The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever

Xie, Fengfeng; Xu, Li-Ba; Zhu, Hongxiang; Chen, Yaling; Li, Yinlan; Nong, Lizhen; Zeng, Yanfang; Cen, Sijie

doi:10.3390/molecules27082465

Cited by 10 publications

(4 citation statements)

References 51 publications

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“…These results indicate a clear link between T core , serum biochemical indices, and metabolites, aligning with prior research. For example, ellagic acid relieved pyrexia by inhibiting yeast-induced overproduction of IL-1β, PGE2, and metabolic biomarkers PE (16:0/20:4), PC (18:2/15:0), and sphingolipid [ 78 ]. Astragali Radix increases T core by elevating the cyclic adenosine monophosphate (cAMP) and PGE2 levels, as well as thermo-related metabolites, such as lipids, choline, and leucine [ 79 ].…”

Section: Resultsmentioning

confidence: 99%

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Chen,

Wu,

et al. 2024

Pharmaceuticals

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Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

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Section: Resultsmentioning

confidence: 99%

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Chen,

Wu,

et al. 2024

Pharmaceuticals

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“…The anti-inflammatory parameters used were lipooxygenase, cyclooxygenase, Interleukin-1β (IL-1β), Nitric Oxide (NO), Malondialdehyde (MDA), Tumor Necrosis Factorα (TNF-α), Cyclooxygenase-2 (COX-2), and Nuclear Factor kappa B (NF-κB) (Xie et al, 2022). Lipooxygenase and cyclooxygenase are enzymatic pathways in arachidonic acid metabolism.…”

Section: Antioxidant and Anti-inflammatory Parametersmentioning

confidence: 99%

Caesalpinia sappan Reduce Fever with An Anti-inflammatory and Antioxidant Mechanism: A Review

Sasongko,

Hedianti,

Safitri

2024

J. Pharm. Sci. Clin. Res.

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Caesalpinia sappan L (Sappan wood) is an herbal plant that has long been trusted by the public as an herbal medicine for tuberculosis, diarrhea, dysentery, skin infections, anemia, and other diseases by utilizing the decoction of C.sappan. Sappan wood is an herbal plant widely used as a raw material for traditional medicinal products. Sappan wood has been reported to have substantial pharmacological effects in analgesic, antioxidant, antibacterial, anti-inflammatory, and anti-viral. Fever is a clinical manifestation of certain conditions or diseases characterized by increased body temperature above the normal range (36.5–37.5 °C). Many studies declare that antioxidant and anti-inflammatory activity in C.sappan reduces oxidative stress and pro-inflammatory cytokines. This literature review shows that the antioxidant and anti-inflammatory properties of C.sappan are linked to fever as a sign of illness. Literature review using the last ten years' Scopus, ScienceDirect, and Pubmed databases. There are as many as 20 journals regarding sappan wood's antioxidant and anti-inflammatory effects. Sappan wood has been shown to have an antioxidant effect by lowering reactive oxygen species levels via SOD, GPx, or CAT markers. It inhibits inflammation cytokines such as IL-1, IL-6, TNF-𝝰, and INF produced during fever. Sappan wood also has an anti-inflammatory effect by inhibiting PGE2 production when someone has a fever. The findings of our review state that C.sappan can be used to treat fever for both of these reasons. The use of C.sappan as a component in producing traditional health beverages has potential.

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“…Metabolomics showed eleven metabolites as biomarkers of the antipyretic mechanism of ellagic acid, mainly involving glycerophospholipid and sphingolipid metabolism, etc. [148]. Mass spectrometry-based metabolomics was employed to discover biomarkers and mechanisms after agarwood intervention.…”

Section: Multi-target and Effect Mechanism Exploration Of Herbal Medi...mentioning

confidence: 99%

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification

Lin,

Tian,

Guo

et al. 2024

Molecules

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As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

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The Potential Antipyretic Mechanism of Ellagic Acid with Brain Metabolomics Using Rats with Yeast-Induced Fever

Cited by 10 publications

References 51 publications

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Caesalpinia sappan Reduce Fever with An Anti-inflammatory and Antioxidant Mechanism: A Review

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification

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