Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency.

Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group；The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4'-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms.

Zhang BX ，Qi XJ ，Cai Q 《-》

Fecal metabonomics study of raw and bran-fried Atractylodis Rhizoma in spleen-deficiency rats.

Processing herbal medicine is a classic characters of traditional Chinese medicine (TCM) clinic. Stir-frying with bran is a common method of processing Atractylodis Rhizoma (AR), which is considered to enhance the therapeutic effect in TCM theory. However, the processing mechanism remains unclear. In our previous study, we found that bran-fried AR was better than raw AR in regulating gut flora. To further compare the effect of raw and bran-fried AR on the symbiotic metabolism of gut flora and host, we established a fecal metabonomics method of ARs intervention on spleen-deficiency rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. 22 potential biomarkers of spleen-deficiency were identified under the positive and negative ion mode. Through the analysis of metabolic pathway, 6 significant changes of metabolic pathway were found, 5 of which were both improved by raw and bran-fried AR. Especially bran-fried AR was better than raw AR in the improvement of tyrosine metabolism and purine metabolism. Correlation analysis between the metabolic potential biomarkers and the microbiological biomarkers published in our previous study revealed that one of the spleen-strengthening mechanisms of ARs could be associated with the improvement of the symbiotic metabolism of gut flora and host by regulating gut-flora. The results can help us to understand the mechanism of AR intervention on spleen deficiency and the enhanced-efficacy mechanism of bran-fried AR.

Liu Y ，Ma S ，Cai Q 《-》

Study on the pharmacodynamics and metabolomics of five medicinal species in Atractylodes DC. on rats with rheumatoid arthritis.

Atractylodes DC. mainly includes Atractylodis Rhizoma and Atractylodis macrocephalae Rhizoma. According to Chinese Pharmacopoeia, Atractylodis Rhizoma is the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis), while Atractylodis macrocephalae Rhizoma is the rhizome of Atractylodes macrocephala Koidz. (A. macrocephala). Although Atractylodes japonica Koidz. ex Kitam. (A. japonica) and Atractylodes coreana (Nakai) Kitam. (A. coreana) are not included in the Pharmacopoeia, they are often used as Atractylodis Rhizoma in northern China. But in Japan, A. japonica is used as Atractylodis macrocephalae Rhizoma. In order to compare the efficacy of A. japonica and A. coreana with that of Atractylodis Rhizoma and Atractylodis macrocephalae Rhizomain in Pharmacopoeia, this paper studies the anti rheumatism of the five medicinal species in Atractylodes DC., and provides the basis for the rational application of A. japonica and A. coreana. With this purpose, the rheumatoid model of rats was established by Freund's complete adjuvant. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF - α), arthritis factor (RF), anti cyclic citrullinated peptide (anti-CCP), interleukin-1β (IL-1β), Nuclear factor-κB (NF - κB), interleukin-10 (IL-10) and Prostaglandin E2 (PGE2) in rats of each group. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to analyze the plasma of each group. After that, multivariate statistical analysis method was used to analyze the data. The results showed that the five medicinal species in Atractylodes DC. can reduce the levels of IL-6, IL-1 β, PGE2 and NF - κB in the plasma of rheumatoid arthritis (RA) rats in varying degrees, among which the regulation of A. macrocephala is relatively weak. A. chinensis, A. lancea, A. coreana and A. japonica can significantly reduce the content of TNF - α, in which A. japonica and A. lancea have better and similar regulatory effects. A. chinensis and A. coreana can significantly reduce the content of RF in arthritis rats. A. coreana, A. lancea and A. japonica can significantly reduce the anti-CCP level, that is, the regulatory effect of A. coreana and A. chinensis is similar. The metabolic disorder of 11-deoxycortisol, taurocholate and other small molecules in the body of rats with RA directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis, leading to the decline of immune function and other symptoms. Most of the metabolic pathways tend to be normal after oral administration of five medicinal species in Atractylodes DC. Among them, the regulating effect of A. coreana and A. chinensis is similar, while that of A. japonica and A. lancea are similar. A. macrocephala had little effect of intervention.

Liu Y ，Zhang B ，Cai Q 《-》

Comparison of the Modulatory Effect on Intestinal Microbiota between Raw and Bran-Fried Atractylodis Rhizoma in the Rat Model of Spleen-Deficiency Syndrome.

Ma S ，Jiang Y ，Zhang B ，Pang J ，Xu X ，Sun J ，Lv X ，Cai Q ... -  《-》

[UFLC/Q-TOF-MS based analysis on material base of atractylodis macrocephalae rhizoma stir-fried with wheat bran].

Cui XB ，Shan CX ，Wen HM ，Li W ，Wu H ... -  《-》