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Colorectal cancer is one of the most common cancers and the main causes of mortality around the world and Oxaliplatin is a first-line chemotherapy agent for treatment of CRC. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Oxaliplatin. Therefore, research strategies to further sensitize CRC cells to Oxaliplatin are urgently needed. In this study, we showed that Semen Raphani exhibited a strong synergy with Oxaliplatin to inhibit CRC tumor growth by remodeling tumor stroma and depredate collagen. Further research found that ATG9A mediated autophagy is critical for the collagen degradation induced by Semen Raphani, this process may be mediated by the degradation of collagen transcription factor STAT3 by autophagy. Taken together, our study is the first to evaluate the synergy of Semen Raphani and Oxaliplatin in CRC and to assess new opportunities for remodeling stroma as a promising approach for future chemotherapy sensitization.

Fatigue is a kind of subhealth status and people paid much more attention on it. Ginseng is used to treating fatigue as a kind of qi -tonifying drug in Chinese medicine. In the traditional applications, there is a viewpoint that ginseng could not be used with semen raphani and supposed that semen raphani is a kind of qi regulating drug, which will reduce the qi invigorating effect of ginseng. However, the underlying combination mechanism of the two drugs remained unclear. The aim of this study is to explore whether ginseng can be used with semen raphani or not to remedy acute and chronic fatigue conditions. We used normal and weight-bearing swimming method combined with appetite control animals. The biochemical indexes in energy metabolism, antioxidant, regulating endocrine system and immunity capacities were performed to explore the antagonism effect of semen raphani on ginseng under acute and chronic fatigue conditions. The serum and urine metabolomics were investigated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Fecal flora was analyzed via 16S rRNA amplicon sequencing. The combination of ginseng with semen raphani have no influence on acute fatigue effect compared with ginseng alone. Both can improve the exhausted swimming time, the activity of GSH-Px, LDH and Na+-K+-ATPase. Furthermore, the combination of ginseng with semen raphani can increase the urine volume of rats and down-regulate the content of AQP-3, which can alleviate the " fireness " side-effect of ginseng. But the abundance and diversity of bacterial are decreased under acute fatigue experiment. Both the combination of ginseng with semen raphani and ginseng alone can remedy chronic-fatigue. They can also regulate the endocrine system, immune system, citric acid cycle metabolism, tryptophan metabolism, fatty acid metabolism, glycolysis/gluconeogenesis, etc. Furthermore, they can promote substance metabolism and energy metabolism in qi deficiency rats, and increase the abundance and diversities of the flora. While with the increased content of semen raphani, the combination of ginseng and semen raphani weaken the capacity of antioxidant, lactic acid metabolism, energy metabolism, flora diversity and regulation of endocrine system. Compared with ginseng alone, the combination of ginseng with semen raphani can weaken the qi invigorating ability under chronic fatigue condition. The more ratios of semen raphani is in the combination of the two drugs, the less the power of treating chronic fatigue is. Compared with ginseng alone, the combination of ginseng with semen raphani have no influence on the qi invigorating ability under actue fatigue experiment. But the combination of ginseng with semen raphani will benefit for the "fireness" side-effect of ginseng. We are submitting a manuscript entitled "Semen raphani weakened the action of ginseng under chronic fatigue condition" for your consideration for publication as a communication in Journal of Ethnopharmacology. The manuscript mainly discussed whether ginseng can be used with semen raphani or not to remedy acute and chronic fatigue conditions. Ginseng is used to treating fatigue as a kind of qi -tonifying drug in Chinese medicine. To explore the antagonism effect of semen raphani on ginseng under acute and chronic fatigue conditions. We used normal and weight-bearing swimming method combined with appetite control animals. The biochemical indexes, methods of metabolomics and 16S rRNA gene sequencing were used. The main experimental ideas are presented as follows. [Display omitted] [ABSTRACT FROM AUTHOR]