Anti-Inflammatory and Cytotoxic Activities of Clerodane-Type Diterpenes

The secondary metabolites of clerodane diterpenoids have been found in several plant species from various families and in other organisms. In this review, we included articles on clerodanes and neo-clerodanes with cytotoxic or anti-inflammatory activity from 2015 to February 2023. A search was conducted in the following databases: PubMed, Google Scholar and Science Direct, using the keywords clerodanes or neo-clerodanes with cytotoxicity or anti-inflammatory activity. In this work, we present studies on these diterpenes with anti-inflammatory effects from 18 species belonging to 7 families and those with cytotoxic activity from 25 species belonging to 9 families. These plants are mostly from the Lamiaceae, Salicaceae, Menispermaceae and Euphorbiaceae families. In summary, clerodane diterpenes have activity against different cell cancer lines. Specific antiproliferative mechanisms related to the wide range of clerodanes known today have been described, since many of these compounds have been identified, some of which we barely know their properties. It is very possible that there are even more compounds than those described today, in such a way that makes it an open field to discover. Furthermore, some diterpenes presented in this review have already-known therapeutic targets, and therefore, their potential adverse effects can be predicted in some way

Anti-Inflammatory Activity of Piquerol Isolated from Piqueria trinervia Cav.

Background: Inflammation is a complex process as a response to several stimuli, such as infection, a chemical irritant, and the attack of a foreign body. Piquerol was isolated from Piqueria trinervia, and its anti-inflammatory activity was evaluated using in vivo and in vitro models. Methods: Piquerol is a monoterpene that was identified using NMR, FT-IR spectroscopy, and mass spectrometry analysis. The anti-inflammatory activity was tested in vivo in ear edema induced with TPA in mice. Piquerol was also tested on J774A.1 macrophages stimulated with lipopolysaccharide (LPS), and the levels of NO, NF-κB, TNF-α, IL-1β, IL-6, and IL-10 were determined using ELISA. Results: The results show that piquerol diminished ear edema (66.19%). At 150.51 µM, it also inhibited the levels of NO (31.7%), TNF-α (49.8%), IL-1β (69.9%), IL-6 (47.5%), and NF-κB (26.7%), and increased the production of IL-10 (62.3%). Piquerol has a membrane stabilization property in erythrocyte, and at 100 µg/mL, the membrane protection was of 86.17%. Conclusions: Piquerol has anti-inflammatory activity, and its possible mechanism of action is through the inhibition of pro-inflammatory mediators. This compound could be a candidate in the development of new drugs to treat inflammatory problems

Anti-Inflammatory Activity of 3, 5-Diprenyl-4-hydroxyacetophenone Isolated from <i>Ageratina pazcuarensis</i>

Inflammation is implicated in a wide variety of physiological and pathological processes. Plants are an important source of active anti-inflammatory compounds. The compound 3, 5-diprenyl-4-hydroxyacetophenone (DHAP) was isolated from the dichloromethane extract of the aerial parts of Ageratina pazcuarensis by chromatography and identified by spectroscopic (IR, NMR) and spectrometric (GC-MS) methods. Anti-inflammatory activity was evaluated on ear edema mouse induced with 12-O-tetradecanoylphorbol 13-acetate (TPA) at 2 mg/ear. The antioxidant activity of DHAP was determined using DPPH assay. Cell viability was tested in J774A.1 macrophages, the levels of NO, TNF-α, IL-1β, IL-6, and IL-10 production in macrophages stimulated with lipopolysaccharide (LPS), and membrane lysis induced by hypotonic solution in erythrocytes were evaluated. DHAP diminished the ear edema mouse in 70.10%, and it had scavenger effect against the radical with IC50 of 26.00 ± 0.37 µg/mL. Likewise, 91.78 µM of this compound inhibited the production of NO (38.96%), IL-1β (55.56%), IL-6 (51.62%), and TNF-α (59.14%) in macrophages and increased the levels of IL-10 (61.20%). Finally, 25 and 50 µg/mL DHAP provided the greatest protection against erythrocyte membrane lysis. These results demonstrate that DHAP has anti-inflammatory activity

Dataset for: Structural study of 1-(2´, 3´-<i>O</i>-isopropylidene-(α-D-allo and –β-L-talofuranosyluron)-5´-cyanohydrin)uracil stereoisomers by NMR spectroscopy and theoretical methods.

The stereochemistry of nucleoside derivatives determines their pharmacological activity such as anticancer, antiviral, against human immunodeficiency virus (HIV) and antimycotic. Therefore, it is necessary to elucidate the structure of each stereoisomer. The isolation and spectroscopic characterization of the 1-(2´, 3´-<i>O</i>-isopropylidene-(α-D-allo and -β-L-talofuranosyluron)-5´-cyanohydrin)uracil stereoisomer is of great importance because these compounds are intermediaries in the development of novel nucleoside derivatives. In this study, we elucidated the structure of 5´(<i>R</i>) and (<i>S</i>)-cyanohydrin stereoisomers by NMR spectroscopy and tridimensional analysis. The structure was modeled based on the conformer with the local minimized energy. 1D-NOESY gave a detailed information about the tridimensional structure of each diastereoisomer. The ratio of the diastereoisomers determined by NMR, using DMSO-d₆ as solvent, was 65% of 5´(<i>R</i>)-cyanohydrin (<b>A</b>) and 35% of 5´(<i>S</i>)-cyanohydrin (<b>B</b>)