Neuroprotective Effects of Propolis: Mechanisms and Evidence
2026-01-04
Propolis, rich in flavonoids, terpenoids, and phenolic compounds, exhibits broad biological and pharmacological activities. Research demonstrates its neuroprotective potential through multiple mechanisms, including antioxidant, anti-inflammatory, anti-apoptotic, and modulation of neurotrophic factors.
Key Mechanisms & Experimental Evidence
The neuroprotective properties are primarily attributed to its potent antioxidant capacity, scavenging free radicals and inhibiting lipid peroxidation critical in neurodegenerative diseases. Shimazawa et al. (2005) showed Brazilian green propolis extract mitigated H₂O₂-induced toxicity in PC12 cells and reduced neuronal damage after cerebral ischemia.
A significant anti-inflammatory effect involves the regulation of nitric oxide (NO) synthesis. Caffeic acid phenethyl ester (CAPE), a key propolis component, inhibits inducible nitric oxide synthase (iNOS) expression. Wei et al. (2004) reported CAPE reduced brain injury in neonatal rats after hypoxia-ischemia, linked to suppressed iNOS and Caspase-1 activation.
Propolis also inhibits apoptosis. Wei et al. (2004) further demonstrated CAPE inhibited hypoxia-ischemia-induced Caspase-3 activation and cytochrome c release. Other studies show propolis flavonoids upregulate anti-apoptotic Bcl-2 while downregulating pro-apoptotic Bax and Caspase-3.
Moreover, propolis modulates signaling pathways and neurotrophic factors. CAPE can inhibit p38 MAPK phosphorylation (Wei, 2008) and upregulate heme oxygenase-1 (HO-1) and brain-derived neurotrophic factor (BDNF) (Kurauchi et al., 2012). Kudo et al. (2015) found propolis-stimulated dental pulp cells secreted increased nerve growth factor (NGF), promoting neurite outgrowth.
Evidence extends across propolis types. Brazilian red propolis hydroalcoholic extract promoted peripheral nerve repair (Barbosa et al., 2016), and a terpene-rich extract reduced anxiety-like behavior in rats (da Silveira et al., 2016).
Conclusion
Propolis and its bioactive components offer multi-target neuroprotection via antioxidative, anti-inflammatory, anti-apoptotic mechanisms, and by enhancing neurotrophic support. This solid scientific foundation highlights its promising role in supporting neurological health.
Reference
- Barbosa RA, Nunes T, da aixao AO, Neto RB, Moura S, Albuquerque RLC, Candido EAF, Padilha FF, Quintans LJ, Gomes MZ (2016) Hydroalcoholic extract of red proplis promotes functional recovery and axon repair after sciatic nerve injury in rats [J]. Pharmaceutical Biology, 54(6):933-1004.
- da Silveira C, Fernandes LMP, Silva ML, Luz DA, Gomes ARQ, Monteiro MC, Machado CS, Torres YR, de Lira TO, Ferreira AG (2016) Neurobehavioral and antioxidant effects of ethanolic extract of yellow propolis [J].Oxidative Medicine and Cellular Longevity, 2016:2906953.
- Kudo D, Inden M, Sekine S, Tamaoki N, Iida K, Naito E, Watanabe K, Kamishina H.Shibata T. HozumiI (2015) Conditioned medium of dental pulp cells stimulated by Chinese propolis show neuroprotection and neurite extension in vitro [J]. Neuroscience Letters, 589:92-97.
- Kurauchi Y, Hisatsune A, Isohama Y, Mishima S, Katsuki H (2012) Caffeic acid phenethylester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor[J]. British Journal of Pharmacology, 166(3):1151-1168.
- Qin YF, Bi DD. (2010) Effects of propolis flavonoids on neuronal apoptosis and the expression of caspase-3, Bcl-2, and Bax in the cerebral cortex following cerebral ischemia-reperfusion in rats. Chinese Journal of Clinicians, 4(7): 1023-1027.
- Shimazawa M, Chikamatsu S, Morimoto N, Mishima S, Nagai H, Hara H(2005) Neuroprotection by Brazilian green propolis against in vitro and in vivo ischemic neuronal damage [J]. Evidence-Based Complementary and Alternative Medicine, 2(2):201-207.
- Wei X, Ma Z, Fontanilla CV, Zhao L, Xu ZC, Taggliabraci V, Johnstone BH, Dodel RC, Farlow MR, Du Y (2008) Caffeic acid phenethyl ester prevents cerebellar granule neurons (CGNs) against glutamate-induced neurotoxicity [J]. Neuroscience, 155(4): 1098-1105.
- Wei X, Zhao L, Ma ZZ, Holtzman DM, Yan C, Dodel RC, Hampel H, Oertel W, Farlow MR, Du YS(2004) Caffeic acid phenethyl ester prevents neonatal hypoxic-ischaemic brain injury [J]. Brain, 127(12):26229-2635.
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