*4.1.1 Flavonols*

Flavonols are O-glycosidic, ketonic chemicals with a 3-position sugar fraction. Flavonols are antioxidants that prevent the development of ROS. Due to UV, ozone radiation, and other damaging substances, the skin is the most prevalent target for oxidative stress. The combination of conjugated double bonds in the C-ring and adjacent hydroxyl groups in the B-ring gives flavonols their antioxidant properties [24]. Quercetin, kaempferol, myricetin, and other compounds are included in this class.

#### *4.1.2 Quercetin*

Quercetin is a flavonol in various foods, including leafy greens, citrus fruits, berries, and other fruits and vegetables. Quercetin inhibits edema, leukocyte production,

#### *Recent Advances in Flavonoid Metabolism: An Updated Review DOI: http://dx.doi.org/10.5772/intechopen.106243*

and irritation. It helps reconstruct the skin's structure by endorsing the synthesis of new collagen fibers and generating ground substances [25]. Inflammatory mediators such as interleukins (IL) and prostaglandins (PGs), which are generated by COX, LOX, and LPS, are likewise suppressed by quercetin. The enzyme nitric oxide synthase, which also creates reactive nitrogen species like peroxynitrite, produces nitric oxide (NO), an inflammatory mediator. Quercetin is an antioxidant that prevents oxidative stress by inhibiting all of the mediators that cause it [26]. It avoids cell death by inhibiting the caspase-3 pathway and lowers mast cell development by inhibiting mast cell synthesis has an anti-allergic impact on histidine decarboxylase, IL-6, and monocyte chemoattractant protein (MCP-1).

#### *4.1.3 Kaempferol*

Kaempferol is primarily present in berries and plants of the allium and brassica family. It has antineoplastic, anti-inflammatory, and anti-allergic properties. It works as an anti-inflammatory drug by inhibiting NO synthase, which produces NO, a pro-inflammatory mediator. With the help of nuclear factor-inducing kinase (NIK) and mitogen-activated protein kinase (MAPKs), it also suppresses (NF-kappa B) [27]. It also inhibits COX-2 via decreasing nitric oxide synthase and TNF-, resulting in anti-inflammatory action. However, because kaempferol suffers significant first-pass metabolism and has a bioavailability of about 2%, topical application is preferable. UVB-induced cancer and photo-inflammation are treated with kaempferol, a new drug. It has been tested in skin cancer patients who have high levels of COX 2 enzymes. JB6 P+ mouse epidermal cells reduce AP-1 (Activator protein) activity via reducing COX-2. To test for AP-1 transactivation, JB6 P+ mouse epidermal cells were transfected with a luciferase reporter plasmid containing AP-1, and it was discovered that kaempferol reduces COX and AP-1 activities in a dose-dependent way, assisting in anticancer activity. The protooncogene tyrosine protein-kinase Src (Src) is a protooncogene that plays a key role in cell propagation, differentiation, and survival. Src activity is inhibited by kaempferol, which strives with ATP for the Src requisite position.

#### **4.2 Flavanones**

Consequent to the flavones origin, these fragrant ketones in citrus fruits like oranges and lemons. As a byproduct of citrus farming, a substantial quantity of hesperidin is produced. They are cytotoxic and inhibit tumor development; therefore, they might be used as anticancer drugs. Flavanones also serve as an anti-inflammatory and constrain protein tyrosine kinase, affecting cell development, distinction, mitosis, and death [28].

#### *4.2.1 Hesperetin and hesperidin*

Hesperidin has anti-inflammatory, antidiabetic, neuroprotective, and other properties. The aglycone component of hesperidin has antioxidant and anti-inflammatory properties by intruding with arachidonic acid, inhibiting COX and LOX enzymes, and limiting inflammatory mediator production [29]. It can whiten skin by reducing hyperpigmentation caused by UV radiation. Hesperetin and hesperidin generate anti-allergic action by constraining the issue of histamine from mast cells. They can also lower HMG CoA reductase and acyl CoA levels, resulting in a hypolipidemic effect. Hesperetin has a log P value ranging from 1.7 to 2.20, making it lipophilic and hard to absorb orally.

#### *4.2.2 Naringenin*

Naringenin has numerous properties, including antioxidant, antidiabetic, anti-inflammatory, and antineoplastic properties. It demonstrates antioxidants. MC1R: Melanocortin 1 receptor, MSH: Melanocyte stimulating hormone, MiTF: Microphthalmia associated transcription factor, Type-1: Tyrosinase related protein 1, Type-2: Tyrosinase related protein 2, ASIP: Agouti signaling protein] [− MSH: Melanocyte stimulating hormone, MC1R: Melanocortin 1 receptor, MiTF: Microphthalmia associated transcription factor, Type-2: Tyrosina Journal of Controlled Release 296 (2019) 190–201 R.L. Nagula, S. Wairkar 195 acts via chelating metal ions and constraining xanthine oxidase, averting oxygen radical generation and lipid peroxidation. It can also scavenge ROS through the ∙OH substitution. Because naringenin is hydrophobic and has low solubility and bioavailability, it can be used topically to create an effective formulation [30].

#### **4.3 Flavanols**

They are not to be mistaken with flavonol since they lack the ketone group. Epigallocatechin-3-gallate, proanthocyanidins, and other members of this class are included. Tea, chocolate, and a variety of vegetables and fruits contain them naturally [31]. The FDA, for use in a variety of medicinal formulations, has approved catechins and their derivatives.

#### *4.3.1 Catechins*

Catechins have antioxidant, photoprotective, anti-aging, anti-inflammatory, anticancer, neuroprotective, cardioprotective, antiviral, and antibacterial properties, among others. Epigallocatechin and epicatechin are abundant in grape seed extract and tea polyphenols. By scavenging free radicals, it has an antioxidant action [32]. Anti-inflammatory action is induced via inhibiting the COX enzyme, NO, PGs, and H2O2 production. Catechins help wounds heal faster by foraging free radicals at the wound site.

#### *4.3.2 Anthocyanins*

Anthocyanins are colorful glycosylated, water-soluble pigments that give fruits and vegetables their blue, red, and purple hues. They have been revealed to have antioxidant, anti-inflammatory, and depigmentation qualities in numerous scientific research.

Delphinidin contains anti-inflammatory, antioxidant, antitumorigenic, and antiangiogenic effects and is identified to suppress osteoclastogenesis in osteoporosis. Delphinidin inhibits the production of seditious intermediaries such as iNOS, NO, IL-6, MCP-1, and TNF-, which are produced when LPS inhibits the NF-B pathway and MEK1/2-ERK1/2 signaling [33]. It was tested for psoriasis on flaky skin mice and shown to reduce epidermal thickness. Infiltrating macrophages and caspase 14 downregulation were also seen. Keratin-14, which induces hyperproliferation, was also reduced. By inhibiting keratin-14, delphinidin serves as an antiproliferative. The level of pathological indicators of psoriasis lesions is reduced when delphinidin is applied to flaky mouse skin.
