**7. Conclusions**

*Beta Thalassemia*

**Figure 3.**

*SOD: Superoxide dismutase.*

that were exposed to either ethanol or excess iron and increase BMP6, intranuclear SMAD4, SMAD4 binding to the HAMP promoter, and hepcidin expression, leading to decreased hepatic iron levels and reduced iron-related damage [81]. Another potent antioxidant is genistein. It reduces inflammation induced by ethanol and oxidative stress in mice [82] and, similar to quercetin, increases HAMP promoter activity in both zebrafish and human hepatocytes via Stat3- and Smad4-dependent process [83]. Silymarin, another flavonoid, is present in milk thistle plant extract and may have iron-chelating properties [84]. It is safe, well tolerated, cost-effective alternative to currently available iron chelation therapies for treating patients with β-thalassemia [84]. Ferulic acid is present in a wide variety of plants, and the antioxidant effects are believed to be mediated via the neutralization of free radicals [85]. The antioxidant effects of resveratrol may prevent adverse changes that lead to cardiovascular disease by modulating vascular cell function, low density lipoprotein (LDL) oxidation, and platelet aggregation, thereby reducing myocardial damage [86, 87]. Both vitamin A and vitamin C have well-established antioxidant properties that are mediated via the attenuation of oxidative damage [88]. Vitamin A and β-carotene increase hepcidin and TfR expression and intestinal iron absorption, reduce inflammatory signaling and ferroportin expression, increase intracellular ferritin levels, and release intracellular trapped iron [89–91]. Vitamin C reduces Fe3+ to Fe2+ and inhibits hepcidin expression [92]. In recent years, research for new therapies based on plant-derived compounds has developed considerably. This is to maximize the benefits of plant phytochemicals and avoid the adverse effects often associated with synthetic pharmaceutical agents [93]. Several plant extracts, such as tucum-do-cerrado, astragalus, *Angelica sinensis*, *Caulis Spatholobi*, *Scutellaria baicalensis*, and others, have been studied for their putative effects on iron homeostasis and oxidative stress. The results obtained are very promising (for esaustive

*Summary of the mechanisms regulating iron and oxidative stress by antioxidants. BMP6-SMAD-HAMP: Bone morphogenetic factor-mothers against decapentaplegic homolog-hepcidin antimicrobial peptide; GPx: Glutathione peroxidase;Nrf2-ARE: Nuclear factor erythroid 2-related factor 2-antioxidant response element;* 

**100**

review, see Ref. [76]).

Alteration in iron homeostasis is associated with oxidative stress and inflammation. Many bioactive antioxidants and plant-derived phytochemicals can regulate iron homeostasis, inflammation, and oxidative stress. Nevertheless, the majority of data collected to date are derived from in vitro and animal experiments, and further studies are needed in order to evaluate the efficacy of these phytochemicals as a natural substitute for pharmaceutical agents. This is very important because many pharmaceutical agents are associated with adverse side effects.
