Table 3.

Selected flavonoids of S. littoralis Hassk. in cosmetic properties based on in silico activity.

Cosmetic properties	The main mechanism	Selected flavonoids	In silico activity	Reference(s)
Antioxidant activity	▪Binding active site target proteins: NADPH oxidase, cytochrome P450, myeloperoxidase, xanthine oxidase, catalase, glutathione peroxidase, acetylcholinesterase, and reactive oxygen species. ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin binds five enzymes that are responsible for ROS: NADPH oxidase (PDB: 2CDU), cytochrome P450 (CP450) (PDB: 1OG5), myeloperoxidase (MP) (PDB: 1DNU), and XO; the docking scores are -6.75; -5.78; -5.19; and -7.83 kcal.mol-1 respectively. Those docking scores are lower than dextromethorphan (DEX) as the positive control. The interaction patterns of catechin and the binding site of the enzyme are: 1. NADPH oxidase→ hydrogen bonds: Asp179, Tyr188, Val214; and pi–c: Lys187. 2. Cytochrome P450 →hydrogen bond: Ser365; pi–pi: Phe476. 3. Myeloperoxidase →hydrogen bond: Asn186, Arg188, Asn189, Phe213. 4. Xanthine oxidase →HB: Glu802, Thr1010; pi–pi: Phe914, Phe1009.	(Kritsi et al., 2022)
		Daidzein	The binding energy of docked complex with Catalase as an antioxidant protein was found to be -100.665 kcal.mol-1. The interaction residues for Catalase were ARG-72, ARG-112, TYR-358, HIS-75, GLY-147, ASN-148, PHE-153, ARG-354, TYR-358, ASP-389, ASN-403, ARG-68, GLU-330, GLU-71, GLU-119, and ARG-170.	(Tidke et al., 2018)
		Formononetin	Docking score for formononetin from vegetal extract to bind glutathione peroxidase 4 (GPX4) (protein target) is -6.547 kcal.mol-1.	(Costea et al., 2022)
		Glycitein	The binding energy of docked complex with Catalase as an antioxidant protein was found to be -97.5342 kcal.mol-1. The interaction residues for Catalase were ARG-72, ARG-112, TYR-358, HIS-75, GLY-147, ASN-148, PHE-153, ARG-354, TYR-358, ASP-389, ASN-403, ARG-68, GLU-330, GLU-71, GLU-119, and ARG-170.	(Tidke et al., 2018)
		Luteolin	Luteolin binds ROS with a docking score of -8.3 kcal.mol-1. Residue interactions were LYS1980, ALA1978, LEU2026, LEU2086, VAL1959.	(Syamsul et al., 2022)
		Apigenin	Docking score for apigenin from vegetal extract to bind GPX4 (protein target) is -6.918 kcal.mol-1.	(Costea et al., 2022)
		Hesperetin	Hesperetin from citrus demonstrated good binding energies for the target enzymes, such as β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and AChE with binding energies -8.3; -8.4 kcal.mol-1 respectively.	(Lee et al., 2018)
		Naringenin	Docking score for naringenin from vegetal extract to bind GPX4 (protein target) is -6.048 kcal.mol-1.	(Costea et al., 2022)
Anti-inflammatory activity	▪Binding target proteins: toll-like receptor 4 (TLR-4), Jun-N- terminal kinase (JNK), NF-κB, AP-1, COX-1, TNF-α, 5-LOX, angiotensin converting enzyme (ACE-2). ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin binds four target proteins: 1.TLR-4 via two H-bonds (Thr B459, ARG A460). Docking score -7.5 kcal.mol-1. 2.JNK via one H-bond (Lys A93). Docking score -7.3 kcal.mol-1. 3.NF-κB via four H-bonds (Thr B122, Gly B162, Gly B181, Gly B180). Docking score -7.3 kcal.mol-1. 4.AP-1 via two H-bonds (Ala B362, Leu B355). Docking score -7.9 kcal.mol-1.	(Khan et al., 2022b)
		Daidzein	Daidzein binds COX-1 with binding energy -110.38 kcal.mol-1. The main residues of interactions for COX-1 were GLN-44, GLN-42, HIS-43, THR-206, ASN-382, ALN-203, GLN-203, HIS-207, PHE-210, HIS-388, LYS-468, ARG-469.	(Tidke et al., 2018)
		Formononetin	Formononetin binds TNF-α with a docking score of -7.626 kcal.mol-1.	(Costea et al., 2022)
		Glycitein	Glycitein binding COX-1 with binding energy -104.35 kcal.mol-1. The main residues of interactions for COX-1 were GLN-44, GLN-42, HIS-43, THR-206, ASN-382, ALN-203, GLN-203, HIS-207, PHE-210, HIS-388, LYS-468, ARG-469.	(Tidke et al., 2018)
		Luteolin	Following docking investigations, luteolin binds to the catalytic iron atom in 5-LOX and generates stabilizing hydrogen bonds with His367 and Thr364. Luteolin binding ACE-2 with binding energy -8.9 kcal.mol-1.	(Kutil et al., 2014) (Alzaabi et al., 2022)
		Apigenin	Apigenin binding ACE-2 with binding energy -8.5 kcal.mol-1.	(Alzaabi et al., 2022)
		Hesperetin	Hesperetin functions as an in silico inhibitor of the SARS spike glycoprotein-Human ACE2 complex with an affinity of -9.2 kcal.mol-1.	(Cheke et al., 2021)
		Naringenin	Naringenin binds ACE-2 with binding energy -8.5 kcal.mol-1.	(Alzaabi et al., 2022)
Tyrosinase inhibitor	▪Binding active site tyrosinase enzyme. ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin had a lower docking score (-9.58 kcal.mol-1) than the inhibitor kojic acid (-7.99 kcal.mol-1) when it came to binding to the active site of the tyrosinase enzyme. Tyrosinase was the target protein, and catechin's binding energy to it was -7.64 kcal.mol-1 via H-bond (HIS296). Compared to kojic acid, the energy value was lower (-5.03 kcal.mol-1). It proved that kojic acid and catechin have different levels of affinity.	(Abdelfattah et al., 2022) (Laksmiani et al., 2020)
		Daidzein	Daidzein isolated from the root of Pueraria lobata inhibited mushroom tyrosinase activity with a docking score of -7.09 kcal.mol-1. The docking score is lower than the positive control (kojic acid), -5.5 kcal.mol-1.	(Wagle et al., 2019)
		Luteolin	The binding energy of luteolin on tyrosinase enzyme was -6.19 kcal.mol-1 which was lower than kojic acid (-5.5 kcal.mol-1). The interactions that occur are H-bond interaction (Cys83, Gly245, Ala246, Val248), electrostatic interaction (Glu322), and hydrophobic interaction (His85 and Val248). Luteolin binds the mushroom tyrosinase with a docking score-7.9 kcal.mol-1. The hydroxyl group on Ring B of luteolin formed H-bond with Glu322.	(Wagle et al., 2018) (Jakimiuk et al., 2021)
		Hesperetin	Hesperetin chelates a copper ion that combines with three histidine residues (HIS259, HIS85, and HIS61) within the active site to inhibit tyrosinase in the competitive pathway (KI=4.030±26 mM).	(Si et al., 2012)
		Naringenin	Naringenin is a similar compound to 2S-Pinocembrin which has one H-bond on the active site of the tyrosinase enzyme.	(Lall et al., 2016)
Elastase inhibitor	▪Binding the active site of elastase enzyme and MMPs. ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin had the best docking score (-20.36 kcal.mol-1) on binding the active site of elastase enzyme compared to -13.32 kcal.mol-1 of kojic acid as an inhibitor. Hydrogen bonding interactions with Pro232 and Arg 249 and hydrophobic contacts to Lys233, Lys241, and Val243.Catechin binds MMP1 with binding affinity -8.5 kcal.mol-1. Possible binding sites were ARG214, HIS218, ASN180, SER239. Common residues were HIS218, GLU219, SER239, PRO238, ARG21. Catechin also binds MMP8 with binding affinity -8.8 kcal.mol-1. Possible binding sites were ALA161, VAL194, HIS197, LEU214, TRY219, ASN218, PRO217. Common residues were LEU160, TRY216, ASN218, LEU214, GLU198, PRO217, HIS197, GLU198, ALA161.	(Abdelfattah et al., 2022) (Kose et al., 2020)
		Luteolin	Luteolin binds MMP8 with a binding affinity was -10.1 kcal.mol-1. Possible binding sites were LEU160, LEU214, PRO217, TYR216, ARG222, GLU198, ALA161. Common residues were LEU160, TRY216, ASN218, LEU214, GLU198, PRO217, HIS197, GLU198, ALA161. Luteolin also binding MMP11 with a binding affinity was -10 kcal.mol-1. Possible sites were HIS219, LEU181, LEU236, SER238, PHE240, TYR241, VAL216, GLN215. Common residues were THR202, ASP200, GLU201, GLN12, GLN209, ASN208, TYR241.	(Kose et al., 2020)
		Apigenin	Apigenin binds MMP2 with a binding affinity was -9 kcal.mol-1. Possible binding sites were VAL198, ILE222, ALA220, PRO215, LEU218, HIS201, TRY223. Common residues were VAL198, ILE222, ALA220, LEU218, LEU197, HIS201, TRY223.	(Kose et al., 2020)
		Naringenin	Naringenin binds MMP8 with binding affinity was ALA112, ASP115, THR224, ARG111, GLU108, SER105. Common residues were LEU160, TRY216, ASN218, LEU214, GLU198, PRO217, HIS197, GLU198, ALA161.	(Kose et al., 2020)
Collagenase inhibitor	▪Binding collagenase enzyme. ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin showed strong binding at the active site of collagenase enzyme with a docking score of -12.71 kcal.mol-1. The docking score of catechin is lower than quercetin as the positive control (-12.20 kcal.mol-1) Epigallocatechin gallate binds collagenase with a docking score of -9.93 kcal.mol-1. Hydrogen bonds: Gly158, Leu160, Ala161, Tyr189, Tyr219, Ala220. Hydrophobic interactions: Leu160, His197. Electrostatic interaction: Glu198.	(Abdelfattah et al., 2022) (Priani and Fakih, 2021)
		Luteolin	Luteolin binds collagenase with a docking score of -11.0 kcal.mol-1. Residue interactions were LEU235, SER239, VAL215, HIS218, LEU181.	(Syamsul et al., 2022)
Hyaluronidase inhibitor	▪Binding active site hyaluronidase enzyme. ▪Hydrophobic interaction and hydrogen bond with amino acid residues.	Catechin	Catechin contained in Warburgia salutaris bark aqueous extract binding active site on hyaluronidase enzyme with docking score -13.73 kcal.mol-1. The docking score of catechin is lower than kojic acid as the positive control (-9.10 kcal.mol-1). Epigallocatechin gallate binds hyaluronidase enzyme with a docking score of -8.9 kcal.mol-1 via H-bonds (ASP56, ASP111, TRP301, SER304) and hydrophobic interactions (ASP111, GLU113, TRP301).	(Abdelfattah et al., 2022) (Younis et al., 2022)
		Daidzein	Daidzein binds energy with an active site in hyaluronidase (-27.08 kJ mol-1). Besides, daidzein binding amino acids via hydrophobic interaction, hydrophilic interaction, and hydrogen bond.	(Zeng et al., 2015)
		Luteolin	Luteolin binds energy with an active site in hyaluronidase (-25.03 kJ mol-1). Besides, daidzein binding amino acids via hydrophobic interaction, hydrophilic interaction, and hydrogen bond. Luteolin binds hyaluronidase with a docking score -6.8 kcal.mol-1. Residue interactions were ASP111, GLU113, TYR55.	(Zeng et al., 2015) (Syamsul et al., 2022)
		Apigenin	Apigenin binds hyaluronidase enzyme with binding energy-56.15 kcal.mol-1.	(Mumpuni and Mulatsari, 2017)
		Naringenin	Naringenin binds energy with an active site in hyaluronidase (-24.28 kJ mol-1). Besides, daidzein binding amino acids via hydrophobic interaction, hydrophilic interaction, and hydrogen bond.	(Zeng et al., 2015)