Abstract
BackgroundCroton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative stress related diseases. The present study aimed to evaluate the antioxidant, anti-inflammatory and cytotoxic properties of different extracts from three Croton species.MethodsAcetone, ethanol and water leaf extracts from C. gratissimus, C. pseudopulchellus, and C. sylvaticus were tested for their free radical scavenging activity. Anti-inflammatory activity was determined via the nitric oxide (NO) inhibitory assay on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and the 15-lipoxygenase inhibitory assay using the ferrous oxidation-xylenol orange assay. The cytotoxicity of the extracts was determined on four cancerous cell lines (A549, Caco-2, HeLa, MCF-7), and a non-cancerous African green monkey (Vero) kidney cells using the tetrazolium-based colorimetric (MTT) assay. The potential mechanism of action of the active extracts was explored by quantifying the caspase-3/− 7 activity with the Caspase-Glo® 3/7 assay kit (Promega).ResultsThe acetone and ethanol leaf extracts of C. pseudopulchellus and C. sylvaticus were highly cytotoxic to the non-cancerous cells with LC50 varying between 7.86 and 48.19 μg/mL. In contrast, the acetone and ethanol extracts of C. gratissimus were less cytotoxic to non-cancerous cells and more selective with LC50 varying between 152.30 and 462.88 μg/mL, and selectivity index (SI) ranging between 1.56 and 11.64. Regarding the anti-inflammatory activity, the acetone leaf extract of C. pseudopulchellus had the highest NO inhibitory potency with an IC50 of 34.64 μg/mL, while the ethanol leaf extract of the same plant was very active against 15-lipoxygenase with an IC50 of 0.57 μg/mL. A linear correlation (r<0.5) was found between phytochemical contents, antioxidant, anti-inflammatory and cytotoxic activities of active extracts. These extracts induced differentially the activation of caspases − 3 and − 7 enzymes in all the four cancerous cells with the highest induction (1.83-fold change) obtained on HeLa cells with the acetone leaf extract of C. gratissimus.ConclusionBased on their selective toxicity, good antioxidant and anti-inflammatory activities, the acetone and ethanol leaf extracts of C. gratissimus represent promising alternative sources of compounds against cancer and other oxidative stress related diseases.
Highlights
Croton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative stress related diseases
Antioxidant phytochemicals found in vegetables, fruits and medicinal plants have been reported to be responsible for health benefits such as the prevention and treatment of chronic diseases caused by oxidative stress [5]
The acetone leaf extract of C. gratissimus had the highest total phenolic content (TPC) with 222.29 mgGAE/g whereas the highest total flavonoid content (TFC) was obtained with the acetone and ethanol leaf extracts of C. sylvaticus with 82.76 and 84.54 mgQE/g respectively
Summary
Croton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative stress related diseases. Antioxidants are helpful in reducing and preventing damage caused by free radicals because of their ability to donate electrons, which neutralize the radicals without forming another. This property has led to the hypothesis that antioxidants, with their ability to decrease the level of free radicals, might lessen the radical damage causing chronic diseases, and even radical damage responsible for aging and cancer. Antioxidant phytochemicals found in vegetables, fruits and medicinal plants have been reported to be responsible for health benefits such as the prevention and treatment of chronic diseases caused by oxidative stress [5]. Many antioxidant phytochemicals have been associated with anti-cancer activities, and this includes curcumin from turmeric, genistein from soybean, tea polyphenols from green tea, resveratrol from grapes, sulforaphane from broccoli, isothiocyanates from cruciferous vegetables, silymarin from milk thistle, diallyl sulfide from garlic, lycopene from tomato, rosmarinic acid from rosemary, apigenin from parsley, and gingerol from gingers [6]
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