European Journal of Medicinal Chemistry
The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs
Marcelo Franchina • Irlan Almeida Freiresb • Josy Goldoni Lazarinia • Bruno Dias Nania • Marcos Guilhermeda Cunhaa • David Fernando Colonc • Severino Matiasde Alencard • Pedro Luiz Rosalena
a Piracicaba Dental School, Department of Physiological Sciences, University of Campinas, 901 Limeira Ave., 13414-903 Piracicaba, SP, Brazil
b University of Florida College of Dentistry, Department of Oral Biology, 1395 Center Drive, 32610 Gainesville, Florida, United States
c Ribeirão Preto Medical School, Department of Immunology, University of São Paulo, 3900 Bandeirantes Ave., 14049-900 Ribeirão Preto SP, Brazil
d Department of Agri-food Industry, Food, and Nutrition, ‘Luiz de Queiroz’ College of Agriculture, University of São Paulo, Pádua Dias Ave., 13418-900 Piracicaba, SP, Brazil
• There is a close relationship between inflammatory diseases and leukocyte recruitment.
• New anti-inflammatory drugs target a more selective action on neutrophil migration.
• Brazilian propolis is a rich source of anti-inflammatory molecules.
• Compounds isolated from Brazilian propolis inhibit neutrophil migration.
Anti-Inflammatory drugs have been routinely used in the management of acute and chronic inflammatory conditions. Nevertheless, their undesirable side and adverse effects have encouraged the development of more selective, tolerable and efficacious drugs able to modulate the inflammatory process through distinct mechanisms than those of drugs currently available in the market, for instance, inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and transmigration). Natural products, including Brazilian propolis, have been considered a rich source of anti-inflammatory molecules due to a very complex phytochemical diversity. Brazil has at least thirteen distinct types of propolis and many bioactive compounds have been isolated therefrom, such as apigenin, artepillin C, vestitol, neovestitol, among others.
These molecules were proven to play a significant immunomodulatory role through (i) inhibition of inflammatory cytokines (e.g. TNF-α) and chemokines (CXCL1/KC and CXCL2/MIP2); (ii) inhibition of IκBα, ERK1/2, JNK and p38MAPK phosphorylation; (iii) inhibition of NF-κB activation; and (iv) inhibition of neutrophil adhesion and transmigration (ICAM-1, VCAM-1 and E-selectin expression). In this review, we shed light on the new advances in the research of compounds isolated from Brazilian propolis from Apis mellifera bees as potentially novel anti-inflammatory drugs. The compilation of data and insights presented herein may open further avenues for the pharmacological management of oral and systemic inflammatory conditions.
Further research should focus on clinical and acute/chronic toxicological validation of the most promising compounds described in this review.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.