Anti-Inflammatory and Cytotoxic Compounds Isolated from Plants of Euphorbia Genus.

Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different Euphorbia species have anti-cancer activity. In this review, we included compounds isolated from species of the Euphorbia genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords Euphorbia with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the Euphorbia genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%).

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.

Synthesis and Biological Activities of Dehydrodiisoeugenol: A Review.

Dehydrodiisoeugenol (DHIE) is a neolignan found in more than 17 plant species, including herbs, fruit, and root. DHIE was, for the first time, isolated from Myristica fragrans bark in 1973. Since then, many methodologies have been used for the obtention of DHIE, including classical chemistry synthesis using metal catalysts and biocatalytic synthesis; employing horseradish peroxidase; peroxidase from Cocos nucifera; laccase; culture cells of plants; and microorganisms. Increasing evidence has indicated that DHIE has a wide range of biological activities: anti-inflammatory, anti-oxidant, anti-cancerogenic, and anti-microbial properties. However, evidence in vivo and in human beings is still lacking to support the usefulness potential of DHIE as a therapeutic agent. This study's review was created by searching for relevant DHIE material on websites such as Google Scholar, PubMed, SciFinder, Scholar, Science Direct, and others. This reviews the current state of knowledge regarding the different synthetical routes and biological applications of DHIE.

Anti-inflammatory activity of Jefea gnaphalioides (a. gray), Astereaceae.

BACKGROUND: Inflammation is a symptom associated with many diseases. This symptom is treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Natural products are an alternative source of new compounds with anti-inflammatory activity. Jefea gnaphalioides (Astereaceae) (A. Gray) is a plant species used to treat inflammatory problems, in Mexico. This study determined the anti-inflammatory activity and the composition of the methanol extract of Jefea gnaphalioides (MEJG). METHODS: The extract was obtained by heating the plant in methanol at boiling point for 4 h, and then the solvent was evaporated under vacuum (MEJG). The derivatization of the extract was performed using Bis-(trimethylsilyl) trifluoroacetamide, and the composition was determined by GC-MS. Total Phenols and flavonoids were determined by Folin-Ciocalteu AlCl3 reaction respectively. The antioxidant activity of MEJG was determined by DPPH method. The acute and chronic anti-inflammatory effects were evaluated on a mouse ear edema induced with 12-O-Tetradecanoylphorbol-13-acetate (TPA). Acute oral toxicity was tested in mice at doses of MEJG of 5000, 2500 and 1250 mg/kg. The levels of NO, TNF-α, IL-1ß and IL-6 were determinate in J774A.1 macrophages stimulated by Lipopolysaccharide. The production of inflammatory interleukins was measured using commercial kits, and nitric oxide was measured by the Griess reaction. RESULTS: The anti-inflammatory activity of MEJG in acute TPA-induced ear edema was 80.7 ± 2.8%. This result was similar to the value obtained with indomethacin (IND) at the same dose (74.3 ± 2.8%). In chronic TPA-induced edema at doses of 200 mg/kg, the inhibition was 45.7%, which was similar to that obtained with IND (47.4%). MEJG have not toxic effects even at a dose of 5000 mg/kg. MEJG at 25, 50, 100 and 200 µg/mL decreased NO, TNF-α, IL-1ß and IL-6 production in macrophages stimulated with LPS. The major compounds in MEJG were α-D-Glucopyranose (6.71%), Palmitic acid (5.59%), D-(+)-Trehalose (11.91%), Quininic acid (4.29%) and Aucubin (1.17%). Total phenolic content was 57.01 mg GAE/g and total flavonoid content was 35.26 mg QE/g MEJG had antioxidant activity. CONCLUSIONS: MEJG has anti-inflammatory activity.

Synthesis and highly potent anti-inflammatory activity of licofelone- and ketorolac-based 1-arylpyrrolizin-3-ones.

Since NSAIDs are commonly used anti-inflammatory agents that produce adverse effects, there have been ongoing efforts to develop more effective and less toxic compounds. Based on the structure of the anti-inflammatory pyrrolizines licofelone and ketorolac, a series of 1-arylpyrrolizin-3-ones was synthesized. Also prepared was a series of substituted pyrroles, mimicking similar known anti-inflammatory agents. The anti-inflammatory activity of the test compounds was determined with a phorbol ester (TPA)-induced murine ear edema protocol. For the most active derivatives, 19b-c/20b-c, the anti-inflammatory effect was the same as that of the reference compound (indomethacin) and was dose-dependent. These compounds have an aryl ring at the C-1 position and a methoxycarbonyl group at the C-2 position of the pyrrolizine framework, which represent plausible pharmacophore groups with anti-inflammatory activity. The anti-inflammatory activity of 1-substituted analogs containing a five- or six-membered heterocycles was lower but still good, while that of the pyrroles was only moderate. Although the docking studies suggests that the effect of analogs 19a-c/20a-c is associated with the inhibition of cyclooxygenase-2, experimental assays did not corroborate this idea. Indeed, a significant inhibition of NO was found experimentally as a plausible mechanism of action.

Anti-inflammatory and antinociceptive effects of tilifodiolide, isolated from Salvia tiliifolia Vahl (Lamiaceae).

Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti-inflammatory effects of TFD (0.1-200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The in vivo anti-inflammatory activity of TFD was assessed using the carrageenan-induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced-writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF-α (IC50 = 5.66 µM) and IL-6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti-inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co-administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti-inflammatory activity and in vivo antinociceptive effects.

Cytotoxic activity of the chloroform extract and four diterpenes isolated from Salvia ballotiflora

Abstract New compounds with chemotherapeutic activity are sought after, and plants are an important source of these compounds. Four diterpenes, 19-deoxyicetexone, 7,20-dihydroanastomosine, icetexone and 19-deoxyisoicetexone, were isolated from the hexane-washed chloroform extract of Salvia ballotiflora. The cytotoxic activity of the hexane-washed chloroform extract and its four diterpenes were tested using the MTT assay against three tumor cell lines: HeLa (cervical cancer), A549 (lung cancer) and MCF7 (breast cancer), and two murine cell line: J774A.1 (epithelial cancer) and CT26 (colon cancer), and their IC50 values were determined. 19-Deoxyisoicetexone had the greatest effect on HeLa cells with IC50 of 3.2 µg/ml (9.36 µM), whereas hexane-washed chloroform extract had the best cytotoxic effect on A549 cells with an IC50 of 2.29 µg/ml. These effects of 19-deoxyisoicetexone and hexane-washed chloroform extract were with similar activity compared to cisplatin (IC50 = 1.06 µg/ml in HeLa cells, and 4.6 µg/ml (15.21 µM) in A549 cells).

Anti-inflammatory activity of standardized dichloromethane extract of Salvia connivens on macrophages stimulated by LPS.

CONTEXT: A previous study demonstrated that the chloroform extract of Salvia connivens Epling (Lamiaceae) has anti-inflammatory activity. OBJECTIVE: Identification of the active components in the dicholorometane extract (DESC), and, standardization of the extract based in ursolic acid. MATERIAL AND METHODS: DESC was prepared by percolation with dichlromethane and after washed with hot hexane, its composition was determined by CG-MS and NMR, and standardized by HPLC. The anti-inflammatory activity was tested on acute TPA-induced mouse ear oedema at doses of 2.0 mg/ear. The cell viability of macrophages was evaluated by MTT method, and pro- and anti-inflammatory interleukin levels were measured using an ELISA kit. RESULTS: Ursolic acid, oleanolic acid, dihydroursolic acid and eupatorin were identified in DESC, which was standardized based on the ursolic acid concentration (126 mg/g). The anti-inflammatory activities of DESC, the acid mixture, and eupatorin (2 mg/ear) were 60.55, 57.20 and 56.40% inhibition, respectively, on TPA-induced ear oedema. The IC50 of DESC on macrophages was 149.4 µg/mL. DESC (25 µg/mL) significantly reduced TNF-α (2.0-fold), IL-1ß (2.2-fold) and IL-6 (2.0-fold) in macrophages stimulated with LPS and increased the production of IL-10 (1.9-fold). DISCUSSION: Inflammation is a basic response to injuries, and macrophages are involved in triggering inflammation. Macrophage cells exhibit a response to LPS, inducing inflammatory mediators, and DESC inhibits the biosynthesis of the pro-inflammatory and promote anti-inflammatory cytokines. CONCLUSION: DESC has an anti-inflammatory effect; reduced the levels of IL-1ß, Il-6 and TNF-α; and increases IL-10 in macrophages stimulated with LPS. Ursolic acid is a good phytochemical marker.

Antispasmodic Effects and Action Mechanism of Essential Oil of Chrysactinia mexicana A. Gray on Rabbit Ileum.

The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1-100 µg·mL(-1)) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 µM, potassium chloride (KCl) 60 mM or Bay K8644 1 µM were reduced by EOCM (30 µg·mL(-1)). Apamin 1 µM and charybdotoxin 0.01 µM decreased the inhibition induced by EOCM. The d-cAMP 1 µM decreased the inhibition induced by EOCM. l-NNA 10 µM, Rp-8-Br-PET-cGMPS 1 µM, d,l-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca(2+), Ca(2+)-activated K⁺ channels and cAMP.

Assessment of the anti-protozoal activity of crude Carica papaya seed extract against Trypanosoma cruzi.

In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage).

Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on Lipopolysaccharide-Stimulated Peritoneal Macrophages.

We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF- α ) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases.

Fungicidal properties of the essential oil of Hesperozygis marifolia on Aspergillus flavus link.

The chemical composition of the essential oil from Hesperozygis marifolia was analyzed by gas chromatography-mass spectrometry (GC-MS), and fourteen compounds were identified. (R)-pulegone (40.75%), isomenthone (30.34%) and menthone (4.46%) were found to be the main components of the oil. The essential oil at a concentration of 2.0 mg/mL and (R)-pulegone at concentration of 0.8 mg/mL completely inhibited the growth of Aspergillus flavus Link. The fungicidal effects of this essential oil warrant further research into its potential for commercial use.

Anti-inflammatory evaluation and antioxidant potential of Senna crotalarioides and Penstemon roseus / Evaluación anti-inflamatoria y potencial antioxidante de Senna crotalarioides y Penstemon roseus

Chloroform, methanol and aqueous extracts of Penstemon roseus and Senna crotalarioides were investigated for their anti-inflammatory and antioxidant properties. The aqueous extract had no activity on TPA-induced ear edema, but the chloroform and methanol extracts of both plants caused a significant inhibition of the edema. The chloroform extracts showed activity on carrageenan-induced paw edema and mouse ear edema induced by multiple topical applications of TPA, and only P. roseus (dose of 100 mg/kg) exhibited anti-arthritic activity. The methanol extracts of P. roseus and S. crotalarioides had the most activity in the DPPH and reducing power tests. The LD50 values in mice of both chloroform extracts were considerate as slight acute toxic and higher than the doses used in this study.

Las propiedades antiinflamatorias y antioxidantes de los extractos de cloroformo, metanol y agua de Penstemon roseus y Senna crotalarioides fueron investigadas. El extracto acuoso no tuvo actividad sobre el edema auricular inducido con TPA, pero el extracto de cloroformo y etanol de ambas plantas inhibieron significativamente el edema. El extracto de cloroformo mostró actividad sobre el edema plantar inducido con carragenina y el edema auricular en ratón inducido por múltiples aplicaciones de TPA, y solo P. roseus y S. crotalarioides tuvieron la mejor actividad en las pruebas de DPPH y poder reductor. Los valores de la DL50 en ratón de ambos extractos de cloroformo son considerados con ligera toxicidad aguda y mayores que las dosis empleadas en el estudio.

Chemical composition and antifungal activity of essential oil of Chrysactinia mexicana gray.

The chemical composition of the essential oil of Chysactinia mexicana was analyzed by gas chromatography-mass spectrometry. Seventeen compounds were characterized; eucalyptol (41.3%), piperitone (37.7%), and linalyl acetate (9.1%) were found as the major components. The essential oil of leaves and piperitone completely inhibited Aspergillus flavus growth at relatively low concentrations (1.25 and 0.6 mg/mL, respectively).

Actividad hipoglucemiante de Bouvardia terniflora, Brickellia veronicaefolia y parmentiera edulis / Hypoglycemic activity of Bouvardia terniflora, Brickellia veronicaefolia and parmentiera edulis

Objetivo. Evaluar la actividad hipoglucemiante de los extractos de hexano, cloroformo y metanol de Brickellia veronicaefolia, Bouvardia terniflora y Parmentiera edulis. Material y métodos. Se probaron los extractos de las plantas (100, 200 y 300 mg/kg, vía intraperitoneal) en ratones normoglucémicos y con diabetes inducida con aloxana. Resultados. La administración de 300 mg/kg de los extractos clorofórmicos de P. edulis, B. terniflora y hexánico de B. veronicaefolia en ratones diabéticos disminuye el nivel de glucosa sanguínea en 43.75, 58.56 y 72.13 por ciento, respectivamente. Estos extractos (300 mg/kg), administrados en ratones normoglucémicos, reducen la glucosa sanguínea en 29.61, 33.42 y 39.84 por ciento, respectivamente. Conclusiones. Con este estudio se confirma la actividad hipoglucemiante de estas plantas usadas en la medicina tradicional para el tratamiento de las diabetes