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1.
Article in Chinese | WPRIM | ID: wpr-1013334

ABSTRACT

ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan (ZSS) on constipation-predominant irritable bowel syndrome (C-IBS) rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank, model, positive drug (pinaverium bromide, 15.625 mg·kg-1), raw ZSS, stir-fried ZSS, bran-fried ZSS, charcoal-fried ZSS and finished ZSS groups (3.75 g·kg-1), with 10 rats in each group. Except for the blank group, which received intragastric administration of 0.9% sodium chloride solution at room temperature, all other groups were administered the ice solution at 0 to 4 ℃ (2 mL·d-1, for a total of 14 d) to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), neuro-peptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP), diamine oxidase (DAO) and D-lactic acid (D-LA) were detected by enzyme linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) and aquaporin-3 (AQP3) mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids (SCFAs) was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group, the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased (P<0.01), and the levels of 5-HT, VIP, CGRP and SP in serum were significantly increased. Simultaneously, the NPY levels significantly decreased (P<0.01), the levels of DAO and D-LA in plasma were significantly increased (P<0.01), and the mucosal epithelium of colon tissue was slightly damaged, with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3, cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased (P<0.05, P<0.01). The total amount of SCFAs in feces showed an obvious decreasing trend, with the contents of acetic acid, isobutyric acid, isovaleric acid, valeric acid and caproic acid decreased significantly, while the contents of propionic acid and butyric acid increased significantly (P<0.05, P<0.01). Compared with the model group, the treatment groups increased the intestinal propulsion rate, improved the intestinal mucosal barrier function, and adjusted the level of serum brain-gut peptide in C-IBS rats (P<0.05, P<0.01). The expression levels of AQP3, cAMP, PKA mRNA and VIP, AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces, and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.

2.
Acta Pharmaceutica Sinica B ; (6): 258-270, 2021.
Article in English | WPRIM | ID: wpr-881135

ABSTRACT

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

3.
China Pharmacy ; (12): 2692-2694, 2015.
Article in Chinese | WPRIM | ID: wpr-500933

ABSTRACT

OBJECTIVE:To compare the differences in the contents of water-soluble total protein,total phenolic acid and total polysaccharides among the water decoctions of crude Cibotium barometz and processed products and to illuminate the effect of pro-cessing on 3 kinds of components of C. barometz. METHODS:UV-visible spectrophotometry was adopted to determine the con-tents of water-soluble total protein,total phenolic acid and total polysaccharides in the water decoction of crude C. barometz and 4 processed products,namely sand-scorch C. barometz,yellow wine C. barometz,salt C. barometz and steamed C. barometz,at wavelengths of 590,760 and 489 nm respectively. RESULTS:The contents of water-soluble total protein in 5 samples were 4.03%,3.32%,3.13%,3.33% and 3.49%,those of total phenolic acid therein were 0.25%,1.34%,1.38%,2.34% and 1.41%,and those of total polysaccharides therein were 28.56%,36.06%,45.21%,49.60% and 49.01%,respectively. CONCLU-SIONS:All above processing methods have an effect to some degree on the contents of the 3 kinds of components of C. barometz, where the contents of water-soluble total protein are lower after processing,while those of total phenolic acid and total polysaccha-rides are higher thereafter.

4.
Article in Chinese | WPRIM | ID: wpr-594207

ABSTRACT

APOBEC(apolipoprotein B mRNA-editing enzyme catalytic-polypeptide) family members were reported as innate immune molecules with anti-viral activity for many viruses, such as HIV and HBV.In order to understand the function of APOBEC, the APOBEC-3F and-3G were cloned, expressed, and the sub-cellular localization of them was detected.The genes of APBEC-3F and-3G were cloned from PHA-stimulated PMBC and expressed in the MDCK cell by transfection.The sub-cellular localization of APOBEC-3F and-3G were detected by immunofluorescence.APOBEC-3F and-3G were cloned by RT-PCR and confirmed by DNA sequencing.The immunofluorescence indicated APOBEC-3F and-3G were located in the cytosal.APOBEC-3F and-3G could inhibit HBV replication effectively in HepG2.2.15 cell.APOBEC-3F and-3G could not be trans-located into nuclear by nuclear location signal(NLS) or bi-NLS(B-NLS).These results will help the future research on the function of APOBEC.

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