Navigating Amaryllidaceae Alkaloids: Bridging Gaps and Charting Biosynthetic Territories - A Comprehensive Review.

Amaryllidaceae alkaloid (AAs) biosynthesis has garnered significant attention in recent years, particularly with the commercialisation of galanthamine as a treatment for the symptoms of Alzheimer's disease. A significant amount of research work over the last 8 decades has focused on the understanding of AA biosynthesis, starting from early radiolabelling studies to recent multi-omics analysis with modern biotechnological advancements. Those studies enabled the identification of hundreds of metabolites, the characterisation of biochemical pathway, an understanding of the environmental stimuli, and of the molecular regulation of these pharmaceutically and agriculturally important metabolites. Despite the numerous works there remain significant gaps in understanding their biosynthesis in Amaryllidaceae plants. As such, further research is needed to fully elucidate the metabolic pathway and facilitate their production. This review aims to provide a comprehensive overall summary of the current state of knowledge on AAs biosynthesis, from elicitation of transcription factors expression in the cell nucleus to alkaloid transport in the apoplast, and to highlight the challenges that need to be overcome for further advancement.

Unveiling Amaryllidaceae alkaloids: from biosynthesis to antiviral potential - a review.

Covering: 2017 to 2023 (now)Amaryllidaceae alkaloids (AAs) are a unique class of specialized metabolites containing heterocyclic nitrogen bridging that play a distinct role in higher plants. Irrespective of their diverse structures, most AAs are biosynthesized via intramolecular oxidative coupling. The complex organization of biosynthetic pathways is constantly enlightened by new insights owing to the advancement of natural product chemistry, synthetic organic chemistry, biochemistry, systems and synthetic biology tools and applications. These promote novel compound identification, trace-level metabolite quantification, synthesis, and characterization of enzymes engaged in AA catalysis, enabling the recognition of biosynthetic pathways. A complete understanding of the pathway benefits biotechnological applications in the long run. This review emphasizes the structural diversity of the AA specialized metabolites involved in biogenesis although the process is not entirely defined yet. Moreover, this work underscores the pivotal role of synthetic and enantioselective studies in justifying biosynthetic conclusions. Their prospective candidacy as lead constituents for antiviral drug discovery has also been established. However, a complete understanding of the pathway requires further interdisciplinary efforts in which antiviral studies address the structure-activity relationship. This review presents current knowledge on the topic.

Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases-A Review.

The limited availability of treatments for many infectious diseases highlights the need for new treatments, particularly for viral infections. Natural compounds from seaweed are attracting increasing attention for the treatment of various viral diseases, and thousands of novel compounds have been isolated for the development of pharmaceutical products. Seaweed is a rich source of natural bioactive compounds, including polysaccharides. The discovery of algal polysaccharides with antiviral activity has significantly increased in the past few decades. Furthermore, unique polysaccharides isolated from seaweeds, such as carrageenan, alginates, fucoidans, galactans, laminarians, and ulvans, have been shown to act against viral infections. The antiviral mechanisms of these agents are based on their inhibition of DNA or RNA synthesis, viral entry, and viral replication. In this article, we review and provide an inclusive description of the antiviral activities of algal polysaccharides. Additionally, we discuss the challenges and opportunities for developing polysaccharide-based antiviral therapies, including issues related to drug delivery and formulation. Finally, this review highlights the need for further research for fully understanding the potential of seaweed polysaccharides as a source of antiviral agents and for developing effective treatments for viral diseases.

Anti-Melanogenesis and Anti-Photoaging Effects of the Sulfated Polysaccharides Isolated from the Brown Seaweed Padina boryana.

Sulfated polysaccharides isolated from seaweeds are thought of as ideal ingredients in the pharmaceutical, nutraceutical, and cosmetics industries. Our previous study isolated and characterized sulfated polysaccharides from Padina boryana. The sulfated polysaccharides of Padina boryana (PBP) were extracted, and the antioxidant activity of PBP was evaluated. The results indicate that PBP possesses antioxidant effects and potential in the cosmetic industry. To further investigate the potential of PBP in cosmetics, the photoprotective and anti-melanogenesis effects of PBP were evaluated. The anti-melanogenesis test results display that PBP reduced the melanin content in the murine melanoma cells stimulated by alpha melanocyte-stimulating hormone from 203.7% to 183.64%, 144.63%, and 127.57% at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL, respectively. The anti-photodamage test results showed that PBP significantly protected skin cells against UVB-stimulated photodamage. PBP suppressed human epidermal keratinocyte (HaCaT cell) death by inhibiting apoptosis and reducing the level of intracellular reactive oxygen species. The intracellular reactive oxygen species level of HaCaT cells irradiated by UVB was reduced from 192.67% to 181.22%, 170.25%, and 160.48% by 25 µg/mL, 50 µg/mL, and 100 µg/mL PBP, respectively. In addition, PBP remarkably reduced UVB-induced human dermal fibroblast damage by suppressing oxidative damage, inhibiting collagen degradation, and attenuating inflammatory responses. These results indicate that PBP possesses photoprotective and anti-melanogenesis activities and suggest that PBP is a potential ingredient in the cosmetic industry.

Recent Reports on Bioactive Compounds from Marine Cyanobacteria in Relation to Human Health Applications.

The ocean is a valuable natural resource that contains numerous biologically active compounds with various bioactivities. The marine environment comprises unexplored sources that can be utilized to isolate novel compounds with bioactive properties. Marine cyanobacteria are an excellent source of bioactive compounds that have applications in human health, biofuel, cosmetics, and bioremediation. These cyanobacteria exhibit bioactive properties such as anti-inflammatory, anti-cancer, anti-bacterial, anti-parasitic, anti-diabetic, anti-viral, antioxidant, anti-aging, and anti-obesity effects, making them promising candidates for drug development. In recent decades, researchers have focused on isolating novel bioactive compounds from different marine cyanobacteria species for the development of therapeutics for various diseases that affect human health. This review provides an update on recent studies that explore the bioactive properties of marine cyanobacteria, with a particular focus on their potential use in human health applications.

Marine Algal Polyphenols as Skin Protective Agents: Current Status and Future Prospectives.

The skin is the outermost anatomical barrier, which plays a vital role in the maintenance of internal homeostasis and protection against physical, chemical, and biological detractors. Direct contact with various stimuli leads to several physiological changes that are ultimately important for the growth of the cosmetic industry. Due to the consequences of using synthetic compounds in skincare and cosmeceutical-related industries, the pharmaceutical and scientific communities have recently shifted their focus to natural ingredients. The nutrient-rich value of algae, which are some of the most interesting organisms in marine ecosystems, has attracted attention. Secondary metabolites isolated from seaweeds are potential candidates for a wide range of economic applications, including food, pharmaceuticals, and cosmetics. An increasing number of studies have focused on polyphenol compounds owing to their promising biological activities against oxidation, inflammation, allergies, cancers, melanogenesis, aging, and wrinkles. This review summarizes the potential evidence of the beneficial properties and future perspectives of using marine macroalgae-derived polyphenolic compounds for advancing the cosmetic industry.

The Role of Seaweed Polysaccharides in Gastrointestinal Health: Protective Effect against Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a prominent global public health issue. Anti-inflammatory medications, immunosuppressants, and biological therapies are currently used as treatments. However, they are often unsuccessful and have negative consequences on human health. Thus, there is a tremendous demand for using natural substances, such as seaweed polysaccharides, to treat IBD's main pathologic treatment targets. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae, and fucoidan in brown algae. These are effective candidates for drug development and functional nutrition products. Algal polysaccharides treat IBD through therapeutic targets, including inflammatory cytokines, adhesion molecules, intestinal epithelial cells, and intestinal microflora. This study aimed to systematically review the potential therapeutic effects of algal polysaccharides on IBD while providing the theoretical basis for a nutritional preventive mechanism for IBD and the restoration of intestinal health. The results suggest that algal polysaccharides have significant potential in complementary IBD therapy and further research is needed for fully understanding their mechanisms of action and potential clinical applications.

Sarcopenia; functional concerns, molecular mechanisms involved, and seafood as a nutritional intervention - review article.

The fundamental basis for the human function is provided by skeletal muscle. Advancing age causes selective fiber atrophy, motor unit loss, and hybrid fiber formation resulting in hampered mass and strength, thus referred to as sarcopenia. Influence on the loss of independence of aged adults, contribute toward inclined healthcare costs conveys the injurious impact. The current understating of age-related skeletal muscle changes are addressed in this review, and further discusses mechanisms regulating protein turnover, although they do not completely define the process yet. Moreover, the reduced capacity of muscle regeneration due to impairment of satellite cell activation and proliferation with neuronal, immunological, hormonal factors were brought into the light of attention. Nevertheless, complete understating of sarcopenia requires disentangling it from disuse and disease. Nutritional intervention is considered a potentially preventable factor contributing to sarcopenia. Seafood is a crucial player in the fight against hunger and malnutrition, where it consists of macro and micronutrients. Hence, the review shed light on seafood as a nutritional intrusion in the treatment and prevention of sarcopenia. Understanding multiple factors will provide therapeutic targets in the prevention, treatment, and overcoming adverse effects of sarcopenia.

Antioxidant and anti-photoaging effects of a fucoidan isolated from Turbinaria ornata.

Fucoidans isolated from brown seaweeds are potential ingredients in the cosmetic industry. In our preosvious study, a fucoidan was isolated from the brown seaweed Turbinaria ornata (TO-F10) and the anti-inflammatory effect of TO-F10 was evaluated. In order to further explore the potential of TO-F10 in cosmetics, in the present study, antioxidant and photoprotective effects of TO-F10 were investigated. TO-F10 remarkably protected Vero cells against AAPH-stimulated cell death by reducing apoptosis via scavenging intracellular reactive oxygen species (ROS). In addition, TO-F10 increased the survival rate of AAPH-treated zebrafish by suppressing oxidative stress displayed in reducing the levels of ROS, cell death, and lipid peroxidation. Furthermore, TO-F10 effectively attenuated UVB-induced in vitro and in vivo photodamage. TO-F10 increased the viability of UVB-irradiated human keratinocytes via suppressing apoptosis by reducing the intracellular ROS level. Besides, TO-F10 effectively attenuated in vivo photodamage stimulated by UVB irradiation via inhibiting oxidative stress and inflammatory response in zebrafish. These results demonstrate that TO-F10 possesses in vitro and in vivo antioxidant and photoprotective effects, and suggest TO-F10 is a potential ingredient in the cosmetic industry.

A Review on Fucoidan Structure, Extraction Techniques, and Its Role as an Immunomodulatory Agent.

Functional ingredients for human health have recently become the focus of research. One such potentially versatile therapeutic component is fucose-containing sulfated polysaccharides (FCSPs), referred to as fucoidans. The exploitation of marine brown algae provides a rich source of FCSPs because of their role as a structural component of the cell wall. Fucoidans are characterized by a sulfated fucose backbone. However, the structural characterization of FCSPs is impeded by their structural diversity, molecular weight, and complexity. The extraction and purification conditions significantly influence the yield and structural alterations. Inflammation is the preliminary response to potentially injurious inducements, and it is of the utmost importance for modulation in the proper direction. Improper manipulation and/or continuous stimuli could have detrimental effects in the long run. The web of immune responses mediated through multiple modulatory/cell signaling components can be addressed through functional ingredients, benefiting patients with no side effects. In this review, we attempted to address the involvement of FCSPs in the stimulation/downregulation of immune response cell signaling. The structural complexity and its foremost influential factor, extraction techniques, have also attracted attention, with concise details on the structural implications of bioactivity.

Eckmaxol Isolated from Ecklonia maxima Attenuates Particulate-Matter-Induced Inflammation in MH-S Lung Macrophage.

Airborne particulate matter (PM) originating from industrial processes is a major threat to the environment and health in East Asia. PM can cause asthma, collateral lung tissue damage, oxidative stress, allergic reactions, and inflammation. The present study was conducted to evaluate the protective effect of eckmaxol, a phlorotannin isolated from Ecklonia maxima, against PM-induced inflammation in MH-S macrophage cells. It was found that PM induced inflammation in MH-S lung macrophages, which was inhibited by eckmaxol treatment in a dose-dependent manner (21.0−84.12 µM). Eckmaxol attenuated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in PM-induced lung macrophages. Subsequently, nitric oxide (NO), prostaglandin E-2 (PGE-2), and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were downregulated. PM stimulated inflammation in MH-S lung macrophages by activating Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. Eckmaxol exhibited anti-inflammatory properties by suppressing the activation of TLRs, downstream signaling of NF-κB (p50 and p65), and MAPK pathways, including c-Jun N-terminal kinase (JNK) and p38. These findings suggest that eckmaxol may offer substantial therapeutic potential in the treatment of inflammatory diseases.

Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CLpro and PLpro.

A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PLpro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CLpro and PLpro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CLpro and PLpro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CLpro and PLpro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CLpro and PLpro of SARS-CoV-2.

Clionasterol-Rich Fraction of Caulerpa racemosa against Particulate Matter-Induced Skin Damage via Inhibition of Oxidative Stress and Apoptosis-Related Signaling Pathway.

The increasing airborne particulate matter (PM) consisting of environmental contaminants such as dust, aerosols, and fibers has become a global concern by causing oxidative stress that leads to apoptosis and skin damage. The current study evaluated the protective effect of Caulerpa racemosa (CR) against PM-induced skin damage using human keratinocytes and a zebrafish model. The clionasterol-rich hexane fraction (CRHF2) of CR exhibited superior protective activity through downregulating intracellular reactive oxygen species levels and mitochondrial ROS levels, as well as the PM-induced increase in apoptotic body formation and upregulation of apoptotic signaling pathway proteins, along with sub-G1 cell accumulation dose-dependently. Furthermore, in vivo results showed that CRHF2 potentially downregulates PM-induced cell death, ROS, and NO production in the zebrafish model. Hence, the results evidenced that the protective effect of CRHF2 is caused by inhibiting oxidative stress and mitochondrial-mediated apoptosis in cells. Therefore, C. racemosa has the potential to be used in the development of pharmaceuticals to attenuate PM-induced skin diseases.

Anti-Fine Dust Effect of Fucoidan Extracted from Ecklonia maxima Laves in Macrophages via Inhibiting Inflammatory Signaling Pathways.

Brown seaweeds contain fucoidan, which has numerous biological activities. Here, the anti-fine-dust activity of fucoidan extracted from Ecklonia maxima, an abundant brown seaweed from South Africa, was explored. Fourier transmittance infrared spectroscopy, high-performance anion-exchange chromatography with pulsed amperometric detection analysis of the monosaccharide content, and nuclear magnetic resonance were used for the structural characterization of the polysaccharides. The toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were evaluated. The results revealed that E. maxima purified leaf fucoidan fraction 7 (EMLF7), which contained the highest sulfate content, showed the best anti-inflammatory activity by attenuating the TLR-mediated NF-κB/MAPK protein expressions in the particulate matter-stimulated cells. This was solidified by the successful reduction of Prostaglandin E2, NO, and pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß. The current findings confirm the anti-inflammatory activity of EMLF7, as well as the potential use of E. maxima as a low-cost fucoidan source due to its abundance. This suggests its further application as a functional ingredient in consumer products.

Antioxidant potential of low molecular weight fucoidans from Sargassum autumnale against H2O2-induced oxidative stress in vitro and in zebrafish models based on molecular weight changes.

In this study, we investigated the potential antioxidant abilities of low-molecular weight fucoidans from enzyme-assisted hydrolysates of Sargassum autumnale, based on molecular weight changes, in vitro and in vivo. The yield and free radical-scavenging activities of enzyme-assisted hydrolysates of S. autumnale were screened. The protamex-assisted hydrolysate of S. autumnale (SAP) presented the highest yield and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging activity; therefore, it was chosen for fucoidan purification. Three fucoidan fractions were observed in SAP, and their antioxidant activity was assessed. Fucoidan fraction 3 of protamex-assisted hydrolysate of S. autumnale (SAPF3) offered significant protection against H2O2-induced oxidative stress, and was structurally and physically similar to commercial fucoidan. Fucose and low-molecular weight fucoidans were highly concentrated in SAPF3. The results of our study show that SAPF3, a low-molecular weight fucoidan from S. autumnale, possesses strong antioxidant properties and may be an effective alternative to antioxidant agents in the functional food industry.

Dietary fucoidan from a brown marine algae (Ecklonia cava) attenuates lipid accumulation in differentiated 3T3-L1 cells and alleviates high-fat diet-induced obesity in mice.

Fucoidan from marine algae is used as a functional ingredient in the food. Here, we purified fucoidan fractions from a crude polysaccharide obtained after the crude polysaccharide of celluclast-assisted hydrolysate from Ecklonia cava (ECC). We evaluated the effect of ECC on lipid accumulation in differentiated 3T3-L1 adipocytes and investigated its anti-obesity effects in vivo in high-fat diet (HFD)-induced obese mice. In vitro Oil Red O staining revealed that treatment with ECC and its purified fucoidan fractions of celluclast assisted hydrolysate from Ecklonia cava (ECFs) remarkably reduced lipid accumulation in 3T3-L1 cells. ECF3 contained the highest contents of polysaccharides and sulfate compared with other fucoidan fractions. ECF3 treatment significantly reduced lipid accumulation in 3T3-L1 cells. Oral administration of ECC significantly reduced body weight, body weight gain, serum lipid content, and total white adipose tissue mass. Histological analysis revealed that ECC reduced lipid accumulation in EAT and liver tissues. Our findings suggest that the anti-obesity effects of ECC are associated with suppressing lipid accumulation in white adipose tissues and increased energy expenditure by upregulating the expression of thermogenic UCP1 and UCP3 in BAT. These results indicate that ECC and its ECFs possess anti-obesity properties and can be used in food and nutraceutical industries.

Sargachromenol Purified from Sargassum horneri Inhibits Inflammatory Responses via Activation of Nrf2/HO-1 Signaling in LPS-Stimulated Macrophages.

In this study, we isolated sargachromenol (SC) from Sargassum horneri and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. SC did not show cytotoxicity at all concentrations and effectively increased the cell viability by reducing the nitric oxide (NO) and intracellular reactive oxygen species (ROS) production in LPS-stimulated RAW 264.7 macrophages. In addition, SC decreased the mRNA expression levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and inflammatory mediators (iNOS and COX-2). Moreover, SC suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and mitogen-activated protein kinase (MAPK) signaling, whereas activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling in LPS-stimulated RAW 264.7 macrophages. Interestingly, the anti-inflammatory effect of SC was abolished by the inhibition of HO-1 in LPS-stimulated RAW 264.7 macrophages. According to the results, this study suggests that the antioxidant capacity of SC leads to its anti-inflammatory effect and it potentially may be utilized in the nutraceutical and pharmaceutical sectors.

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression.

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.

Sargachromenol Isolated from Sargassum horneri Inhibits Particulate Matter-Induced Inflammation in Macrophages through Toll-like Receptor-Mediated Cell Signaling Pathways.

Sargassum horneri is an invasive brown seaweed that grows along the shallow coastal areas of the Korean peninsula, which are potentially harmful to fisheries and natural habitats in the areas where it is accumulated. Therefore, the author attempted to evaluate the anti-inflammatory mechanism of Sargachromenol isolated from S. horneri against particulate matter (PM)-stimulated RAW 264.7 macrophages. PM is a potent inducer of respiratory diseases such as lung dysfunctions and cancers. In the present study, the anti-inflammatory properties of Sargachromenol were validated using enzyme-linked immunosorbent assay (ELISA), Western blots, and RT-qPCR experiments. According to the results, Sargachromenol significantly downregulated the PM-induced proinflammatory cytokines, Prostaglandin E2 (PGE2), and Nitric Oxide (NO) secretion via blocking downstream activation of Toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) and MAPKs phosphorylation. Thus, Sargachromenol is a potential candidate for innovation in various fields including pharmaceuticals, cosmeceuticals, and functional food.

Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from Padina boryana as a Potent Protector, Activated via NF-κB/MAPK Pathways and Nrf2/HO-1 Involvement.

Fucosterol is a phytosterol that is abundant in marine brown algae and is a renowned secondary metabolite. However, its ability to protect macrophages against particulate matter (PM) has not been clarified with regard to inflammation; thus, this study aimed to illustrate the above. Padina boryana, a brown algae that is widespread in Indo-Pacific waters, was applied in the isolation of fucosterol. Isolation was conducted using silica open columns, while identification was assisted with gas chromatography-mass spectroscopy (GC-MS) and NMR. Elevated levels of PM led the research objectives toward the implementation of it as a stimulant. Both inflammation and oxidative stress were caused due the fact of its effect. RAW 264.7 macrophages were used as a model system to evaluate the process. It was apparent that the increased NO production levels, due to the PM, were mediated through the inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines (i.e., interleukin-6 (IL-6), interleukin-1 (IL-1ß) and tumor necrosis factor-α (TNF-α), including prostaglandin E2 (PGE2)). Further, investigations provided solid evidence regarding the involvement of NF-κB and mitogen-activated protein kinases (MAPKs) in the process. Oxidative stress/inflammation which are inseparable components of the cellular homeostasis were intersected through the Nrf2/HO-1 pathway. Conclusively, fucosterol is a potent protector against PM-induced inflammation in macrophages and hence be utilized as natural product secondary metabolite in a sustainable manner.