ObjectiveQuercus infectoria galls (QIG) is being widely used in Traditional Uyghur Medicine. To gather preclinical safety information for the aqueous extract of QIG, a toxicity study was performed.MethodsSubject animals were randomized, and devided into exposure and control groups. In the acute toxicity phase, three different doses—5, 7.5, and 10 g/kg, respectively—were administered via enema to imprinting control region (ICR) mice. An experiment using the maximum tolerance dose (MTD) i.e.10 g/kg was also performed. Data were gathered for 14 days, and study parameters were clinical signs, body weight, general behavior, adverse effects and mortality. At the day 14, major organs of the subjects were examined histologically. Chronic toxicity was also evaluated in Wistar rats for over 180 consecutive days. The rats were divided into three groups with different doses of 0.2 g/kg, 0.8 g/kg, and 2 g/kg, QIG. Furthermore, observations were carried out in rabbits to investigate if there were signs of irritation.ResultsIn comparison to control group, acute, chronic toxicity and mortality were not significantly increased in exposure group.ConclusionStudy result suggests that the aqueous extract of QIG is unlikely to have significant toxicity and that clinical trials may proceed safely.
Background
The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie’an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract.
Methods
CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells.
Results
First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration.
Conclusion
Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.
Quercus infectoria galls (QIGs) have a long history of treating ulcerative colitis (UC). The aqueous extract of QIG has an anti-UC effect. However, QIG’s enema is easy to leak, and the action time and dose of the drug cannot be controlled well. Thus, QIG is inconvenient to use. This study aims to screen and prepare an optimized thermosensitive in situ gel with slow release and retention. Taking the transition sol-gel temperature (Tsol-gel) as the investigation index, the Box-Behnken design response surface method (BBD-RSM) was used to optimize the dosages of Poloxamer 407 (P407), Poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC). Moreover, three formulations were selected, and the in vitro release rates were further optimized. The optimized rates of P407, P188, and HPMC were 24.07%, 1.22%, and 0.60%, respectively, and Tsol-gel was 32.8°C ± 0.4°C. The cumulative release of gallic acid in the gel conformed to the first-order kinetic equation, and gallic acid was released entirely within 24 h. In addition, the morphological and chemical characterization of thermosensitive in situ gel demonstrated that excipients did not affect the characteristic functional groups of QIG and that the surface of the QIG gel had a porous and loose structure. Rheological methods showed that the QIG thermosensitive in situ gel was fluid at low temperature and semisolid at gelation temperature. Therefore, the prepared gel was sensitive to temperature and had slow-release, local retention properties.
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