Effect of Combined Therapy of Lung and Intestine on VIP and p38 MAPK Signaling Pathways in Bronchial Asthma Mice / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effects of the combined therapy of lung and intestine， a common treatment for pulmonary diseases in traditional Chinese medicine （TCM）， on bronchial asthma mice， and further detect the changes of vasoactive intestinal peptide （VIP） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway-related proteins which are closely related to the pathogenesis of asthma， in order to elucidate the mechanism of the combined therapy of lung and intestine in the treatment of bronchial asthma. MethodA total of 60 Kunming mice were randomly divided into normal group， model group， dexamethasone group （0.5 mg·kg-1·d-1）， TCM group （2.73 g·kg-1·d-1）， and lung-intestine treatment group （6.825 g·kg-1·d-1）， 12 mice in each group. All mice except the normal group were sensitized by ovalbumin to induce bronchial asthma. After 30 days of intragastric administration， serum and lung tissue samples were obtained. The content of VIP， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum of mice in each group was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of TNF-α， IL-6， and p38 MAPK in lung tissues of mice were detected by real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of TNF-α， IL-6， p38 MAPK， and phosphorylated p38 MAPK （p-p38 MAPK） in lung tissues of mice were assayed by Western blot （WB）. ResultCompared with the normal group， the model group showed decreased content of serum VIP （P<0.05）， increased content of TNF-α and IL-6 （P<0.05）， up-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and elevated protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. Compared with the model group， the treatment groups exhibited increased content of serum VIP， TNF-α， and IL-6 （P<0.05）， down-regulated mRNA levels of TNF-α， IL-6， and p38 MAPK， and lower protein levels of TNF-α， IL-6， and p-p38 MAPK/p38 MAPK in lung tissues （P<0.05）. As compared with the lung-intestine treatment group， the serum TNF-α and IL-6 levels in the dexamethasone group were increased （P<0.05）， and the mRNA and protein levels of TNF-α and IL-6 in lung tissues were down-regulated （P<0.05）， while the levels of p38 MAPK， VIP mRNA， and p-p38 MAPK/p38 MAPK protein in lung tissues were up-regulated （P<0.05）. The serum VIP， TNF-α， and IL-6 levels in the TCM group were decreased （P<0.05）， and the mRNA levels of TNF-α， IL-6， p38 MAPK and protein levels of TNF-α， IL-6， p-p38 MAPK/p38 MAPK in lung tissues were up-regulated （P<0.05）， while the level of VIP mRNA in lung tissues was down-regulated （P<0.05）. ConclusionThrough increasing endogenous VIP and inhibiting the excessive activation of p38 MAPK signaling pathway， the combined therapy of lung and intestine can reduce the release of inflammatory factors， inhibit pulmonary inflammation response， and treat bronchial asthma.

Textual Research on Ancient and Modern Literature of Xiao Chengqitang / 中国实验方剂学杂志

Xiao chengqitang is recorded in Treatise on Febrile Diseases written by ZHANG Zhong-jing in the Eastern Han dynasty. It is composed of Rhei Radix et Rhizoma， Magnoliae Officinalis Cortex and Aurantii Fructus Immaturus， which is mainly used to treat mild exogenous Yangming Fu-viscera excess syndrome. This formula has been included in the Catalogue of Ancient Classical Prescription （The First Batch）. However， the processing specifications and doses recorded in the original formula are different from the modern usage， which results in some difficulties in the research and development of Xiao Chengqitang granules. For clarifying the key information， such as historical evolution of prescription， dose conversion， the origin and processing specifications of each medicine in the prescription， the paper systematically analyzes the ancient medical books and related literature in the past dynasties and refers to the life experience of ZHANG Zhong-jing. Then the modern prescription and decocting methods of Xiao Chengqitang were determined as follows：composing 55.2 g of Rhei Radix et Rhizoma （Rheum officinale） washed with wine， 27.6 g of Magnoliae Officinalis Cortex （Magnolia officinalis） processed with ginger and 39.0 g of stir-fried Aurantii Fructus Immaturus （Citrus aurantium）， adding 800 mL of water， decocting to 240 mL and filtrating.

Clinical Efficacy of Modified Xiao Chengqitang Combined with Acupoint Catgut Implantation in Treating Diet-induced Obesity Syndrome of Stomach Heat Dampness Obstruction / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and safety of modified Xiao Chengqitang combined with acupoint catgut implantation in treating diet-induced obesity （DIO） syndrome of stomach heat dampness obstruction. Method:One hundred and seventy-two patients were randomly divided into control group（84 cases） and observation group（88 cases）. Both groups of patients received diet and exercise lifestyle adjustments， and acupoint catgut implantation was performed， 10 days for 1 time， 5 days intervals and then catgut implantation again， for a total of 6 times. Patients in observation group took modified Xiao Chengqitang granular powder， 10 g/time， with lukewarm boiled water in morning and evening. Patients in control group took modified Xiao Chengqitang granular powder simulant， 10 g/time， with lukewarm boiled water， 2 times/day. The treatment courses continued 4 months in two groups. Then the body mass index （BMI）， fat percentage （F%）， obesity， waist to hip ratio （WHR） were measured before and after treatment. Color Doppler ultrasonography was used to measure abdominal fat thickness， prehepatic fat thickness （AHF）， perirenal fat thickness （PRF）， and visceral fat index （UVI）. Fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein-cholesterol （HDL-C）， low-density lipoprotein-cholesterol （LDL-C）， fasting insulin （FINS）， leptin （LP）， and adiponectin （APN） were detected before and after treatment， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. In addition， safety evaluation was also conducted. Result:The BMI， F%， obesity degree and WHR in observation group were all lower than those in control group （<italic>P</italic><0.05 or <italic>P</italic><0.01）. Subcutaneous fat thickness， AHF， PRF and UVI in observation group were lower than those in control group （<italic>P</italic><0.01）. The TG， TC， LDL-C and FINS levels in observation group were lower than those in control group （<italic>P</italic><0.01）. The LP and HOMA-IR were also lower than those in control group （<italic>P</italic><0.01）， while the APN was higher than that in control group （<italic>P</italic><0.01）. The total effective rate in clinical application was （71/80） 88.75% in the observation group， higher than （57/75） 76.00% in the control group （<italic>χ</italic>²=4.374，<italic> P</italic><0.05）. Conclusion:Modified Xiao Chengqitang combined with acupoint catgut implantation in treating DIO syndrome of stomach heat dampness obstruction can adjust LP， APN and other factors， improve energy metabolism such as sugar and fat， and effectively control obesity with high safety， so it is worthy of clinical use.

Analysis on Chemical Constituents in Xiao Chengqitang by UPLC-Q-Orbitrap-MS / 中国实验方剂学杂志

Objective:To rapidly identify the chemical constituents in Xiao Chengqitang by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. Method:The method was established by the Waters CORTECS T3 column （2.1 mm×150 mm， 1.6 μm）， mobile phase was methanol （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-5 min， 3%-21%A； 5-20 min， 21%-36%A； 20-32 min， 36%-50%A； 32-42 min， 50%-62%A； 42-50 min， 62%-85%A； 50-60 min， 85%-95%A）， the flow rate was 0.2 mL·min^-1， and the column temperature was 30 ℃. UPLC-Q-Orbitrap-MS was operated in positive and negative ion modes， the scanning range was 100-1 200 with mode of Full MS/dd-MS²， and the collision energies were 20， 40 eV. The compounds were identified by comparing with reference substances and combining with literature reports and MS database information. Result:A total of 123 components were identified in Xiao Chengqitang， including 33 flavonoids， 25 anthraquinones and anthrones， 23 phenylpropanoids， 15 tannins， 10 nitrogen-containing components and 17 other components. Among them， 32 components were determined by reference substances. Conclusion:The material basis of Xiao Chengqitang is flavonoids， anthraquinones and anthrones， phenylpropanoids， which is derived from Aurantii Fructus Immaturus，<italic> </italic>Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex， respectively.

HPLC Fingerprint Analysis of Substance Benchmark of Xiao Chengqitang / 中国实验方剂学杂志

Objective:To establish a high performance liquid chromatography （HPLC） fingerprint of the substance benchmark of Xiao Chengqitang and evaluate its quality with chemical pattern recognition method. Method:Diamonsil C₁₈ column （4.6 mm×150 mm， 5 μm） was used， mobile phase was consisted of methanol （A）-0.1% phosphoric acid solution （B） for gradient elution （0-60 min， 20%-90%A； 60-70 min， 90%-100%A）， the flow rate was 1 mL·min^-1， the column temperature was 25 ℃， and the detection wavelength was 254 nm. The similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine （2012 edition） was used to evaluate the similarity of HPLC fingerprint of 15 batches of substance benchmark of Xiao Chengqitang， and the chromatographic data were analyzed by cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis， in order to evaluate the quality difference between different batches of substance benchmarks of Xiao Chengqitang and find out the main chemical components that caused the quality difference. Result:The HPLC fingerprint of Xiao Chengqitang substance benchmarks was established， 31 common peaks were identified， and 18 components were identified by comparing with the reference substances. The similarities of 15 batches of HPLC fingerprint of Xiao Chengqitang substance benchmarks were >0.92. The samples could be divided into two categories by three chemical pattern recognition methods. Nine main components leading to the quality discrepancy of samples between batches were screened out， including rhein， chrysophanol-8-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， aloe-emodin-8-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， sennoside A， chrysophanol-1-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucoside， rhein-8-<italic>O</italic>-glucoside and others. Conclusion:The established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition characteristics of Xiao Chengqitang， and can be used for the quality control of Xiao Chengqitang preparations.

Review of Research on Xiao Chengqitang / 中国实验方剂学杂志

Xiao Chengqitang, derived from Treatise on Febrile Diseases, is composed of Rhei Radix et Rhizoma, Magnoliae Officinalis Cortex and Aurantii Fructus Immaturus. It is often used to treat Yangming Fushi light syndrome. This formula was included in the Catalogue of Ancient Classical Prescription (The First Batch), which has a high clinical application value. Current researches on the chemical composition, pharmacological effect and clinical application of Xiao Chengqitang have been carried out, but the history of Xiao Chengqitang is unclear and the dose conversation method is vague. It has great difficulties in clinical rational applications of Xiao Chengqitang and the research and development of its compound preparations. In this article, the literature reports on Xiao Chengqitang were summarized from the aspects of historical evolution, literature researching of Chinese herbs, dosage conversation method, modern research in case to clarify the historical context of Xiao Chengqitang and to provide basis for the clinical application and modern scientific research of this formula.