Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats.

BACKGROUND: Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it's often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM: To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS: The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS: 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1ß, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION: These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

[Study on Serum Metabolite Profiling in Pi-deficiency Rats Based on LC-MS Technique].

OBJECTIVE: To explore metabolite profiling changes in serum of rats with pi-qi deficiency syndrome (PQDS) and pi-yang deficiency syndrome (PYDS) based on liquid chromatograph-mass spectrometer (LC-MS) technique, and to explore the essence of Pi-deficiency syndrome (PDS) from small molecule metabolite level. METHODS: Totally 21 male SD rats of SPF grade were randomly divided into three groups, the normal control group, the PQDS group, and the PYDS group, 7 in each group. Rats in the PQDS group overate for 1 day and fasted for 2 days. They drank freely and then swam to be exhausted in water at 35 degrees C - 37 degrees C for 15 successive days. The PYDS model was established by the same method for PQDS rats plus drenching 20% Folium sennae water extract (2 mL/100 g), once in the morning and once in the evening for one successive week. After modeling, models were evaluated according to rat general state, changes in body weight and rectal temperature. Serum metabonomic profiles were detected using LC-MS technique. Difference in inter-group metabolite spectrograms was analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA). Potential biomarkers related to syndrome types in rat serum were selected via the parameter of variable importance in the projection (VIP). RESULTS: The weight of rats in the PQDS group and the PYDS group decreased more significantly after modeling. The difference in prepost weight was statistically significant from that of the normal control group (P < 0.01). It was more obviously lowered in the PYDS group than in the PQDS group (P < 0.05). Compared with the normal control group, the rectal temperature of rats in the PYDS group and the PQDS group decreased (P < 0.05, P < 0.01). It decresed more in the PYDS group than in the PQDS group (P < 0.05, P < 0.01). Compared with the normal control group, levels of PC(19:0)/PE(22:0), PC(17:0)/PE(20:0), capric acid, oleic acid, stearic acid, succinic acid, fumaric acid, malic acid, glucose increased; arachidonic acid, linolenic acid, lauric acid, androsterone, 4-heptanone, dihydroxyacetonephosphate (DHAP) (6:0), and uridine decreased in the PYDS group and the PQDS group. Compared with the PQDS group, levels of PC(22:1), PC (22:6), PE (18:0)/PC (15:0), retinol, and deoxycytidine increased significantly in the PYDS group; PC (18:1), PC(19 :3), PC (20:3), PC (17:0)/PE (20:0), PC (19:1)/PE (22:1), PC (19:0)/PE (22:0), PC (17:1)/PE (20: 1), PC (16:1)/PE (19:1), cholic acid, hippuric acid, furoic acid, undecanedicarboxylic acid, palmitoleic acid, hydroxy stearic acid, eicosatrienoic acid, phenylalanine, tyrosine, glutamic acid, serine, carbamoyl aspartic acid, palmitoyl carnitine, tetradecanoyl carnitine, acetylcarnitine, and linoleylcarnitine decreased more significantly in the PYDS group. CONCLUSIONS: Comparative contents of various serum metabolites changed significantly in PQDS and PYQS model groups. Some potential small molecular biomarkers related to PDS were preliminarily identified. These results might provide some data reference for exploring scientific connotation and pathological mechanisms of PDS.