Exploring four South African Croton species for potential anti-inflammatory properties: in vitro activity and toxicity risk assessment

Rampa, Khumo M.; Venter, Maryna van de; Koekemoer, Trevor; Swanepoel, Bresler; Venables, Luanne; Hattingh, Anna C.; Viljoen, Alvaro; Kamatou, Guy

doi:10.1016/j.jep.2021.114596

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…Recently, the potential anti-inflammatory properties of four South African Croton species-C. gratissimus, C. pseudopulchellus, C. sylvaticus and C. steenkampianus-was reported. These species demonstrated a high capacity to attenuate NO production with negligible cytotoxicity [39].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the potential anti-inflammatory properties of four South African Croton species— C. gratissimus, C. pseudopulchellus , C. sylvaticus and C. steenkampianus —was reported. These species demonstrated a high capacity to attenuate NO production with negligible cytotoxicity [ 39 ]. Associated with this activity, the phenylpropanoid derivatives obtained from C. velutinus , exhibited concentration-dependent suppressive activity on the production of nitrite and IL-1β by macrophages stimulated with LPS and IFN-γ [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory Effect on Nitric Oxide Release in LPS-Stimulated Macrophages and Free Radical Scavenging Activity of Croton linearis Jacq. Leaves

et al. 2022

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Oxidative stress is an important component of many diseases including cancer, along with inflammatory and neurodegenerative processes. Natural antioxidants have emerged as promising substances to protect the human body against reactive oxygen and nitrogen species. The present study evaluates the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 murine macrophages and the free radical scavenging activity of Croton linearis Jacq. leaves. UPLC-QTOF-MS analysis identified 18 compounds: nine alkaloids with a morphinane, benzylisoquinoline or aporphine nucleus, and nine O-glycosylated-flavonoids with quercetin, kaempferol and isorhamnetin as the aglycones. The crude extract (IC50 21.59 µg/mL) and the n-hexane fraction (IC50 4.88 µg/mL) significantly reduced the NO production in LPS-stimulated macrophages but with relatively high cytotoxicity (CC50 75.30 and CC50 70.12 µg/mL, respectively), while the ethyl acetate fraction also showed good activity (IC50 40.03 µg/mL) without affecting the RAW 264.7 cell viability. On the other hand, the crude extract, as well as the dichloromethane and ethyl acetate fractions, showed better DPPH and ABTS free radical scavenging activities. Considering the chemical composition and the activity observed for Croton linearis leaves, they may be considered a good source of antioxidants to combat oxidative damage-related diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect on Nitric Oxide Release in LPS-Stimulated Macrophages and Free Radical Scavenging Activity of Croton linearis Jacq. Leaves

et al. 2022

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“…Indeed, Bowes et al published a review of the most common targets associated with adverse effect-based drug attrition which has led to the development of various in vitro pharmacological profiling panels used ALTEX, accepted manuscript published July 4, 2022 doi:10.14573/altex.2204281 widely today (Bowes et al, 2012). Examples of the use of NAMs in hazard identification and screening include assessment of hepatoxicity and genotoxicity potential of new anti-inflammatory actives using a Cellomics approach (Rampa et al, 2021) that concluded a potential risk for steatosis and genotoxicity, and a review of PFAS looking at cytotoxicity, biotransformation data and cellular responses at the gene level in placental cell lines, determined the potential for developmental toxicity (Solan and Lavado, 2021).…”

Section: Using Nams Not Rodentsmentioning

confidence: 99%

Ready for regulatory use: NAMs and NGRA for chemical safety assurance

Carmichael

2022

ALTEX

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New Approach Methodologies (NAMs) that do not use experimental animals are, in certain settings, entirely appropriate for assuring the safety of chemical ingredients, although regulatory adoption has been slow. In this opinion article we discuss how scientific advances that utilize NAMs to certify systemic safety are available now and merit broader acceptance within the framework of Next Generation Risk Assessments (NGRA). Introduction to the advancementsThe science of assuring the safe use of chemicals in products for the consumers who use them and the people in factories who work with them, has advanced a great deal since the 1950s when the only tools for determining the safety of chemicals were experimental animals. Over the intervening decades, an inexorable scientific progression has taken place, towards the elimination of animal testing in chemical safety assessments and the introduction of advances from biomedical sciences to focus on better protecting human and environmental health. During the 1980s and 1990s considerable investment into 'alternatives to animal testing' resulted in the development of several new tests for topical toxicity that could reliably predict the results of animal tests. A regulatory framework then grew around the animal tests and these newer 'animal replacements'.The pace of change has, however, recently quickened as advanced methodologies, that can characterize fundamental biological alterations, have been evaluated and implemented in toxicology in a concerted effort to assure safety in a more human-focused and more exposure-relevant way. A key landmark precipitating the change was the publication of the principles outlined in 'Toxicity Testing in the 21 st Century: A Vision and a Strategy' from the National Academy of Sciences and National Research Council of the USA (NRC, 2007). The book opened the door to a new paradigm whereby advances that have been made in systems biology and associated computational modelling, could be used to transform toxicity testing from its historical animal test base to one founded on in vitro and in silico methods that evaluate pathway changes in cells of human origin. Today, many industry, academic and regulatory toxicologists involved in this evolution face a decision point: whether to adopt these new ways, evaluate their use and seek to improve them, or remain wedded to using traditional animal tests (with the associated ethical and scientific issues they pose in modern society). This decision on whether to adopt or not, occurs against the backdrop of generally slow uptake from regulatory agencies in many geographies, that make it difficult to allow such a transition. Indeed, new approach methodologies (NAMs 1 ), which are increasingly used to assure consumer safety of chemicals in cosmetics (SCCS, 2021;Bernauer, et al., 2021;Dent et al., 2018 and, are generally not yet recognized as a valid route to provide the regulatory safety data in many cases, e.g., to fulfil REACH information requirements for occupational and environmental safety, of the s...

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“…gratissimus extract significantly diminished Vero and C3A cell density. It was also noted that a potent dose-dependent increase in lipid content and lysosomal compartment expansion identifies a potential risk, excess lipid within hepatocytes (steatosis) [ 65 ].…”

Section: Toxicitymentioning

confidence: 99%

“…Changes in nuclear morphology and cell ploidy further proved the associated genotoxicity risk and suggests the extract from C . gratissimus may function as an aneugen, affected cell division by interaction with the spindle apparatus and not directly by interacting with DNA [ 65 ].…”

Section: Toxicitymentioning

confidence: 99%

Phylogeny, Phytomedicines, Phytochemistry, Pharmacological Properties, and Toxicity of Croton gratissimus Burch (Euphorbiaceae)

Magwilu

Nguta

Mapenay

et al. 2022

Advances in Pharmacological and Pharmaceutical Sciences

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Croton gratissimus is an important plant in Africa setup and across the globe for its ethnomedicinal uses in managing a wide range of diseases. Its phylogeny, pharmacological properties, ethnomedicinal uses, phytochemistry, and cytotoxicity have been highlighted in various articles and journals. This review article aims to give a comprehensively overviewed literature about Croton gratissimus genus. Authentic literature sources such as books, peer reviewed articles, journals, theses, Google Scholar, Science Direct, and any other validated internet source have been used to develop this review. Croton gratissimus is richly found across different climatic zones because of its ability to adapt to various climatic conditions. It is mainly found in rocky hills as a scrub that is about 12–15 m tall. Its leaves are glossy, green on the top, and silvery underneath. Some of the leaves may look brick red rusty. Croton gratissimus has been explored traditionally to manage a number of diseases among the human race since time immemorial. It has been used to treat different ailments ranging from respiratory tract infections, urinary tract infections, malaria, diabetes, hypertension, dermatological conditions, arthritis, gastrointestinal disorders, fever, sexually transmitted diseases, and infertility. Studies have shown that parts of this plant have antioxidative, antimicrobial, anticholinesterases inhibitory, antidiabetic, antihyperlipidemic, anticonvulsant, antiulcer, antihypertensive, antiproliferative, antiplasmodial, and anti-inflammatory activities. Terpenoids and flavonoids have shown to be the major classes of compounds in this plant. Its toxicity has not been well established; some studies have suggested that Croton gratissimus can cause hepatotoxicity and genotoxicity. More studies are needed to elucidate the compounds and their structures giving this plant a wide range of pharmacological activities, efficacy, safety, and toxicity levels, since the plant has greater ethnomedicinal uses. This would give a great indication of discovering new novelties that can give a breakthrough in drug discovery.

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Exploring four South African Croton species for potential anti-inflammatory properties: in vitro activity and toxicity risk assessment

Cited by 5 publications

References 37 publications

Inhibitory Effect on Nitric Oxide Release in LPS-Stimulated Macrophages and Free Radical Scavenging Activity of Croton linearis Jacq. Leaves

Inhibitory Effect on Nitric Oxide Release in LPS-Stimulated Macrophages and Free Radical Scavenging Activity of Croton linearis Jacq. Leaves

Ready for regulatory use: NAMs and NGRA for chemical safety assurance

Phylogeny, Phytomedicines, Phytochemistry, Pharmacological Properties, and Toxicity of Croton gratissimus Burch (Euphorbiaceae)

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