The review by authors from the University of Rijeka, Croatia, focused on the neuroprotective potential of leaf extracts of Laurus nobilis, Aronia melanocarpa (black chokeberry extracts), and celastrol, a chemical compound isolated from the root extracts of Tripterygium wilfordii and T. regelii, all known to be enriched with antioxidant polyphenols.
The review concluded the plants offer great antioxidant activity making them promising in terms of their therapeutic potential, but that further research is warranted into these potential benefits. The authors state: “Despite the promising results of numerous in vitro and in vivo studies, their therapeutic potential still seems to be underestimated in science and medicine, especially when compared to their better-known counterparts such as green tea polyphenols, curcumin from turmeric, or resveratrol from grapes.
“We hope that this review is convincing enough to demonstrate the need for further research on the potential benefits of the reviewed plant-derived pharmaceuticals with pronounced antioxidant activity for the treatment of NDDs."
Neurodegenerative diseases (NDDs) and plant-based antioxidants
The progressive loss of neuronal cell structure and function is the hallmark of neurodegenerative diseases (NDDs).
Recent studies demonstrate the neuroprotective effects of natural plant products as well as their ability to lower oxidative stress (OS) and inflammation.
Natural antioxidants are substances like polyphenols, carotenoids, and vitamins C and E that can be found in fruits, vegetables, nuts, and herbs.
The new review explored under-discussed antioxidant and anti-inflammatory properties of the botanicals of Laurus nobilis, Aronia melanocarpa, and celastrol.
The authors state: “Throughout history, people around the world used medicinal plants and their preparations to improve health. Today, many plant species already have an established place in scientific medicine and are used in the treatment of a wide range of health conditions, including NDDs.
“However, the golden field of medicinal plants still hides many secrets and is a great challenge for modern scientific research in discovering new potential phytotherapeutics.”
Laurus nobilis L. (Lauraceae), also known as bay, is a perennial evergreen shrub/tree which is cultivated in many warm regions of the world, with natural populations in southern Europe, especially in the Mediterranean region.
Exploring the benefits of the essential oil extracted from L. nobilis leaves (LNEO), a previous study found that it exhibited beneficial functions, such as antibacterial, antifungal, and antioxidant activities. Recent pharmacological studies have demonstrated an anti-acetylcholinesterase property of LNEO, and laurel bay extracts have also been found to have antioxidant properties.
The polyphenolic profile of LNEO contains substances from the flavonol classes, with kaempferol and quercetin glycosides making up the majority.
Quercetin has been shown to have protective effects in the treatment of NDDs in both in vitro and in vivo studies. By reducing OS, inflammation, and promoting neurogenesis, quercetin works as an efficient therapeutic agent for several NDDs. Additionally, it has been reported to be capable of reversing cognitive decline and enhancing memory function as people age.
The report also includes that the antioxidant activity of quercetin is significantly influenced by the presence of a specific number of free hydroxyl groups in its chemical structure, and notes that the ability of quercetin to chelate metals and its direct and indirect antioxidant activity both contribute significantly to the reduction of ROS-induced neuronal injury.
However, the authors of the review note that in future research of Laurus nobilis, the focus should be on improved drug delivery systems to increase bioavailability, further clinical trials to determine the effective dose for the treatment of NDD, additional analysis of the distribution of quercetin metabolites in the central nervous system (CNS) of experimental models of NDDs, and in vivo toxicity profiles to evaluate neurotoxic effects.
Aronia melanocarpa (Rosaceae)
The Rosaceae plant family is one of the largest families of flowering plants, with over 3000 species worldwide. It includes Aronia melanocarpa, which is specifically known for its small, white flowers and edible fruits that are rich in antioxidants and vitamins. The functional components of Aronia berry have been found to consist of nutrients, fiber, and sorbitol, while organic acids, proteins, and lipids are responsible for the quality and stability of this fruit.
Aronia berry has been well-researched for its numerous health benefits, which are mainly attributed to its high content of polyphenols, including anthocyanins and proanthocyanidins. Anthocyanins are powerful antioxidants that protect the plant from OS and free radical damage, while proanthocyanidins, which are believed to have numerous health benefits for humans, also have antioxidant properties that have been demonstrated to protect the body from OS and free radical damage. The authors hypothesise: “The anti-inflammatory effects of proanthocyanidins may be responsible for improving cardiovascular health by increasing blood vessel flexibility and reducing oxidative damage to LDL cholesterol.”
The report referenced past studies that suggest that Aronia berry may help improve cognitive function and memory. In a memory impairment study model in mice, Aronia extract attenuated scopolamine-induced learning and memory impairment through decreased hippocampal AChE levels, and increased hippocampal BDNF and p-CREB expression.
Additionally, in an aged rat study, aronia fruit juice was found to have a neuroprotective effect by improving cognitive and locomotor functions, by increasing the density of nerve fibers in the perforant path of this brain region.
Several human intervention studies with Aronia supplementation were referenced, yet the report notes that few of them addressed CNS effects. However, in one study, the intake of Aronia extract supplementation showed a positive effect on cognitive performance and blood pressure in these at-risk individuals.
With specific reference to the NDD Parkinson’s disease (PD), the authors state: “There is evidence of the protective role of anthocyanins extracted from aronia berry against mitochondrial dysfunction, and because mitochondrial dysfunction plays an important role in the pathogenesis of PD, it is certainly interesting to investigate, in the future, whether there is a potential for the use of Aronia berry and Aronia-derived therapeutics for the prevention and treatment of this disease.”
Celastrol is a bioactive component that can be extracted from several autochthonous Chinese medicinal plants, including T. wilfordii (Lei Gong Tank; Thunder of God Wine) and T. regelii (Regel’s Three-Winged Nut, Yellow Wine).
Its potential therapeutic effects in the treatment of several diseases, including neurological disorders, obesity, diabetes, and cancer, were investigated in recent years. Previous experimental in vivo and in vitro studies have been carried out to examine the therapeutic potential of various NDDs due to their anti-inflammatory and antioxidant properties, as well as their capacity to modulate the immune system.
Previous data reported in the review suggested that the neuroprotection of celastrol could be explained by the inhibition of apoptosis (IAP) proteins due to a decrease in caspase activation (cell regulatory networks controlling inflammation and cell death), inhibition of Aβ production (which disrupts cell function), and modulation of autophagy (the mechanism which controls orderly cell degradation and the recycling of cellular components).
“Plant-Based Antioxidants for Prevention and Treatment of Neurodegenerative Diseases: Phytotherapeutic Potential of Laurus nobilis, Aronia melanocarpa, and Celastrol”
Authors: Kristina Pilipović, Renata Jurišić Grubešić, Petra Dolenec, Natalia Kučić, Lea Juretić and Jasenka Mršić-Pelč