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Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs.

ABSTRACT: Neutrophilic inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), or psoriasis, exert a huge burden on the global health system due to the lack of safe and effective treatments. Volatile oils from terrestrial plants showed impressive therapeutic effects against disorders of the skin, digestive system, lungs, liver, metabolism, and nervous system. However, their effect on the immune system and neutrophil function is still elusive. Fennel, cumin, marjoram, lavender, caraway, and anise are the common nutraceuticals that are widely used in the Mediterranean diet. The volatile oils of these herbs were screened for various biological activities, including anti-inflammatory, anti-allergic, antimicrobial, and antiviral effects. Several oils showed anti-inflammatory and antimicrobial potential. Fennel (Foeniculum vulgare) and cumin (Cuminum cyminum) fruits' volatile oils significantly suppressed the activation of human neutrophils, including respiratory burst and the degranulation induced by formyl peptide receptor agonists fMLF/CB and MMK1 in the human neutrophils (IC₅₀, 3.8-17.2 µg/ml). The cytotoxic effect and free-radical scavenging effects (ABTS, DPPH) of these oils did not account for the observed effects. Both fennel and cumin volatile oils significantly shortened calcium influx recovery time and inhibited phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK) expression. The gas chromatography-mass spectrometry analysis of these oils revealed the presence of estragole and cuminaldehyde as the major components of fennel and cumin volatile oils, respectively. Our findings suggested that cumin and fennel, common in the Mediterranean diet, hold the potential to be applied for the treatment of neutrophilic inflammatory diseases.

SUBMITTER: Korinek M

PROVIDER: S-EPMC8545060 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs.

Korinek Michal M Handoussa Heba H Tsai Yi-Hong YH Chen You-Ying YY Chen Meng-Hua MH Chiou Zan-Wei ZW Fang Yu Y Chang Fang-Rong FR Yen Chia-Hung CH Hsieh Chung-Fan CF Chen Bing-Hung BH El-Shazly Mohamed M Hwang Tsong-Long TL

Frontiers in pharmacology 20211011

Neutrophilic inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), or psoriasis, exert a huge burden on the global health system due to the lack of safe and effective treatments. Volatile oils from terrestrial plants showed impressive therapeutic effects against disorders of the skin, digestive system, lungs, liver, metabolism, and nervous system. However, their effect on the immune system and neutrophil function is still elusive ...[more]

PMID: 34707494

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Project description:BackgroundAbnormal activation of microglia is involved in the pathogenesis of schizophrenia. Minocycline and antipsychotics have been reported to be effective in inhibiting the activation of microglia and thus alleviating the negative symptoms of patients with schizophrenia. However, the specific molecular mechanism by which minocycline and antipsychotics inhibit microglial activation is not clear. In this study, we aimed to explore the molecular mechanism of treatment effect of minocycline and antipsychotics on schizophrenia.MethodsMicroglia cells were activated by lipopolysaccharide (LPS) and further treated with minocycline, haloperidol, and risperidone. Then cell morphology, specific marker, cytokines, and nitric oxide production process, and the proteins in related molecular signaling pathways in LPS-activated microglia were compared among groups.ResultsThe study found that minocycline, risperidone, and haloperidol significantly inhibited morphological changes and reduced the expression of OX-42 protein induced by LPS. Minocycline significantly decreased the production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β). Risperidone also showed significant decrease in the production of IL-6 and TNF-α, while haloperidol only showed significant decrease in the production of IL-6. Minocycline, risperidone, and haloperidol were found to significantly inhibit nitric oxide (NO) expression, but had no effect on inducible nitric oxide synthase (iNOS) expression. Both minocycline and risperidone were effective in decreasing the activity of c‑Jun N‑terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinases (MAPKs) signal pathway. Additionally, minocycline and risperidone were found to increase the activity of phosphorylated-p38. In contrast, haloperidol only suppressed the activity of ERK. Minocycline also suppressed the activation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), while risperidone and haloperidol only suppressed the activation of STAT3.ConclusionsThe results demonstrated that minocycline and risperidone exert stronger anti-inflammatory and neuroprotective effects stronger than haloperidol, through MAPKs and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways in BV2 cells stimulated with LPS, revealing the underlying mechanisms of minocycline and atypical antipsychotics in the treatment of negative schizophrenia symptoms.

Project description:Echinacea purpurea (L.) Moench is a medicinal plant commonly used for the treatment of upper respiratory tract infections, the common cold, sore throat, migraine, colic, stomach cramps, and toothaches and the promotion of wound healing. Based on the known pharmacological properties of essential oils (EOs), we hypothesized that E. purpurea EOs may contribute to these medicinal properties. In this work, EOs from the flowers of E. purpurea were steam-distilled and analyzed by gas chromatography-mass spectrometry (GC-MS), GC with flame-ionization detection (GC-FID), and chiral GC-MS. The EOs were also evaluated for in vitro antimicrobial and innate immunomodulatory activity. About 87 compounds were identified in five samples of the steam-distilled E. purpurea EO. The major components of the E. purpurea EO were germacrene D (42.0 ± 4.61%), α-phellandrene (10.09 ± 1.59%), β-caryophyllene (5.75 ± 1.72%), γ-curcumene (5.03 ± 1.96%), α-pinene (4.44 ± 1.78%), δ-cadinene (3.31 ± 0.61%), and β-pinene (2.43 ± 0.98%). Eleven chiral compounds were identified in the E. purpurea EO, including α-pinene, sabinene, β-pinene, α-phellandrene, limonene, β-phellandrene, α-copaene, β-elemene, β-caryophyllene, germacrene D, and δ-cadinene. Analysis of E. purpurea EO antimicrobial activity showed that they inhibited the growth of several bacterial species, although the EO did not seem to be effective for Staphylococcus aureus. The E. purpurea EO and its major components induced intracellular calcium mobilization in human neutrophils. Additionally, pretreatment of human neutrophils with the E. purpurea EO or (+)-δ-cadinene suppressed agonist-induced neutrophil calcium mobilization and chemotaxis. Moreover, pharmacophore mapping studies predicted two potential MAPK targets for (+)-δ-cadinene. Our results are consistent with previous reports on the innate immunomodulatory activities of β-caryophyllene, α-phellandrene, and germacrene D. Thus, this study identified δ-cadinene as a novel neutrophil agonist and suggests that δ-cadinene may contribute to the reported immunomodulatory activity of E. purpurea.

Dataset Information

Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs.

Publications

Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs.

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