Research Journal of Medicinal Plants1819-34552151-7924Science International10.3923/rjmp.2021.18.28Darmanin-EllulRita AttardEveraldo FenechAnthony Ellul-MicallefRoger 12021151Background and Objective: The Nuclear Factor-κB (NF-κB) family of transcription factors is known to have a central regulatory effect on many physiological processes including the immune response and cell survival. Besides, the modulation of the NF-κB transduction pathway is a principal therapeutic target in cancer and inflammatory disease states. Many natural products have been shown to modulate the transcriptional activity of NF-κB. This research work was aimed at determining the phytochemical content of selected Maltese medicinal plants and investigating their ability to modulate the activity of NF-κB. Materials and Methods: Extracts with different polarities were prepared from Aloe vera L. (Aloaceae), Jasonia bocconei (Brullo) M. Pardo and R. Morales (Asteraceae), Calendula suffruticosa Vahl (Asteraceae) and Ruta bracteosa DC. (Rutaceae). The extracts were studied for the total content of phenols and alkaloids and DPPH free radical-scavenging activity. Further studies were carried out to investigate extract-induced modulation of the transcriptional activity of NF-κB in human embryonic kidney (HEK293) cells that had been stably transfected with an NF-κB-luciferase reporter construct. Results: Extracts from Ruta bracteosa caused increased luciferase activity. Besides, significant positive statistical correlations were found between alkaloidal content, increased luciferase activity and increased EC50 values for DPPH free radical scavenging activity. Conclusion: Polar extracts from Ruta bracteosa with high alkaloidal content exerted increased transcriptional activity of NF-κB. 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