In vitro studies have identified a number of active propolis constituents and potential mechanisms. Generally, antimicrobial and antioxidant activities are related to total phenolic contents ⁽¹⁵⁾. Caffeic acid phenethyl ester (CAPE) and artepillin C are well-known anti-inflammatory components ⁽²⁵⁾. The main active anticancer constituents are CAPE and chrysin ⁽²³⁾. However, all of these constituents possess these other characteristics to some degree and vary with geographic origin.

CAPE specifically inhibits NF-kB ⁽⁴¹⁾. In human breast cancer cells, it also inhibits MDR gene expression, EGFR, and VEGF ⁽²⁰⁾. CAPE decreased malignancy potential of breast cancer stem cells via inhibition of self-renewal, progenitor formation, and clonal growth, and significantly decreased CD44 expression ⁽⁴²⁾. CAPE-initiated S- and G2/M-phase cell-cycle arrests and apoptosis in human cervical cancer lines was associated with increased E2F-1 expression ⁽⁴³⁾.

The flavonoid chrysin demonstrated photoprotective effects by attenuating UVA- and UVB-induced apoptosis, ROS production, and COX-2 expression ⁽⁴⁴⁾. Chrysin inhibits aromatase, an enzyme converting testosterone into estrogen ⁽³⁹⁾, as well as histone deacetylase and HDAC8 enzymatic activity ⁽²³⁾. Chrysin may overcome TNF-related apoptosis-inducing ligand (TRAIL) resistance through Mcl-1 downregulation via STAT3 phosphorylation inhibition ⁽⁴⁵⁾.

The phenolic compound artepillin C is the major constituent that stimulates pungent taste by activating TRPA1 channels ⁽⁴⁷⁾. Immunomodulating effects are attributed to suppression of IL-2, IFN-γ and IL-17 expression in alloreactive CD4 T cells, suggesting potential to treat graft versus host disease ⁽⁴⁸⁾. Artepillin C also sensitizes prostate cancer cells to TRAIL-induced apoptosis by engaging both extrinsic receptor-mediated and intrinsic mitochondrial apoptotic pathways ⁽²¹⁾. In different tumor cell lines, artepillin C and baccharin were more cytotoxic than propolis, without additive or synergistic effects when combined ⁽⁴⁹⁾.

Propolis as a whole modulates key inflammatory mediators of mRNA transcription, inhibiting specific inflammatory cytokines, and blocking NF-kB activation ⁽⁵⁵⁾. Synergy between propolis and temozolomide in human glioblastoma cell lines is also partly attributed to reduced NF-kB activity ⁽¹⁸⁾. Propolis also inhibited proliferation of human leukemia cells via caspase-3 activation ⁽²⁾.

In animal models, propolis promotes wound healing via downregulation of type I allergy and inflammation ⁽²⁵⁾ and modifying fibronectin metabolism ⁽²⁶⁾. Immunomodulatory effects occur through increased toll-like receptor expression and IL-1β and IL-6 production ⁽¹²⁾. Pretreatment with orally-administered propolis extract reduced doxorubicin-induced oxidative damage to heart mitochondria ⁽³⁾. Diabetic hepatorenal damage was attenuated via antioxidant activity including free-radical scavenging, and was more pronounced in ethanol than water extracts ⁽⁵⁶⁾.