ABSTRACT
An infusion prepared from the aerial parts of Salvia amarissima Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC50~88 and 33 µg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide (1), 5,6,4'-trihydroxy-7,3'-dimethoxyflavone (2), 6-hydroxyluteolin (3), rutin (4), rosmarinic acid (5), isoquercitrin (6), pedalitin (7) and a new neo-clerodane type diterpenoid glucoside, named amarisolide G (8a,b). Compound 8a,b is a new natural product, and 2-6 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 (7). Docking analysis predicted that compound 7 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 (15) and ß-selinene (16), followed by ß-caryophyllene (13) and spathulenol (17) were their major components. An ultra-high performance liquid chromatography coupled to mass spectrometry method was developed and validated to quantify amarisolide (1) in the ethyl acetate soluble fraction of the infusion of S. amarissima.
Subject(s)
Flavonoids/isolation & purification , Flavonoids/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Salvia/chemistry , Terpenes/isolation & purification , Terpenes/pharmacology , Allosteric Site , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/pharmacology , In Vitro Techniques , Mexico , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/chemistryABSTRACT
A new fatty acid ester (1) and seven known phenolic compounds, i.e. salfredin B11 (2), nigephenol C (3), nigephenol B (4), acetovanillion (5), p-hydroxybenzoic acid (6), p-hydroxy-acetophenone (7) and p-hydroxybenzaldehyde (8), were isolated from the seeds of Nigella sativa var. hispidula. Among them, compounds 5, 7 and 8 were isolated from Nigella for the first time. Their structures were elucidated with HR-ESI-MS, 1D and 2D NMR spectra. Evaluation of the isolated compounds on protein tyrosine phosphatase (PTP1B) assay indicated that although compounds 2-8 show no promising anti-PTP1B activities, compound 1 possess anti-PTP1B activity with an IC50 value of 7.38 ± 0.14 µM in vitro.