Neuroprotective Effects of Bromelain on the Common Neurodegenerative Diseases: A Systematic Review

In recent years, neurodegenerative diseases (NDs) have increased around the world and current treatments only provide temporary relief of the symptoms. So, we aimed to investigate the neuroprotective effects and possible mechanisms of bromelain on the main NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple sclerosis (MS). In this systematic review, we followed the PRISMA checklist 2020 guidelines. Embase, PubMed, Web of Science, Scopus, and Cochrane Library were searched for related articles published before August 1, 2023, using the combination of keywords that were derived based on MeSH terms and similar systematic review studies. The required information was extracted from the publications and recorded in Excel form, and the outcome and mechanisms were reviewed. Finally, 17 studies were selected for the investigation. Bromelain alleviates neuroinflammation by downregulating pro-inflammatory cytokines in the central nervous system. Bromelain also neutralizes free radicals and up-regulated levels of endogenous antioxidant enzymes and improves mitochondrial function in neural cells. So, by antioxidant and anti-inflammatory activity, bromelain neutralizes apoptosis and neuronal damage. Moreover, the immune response in the CNS may be regulated by bromelain. apoptosis and neuronal damage. This proteolytic enzyme also reduced beta-amyloid aggregation in AD. In vivo, in vitro, and ex vivo studies revealed that bromelain shows promising neuroprotective effects on NDs by reducing inflammatory factors, and oxidative stress, regulating the immune system, and reducing neurotoxicity. However, more clinical trial studies are needed in this field.