Propolis, a resin produced by honeybees, has long been used as a dietary supplement and folk remedy, and more recent preclinical investigations have demonstrated a large spectrum of potential therapeutic bioactivities, including antioxidant, antibacterial, anti-inflammatory, neuroprotective, immunomodulatory, anticancer, and antiviral properties. As an antiviral agent, propolis and various constituents have shown promising preclinical efficacy against adenoviruses, influenza viruses, respiratory tract viruses, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 300 chemical components have been identified in propolis, including terpenes, flavonoids, and phenolic acids, with the specific constituent profile varying widely according to geographic origin and regional flora. Propolis and its constituents have demonstrated potential efficacy against SARS-CoV-2 by modulating multiple pathogenic and antiviral pathways. Molecular docking studies have demonstrated high binding affinities of propolis derivatives to multiple SARS-CoV-2 proteins, including 3C-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), the receptor-binding domain (RBD) of the spike protein (S-protein), and helicase (NSP13), as well as to the viral target angiotensin-converting enzyme 2 (ACE2). Among these compounds, retusapurpurin A has shown high affinity to 3CLpro (ΔG = −9.4 kcal/mol), RdRp (−7.5), RBD (−7.2), NSP13 (−9.4), and ACE2 (−10.4) and potent inhibition of viral entry by forming hydrogen bonds with amino acid residues within viral and human target proteins. In addition, propolis-derived baccharin demonstrated even higher binding affinity towards PLpro (−8.2 kcal/mol). Measures of drug-likeness parameters, including metabolism, distribution, absorption, excretion, and toxicity (ADMET) characteristics, also support the potential of propolis as an effective agent to combat COVID-19.
Lantana camara L. and Lantana montevidensis Briq. (F. Verbenaceae) are invasive ornamental weeds native to the tropical regions of Africa and America. The leaves of both species have been traditionally used as infusions for treating fever, rheumatism, and cancer. LC–MS–MS-guided profiling of the methanolic extracts of the leaves of L. camara and L. montevidensis growing in Egypt led to the putative identification of 59 compounds belonging to terpenoids, flavonoids, iridoid glycosides, phenolic acids, and their derivatives. The in-vitro antioxidants and anti-inflammatory and anticancer activities of the two extracts were investigated. L. camara and L. montevidensis inhibited DPPH• (IC50 = 34.01 ± 1.32 and 47.43 ± 1.74 µg/mL), ABTS+ (IC50 = 30.73 ± 1.42 and 40.37 ± 1.51 µg/mL), and superoxide anion (IC50 = 1.57 ± 0.19 and 1.31 ± 0.14 μg/mL) free radicals. A potent anti-inflammatory effect was observed for both species through the inhibition of elastase release in fMLF/CB-induced human neutrophils (IC50 = 2.40 ± 0.16 and 1.90 ± 0.07 μg/mL). The extracts showed significant cytotoxic activity against a panel of cancer cell lines with the most potent activity against Caco cells (IC50 = 45.65 ± 1.64 and 40.67 ± 1.52 µg/mL for L. camara and L. montevidensis, respectively). Western blotting supported by FACS analysis revealed that the extracts inhibited cancer cell proliferation, reduced metastasis, and induced apoptosis resulting in cell cycle arrest. This was achieved via increasing mRNA and protein expressions of p53 and GSK-3β as well as decreasing the expression of PI3K, Akt, and cyclin D1.
Anastatica hierochuntica L. (Cruciferae) has been known in Egyptian folk medicine as a remedy for gastrointestinal disorders, diabetes and heart diseases. Despite the wide usage, A. hierochuntica research provides insufficient data to support its traditional practice. The cytotoxicity of A. hierochuntica methanolic extract was investigated on acute myeloid leukemia blasts (AML) and normal human peripheral leucocytes (NHPL). The phytochemical identification of bioactive compounds using 1H-NMR and LC-ESI-MS was also performed. A. hierochuntica extract caused non-significant cytotoxicity on NHPL, while the cytotoxicity on AML was significant (IC50: 0.38±0.02 μg/mL). The negative expression of p53, upregulation of Caspase-3 and increase in the BAX/BCL-2 ratio were reported at the protein and mRNA levels. The results suggest that A. hierochuntica extract induced AML cell death via the p53-independent mitochondrial intrinsic pathway and further attention should be paid to this plant as a promising natural anticancer agent.
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