Flavonoids and Terpenoids with PTP-1B Inhibitory Properties from the Infusion of <i>Salvia amarissima</i> Ortega

• Main Authors: Eric Salinas-Arellano, Araceli Pérez-Vásquez, Isabel Rivero-Cruz, Rafael Torres-Colin, Martín González-Andrade, Manuel Rangel-Grimaldo, Rachel Mata
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Molecules
• Subjects: <i>Salvia amarissima</i>; PTP-1B activity; amarisolide G; diabetes
• Online Access: https://www.mdpi.com/1420-3049/25/15/3530

An infusion prepared from the aerial parts of <i>Salvia amarissima</i> Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC₅₀~88 and 33 μg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide (<b>1</b>), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (<b>2</b>), 6-hydroxyluteolin (<b>3</b>), rutin (<b>4</b>), rosmarinic acid (<b>5</b>), isoquercitrin (<b>6</b>), pedalitin (<b>7</b>) and a new <i>neo</i>-clerodane type diterpenoid glucoside, named amarisolide G (<b>8a</b>,<b>b</b>). Compound <b>8a</b>,<b>b</b> is a new natural product, and <b>2</b>–<b>6</b> are reported for the first time for the species. All compounds were tested for their inhibitory activity against PTP-1B; their IC₅₀ values ranged from 62.0 to 514.2 μM. The activity was compared to that of ursolic acid (IC₅₀ = 29.14 μM). The most active compound was pedalitin (<b>7</b>). Docking analysis predicted that compound <b>7</b> has higher affinity for the allosteric site of the enzyme. Gas chromatography coupled to mass spectrometry analyses of the essential oils prepared from dried and fresh materials revealed that germacrene D (<b>15</b>) and β-selinene (<b>16</b>), followed by β-caryophyllene (<b>13</b>) and spathulenol (<b>17</b>) were their major components. An ultra-high performance liquid chromatography coupled to mass spectrometry method was developed and validated to quantify amarisolide (<b>1</b>) in the ethyl acetate soluble fraction of the infusion of <i>S. amarissima</i>.