In the last few sessions, we discussed about cancer, neurological conditions and gastroenterological disorders. Today, we look at the roles of nutraceuticals to fight against inflammatory diseases.

Resveratrol is a natural phytoalexin polyphenol predominantly found in berries and grapes. Meng et al. [9] reviewed its anti-inflammatory actions and mechanisms. Resveratrol appeared to regulate inflammatory response through various signaling pathways, including the arachidonic acid, NF-κB, MAPK, activator protein (AP)-1 transcription factor, and antioxidant defense pathways. Hence, there exist multiple lines of compelling evidence that resveratrol can play a promising role in managing autoimmune and inflammatory chronic diseases. One such condition is Duchenne muscular dystrophy (DMD), a progressive and fatal neuromuscular disorder with no cure. Woodman et al. [10] treated mdx mice with a low dose of resveratrol (5 mg/kg body weight/day) for 15 weeks. The study found resveratrol to reduce exercise-induced muscle necrosis in dystrophic muscle and lower gene expression of immune cell markers CD86 and CD163. Nevertheless, signaling targets associated with resveratrol’s mechanism of action, including Sirtuin 1 and NF-κB, were unchanged. This study confirmed that resveratrol could be a therapeutic candidate for DMD treatment.

Astaxanthin is another nutraceutical compound with potent anti-inflammatory properties. It is a lipid-soluble, red-orange carotenoid accumulated in many marine creatures, such as lobsters, shrimp, trout, and salmon. Chang and Xiong [11] reviewed the anti-inflammatory mechanisms of astaxanthin. Astaxanthin was found to attenuate many inflammatory biomarkers through multiple signaling pathways, including phosphatidylinositol-3-kinase/protein kinase B (Akt), nuclear factor erythroid 2-like 2, NF-κB, extracellular-signal-regulated kinase, c-Jun N-terminal kinases, p38 MAPK, and the Janus kinase 2/signal transducer and activator of transcription 3. Moreover, astaxanthin was confirmed experimentally to alleviate chronic and acute inflammation in various diseases, such as neurodegenerative disorders, diabetes, gastrointestinal disease, renal inflammation, as well as skin and eye diseases.

Atherosclerosis is characterized by low-grade, chronic inflammation of the arterial wall. The review by Eshghjoo et al. [12] showed that many microbiota-derived metabolites were associated with atherosclerosis. For example, trimethylamine-N-oxide, a by-product of gut microbial metabolism of L-carnitine and choline after ingestion of eggs, meat, or fish, can elevate oxidized low-density lipoprotein and increased plaque formation. Accumulation of indoxyl sulphate, a metabolite converted from dietary tryptophan, can cause coronary calcification leading to atherosclerosis. Whereas indole, another gut microbiota-derived tryptophan catabolite, is an agonist for the aryl hydrocarbon receptor with anti-inflammatory effects that can prevent atherosclerosis. Hence, indole can be a promising nutraceutical for cardiovascular disease prevention.

Two studies investigated the role of different nutraceuticals in suppressing airway inflammation. In the first study, Shin et al. [13] studied how Korean red ginseng (KRG) could prevent airway inflammation triggered by Asian sand dust (ASD). KRG and its active compound ginsenoside Rg3 significantly suppressed ASD-induced NF-κB expression and activity. Furthermore, KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells in vitro. In another study, Choi et al. [14] demonstrated that the antioxidant lycopene could inhibit cytokine expression induced by house dust mites. Lycopene, a naturally occurring chemical that gives fruits and vegetables a red color, possibly suppressed the activation of toll-like receptor 4 and reduced the intracellular and mitochondrial oxidative stress in respiratory epithelial cells.
Interferonopathies are monogenic autoinflammatory diseases characterized by disturbance of interferon-mediated immune responses. Genova et al. [15] showed that sulforaphane, a bioactive molecule in cruciferous vegetables, could modulate the stimulator of interferon genes (STING) mediated inflammation and interferon-stimulated genes expression in vitro. However, the study could only reproduce a trend towards the downregulation of STING in vivo. Further in vivo research is needed to confirm the findings.

[References]

9. Meng, T.; Xiao, D.; Muhammed, A.; Deng, J.; Chen, L.; He, J. Anti-inflammatory action and mechanisms of resveratrol. Molecules 2021, 26, 229, doi:10.3390/molecules26010229.
10. Woodman, K.G.; Coles, C.A.; Lamandé, S.R.; White, J.D. Resveratrol promotes hypertrophy in wildtype skeletal muscle and reduces muscle necrosis and gene expression of inflammatory markers in mdx mice. Molecules 2021, 26, 853, doi:10.3390/molecules26040853.
11. Chang, M.X.; Xiong, F. Astaxanthin and its effects ininflammatory responses and inflammation-associated diseases: Recent advances and future directions. Molecules 2020, 25, 5342, doi:10.3390/molecules25225342.
12. Eshghjoo, S.; Jayaraman, A.; Sun, Y.; Alaniz, R.C. Microbiota-mediated immune regulation in atherosclerosis. Molecules 2021, 26, 179, doi:10.3390/molecules26010179.
13. Shin, S.H.; Ye, M.K.; Lee, D.W.; Kang, B.J.; Chae, M.H. Effect of korean red ginseng and rg3 on asian sand dust-induced MUC5AC, MUC5B, and MUC8 expression in bronchial epithelial cells. Molecules 2021, 26, 2002, doi:10.3390/molecules26072002.
14. Choi, J.; Lim, J.W.; Kim, H. Lycopene inhibits toll-like receptor 4-mediated expression of inflammatory cytokines in house dust mite-stimulated respiratory epithelial cells. Molecules 2021, 26, 3127, doi:10.3390/molecules26113127.
15. Genova, E.; Apollonio, M.; Decorti, G.; Tesser, A.; Tommasini, A.; Stocco, G. In vitro effects of sulforaphane on interferon-driven inflammation and exploratory evaluation in two healthy volunteers. Molecules 2021, 26, 3602, doi:10.3390/molecules26123602.