Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression

Zhu, Jiajie; Liu, Haiyan; Zheng, Fang; Fu, Rui; Chen, Jiabin; Liu, Shan; Fei, Bao-Ying

doi:10.1099/jmm.0.001692

Cited by 4 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another related study provided evidence that the signaling pathway might be inhibited by HQD-mediated production of SCFAs. In this study, Zhu et al [ 92 ] found that HQD could enhance the abundance of Clostridium and trigger the production of butyric acid. Using in vitro studies, the researchers found that sodium butyrate (NaB) could enhance cellular apoptosis and reduce the PI3K-AKT pathway.…”

Section: Traditional Medicine and Their Derivatives Act On Scfas To A...mentioning

confidence: 79%

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Yao,

Liu,

et al. 2024

Molecules

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn’s disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

show abstract

Section: Traditional Medicine and Their Derivatives Act On Scfas To A...mentioning

confidence: 79%

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Yao,

Liu,

et al. 2024

Molecules

View full text Add to dashboard Cite

show abstract

“…Studies have indicated that HQD as an adjunct to chemotherapy significantly improves survival and enhances tumor response [ 13 ]. In our previous research, we demonstrated that four components (i.e., baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from HQD exert similar anticancer effects to HQD [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer

Zhou,

Hu,

Zhao

et al. 2024

Chin Med

View full text Add to dashboard Cite

Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

show abstract

Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway

Liu,

Fan,

Meng

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3′-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.

show abstract

Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression

Cited by 4 publications

References 49 publications

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer

Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway

Contact Info

Product

Resources

About