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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Background Quercus Infectoria galls (QIG) has multiple therapeutic properties and are widely used in Traditional Medicine (TM) as an anti-inflammatory agent for inflammatory bowel disease (IBD). QIG aqueous extract has been verified to inhibit the proliferation of Colorectal cancer (CRC) cells but there is no relevant research on the contribution of material basis of QIG towards the efficacy at present. This research aims to clarify the pharmacodynamic discrepancy of different polar solvent extracts of QIG and the underlying link between material basis and anti CRC efficacy. Methods Four different QIG extracts and residues was prepared by using a modified method and the effective compounds polyphenols, tannins and gallic acid (GA) was determined by analytical methods including Thin Layer Chromatography, Ultraviolet-visible spectrophotometry, High Performance Liquid Chromatography and Infrared spectroscopy. Then GA and four different QIG extracts’ anti CRC activity against human HCT-116 and Caco-2 cells were tested in vitro by CCK-8 assay, wound-healing assay and apoptosis assay, at the end entropy weight method was used to comprehensively assess the anti CRC activities for discern the most active one among the four different QIG extracts. Results The content determination experiment shows that the content of active compounds in the four extracts increased with the increase of the polarity of the extraction solvent. The content of polyphenols, tannins and GA in aqueous extracts ranks first, reaching 562.66 ± 8.45 mg·mL− 1, 463.85 ± 4.62mg·mL− 1, 169.86 ± 3.24mg·mL− 1, respectively, followed by methanol, ethanol, and acetone, and the content order of them in residues is opposite to that in extracts. The in vitro pharmacodynamic experiments showed that all four extracts and GA could inhibit the proliferation and migration, induce apoptosis of CRC cells in different degrees. The entropy score of ethanol extract ranks first (0.5546 and 0.5436), followed by methanol (0.2264 and 0.1989), acetone (0.1961 and 0.1011) and aqueous (0.0596 and 0.1454). After the intervention of ethanol extract, the proliferation inhibition rate of ethanol extract on HCT-116 and Caco-2 cells reached 76.55% and 78.8%, migration inhibition rate reached 76.48% and 64.85%, and the induced apoptosis rate increased by 20.1% and 12.6%, respectively. Therefore, it is verified that QIG ethanol extract possess the strongest inhibitory effect on CRC cells. In addition, GA also showed strong anti-cancer activity as the main compound of QIG. Conclusions These findings will lead to further studies on the bioactivity-guided isolation of compounds from the ethanol extracts of QIG, and provide a basis for the research of mechanism.