium, and high-doses, and there were six rats in each group. The hepatic fibrosis model was established by subcutaneous injection of 40% carbon tetrachloride, and the intragastric administration was performed at the third week of modeling. The blood and liver samples of rats were taken and carried out for pharmacodynamic index detection and UHPLC-Q-TOF-MS/MS analysis after intragastric administration for six weeks. The results of pharmacodynamic investigation showed that both the crude and wine-processed Fructus Corni had the effects of anti-hepatic fibrosis in rats. Metabonomics analysis indicated that, compared to the blank control group, the twenty-four potential biomarkers related to hepatic fibrosis were screened and identified in the model group, which mainly involved in primary bile acid metabolism, glycerol phospholipid metabolism, pentose and glucuronide metabolism, retinol metabolism, and arachidonic acid metabolism. The crude and wine-processed Fructus Corni extracts had different degrees of callback effects on the ten of the above potential biomarkers, and the effect of wine-processed Fructus Corni was better than that of crude one. The present study clarifies the mechanism of enhanced efficiency of wine-processed Fructus Corni from the perspective of plasma metabolism, and provides the theoretical foundation for further development and clinical application of Fructus Corni.

Effect of wuhu decoction on surface co-stimulation molecule expression of peripheral dendritic cells in infants with asthma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Wuhu Decoction (WHD) on the expression of co-stimulation molecule of peripheral dendritic cells (DC), CD80, CD83 and CD86, in infants with asthma, in order to provide practical basis for further elucidate the action mechanism of WHD in preventing and treating infantile asthma.</p><p><b>METHODS</b>Sixty infants with asthma of Fei phlegm-heat accumulation syndrome type were randomized into the treatment group treated with WHD and the control group treated with Western medicine (fluticasone propionate oral taking or inhalation). And 10 healthy infants were set as normal control. With Thomas method adopted, the DC were isolated from peripheral blood of all infants subjected. The expressions of surface co-stimulation molecules of DC, CD80, CD83 and CD86, were detected by flow cytometry. Their changes before and after treatment in different groups were analyzed and compared.</p><p><b>RESULTS</b>Expressions of CD80 and CD86 of peripheral blood DC in asthmatic infants were remarkably higher than those in the normal control (P<0.01). In the treated group, CD80 expression lowered from 18.06 +/- 4.53 before treatment to 13.18 +/- 3.02 after treatment and CD86 expression lowered from 38.61 +/- 10.54 to 29.65 +/- 8.55; while in the control group, the two expressions were lowered from 18.40 +/- 3.86 to 15.34 +/- 3.90, and from 38.29 +/- 11.67 to 35.88 +/- 13.85 respectively, the lowering in both groups were statistically significant (P<0.01 and P<0.05), but it was more significant in the treated group (P<0.05). As for CD83, no significant difference existed between groups and no change was found in either group after treatment (P>0.05).</p><p><b>CONCLUSION</b>WHD can regulate the co-stimulation molecules of dendritic cells in asthma infants to reduce the expressions of CD80 and CD86.</p>

Clinical study on effect of jiexiao oral liquid in preventing and curing virus induced asthma in children / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect and the possible mechanism of Jiexiao Oral Liquid (JXOL) in preventing and curing virus induced asthma in children.</p><p><b>METHODS</b>One hundred and sixty patients of acute upper respiratory tract infection (AURTI) with asthma history were randomly divided into 2 groups. JXOL was given to the treated group within 24 hrs after occurrence of AURTI symptoms, and virazole of 10-15 mg.kg-1.d-1 was given to the control group, the therapeutic course for both groups was 7 days. Changes of clinical symptoms, signs, therapeutic effect, pulmonary function and immuno-globulin in patients were observed.</p><p><b>RESULTS</b>The total effective rate of the treated group was 83.8%, the clinical control rate was 48.8%, while those in the control group were 62.5% and 23.8% respectively, showing significant difference between them (P < 0.01). JXOL could obviously improve the indexes of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), reduce the level of IgE, as compared with those before treatment, the difference was significant (P < 0.01 or P < 0.05); it also showed significant difference as compared with those in the control group after treatment. The changes of IgA, IgG and IgM after treatment showed insignificant difference.</p><p><b>CONCLUSION</b>JXOL was effective in preventing and curing virus induced asthma in children, it also shows pulmonary function improving and immune regulating effects.</p>