Marine-Derived Components: Can They Be a Potential Therapeutic Approach to Parkinson's Disease?

The increase in the life expectancy average has led to a growing elderly population, thus leading to a prevalence of neurodegenerative disorders, such as Parkinson's disease (PD). PD is the second most common neurodegenerative disorder and is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). The marine environment has proven to be a source of unique and diverse chemical structures with great therapeutic potential to be used in the treatment of several pathologies, including neurodegenerative impairments. This review is focused on compounds isolated from marine organisms with neuroprotective activities on in vitro and in vivo models based on their chemical structures, taxonomy, neuroprotective effects, and their possible mechanism of action in PD. About 60 compounds isolated from marine bacteria, fungi, mollusk, sea cucumber, seaweed, soft coral, sponge, and starfish with neuroprotective potential on PD therapy are reported. Peptides, alkaloids, quinones, terpenes, polysaccharides, polyphenols, lipids, pigments, and mycotoxins were isolated from those marine organisms. They can act in several PD hallmarks, reducing oxidative stress, preventing mitochondrial dysfunction, α-synuclein aggregation, and blocking inflammatory pathways through the inhibition translocation of NF-kB factor, reduction of human tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). This review gathers the marine natural products that have shown pharmacological activities acting on targets belonging to different intracellular signaling pathways related to PD development, which should be considered for future pre-clinical studies.

Saccorhiza polyschides-A Source of Natural Active Ingredients for Greener Skincare Formulations.

The growing knowledge about the harmful effects caused by some synthetic ingredients present in skincare products has led to an extensive search for natural bioactives. Thus, this study aimed to investigate the dermatological potential of five fractions (F1-F5), obtained by a sequential extraction procedure, from the brown seaweed Saccorhiza polyschides. The antioxidant (DPPH, FRAP, ORAC and TPC), anti-enzymatic (collagenase, elastase, hyaluronidase and tyrosinase), antimicrobial (Staphylococcus epidermidis, Cutibacterium acnes and Malassezia furfur), anti-inflammatory (nitric oxide, tumor necrosis factor-α, interleukin-6 and interleukin-10) and photoprotective (reactive oxygen species) properties of all fractions were evaluated. The ethyl acetate fraction (F3) displayed the highest antioxidant and photoprotective capacity, reducing ROS levels in UVA/B-exposed 3T3 fibroblasts, and the highest anti-enzymatic capacity against tyrosinase (IC50 value: 89.1 µg/mL). The solid water-insoluble fraction (F5) revealed the greatest antimicrobial activity against C. acnes growth (IC50 value: 12.4 µg/mL). Furthermore, all fractions demonstrated anti-inflammatory potential, reducing TNF-α and IL-6 levels in RAW 264.7 macrophages induced with lipopolysaccharides. Chemical analysis of the S. polyschides fractions by NMR revealed the presence of different classes of compounds, including lipids, polyphenols and sugars. The results highlight the potential of S. polyschides to be incorporated into new nature-based skincare products.

Antioxidant and antimicrobial potential of six Fucoids from the Mediterranean Sea and the Atlantic Ocean.

BACKGROUD: In recent years, research on the bioactive properties of macroalgae has increased, due to the great interest in exploring new products that can contribute to improve human health and wellbeing. In the present study, the antioxidant and antimicrobial potential of six different brown algae of the Fucales order were evaluated, namely Ericaria selaginoides, Ericaria amentacea, Gongolaria baccata, Gongolaria usneoides, Cystoseira compressa and Sargassum vulgare (collected along the Mediterranean and Atlantic coasts). The antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, the oxygen radical absorbent capacity (ORAC) and the ferric reducing antioxidant power (FRAP) and were related to the total phenolic content (TPC). The antimicrobial activity was evaluated measuring the growth inhibition of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. RESULTS: The highest antioxidant capacity was obtained for Ericaria selaginoides revealing the highest capacity to scavenge DPPH radical [half maximal effective concentration (EC50 ) = 27.02 µg mL-1 ], highest FRAP (1761.19 µmol FeSO4 equivalents g-1 extract), high ORAC (138.92 µmol TE g-1 extract), alongside to its high TPC (121.5 GAE g-1 extract). This species also reported the highest antimicrobial capacity against Staphylococcus aureus [half maximal inhibitory concentration (IC50 ) = 268 µg mL-1 ]. CONCLUSIONS: Among all studied seaweed, Ericaria selaginoides reveals the highest antioxidant and antimicrobial activities, and thus should be explored as a natural food additive and/or functional ingredient. © 2022 Society of Chemical Industry.

Antimicrobial and antileukemic effects: in vitro activity of Calyptranthes grandifolia aqueous leaf extract.

Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemically-resemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.

Neuroprotective potential of Myrciaria plinioides D. Legrand extract in an in vitro human neuroblastoma model.

Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system affecting approximately 30 million individuals worldwide. Mitochondrial dysfunction and oxidative stress have also been implicated in causing neurodegeneration. As life expectancy is increasing, neurodegenerative disorders are becoming a major social issue. None of the drugs currently available for treatment are capable of healing the patient. This means that new molecules should be explored. Plants have been used for treatment of countless medical conditions and extensive research is being carried out on species of the Myrtaceae family, widely used in traditional medicine. To date, Myrciaria plinioides D. Legrand has not been studied for its therapeutic use. To evaluate the neuroprotective effect of aqueous and ethanol extracts of this plant, we investigated the protective effects in human neuroblastoma cells (SH-SY5Y). High-performance liquid chromatography fingerprinting of extracts revealed the presence of phenolic compounds and flavonoids. Extracts showed antioxidant activity in the ORAC, DPPH, FRAP and GAE methods. Ethanol extract presented a strong inhibitory activity toward p38 and JNK3 MAPKs and AChE activity and also toward TNF-α release in human whole blood. None of the extracts significantly affected cell viability; the ethanol extract, however, reversed 6-OHDA-induced toxicity. Particularly the ethanol extract suggests neuroprotective effects by preventing membrane depolarization and by significantly decreasing H2O2 production and caspase-3 activity. The present results indicate that the ethanol extract protects SH-SY5Y cells against oxidative damage and apoptosis, as shown by the antioxidative activity of the extract as well as by the inhibition of important proteins such as caspase-3, p38 and JNK3 and the cytokine TNF-α.

Antioxidant and Neuroprotective Potential of the Brown Seaweed Bifurcaria bifurcata in an in vitro Parkinson's Disease Model.

Bifurcaria bifurcata is a marine brown seaweed mainly found on the Atlantic coast. Herein, we report the antioxidant and neuroprotective activities of seven fractions (F1⁻F7) obtained by normal phase chromatography from the B. bifurcata dichloromethane extract, as well as of its two major isolated diterpenes. Total phenolic content of fractions was determined by the Folin⁻Ciocalteu method, while antioxidant activity was evaluated by the DPPH, ORAC, and FRAP assays. Neuroprotective effects were evaluated in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y), while the mechanisms associated to neuroprotection were investigated by the determination of mitochondrial membrane potential, H2O2 production, Caspase-3 activity, and by observation of DNA fragmentation. Fractions F4 and F5 exhibited the best neuroprotective and antioxidant activities, respectively. F4 fraction prevented changes in mitochondrial potential, and induced a reduction of H2O2 levels production and an increase in cell viability, suggesting that it may contain multi-target compounds acting on different pathways. Hence, this fraction was subjected to purification steps, affording the known diterpenes eleganolone and eleganonal. Both compounds exhibited antioxidant potential, being interesting candidates for further neuroprotective studies.

In vitro activities of Ceiba speciosa (A.St.-Hil) Ravenna aqueous stem bark extract.

Several species of the genus Ceiba (Malvaceae) are ethnopharmacologically used. Thus, this study aimed to investigate the in vitro beneficial properties of the aqueous stem bark extract of Ceiba speciosa. The extract presented a great amount of phenolic compounds (117.4 ± 6.2 mg GAE/g). The antioxidant activity was assessed by DPPH (IC50 = 42.87 µg/mL), ORAC (2351.17 µmol TE/g) and FRAP (235.94 µM FeSO4/g) methods. In addition, the extract reduced MCF-7 cell viability as assessed by MTT. However, it prevented mitochondrial membrane depolarization and reduced caspase-9 activity induced by hydrogen peroxide. In conclusion, these findings indicate the extract is an excellent source of natural antioxidants and is able to protect ROS-induced cell death. Therefore, C. speciosa extract may possess beneficial properties for application in pharmaceutical industry as an antioxidant. However, further studies to better elucidate its mechanisms and to isolate its active compounds are required.

Neuroprotective effects of seaweeds against 6-hydroxidopamine-induced cell death on an in vitro human neuroblastoma model.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. Although the causes of PD pathogenesis remain incomplete, some evidences has suggested that oxidative stress is an important mediator in its pathogenesis. The aim of this study was to evaluate the protective effects of seaweeds with high antioxidant activity on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the human neuroblastoma cell line SH-SY5Y, as well as the associated intracellular signaling pathways. METHODS: Cell viability studies were assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium (MTT) bromide assay and the intracellular signaling pathways analyzed were: hydrogen peroxide (H2O2) production, changes in the mitochondrial membrane potential and Caspase-3 activity. RESULTS: Exposure of SH-SY5Y cells to 6-OHDA (10-1000 µM) reduced cell's viability in a concentration and time-dependent manner. The data suggest that the cell death induced by 6-OHDA was mediated by an increase of H2O2 production, the depolarization of mitochondrial membrane potential and the increase of Caspase-3 activity. Extracts from S. polyshides, P. pavonica, S. muticum, C. tomentosum and U. compressa revealed to efficiently protect cell's viability in the presence of 6-OHDA (100 µM; 24 h). These effects appear to be associated with the reduction of H2O2 cell's production, the protection of mitochondrial membrane's potential and the reduction of Caspase-3 activity. CONCLUSIONS: These results suggest that seaweeds can be a promising source of new compounds with neuroprotective potential.

An Insight into Sargassum muticum Cytoprotective Mechanisms against Oxidative Stress on a Human Cell In Vitro Model.

Sargassum muticum is a brown seaweed with strong potential to be used as a functional food ingredient, mainly due to its antioxidant properties. It is widely used in traditional oriental medicine for the treatment of numerous diseases. Nevertheless, few studies have been conducted to add scientific evidence on its effects as well as on the mechanisms of action involved. In this work, the human cell line MCF-7 was used as an in vitro cellular model to evaluate the capability of Sargassum muticum enriched fractions to protect cells on an oxidative stress condition. The concentration of the bioactive compounds was obtained by vacuum liquid chromatography applied on methanol (M) and 1:1 methanol:dichloromethane (MD) crude extracts, resulting in seven enriched fractions from the M extraction (MF2-MF8), and eight fractions from the MD extraction (MDF1-MDF8). All fractions were tested for cytotoxic properties on MCF-7 cells and the nontoxic ones were tested for their capacity to blunt the damaging effects of hydrogen peroxide-induced oxidative stress. The nontoxic effects were also confirmed in 3T3 fibroblast cells as a nontumor cell line. The antioxidant potential of each fraction, as well as changes in the cell's real-time hydrogen peroxide production, in the mitochondrial membrane potential, and in Caspase-9 activity were evaluated. The results suggest that the protective effects evidenced by S. muticum can be related with the inhibition of hydrogen peroxide production and the inhibition of Caspase-9 activity.

Lymphocyte genotoxicity and protective effect of Calyptranthes tricona (Myrtaceae) against H2O2-induced cell death in MCF-7 cells.

Calyptranthes tricona is a species (Myrtaceae) native to South Brazil. Plants belonging to this family are folkloric used for analgesia, inflammation, and infectious diseases. However, little is known about the toxic potential of C. tricona. The present study aimed to evaluate the antioxidant activity of C. tricona ethanol and hexane leaf extracts, as well as verify their effect on human lymphocytes and MCF-7 cells. The extracts were subjected to preliminary phytochemical screening, antioxidant activity using DPPH and ORAC methods. Genotoxic and mutagenic effects in cultured human lymphocytes were assessed using the comet assay and the micronucleus assay, respectively. In addition, cell viability by MTT assay and fluorometric analysis of mitochondrial potential and caspases-9 activity were performed in order to verify the possible effects of both extracts on H2O2-induced cell death of MCF-7 cells. Our findings revealed that the phenol content and the antioxidant activity were only present in the ethanol extract. Also, the phytochemical screening presented steroids, triterpenoids, condensed tannins, and flavones as the main compounds. However, both extracts were capable of inducing concentration-dependent DNA damage in human lymphocytes. When treating MCF-7 cells with the extracts, both of them inhibited MCF-7 cell death in response to oxidative stress through a decrease of mitochondrial depolarization and caspases-9 activity. Thus, our results need to be considered in future in vitro and in vivo studies of C. tricona effects. In the meanwhile, we recommend caution in the acute/chronic use of this homemade preparation for medicinal purpose.

Neuromodulatory effects of Calyptranthes grandifolia extracts against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells.

Alzheimer's and Parkinson's diseases are neurodegenerative disorders characterized by progressive neuronal dysfunction. Previous studies revealed that some natural products have neuroprotective properties, including species of the Myrtaceae family. However, the neuromodulatory potential of Calyptranthes grandifolia is not clear. In the present study, we examined the ability of the ethanol and hexane leaf extracts of C. grandifolia to prevent 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Initially, we investigated the potential of the extracts to inhibit the neurodegenerative-related enzymes c-Jun N-terminal kinase 3 (JNK3) and acetylcholinesterase (AChE). In addition, SH-SY5Y cell viability was assessed by MTT assay after 100µM 6-OHDA-induced cell damage. In order to verify the possible effects of both extracts on 6-OHDA-induced cell death, hydrogen peroxide generation, mitochondrial potential and caspases-3 activity were assessed. Our findings revealed that ethanol extract exhibited inhibitory activity against JNK3 and AChE. In addition, when co-treating SH-SY5Y cells with 6-OHDA and the extracts, oxidative stress was inhibited by both extracts through a decrease of mitochondrial depolarization and caspases-3 activity. In summary, ethanol and hexane extracts of C. grandifolia have some suppressive property against neurotoxicity induced by 6-OHDA.