Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling
Allyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. Th...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/18/7/1423 |
| _version_ | 1811282062272888832 |
|---|---|
| author | Lalita Subedi Ramu Venkatesan Sun Yeou Kim |
| author_facet | Lalita Subedi Ramu Venkatesan Sun Yeou Kim |
| author_sort | Lalita Subedi |
| collection | DOAJ |
| description | Allyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production. Pretreatment with AITC significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) production in activated microglia, and increased the nerve growth factor (NGF) and neurite outgrowth in neuroblastoma cells. AITC inhibited the nuclear factor (NF-κB-mediated transcription by modulating mitogen activated protein kinase (MAPK) signaling, particularly downregulating c-Jun N-terminal kinase (JNK) phosphorylation, which was followed by a reduction in the TNF-α expression in activated microglia. This promising effect of AITC in controlling JNK/NF-κB/TNF-α cross-linking maintains the Bcl-2 gene family and protects neuroblastoma cells from activated microglia-induced toxicity. These findings provide novel insights into the anti-neuroinflammatory effects of AITC on microglial cells, which may have clinical significance in neurodegeneration. |
| first_indexed | 2024-04-13T01:44:50Z |
| format | Article |
| id | doaj.art-0dfcf7192db5456c994af831437cd7c6 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T01:44:50Z |
| publishDate | 2017-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0dfcf7192db5456c994af831437cd7c62022-12-22T03:08:04ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-07-01187142310.3390/ijms18071423ijms18071423Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α SignalingLalita Subedi0Ramu Venkatesan1Sun Yeou Kim2Laboratory of Pharmacognosy, College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaLaboratory of Pharmacognosy, College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaLaboratory of Pharmacognosy, College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaAllyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production. Pretreatment with AITC significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) production in activated microglia, and increased the nerve growth factor (NGF) and neurite outgrowth in neuroblastoma cells. AITC inhibited the nuclear factor (NF-κB-mediated transcription by modulating mitogen activated protein kinase (MAPK) signaling, particularly downregulating c-Jun N-terminal kinase (JNK) phosphorylation, which was followed by a reduction in the TNF-α expression in activated microglia. This promising effect of AITC in controlling JNK/NF-κB/TNF-α cross-linking maintains the Bcl-2 gene family and protects neuroblastoma cells from activated microglia-induced toxicity. These findings provide novel insights into the anti-neuroinflammatory effects of AITC on microglial cells, which may have clinical significance in neurodegeneration.https://www.mdpi.com/1422-0067/18/7/1423allyl isothiocyanatemicroglianeuronastrocyteneuroinflammationneuroprotection |
| spellingShingle | Lalita Subedi Ramu Venkatesan Sun Yeou Kim Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling International Journal of Molecular Sciences allyl isothiocyanate microglia neuron astrocyte neuroinflammation neuroprotection |
| title | Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling |
| title_full | Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling |
| title_fullStr | Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling |
| title_full_unstemmed | Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling |
| title_short | Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling |
| title_sort | neuroprotective and anti inflammatory activities of allyl isothiocyanate through attenuation of jnk nf κb tnf α signaling |
| topic | allyl isothiocyanate microglia neuron astrocyte neuroinflammation neuroprotection |
| url | https://www.mdpi.com/1422-0067/18/7/1423 |
| work_keys_str_mv | AT lalitasubedi neuroprotectiveandantiinflammatoryactivitiesofallylisothiocyanatethroughattenuationofjnknfkbtnfasignaling AT ramuvenkatesan neuroprotectiveandantiinflammatoryactivitiesofallylisothiocyanatethroughattenuationofjnknfkbtnfasignaling AT sunyeoukim neuroprotectiveandantiinflammatoryactivitiesofallylisothiocyanatethroughattenuationofjnknfkbtnfasignaling |