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Ensayo de intervención → Metabolitos descritos comercialmente disponibles

Lippia citriodora

Olea europaea

Hibiscus sabdariffa
Hibiscic acid

Silybum marianum
Silibinin  Silibinin (16 stereoisomers)
Myricetin 3-glucoside

Lippia citriodora

Tentative name m/z Molecular formula
Gardoside 373.1149 C16 H22 O10
Verbascoside 623.2002 C29 H36 O15

Olea europaea

Tentative name m/z Molecular formula
10-Hydroxyoleuropein 555.1720 C25 H32 O14
Oleuropein 539.1869 C25 H32 O13

Hibiscus sabdariffa

Tentative name m/z Molecular formula
Hibiscus acid 207.12 C6 H8 O8

Silybum marianum

Tentative name m/z Molecular formula
Silibinin 481.11 C25 H22 O10
Myricetin 3-O-D-glucoside 479.0977 C21 H20 O13

For AMPK-alpha2 (UniProt P54646), the catalytic subunit alpha-2 AMPK, there are 11 high-resolution structures in which alpha-2 and beta-1 subunits (UniProt Q9Y478) form a binding site in the contact region of both subunits. For the gamma-1 subunit (UniProt P54619) of AMPK there are 13 high-resolution structures that allow detailed study of the AMP binding site.

Many resolved structures are also known for mTOR protein kinase (UniProt P42345), which allow us to study both the ATP and the rapamycin.

The SIRT1 (UniProt Q96EB6) is an NAD+-dependent protein deacetylase that acts as a sensor of the cytosolic ratio of NAD+/NADH.

PCG-1 (UniProt Q9UBK2) is a transcriptional coactivator for steroid receptors and nuclear receptors.

The signaling pathway of Nrf2 (UniProt Q16236) plays fundamental roles in inflammation. It is related to the nuclear factor kappa B (NFκB) pathway. NFκB together with JAK (janus kinase)-STAT (signal transducers and activators of transcription) signaling pathways are involved in the development of the classical pathway of inflammation. There is abundant structural information of both proteins, especially for JNK (UniProt P53779), of which 48 structures are currently available in the PDB. Of the proteins encoded by the nfkb1 and nfkb2 genes, p50/p105 (UniProt P19838) and p52/p100 (UniProt Q00653), respectively, abundant structural information useful in molecular docking experiments is available.

MAPKs include p38 MAPK14 (UniProt Q16539), which is involved in the cascades of cellular responses that are triggered by extracellular stimuli such as physical stress or the presence of proinflammatory cytokines.

γ-H2A.X (UniProt P16104) and Insulin-like growth factor-1, IGF-1 (UniProt P05019) are the last two age-related marker proteins with interest for this project.

Gamma-H2AX (UniProt P16104) results after the phosphorylation of the H2AX protein, a variant of the histone H2A protein family, which is generated because of DNA damage. IGF-1 is strongly structurally and functionally homologous with insulin. Its binding to integrins and subsequent ternary complex formation with integrins and IGF Receptor 1 is essential for IGF-1 signaling.

PARP1 (UniProt P09874) activity increase ensures DNA integrity, but at the same time makes the organism more susceptible to metabolic diseases.

Molecular docking simulations of the selected metabolites against the putative binding sites of the protein targets: AMPK, mTOR, SIRT1 and PGC-1α; mTOR, p38 MAPK14, γ-H2A.X, IGF-1, PARP-1; Nrf2, NFκB, JNK, ERK.

AMPK: 5'-AMP-activated protein kinase, models from Swuiss-prot.

mTor: Serine/threonine-protein kinase mTOR, models from Swuiss-prot.