Anti-inflammatory and immunomodulatory effects of carrot-derived polyacetylenes in acute intestinal and systemic inflammation and an evaluation of potential of agronomic techniques for their enhancement in carrot
Nrf2 is a transcription factor involved in regulating the expression level of a battery of anti-oxidant, anti-inflammatory, and DNA repair genes. Polyacetylenes (PA) are plant phytochemicals whose health-promoting effects are not well studied, but are abundant in medicinal plants such as ginseng and not widely dispersed in dietary plants. Some horticultural crops from the Apiaceae family produce PA including parsnip, fennel, celery and many herbs (parsley, dill, lovage, etc) among which carrot is the most widely consumed. The most abundant PA in carrot are falcarinol (FA) and falcarindiol (FD). We sought to evaluate the anti-inflammatory and immunomodulatory effects of PA due to their ability to activate the Nrf2 pathway by pretreating mice with diet-achievable phytochemical doses (5 mg/kg) twice per day for 7 days prior to the induction of acute inflammation via lipopolysaccharide (LPS) injection (5 mg/kg i.p.). FA-treated mice were terminated after 4 and 24 hours and FD mice were terminated after 24 hours. We found that FA was more effective than SF – commonly thought to be the most effective natural product Nrf2 activator – at upregulating Nrf2 target Ho1 at the protein and mRNA levels in the intestine while neither phytochemical upregulated Nqo1 at the low/dietary levels used in this study. FA was also a more potent anti-inflammatory than SF in the intestine and to a lesser extent systemically, downregulating proinflammatory gene expression (4 hours) and proinflammatory cytokines (24 hours). An additional novel finding of this study was the development of a Th2/Th9 plasma cytokine profile in an anti-inflammatory context during late acute inflammation with FA treatment (significantly increased IL-10 and lower classic inflammatory cytokines); FD produced a less perspicuous Th2/Th9 profile but in the absence of anti-inflammatory context (no increase in IL-10 and higher classical proinflammatory cytokines). Due to their potential health promoting properties, we also performed a series of agronomic treatments in carrot production to evaluate their potential for modulating PA content of carrots as well as other quality and sensory characteristics. While we did not discover new agronomic treatments specific to PA modulation, we did observe that soil fertility status was correlated with the nutritional quality of carrot.