Alternatively, hesperidin methyl chalcone, the methylation process of hesperidin with higher water solubility, significantly reduced TNF-α, IL-6, IL-1β, and IL-33 production and inhibited NF-κB activation as observed by an increase in the total p65/phosphorylated-p65 ratio in a mouse model of acetic acid-induced colitis [57]. The gene discussed is RELA; the disease is colitis.