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Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including anti-inflammatory and anti-cancer properties, but the potential effects on the colitis-associated carcinogenesis have not been thoroughly investigated. Recent clinical data show that, as yet, few agents clearly inhibited CRC development in long-standing inflammatory bowel diseases. Here, we identified that FAE showed significant efficiency to inhibit HT-29 cell proliferation. The potential of FAE in vivo was further evaluated in an AOM/DSS-induced CAC mouse model. Intriguingly, FAE diminished the number of polyps in mice. Furthermore, FAE inhibited CAC by regulating the gene expression of Notch/ NF-κB/IL-1 signaling pathways. Collectively, these results were indicative of FAE has great potential in CAC prevention and treatment.

Fructus Aurantii (FA) is a traditional herbal medicine that has been widely used for thousands of years in China and possesses a variety of pharmacological effects. FA is full of flavonoids. Several natural bioactive compounds of FA are involved in the treatment of various types of cancers, however, the beneficial effects of FA in hepatocarcinoma and the potential mechanisms of its therapeutic effects have not been fully explored. The present study investigates the anticancer role of flavonoids extracted from FA on human hepatoblastoma cell, HepG2. Eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, hesperitin, poncirin, meranzin, nobiletin and tangeretin were identified in FAE. The FAE inhibit the proliferation of HepG2 cells in a dose-dependent manner. Metabolic alteration was detected by cell metabolomics and quantitative real time polymerase chain reaction. Flavonoids decreased the level of glycolysis rate-limiting enzymes gene expression in HepG2 cells. It was also observed that the PD-1 and PD-L1 gene expression level were decreased in FAE-treated cells. Collectively, these results suggest that flavonoid extracted from FA inhibits HepG2 cell proliferation by glycolysis and its downstream of PD-1/PD-L1 pathway. These findings suggest that the possible mechanism by which FA exerts its activities in the treatment of hepatocarcinoma and lays a foundation for further experiments and the development of a rational clinical application of FA, which still needs further in vivo investigation in animals and human beings.

A multifunctional integrated microfluidic biochip device was engineered to estimate the activity-toxicity and composition principle of medicine in a cell model in vitro. This biochip could be used for disease cells and healthy cells in two modules of “Yin-Yang” on the same chip for detecting the medicine efficacy-toxicity simultaneously, as well as adjust different gradient ratios of concentration through the Christmas tree structure in both “Yin-Yang” modules autonomously for detecting the best compatibility of medicine in maximum efficacy and minimal toxicity. In the applicability experiment, the best concentration of three chemical compounds including dinatin, diosmetin and cisplatin, were detected using the biochip and traditional 96-cell plate. Biochip assays showed perfect positive correlation compared with the results of traditional 96-cell plate, in addition presented advantages as less detection time and much lower price than the traditional 96-cell plate, which indicated the biochip is both convenient and feasible. Thus, the novel microfluidic chip-based multifunctional integrated system congregated the virtues of high throughput, rapid, sensitive, specific, cost-effective, and similar to the physical environment of the human body, which was especially suitable for the medicine efficacy-toxicity and compatibility evaluation.

Ethnopharmacological relevance Glycyrrhiza is the dry root and rhizome of the leguminous plant, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., which was firstly cited in Shennong's Herbal Classic in Han dynasty and was officially listed in the Chinese Pharmacopoeia, has been widely used in China during the past millennia. Licoflavone is the major component of Glycyrrhiza with anti-ulcer activity. The present study is based on clarifying the anti-ulcer effect of licoflavone, aiming at elucidating the possible molecule mechanisms of its action for treating gastric ulcer rats induced by acetic acid. Materials and methods Rats were divided into 7 groups, and drugs were administered from on the day after the onset of gastric ulcer (day 3) until day 11 of the experiment once daily continuously. The plasma were analyzed by high-performance liquid chromatography combined with time-of-flight mass spectrometry (HPLC/ESI-TOF-MS), significant different metabolites were investigated to explain its therapeutic mechanism. Furthermore, quantitative real time polymerase chain reaction (RT-PCR) analysis was performed to detect the expression of RNA in stomach tissue for verifying the above results. Results Licoflavone can effectively cure the gastric ulcer, particularly the middle dose group. According to the statistical analysis of the plasma different metabolites from each groups and the expression of genes in tissues, sixteen significant different metabolites, including histamine, tryptophan, arachidonic acid, phingosine-1-phosphate etc., contributing to the treatment of gastric ulcer were discovered and identified. In RT-PCR analysis, the results of the expression of RNA were corresponded with what we discovered. Conclusions Our study indicated licoflavone plays the role of treating gastric ulcer by regulating inflammation mediators and amino acid metabolism. We demonstrated that metabolomics technology combined with gene technology is a useful tool to search different metabolites and to dissect the potential mechanisms of traditional Chinese medicine (TCM) in treating gastric ulcer.