Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer <i>via</i> the modulation of complex metabolic networks

Sun, Hui; Zhang, Aihua; Zhang, Honglian; Zhou, Xiaohang; Liu, Liang; Wang, Xijun

doi:10.1039/c9ra07687e

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…Mangxiao (MX) is another famous purgative mineral crude drug that was a crystalline substance purified from mirabilite containing mainly hydrated sodium sulfate Na 2 SO 4 ▪10H 2 O, which was first recorded in traditional Chinese medicine (TCM) classical book “Miscellaneous Records of Famous Physicians (Mingyi Bielu)” published in Han Dynasty. It has been used to treat gastrointestinal tumors and associated complications, 11 and in our previous study, we found MX could effectively treat colorectal cancer (CRC) by modulating systems‐metabolism network 12,13 . These results suggested that MX can act as a mineral agent for the CRC treatment and demonstrated a great application value.…”

Section: Introductionmentioning

confidence: 75%

“…It has been used to treat gastrointestinal tumors and associated complications, 11 and in our previous study, we found MX could effectively treat colorectal cancer (CRC) by modulating systems‐metabolism network. 12 , 13 These results suggested that MX can act as a mineral agent for the CRC treatment and demonstrated a great application value. However, unclear in‐depth mechanism of the therapeutic effects greatly restricted its further clinical and widespread usage.…”

Section: Introductionmentioning

confidence: 84%

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Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis

Zhou,

Sun,

Ren

et al. 2024

MedComm

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Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic‐based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus–bile acid–intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 84%

Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis

Zhou,

Sun,

Ren

et al. 2024

MedComm

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“…In addition, mirabilite can significantly reduce apoptotic factors and inhibit the proliferation of intestinal tumor cells. ( Sun et al, 2018 ; Sun et al, 2019 ) also found that mirabilite can inhibit colorectal cancer by regulating the distribution of overall metabolic disorders, and bile acid metabolism is its main targeted pathway. The results of network pharmacology showed that the action sites included amino acid residues Arg-364 and Asp-533 and nucleotides TPC-11, DG-112 and DA-113.…”

Section: Pharmacological Actions Of Mirabilitementioning

confidence: 96%

The application of mirabilite in traditional Chinese medicine and its chemical constituents, processing methods, pharmacology, toxicology and clinical research

Tao,

Fu,

Wang

et al. 2024

Front. Pharmacol.

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Purpose: This study reviews the use of mirabilite in traditional Chinese medicine and various preparations by describing its chemical composition, processing methods, pharmacology, toxicology, and clinical research progress.Methods: The applications and processing methods of mirabilite are searched in traditional and modern Chinese medical writings, and the articles on chemical composition, pharmacological effects, toxicology, and clinical studies of mirabilite and its combinations in PubMed and China Knowledge Network are reviewed, sorted, and analyzed.Results: The main chemical component of mirabilite is sodium sulfate decahydrate (Na2SO4·10H2O), followed by small amounts of sodium chloride, magnesium sulfate, calcium sulfate, and other inorganic salts. This study systematically organizes the history of the medicinal use of mirabilite in China for more than 2,000 years. This mineral has been used by nine Chinese ethnic groups (Han, Dai, Kazakh, Manchu, Mongolian, Tujia, Wei, Yi, and Tibetan) in a large number of prescription preparations. The Pharmacopoeia of the People’s Republic of China (2020 edition) records stated that mirabilite can be used for abdominal distension, abdominal pain, constipation, intestinal carbuncle, external treatment of breast carbuncle, hemorrhoids, and other diseases. The traditional processing methods of mirabilite in China include refining, boiling, sautéing, filtration after hot water blistering, and firing. Since the Ming Dynasty, processing by radish has become the mainstream prepared method of mirabilite. Mirabilite can exhibit anti-inflammatory detumescence effects by inhibiting AMS, LPS, IL-6, IL-10, TNF-α, and NO levels and attenuating the upregulation of TNF-α and NF-κB genes. It can promote cell proliferation and wound healing by increasing the production of cytokines TGFβ1 and VEGF-A and gastrointestinal motility by increasing the release of vasoactive intestinal peptide, substance P, and motilin. It can increase the expression of low-density lipoprotein receptor and AKT phosphorylation in the liver by up-regulating bile acid synthesis genes; reduce TRB3 expression in the liver, FGF15 co-receptor KLB expression, and FGF15 production in the ileum, and JNK signal transduction; and increase the transcription of CYP7A1 to achieve a cholesterol-lowering effect. Mirabilite also has a variety of pharmacological effects, such as regulating intestinal flora, anti-muscle paralysis, anti-colon cancer, promoting water discharge, and analgesic. Only a few toxicological studies on mirabilite are available. External application of mirabilite can cause local skin to be flushed or itchy, and its oral administration is toxic to neuromuscular cells. The sulfur ions of its metabolites can also be toxic to the human body. At present, no pharmacokinetic study has been conducted on mirabilite as a single drug. This mineral has been widely used in the clinical treatment of inflammation, edema, wound healing, digestive system diseases, infusion extravasation, hemorrhoids, skin diseases, breast accumulation, muscle paralysis, intestinal preparation before microscopic examination, and other diseases and symptoms.Conclusion: Mirabilite has good application prospects in traditional Chinese medicine and ethnomedicine. In-depth research on its processing methods, active ingredients, quality control, pharmacokinetics, pharmacological and toxicological mechanisms, and standardized clinical application is needed. This paper provides a reference for the application and research of mirabilite in the future.

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“…For this reason, small variations in the body can indicate early biological changes to the host due to perturbations in metabolic pathways. Therefore, the metabolome could be regarded as the amplified output of a biological system ( 8 , 9 ). Monitoring fluctuations of certain metabolite levels in body fluids has become an important way to detect early stages in CRC.…”

Section: Introductionmentioning

confidence: 99%

Untargeted GC-MS-Based Metabolomics for Early Detection of Colorectal Cancer

Zhu

Wang

et al. 2021

Front. Oncol.

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BackgroundColorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers in the world with a 5-year survival rate of approximately 68%. Although researchers accumulated many scientific studies, its pathogenesis remains unclear yet. Detecting and removing these malignant polyps promptly is the most effective method in CRC prevention. Therefore, the analysis and disposal of malignant polyps is conducive to preventing CRC.MethodsIn the study, metabolic profiling as well as diagnostic biomarkers for CRC was investigated using untargeted GC-MS-based metabolomics methods to explore the intervention approaches. In order to better characterize the variations of tissue and serum metabolic profiles, orthogonal partial least-square discriminant analysis was carried out to further identify significant features. The key differences in tR–m/z pairs were screened by the S-plot and VIP value from OPLS-DA. Identified potential biomarkers were leading in the KEGG in finding interactions, which show the relationships among these signal pathways.ResultsFinally, 17 tissue and 13 serum candidate ions were selected based on their corresponding retention time, p-value, m/z, and VIP value. Simultaneously, the most influential pathways contributing to CRC were inositol phosphate metabolism, primary bile acid biosynthesis, phosphatidylinositol signaling system, and linoleic acid metabolism.ConclusionsThe preliminary results suggest that the GC-MS-based method coupled with the pattern recognition method and understanding these cancer-specific alterations could make it possible to detect CRC early and aid in the development of additional treatments for the disease, leading to improvements in CRC patients’ quality of life.

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Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer via the modulation of complex metabolic networks

Abstract: Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders.

Cited by 5 publications

References 30 publications

Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis

Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus–bile acid–intestinal farnesoid X receptor axis based on multiomics integration analysis

The application of mirabilite in traditional Chinese medicine and its chemical constituents, processing methods, pharmacology, toxicology and clinical research

Untargeted GC-MS-Based Metabolomics for Early Detection of Colorectal Cancer

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