## 4 Natural Antioxidants and Their Role in Cosmetics
### Phenolic Compounds
#### 4.3.1 Flavonoids  
Hesperidin (Figure 4) has been reported to present various biological activities with the potential to be applied in the skincare. Hesperidin acts as a scavenger against free radicals. This activity is related to the releasing of protons from this flavone, modulating the radicals' synthesis toward the hesperidin structure. Hesperidin can inhibit the UV effects by reducing epidermal thickening, by regulating the expression of angiogenesis-related factors, by modulating apoptotic proteins induced by oxidative stress, and by regulating some immune cells and inflammatory cytokines, contributing to reducing inflammation. In addition, hydrogels formulated with nano-lipid carriers (NLCs) loaded with hesperidin showed a remarkable photoprotective effect, absorbing 99% of UVB radiation and 83% of UVB radiation. Thus, hesperidin may be a suitable ingredient in sunscreen. Hesperidin from orange peels, as an antioxidant molecule, has shown both anti-melanogenic and melanogenic activities, depending on its application. The oral intake of hesperidin helps to treat pigmented purpuric dermatosis lesions in a human case report and to treat atopic dermatitis in an animal testing model [82]. The production of hesperidin for cosmetic use encompasses various extraction (solvent extraction, microwave-assisted extraction, enzymatic extraction, and supercritical fluid extraction) and processing methods, each with its advantages and challenges. Innovations like nanocrystal formulation and biotechnological production hold promise for the more efficient and sustainable utilization of hesperidin in cosmetology. Advancements in biotechnology are exploring microbial fermentation and plant cell culture methods to produce hesperidin. These approaches aim to provide sustainable and controllable production processes, potentially increasing yield and optimizing properties through genetic engineering [83]. Xanthohumol  
Xanthohumol (2_AA_-trihydroxy-6-methoxy-3-(3-methyl-but-2-en-1-yl) chalcone) (Figure 4) is a highly active flavonoid. It is characterized by a fairly broad spectrum of biological activity. It has antifungal, antiviral, antibacterial and antimalarialal effects. It also prevents ischemic heart disease and reduces the risk of cancer [84]. First of all, xanthohumol is one of the strongest antioxidants that effectively protects the skin from oxidative stress. It prevents unfavorable changes in cell proteins, such as oxidation or amino acid modification, which lead to the weakening of collagen fibers contained in the skin. Studies have shown that xanthohumol reduces lipid peroxidation. It reduces their permeability, and also prevents disorders of transmembrane transport and increases its stability. These lipids are responsible for the construction of the lipid coat. In addition, studies confirm that xanthohumol is a 30 times stronger antioxidant than vitamin C. It works in the first line of antioxidant defense and does not allow hydrogen peroxide to transform into a free radical [85; 86]. Xanthohumol inhibits the excessive production of IL-12 interleukins in the autoimmune response to inflammation in the body, which confirms its anti-inflammatory effect. It also inhibits the growth of Gram-positive bacteria, such as _Staphylococcus aureus_, _Staphylococcus epidermidis_, _Propionibacteriumum acnes_, and _Kocura rhizophila_, which can cause purulent skin infections. High activity, which limits the growth of bacteria, can contribute to effective care of problematic skin, with changes in rosacea and acne vulgaris [86]. Metalloproteinases participate in the skin aging process, as they increase the decomposition of extracellular matrix components, especially elastin, collagen, and fibronectin. Figure 4: Chemical structures of antioxidant phenolics: (**10**) hesperidin, (**11**) xanthohumol, (**12**) taxifolia, (**13**) ferulic acid, (**14**) resveratrolol, and (**15**) bakuchiol. Xanthohumol has an inhibitory effect on metalloproteinases MMP-1 and MMP-8.