Potential Application of Marine Algae and Their Bioactive Metabolites in Brain Disease Treatment: Pharmacognosy and Pharmacology Insights for Therapeutic Advances.

Seaweeds, also known as edible marine algae, are an abundant source of phytosterols, carotenoids, and polysaccharides, among other bioactive substances. Studies conducted in the past few decades have demonstrated that substances derived from seaweed may be able to pass through the blood-brain barrier and act as neuroprotectants. According to preliminary clinical research, seaweed may also help prevent or lessen the symptoms of cerebrovascular illnesses by reducing mental fatigue, preventing endothelial damage to the vascular wall of brain vessels, and regulating internal pressure. They have the ability to control neurotransmitter levels, lessen neuroinflammation, lessen oxidative stress, and prevent the development of amyloid plaques. This review aims to understand the application potential of marine algae and their influence on brain development, highlighting the nutritional value of this "superfood" and providing current knowledge on the molecular mechanisms in the brain associated with their dietary introduction.

Brown Macroalgae Sargassum cristaefolium Extract Inhibits Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells.

The brown macroalgae Sargassum has been reported for its anti-UV and photoprotective potential for industrial applications. This study evaluated the melanin inhibition activity of Sargassum cristaefolium (SCE) ethanol extract. Melanogenesis inhibition by SCE was assessed in vitro with B16-F10 melanoma cell models and in silico against melanin regulatory proteins Tyrosinase (TYR) and Melanocortin 1 Receptor (MC1R). The regulatory properties evaluated were the melanin content, intracellular tyrosinase activity and cellular antioxidant activities. In addition, the bioactive compounds detected in SCE were subjected to molecular docking against TYR and MC1R. Based on the results, 150 µg/mL SCE effectively inhibited the production of melanin content and intracellular tyrosinase activity. Cellular tyrosinase activity was reduced by SCE-treated cells in a concentration-dependent manner. The results were comparable to the standard tyrosinase inhibitor kojic acid. In addition, SCE effectively decreased the intracellular reactive oxygen species (ROS) levels in B16-F10 cells. The antioxidant properties may also contribute to the inhibition of melanogenesis. In addition, LCMS UHPLC-HR-ESI-MS profiling detected 33 major compounds. The results based on in silico study revealed that the bioactive compound putative kaurenoic acid showed a strong binding affinity against TYR (-6.5 kcal/mol) and MC1R (-8.6 kcal/mol). However, further molecular analyses are needed to confirm the mechanism of SCE on melanin inhibition. Nevertheless, SCE is proposed as an anti-melanogenic and antioxidant agent, which could be further developed into cosmetic skin care products.

Multivariate Analysis Revealed Ultrasonic-Assisted Extraction Improves Anti-Melanoma Activity of Non-Flavonoid Compounds in Indonesian Brown Algae Ethanol Extract.

Indonesia has high biodiversity of algae that are under-utilised due to limitations in the processing techniques. Here, we observed the effect of two different extraction methods (cold maceration and ultrasonic-assisted extraction (UAE)) on multiple variables of Indonesian brown algae ethanol extracts (Sargassum polycystum, Sargassum cristaefolium, Sargassum aquifolium and Turbinaria ornata). The variables observed included metabolites screening by untargeted metabolomics liquid chromatography-high-resolution mass spectrometry (LC-HRMS), observation of total phenolic content (TPC), total flavonoid content (TFC), anti-oxidant and B16-F10 melanoma cells cytotoxicity. UAE extracts had higher extraction yield and TPC, but no TFC difference was observed. UAE extract had more lipophilic compounds, such as fatty acids (Palmitic acid, Oleamide, Palmitoleic acid, Eicosapentaenoic acid, α-Linolenic acid, Arachidonic acid), lipid-derived mediators (11,12-Epoxyeicosatrienoic acid ((±)11(12)-EET)), steroid derivatives (Ergosterol peroxide), lipophilic metabolite (Fucoxanthin), and lipid-soluble vitamins (all-trans-retinol). Principle component analysis (PCA) revealed that TPC, not TFC, in the UAE extracts was correlated with the anti-oxidant activities and cytotoxicity of the extracts towards B16-F10 melanoma cells. This means other non-flavonoid phenolic and lipophilic compounds may have contributed to its bioactivity. These results suggest that out of the two methods investigated, UAE could be a chosen method to extract natural anti-melanogenic agents from brown algae.

The Antiproliferative and Apoptosis-Inducing Effects of the Red Macroalgae Gelidium latifolium Extract against Melanoma Cells.

The red macroalga Gelidium latifolium is widely distributed in the coastal areas of Indonesia. However, current knowledge on its potential biological activities is still limited. In this study, we investigated the potential bioactive compounds in Gelidium latifolium ethanol extract (GLE), and its cytotoxic effects against the murine B16-F10 melanoma cell line. GLE shows high total phenolic content (107.06 ± 17.42 mg GAE/g) and total flavonoid content (151.77 ± 3.45 mg QE/g), which potentially contribute to its potential antioxidant activity (DPPH = 650.42 ± 2.01 µg/mL; ABTS = 557.01 ± 1.94 µg/mL). ESI-HR-TOF-MS analysis revealed large absorption in the [M-H]- of 327.2339 m/z, corresponding to the monoisotopic molecular mass of brassicolene. The presence of this compound potentially contributes to GLE's cytotoxic activity (IC50 = 84.29 ± 1.93 µg/mL). Furthermore, GLE significantly increased the number of apoptotic cells (66.83 ± 3.06%) compared to controls (18.83 ± 3.76%). Apoptosis was also confirmed by changes in the expression levels of apoptosis-related genes (i.e., p53, Bax, Bak, and Bcl2). Downregulated expression of Bcl2 indicates an intrinsic apoptotic pathway. Current results suggest that components of Gelidium latifolium should be further investigated as possible sources of novel antitumor drugs.

Carrageenan delays cell cycle progression in human cancer cells in vitro demonstrated by FUCCI imaging.

BACKGROUND: Carrageenan is a sulfated polysaccharide that exists in red seaweeds recently shown to have anticancer properties. Previous findings show various effects of carrageenan suppressing tumor cell growth. One of the hallmarks of cancer is uncontrolled proliferation, a consequence of loss of normal cell-cycle control, that underlies tumor growth. Recently there is an increasing interest in potential anticancer agents that affect cell cycle in cancer cells. Thus, in this study we investigated the effects of carrageenan on the tumor cell cycle. METHODS: Using human cervical carcinoma cells (HeLa) cells as and human umbilical vein endothelial cells (HUVEC), the cytotoxic effects of kappa carrageenan (k-CO) and lambda carrageenan (λ-CO) at the concentrations of 250-2500 µg/mL were observed. Cell viability was determined using the MTT assay while cell death rates were determined using staining with calcein-AM/propidium iodide. Cell-cycle profile and progression were demonstrated with HeLa cells expressing FUCCI (fluorescence ubiquitination-based cell-cycle indicator) probes (HeLa-FUCCI). RESULTS: Carrageenan had no significant effect on HUVEC (normal cells). In contrast both forms of carrageenan were cytotoxic towards HeLa cells (cancer cells). Furthermore, according to cell-cycle analysis with FUCCI cells, the cell cycle of HeLa cells was delayed in specific phases due to different carrageenan treatments. CONCLUSION: Considering these results, it could be suggested that carrageenan affects the cell-cycle of HeLa cells not only by arresting the cell cycle in specific phases but also by delaying the time needed for the cell to progress through the cell cycle. Additionally, different types of carrageenans have different effects on cell cycle progression. This effect of carrageenan towards cancer cells could possibly be developed into a tumor cell-specific anticancer agent.