HMG – CoA reductase inhibition mediated hypocholesterolemic potential of myricetin and quercetin: in-silico and in-vivo studies

Figures & data

Figure 1. Chemical structures of myricetin and quercetin.

Figure 2. 3D Figures posing the molecular interactions of ligand-protein myricetin(1a) and quercetin(1b) with HMG CoA reductase studied through docking analysis. The dotted line indicates the hydrogen bond interactions.

Figure 3. 2D figures posing the ligand-protein interactions of Myricetin(2a) and Quercetin(2b) with HMG CoA reductase.

Table 1. Molecular docking of myricetin and quercetin compound against target enzyme of HMG CoA reductase.

Ligand	Myricetin	Quercetin	Atorvastatin
Binding Energy (Kcal/mol)	−8.4	−8.4	−6.2
No. of H-bonds	9	8	8
Bond length (Å)	3.69, (4.38,5.29,5.27), (2.65,2.15), 2.25, (2.79,2.68)	2.46,2.44,2.34,2.69,4.43, (2.67,2.10), 3.72	2.63,3.40, (2.34,4.42,4.76,5.45), (3.69,5.35)
Interacting residues	Glu610, His635, Lys606, Ser637, Ile638	Ile699, Trp698, Ser637, Ile638, His635, Lys606, Glu610	Thr636, Glu700, Lys633, His635

Table 2. Pharmacokinetics ADMET predictions of myricetin and quercetin by SwissADME.

Compound	Myricetin	Quercetin	Atorvastatin
MW	318.24	302.24	558.64
ilogP	1.08	1.63	3.81
ClogP	0.79	1.23	4.99
HBA	8	7	6
HBD	6	5	4
nHB	14	12	10
TPSA	151.59	131.36	111.79
N violations	1	0	1
Drug likeness	Yes	Yes	Yes
Filter L/B	L	L	L

MW = molecular weight; ilogP = partition coefficient; ClogP = consensus log P; HBA = hydrogen bond acceptor; HBD = hydrogen bond donor; nHB = number of hydrogen bond; TPSA = total polar surface area; violations = number of violations; Filter L = Lipinski rule of five and B = blood brain barrier.

Table 3. In silico toxicity study of myricetin and quercetin compound by ProTox-II.

Compound	Myricetin	Quercetin	Atorvastatin
Hepatotoxicity	Inactive	Inactive	Active
Carcinogenicity	Active	Active	Inactive
Immunotoxicity	Inactive	Inactive	Inactive
Mutagenicity	Active	Active	Inactive
Cytotoxicity	Inactive	Inactive	Inactive
Predicted LD50 (mg/kg)	159	159	5000
Predicted Toxicity class	3	3	5

Figure 4. Myricetin and quercetin interaction energies with HMGCR.

Figure 5. Free energy of solvation of myricetin and quercetin with HMGCR.

Figure 6. RSMF calculation of myricetin and quercetin with HMGCR.

Figure 7. Calculation of SASA for myricetin and quercetin with HMGCR.

Figure 8. Calculation of radius of gyration for myricetin and quercetin with HMGCR.

Figure 9. RSMD calculation of myricetin and quercetin with HMGCR.

Figure 10. Effect of treatments of myricetin and quercetin on lipid profile. Data are means ± S.E.M. (n = 5); c P ≤ .001 as significant; and d was non-significant as compared to the respective control values. g P ≤ .001 as significant; and h was non-significant as compared to the respective values of the hypercholesterolemic control group.

Figure 11. Effect of treatments of myricetin and quercetin on lipid profile. Data are means ± S.E.M. (n = 5); c P ≤ .001 as significant; and d was non-significant as compared to the respective control values. g P ≤ .001 as significant; and h was non-significant as compared to the respective values of the hypercholesterolemic control group.

Figure 12. Effect of treatments of myricetin and quercetin on oxidative stress. Data are means ± S.E.M. (n = 5); c P ≤ .001 as significant; and d was non-significant as compared to the respective control values. g P ≤ .001 as significant; and h was non-significant as compared to the respective values of the hypercholesterolemic control group.

Data availability statement

The data have already been incorporated into the manuscript.