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

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 β-selinene (16), followed by β-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.

Antihyperglycemic and Lipid Profile Effects of Salvia amarissima Ortega on Streptozocin-Induced Type 2 Diabetic Mice

“…From the three different evaluated doses, the selected dose was 50 mg/kg b.w., which showed antihyperglycemic activity at the fifth and seventh hours of treatment, being similar in time to PEfAPSa. This similarity is related to the presence of compounds that generate a glycemia reduction in STID mice, and these results show that the non-polar compounds obtained from petroleum ether extract can be as effective as polar and non-polar extracts, while fresh parts can be used in place of dry parts [ 14 , 15 , 24 , 25 , 26 ]. The benefit of the extended time effect in acute assays of PEfAPSa and F6Sa indicates that these treatments could be administrated less frequently throughout the day, while still being effective.…”

“…S. amarissima is a plant used in traditional Mexican medicine to treat DM. The background of the plant includes ethnomedical uses [ 21 , 23 ], and use in the evaluation of polar and medium polar extracts (MeOH:acetone and aqueose extracts), as well as in products obtained from these extracts (flavonoids and diterpens) [ 14 , 15 , 24 , 25 , 26 ]. The aforementioned studies focus on acute assays and some tolerances, while the present work provides information regarding acute, sub-chronic, and oral tolerance test assays of a non-polar extract and fraction.…”

“…The information obtained in this study could be used to expand the knowledge and use of Salvia amarissima Ortega. Recent studies of potential antidiabetic plants were related to diverse mechanisms of how they generate antihyperglycemic activity, such as α-glucosidase inhibitors, protein tyrosine phosphatase 1B inhibitors (PTP-1B), insulin secretion, or inhibition of DPP-IV [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Rural populations use herbal products or combine them with allopathic treatments for the control of blood glucose levels [ 21 , 22 ].…”

“…), which is a perennial aromatic shrub native to Mexico, commonly known as “bretónica”, “diabetina”, “prodigiosa”, “salvia”, or “insulina”, and used in Mexican traditional medicine for the treatment of ulcers, helminthiasis, and diabetes [ 9 , 21 , 23 , 24 ]. In previous studies, medium and high polarity extracts were isolated from S. amarissima : phenolic compounds (rosmarinic acid, rutin, pedalitin, apigenin-7- O -β- d -glucoside, 6-hydroxyluteoline, 2-(3-4-dimethoxyphenyl)-5-6-dihydroxy-7-methoxy-4 H -chromen-4-one, 5,6,4′-trihydroxy-7-3′-dimethoxyflavone, and isoquercitrin) and terpenoids (amarisolides A–G, amarissinines A–C, acetylamarisine B, teotihuacanin, α-bourbanene, β-caryophyllene, δ-elemene, α-caryophyllene, β-selinene, germacrene D, and spathulenol [ 14 , 15 , 24 , 25 , 26 ]. Among these, amarisolide A, rutin, pedalitin, apigenin-7- O -β- d -glucoside, and 2-(3-4-dimethoxyphenyl)-5-6-dihydroxy-7-methoxy-4 H -chromen-4-one are α-glucosidase inhibitors.…”

“…Among these, amarisolide A, rutin, pedalitin, apigenin-7- O -β- d -glucoside, and 2-(3-4-dimethoxyphenyl)-5-6-dihydroxy-7-methoxy-4 H -chromen-4-one are α-glucosidase inhibitors. In addition, amarisolide A, rutin, rosmarinic acid, isoquercitrin, and pedalitin are protein–tyrosine phosphatase 1B inhibitors (PTP-1B) [ 14 , 24 ]. It is important to highlight that low polarity extracts of fresh aerial parts have not been studied; however, the study of non-polar compounds is scarce, including when they showed effects in pre-clinical sub-chronic studies [ 9 , 15 , 24 ].…”