Chemoprotective effect of nimbolide against N-methyl-N-nitrosourea induced gastric cancer via alteration of apoptosis and NF-κB signaling pathway
ABSTRACT Purpose: Gastric cancer (GC) ranks as the third most common cause of cancer related mortality and as the fifth most frequently diagnosed cancer globally. Less than 30% of people with GC survive for more than five years. Methods: Nimbolide has been shown to have anticancer, anti-inflammato...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
2025-03-01
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| Series: | Acta Cirúrgica Brasileira |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502025000100217&lng=en&tlng=en |
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| Summary: | ABSTRACT Purpose: Gastric cancer (GC) ranks as the third most common cause of cancer related mortality and as the fifth most frequently diagnosed cancer globally. Less than 30% of people with GC survive for more than five years. Methods: Nimbolide has been shown to have anticancer, anti-inflammatory, antiparasitic, and antioxidant properties. The current investigation showed the anticancer effect of nimbolide against N-methyl-N-nitrosourea (MNU) induced GC in rats. Rats were given MNU (100 mg/kg) orally to induce GC and received the oral administration of nimbolide (10, 20 and 40 mg/kg). The different biochemical parameters were estimated. Results: Nimbolide significantly (p < 0.001) altered the level of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cytochrome P450, cytochrome B5 and histone deacetylase (HDAC) activity. Nimbolide treatment significantly (p < 0.001) altered the level of antioxidant parameters like superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA); cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6; inflammatory parameters viz., cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the serum and stomach tissue. Nimbolide considerably altered (p < 0.001) the level of apoptosis parameters (Bcl-2, Bax and caspase-3), and the mRNA expression of VCAM-1, ICAM-1, TNF-α, IL-1β, IL-6, MCP-1, TLR4 and NF-κB. Conclusion: Nimbolide treatment considerably altered the GC against MNU induced GC via alteration of apoptosis and NF-κB signaling pathway. |
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| ISSN: | 1678-2674 |