ABSTRACT
Fractionation of an EtOAc extract of the roots of Perovskia abrotanoides yielded 28 diterpenoids, including 12 new analogues, 1-12. The structures of these diterpenoids were established using comprehensive spectroscopic data analysis, including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectroscopy, and comparison with literature data. The extract and some of the tested compounds showed significant anti-inflammatory activity on J774A.1 macrophage cells stimulated with E. coli lipopolysaccharide. In particular, the tested compounds significantly inhibited the release of nitric oxide and the expression of related proinflammatory enzymes, such as inducible nitric oxide synthase.
Subject(s)
Abietanes/pharmacology , Anti-Inflammatory Agents/pharmacology , Macrophages/drug effects , Salvia/chemistry , Abietanes/isolation & purification , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Line , Iran , Mice , Molecular Structure , Nitric Oxide , Nitric Oxide Synthase Type II , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Roots/chemistryABSTRACT
Phytochemical investigation of the lipophilic extract of the roots of Salvia leriifolia resulted in the isolation of the new rearranged abietane diterpenoids leriifoliol (1) and leriifolione (2), together with 10 known diterpenoids. Structure elucidations were performed via extensive NMR and HRESIMS data, and the absolute configurations of compounds 1 and 3-5 were established by evaluation of experimental and calculated ECD spectra. The antiplasmodial activity of the new isolates was assayed against Trypanosoma brucei rhodesiense, T. cruzi, Plasmodium falciparum, and Leishmania donovani and also toxicity against rat myoblast (L6) cells. Compound 1 displayed antimalarial and low cytotoxic activity with IC50 values of 0.4 and 33.6 µM, respectively, and a selectivity index of 84. Compound 2 displayed activity against T. brucei, T. cruzi, and L. donovani, with IC50 values of 1.0, 4.6, and 1.0 µM, respectively. Putative biosynthetic pathways toward the formation of 1, 2, and 3 are proposed. Leriifoliol (1) is the first 20- nor-9,10- seco-abietane, while 2 exhibits an uncommon 6-6-5 fused-ring system.
Subject(s)
Abietanes/chemistry , Abietanes/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Phytochemicals/pharmacology , Plant Roots/chemistry , Salvia/chemistry , Antimalarials/chemistry , Antimalarials/pharmacology , Inhibitory Concentration 50 , Leishmania donovani/drug effects , Parasitic Sensitivity Tests/methods , Phytochemicals/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plasmodium falciparum/drug effects , Trypanosoma brucei rhodesiense/drug effects , Trypanosoma cruzi/drug effectsABSTRACT
In the present study, the neuroprotective effect of 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4'-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aß)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aß injection. Seven days after Aß administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.