Dataset Information

Garlic-Derived Organosulfur Compounds Regulate Metabolic and Immune Pathways in Macrophages and Attenuate Intestinal Inflammation in Mice.

ABSTRACT:

Scope

Garlic is a source of bioactive phytonutrients that may have anti-inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear.

Methods and results

This study investigates if a garlic-derived preparation (PTSO-PTS) containing two organosulfur metabolites, propyl-propane thiosulfonate (PTSO), and propyl-propane thiosulfinate (PTS), regulate inflammatory responses in murine macrophages and intestinal epithelial cells (IEC) in vitro, as well as in a model of enteric parasite-induced inflammation. PTSO-PTS decreases lipopolysaccharide-induced secretion of TNFα, IL-6, and IL-27 in macrophages. RNA-sequencing demonstrates that PTSO-PTS strongly suppresses pathways related to immune and inflammatory signaling. PTSO-PTS induces the expression of a number of genes involved in antioxidant responses in IEC during exposure to antigens from the parasite Trichuris muris. In vivo, PTSO-PTS does not affect T. muris establishment or intestinal T-cell responses but significantly alters cecal transcriptomic responses. Notably, a reduction in T. muris-induced expression of Tnf, Saa2, and Nos2 is observed.

Conclusion

Garlic-derived organosulfur compounds exert anti-inflammatory effects in macrophages and IEC, and regulate gene expression during intestinal infection. These compounds and related organic molecules may thus hold potential as functional food components to improve gut health in humans and animals.

SUBMITTER: Zhu L

PROVIDER: S-EPMC9286605 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Garlic-Derived Organosulfur Compounds Regulate Metabolic and Immune Pathways in Macrophages and Attenuate Intestinal Inflammation in Mice.

Zhu Ling L Myhill Laura J LJ Andersen-Civil Audrey I S AIS Thamsborg Stig M SM Blanchard Alexandra A Williams Andrew R AR

Molecular nutrition & food research 20220307 7

<h4>Scope</h4>Garlic is a source of bioactive phytonutrients that may have anti-inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear.<h4>Methods and results</h4>This study investigates if a garlic-derived preparation (PTSO-PTS) containing two organosulfur metabolites, propyl-propane thiosulfonate (PTSO), and propyl-propane thiosulfinate (PTS), regulate inflammatory ...[more]

PMID: 35107883

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Project description:Among healthy vegetables, those of the genus Allium stand out. Antioxidant and anti-inflammatory properties have been associated with these vegetables, attributed mainly to organosulfur compounds (OSCs). In turn, they are linked to a protective effect counteracting cardiovascular disease development. Now, to really ensure the bioactive efficacy of the said compounds once consumed, it is necessary to previously evaluate the ADME (absorption, distribution, metabolism, and excretion) profile. Alternatively, in vitro and in silico methods attempt to avoid or reduce experimental animals' use and provide preliminary information on drugs' ability to overcome the various biological barriers inherent in the ADME process. In this sense, in silico methods serve to provide primary information on drugs' bioavailability mechanisms. High-performance liquid chromatography (HPLC) using a stationary phase composed of phospholipids, the so-called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds which are extensively used in studies of quantitative structure-activity relationships (QSARs). In the present study, the chromatographic capacity factors (log k' (IAM)) for 28 OSCs were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, several quantitative structure-retention relationships (QSRRs) were derived from exploring fundamental intermolecular interactions that govern the retention of compounds under study on IAM phases. As expected, the hydrophobic factors are of prime importance for the IAM retention of these compounds. However, the molecular flexibility and specific polar interactions expressed by several electronic descriptors (relative negative charge, RNCG, and Mulliken electronegativity) are also involved. We also evaluated the IAM phase ability to assess several ADME parameters for the OSCs under study obtained using the SwissADME web tool integrated into the SwissDrugDesign workspace and the PreADMET web tool. The human gastrointestinal absorption (HIA), blood-brain barrier (BBB) permeation, and skin permeability were investigated through QSAR modeling, using several chemometric approaches. The ADME properties under study are strongly dependent on hydrophobic factors as expressed by log k'(IAM), which provide evidence for the great potential of the IAM phases in the development of QSAR models.

Project description:Garlic (Allium sativum L.) possesses numerous pharmacological potential, including antibacterial, antiarthritic, antithrombotic, anticancer, hypoglycemic, and hypolipidemic effects. The anti-cancer action of garlic is likely the best researched of the many advantageous pharmacological effects, and its use offers significant protection against the risk of developing cancer. A few active metabolites of garlic have been reported to be essential in the destruction of malignant cells due to their multi-targeted activities and lack of significant toxicity. The bioactive compounds in garlic having anticancer properties include diallyl trisulfide, allicin, allyl mercaptan diallyl disulfide, and diallyl sulphide. Different garlic-derived constituents and their nanoformulations have been tested for their effects against various cancers including skin, ovarian, prostate, gastric, breast, and lung, colorectal, liver, oral, and pancreatic cancer. The objective of this review is to summarize the antitumor activity and associated mechanisms of the organosulfur compounds of garlic in breast carcinoma. Breast cancer continues to have a significant impact on the total number of cancer deaths worldwide. Global measures are required to reduce its growing burden, particularly in developing nations where incidence is increasing quickly and fatality rates are still high. It has been demonstrated that garlic extract, its bioactive compounds, and their use in nanoformulations can prevent breast cancer in all of its stages, including initiation, promotion, and progression. Additionally, these bioactive compounds affect cell signaling for cell cycle arrest and survival along with lipid peroxidation, nitric oxide synthase activity, epidermal growth factor receptor, nuclear factor kappa B (NF-κB), and protein kinase C in breast carcinoma. Hence, this review deciphers the anticancer potential of garlic components and its nanoformulations against several breast cancer thereby projecting it as a potent drug candidate for efficient breast cancer management.

Dataset Information

Garlic-Derived Organosulfur Compounds Regulate Metabolic and Immune Pathways in Macrophages and Attenuate Intestinal Inflammation in Mice.

Scope

Methods and results

Conclusion

Publications

Garlic-Derived Organosulfur Compounds Regulate Metabolic and Immune Pathways in Macrophages and Attenuate Intestinal Inflammation in Mice.

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