scholarly journals Therapeutic Assessment of Fractions of Hawthorn on Gastrointestinal Motility Disorder by UPLC-MS/MS-based Metabolomics

2020 ◽  
Author(s):  
Kaiyang Wang ◽  
Lan Luo ◽  
Xiaoli Xu ◽  
Xingyu Chen ◽  
Qiong He ◽  
...  
Keyword(s):  
Small Intestine ◽  
Therapeutic Effect ◽  
Gastrointestinal Motility ◽  
High Performance ◽  
Motility Disorder ◽  
Therapeutic Effects ◽  
Gastric Emptying Rate ◽  
Gastrointestinal Motility Disorder ◽  
Underlying Mechanisms ◽  
Polar Parts

Abstract Background: Hawthorn, a commonly-used traditional Chinese medicine (TCM) for treating dyspepsia，dysmenorrhea and hyperlipidemia, etc., has been proven to improve gastrointestinal motility, avoid food retention. Due to its complex ingredients, the active fractions responsible for the treatment of improving digestion remain largely unknown. To explore the underlying material and interpret its potential mechanism, the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder was studied based on the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics . Materials and Methods: The rat model of gastrointestinal motility disorder was established by subcutaneous injecting with atropine. The modeled rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn for 5 consecutive days. The stomach, small intestine, plasma samples were collected and then subjected to related measurement (gastric emptying rate and small intestine propulsion rate), UPLC-MS/MS metabolic profiling and multivariate/univariate statistical analysis. Results: The results showed that T3 had the best therapeutic effect, and T1, T2 and T4 with no obvious therapeutic effect, demonstrating that the effective components of hawthorn should be compounds of medium polarity. T3 achieved good therapeutic effects due to the gastrointestinal motility promotion activity, and by rectifying the disturbed amino acid metabolism in gastrointestinal motility disorder model. Conclusion: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux

2020 ◽  
Vol 41 (11) ◽  
pp. 1583-1591 ◽  
Author(s):  
Rui Li ◽  
Chengyong Dong ◽  
Keqiu Jiang ◽  
Rui Sun ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Liver Cancer ◽  
Therapeutic Effect ◽  
Efflux Pump ◽  
Human Life ◽  
Therapeutic Effects ◽  
Drug Efflux ◽  
Glycoprotein P ◽  
Chemotherapy Drugs ◽  
Underlying Mechanisms

Abstract Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer.

T1777 Decreased Ghrelin Response Mediates Upper Gastrointestinal Motility Disorder in Experimental GERD Rats

2009 ◽  
Vol 136 (5) ◽  
pp. A-577
Author(s):  
Shuichi Muto ◽  
Hiroshi Takeda ◽  
Nobuhiko Oridate ◽  
Takehiko Katsurada ◽  
Kazuaki Tsuchiya ◽  
...  
Keyword(s):  
Gastrointestinal Motility ◽  
Motility Disorder ◽  
Gastrointestinal Motility Disorder ◽  
Upper Gastrointestinal

scholarly journals Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats

2019 ◽  
Vol 20 (15) ◽  
pp. 3800
Author(s):  
Li Yang ◽  
Jian Pan
Keyword(s):  
Oral Cavity ◽  
Therapeutic Effect ◽  
Oral Mucositis ◽  
Influential Factor ◽  
Therapeutic Effects ◽  
X Rays ◽  
Weight Changes ◽  
Cortex Moutan ◽  
Radiation Induced ◽  
Underlying Mechanisms

Radiation-induced oral mucositis represents an influential factor in cancer patients’ accepted radiation therapy, especially in head and neck cancer. This research investigates the treatment effect of Ecdysterone (a steroid derived from the dry root of Achyranthes bidentate) and Paeonol (a compound derived from Cortex Moutan) on radiation-induced oral mucositis and possible underlying mechanisms. Concisely, 20 Gy of X-rays (single-dose) irradiated the cranial localization in rats for the modeling of oral mucositis. The therapeutic effects of Ecdysterone-Paeonol oral cavity directly administered on radiation-induced oral mucositis were investigated by weight changes, direct observations, visual scoring methods, ulcer area/total area, and basic recovery days. Assessments of tumor necrosis factor α and interleukin-6 were performed to evaluate the inflammatory cytokines secretion in the damaged areas of tongues harvested post-treatment, and changes in signaling pathways were investigated by Western blotting. System Drug Target (SysDT) methods revealed the targets of Ecdysterone-Paeonol in order to support compound-target network construction. Four representative targets with different functions were chosen. The binding interactions between the compound and receptor were evaluated by molecular docking to investigate the binding affinity of the ligand to their protein targets. Ecdysterone-Paeonol, administered orally, effectively improved radiation-induced oral mucositis in rats, and the therapeutic effect was better than Ecdysterone administered orally on its own. In this study, calculational chemistry revealed that Ecdysterone-Paeonol affected 19 function targets associated with radiation-induced oral mucositis, including apoptosis, proliferation, inflammation, and wound healing. These findings position Ecdysterone-Paeonol as a potential treatment candidate for oral mucositis acting on multiple targets in the clinic.

DDRE-18. THERAPEUTIC EFFECTS OF TASQUINIMOD ON GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi78-vi78
Author(s):  
Junfeng Liu ◽  
Raziye Piranlioglu ◽  
Naoyuki Shono ◽  
Alexander Lee Ling ◽  
Himanshu Soni ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Bone Marrow Cells ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects ◽  
M1 Phenotype ◽  
Suppressive Phenotype ◽  
Human Gbm ◽  
Underlying Mechanisms

Abstract Glioblastoma is the most aggressive and most common primary malignant brain tumor in adults. This disease is still incurable despite multimodal therapies. We evaluated Tasquinimod, an oral HDAC4 inhibitor, in use with oncolytic HSV therapy. Tasquinimod is known to bind to HDAC4 and S100A9 to modulate myeloid population and angiogenesis in the tumors. This drug is being clinically evaluated in prostate and other solid tumors and multiple myeloma. However, the therapeutic effect of Tasquinimod in glioblastoma is not known. We found that Tasquinimod could change the immune-suppressive phenotype of MDSCs and polarize M2 macrophages towards M1 phenotype in ex vivo assay using mouse bone marrow cells treated with glioma conditioned media. We also tested Tasquinimod and oncolytic HSV in murine CT2A in C57/B6 mice and primary human GBM xenograft model in athymic mice. While the therapeutic effect of Tasquinimod or oHSV alone was not significant or marginal, the combo group show significantly longer survival. The study of underlying mechanisms is still ongoing. In conclusion, Tasquinimod combined with oncolytic HSV could have a better therapeutic effect on glioblastoma.

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