β-Carotene attenuates LPS-induced rat intestinal inflammation via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways.

Abstract

Inflammation is a protective response of the immune defense system and inflammatory response could be regulated by autophagy. β-Carotene has shown anti-inflammatory potential. However, whether β-carotene could alleviate rat intestinal inflammation by modulating autophagy and its anti-inflammation underlying mechanisms remain unknown. In this study, we found that β-carotene significantly reduced (p<.05) the production of nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β) levels by the Griess reaction and enzyme-linked immunosorbent assay (ELISA), and we found that β-carotene significantly suppressed (p<.05) the mRNA expression levels of IL-1β and TNF-α by RT-PCR. In addition, H&E staining revealed that β-carotene could improve intestinal morphology and cell morphology. Furthermore, the levels of signaling proteins of microtubule-associated protein light chain 3 (LC3), AKT, Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) were detected by Western blot analysis. We found that β-carotene significantly attenuated (p<.05) the related signaling proteins activated by lipopolysaccharide (LPS) stimulation in rats. Moreover, this conclusion was also verified in intestinal epithelial cell (IEC)-6. 3-Methyladenine (3-MA) is widely used as inhibitor of autophagy via its inhibitory effect on class III PI3K. Simultaneously, pretreatment of 3-MA suppressed the inhibiting effects of β-carotene on the related signaling proteins. This study demonstrates that β-carotene could attenuate the LPS-induced intestinal inflammation in rats via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways. We also found the same phenomenon when we verified the results with the IEC-6 cells. These findings provide new insights into improving the nutritional value of basic diets and enhancing immune performance. PRACTICAL APPLICATIONS: β-Carotene is a generally acknowledged natural carotenoid nutrient that exhibits provitamin A activity, and it is widely found in fruits or vegetables. Our study provide a new insight into the anti-inflammatory mechanism of β-carotene. Treatment with β-carotene can be used for the beneficial effect against LPS-induced inflammation damage. This study not only lays the foundation for the related research on the anti-inflammatory properties of β-carotene in vitro and in rat models, but also holds important significance in the field of food.