Sargahydroquinoic Acid Research Articles

Sargahydroquinoic Acid from Brown Seaweed Induces Apoptosis in High Glucose Treated-Human Colon Cancer HCT116 Cells

Sargahydroquinoic Acid from Brown Seaweed Induces Apoptosis in High Glucose Treated-Human Colon Cancer HCT116 Cells

The beneficial effects of ethanolic extract of Sargassum serratifolium in DNCB-induced mouse model of atopic dermatitis

Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.

The Role of Sargahydroquinoic Acid and Sargachromenol in the Anti-Inflammatory Effect of Sargassum yezoense.

The anti-inflammatory effect of the ethanol extract of Sargassum yezoense and its fractions were investigated in this study. The ethanol extract exhibited a strong anti-inflammatory effect on lipopolysaccharide-stimulated RAW 264.7 macrophages and effectively suppressed the M1 polarization of murine bone-marrow-derived macrophages stimulated by lipopolysaccharides and IFN-γ (interferon-gamma). Through a liquid-liquid extraction process, five fractions (n-hexane, chloroform, ethyl acetate, butanol, and aqueous) were acquired. Among these fractions, the chloroform fraction (SYCF) was found to contain the highest concentration of phenolic compounds, along with two primary meroterpenoids, sargahydroquinoic acid (SHQA) and sargachromenol (SCM), and exhibit significant antioxidant capacity. It also demonstrated a robust anti-inflammatory effect. A direct comparison was conducted to assess the relative contribution of SHQA and SCM to the anti-inflammatory properties of SYCF. The concentrations of SHQA and SCM tested were determined based on their relative abundance in SYCF. SHQA contributed to a significant portion of the anti-inflammatory property of SYCF, while SCM played a limited role. These findings not only highlight the potential of the chloroform-ethanol fractionation approach for concentrating meroterpenoids in S. yezoense but also demonstrate that SHQA and other bioactive compounds work additively or synergistically to produce the potent anti-inflammatory effect of SYCF.

Sargahydroquinoic acid from Sargassum macrocarpum attenuates TNF-α and UV-induced skin aging in human dermal fibroblasts

Both pro-inflammatory cytokines and ultraviolet (UV) radiation can cause skin aging by reducing collagen synthesis and enhancing the activity of matrix metalloproteinases (MMPs). Sargahydroquinoic acid (SHQA), a meroterpenoid purified from Sargassum macrocarpum, has demonstrated a range of pharmacological properties, including anti-senescence, anti-oxidant and anti-inflammatory. Despite these properties, the protective effect of SHQA against skin aging has not been thoroughly examined. In this study, we investigated the impact of SHQA on collagen and MMPs using human skin fibroblast culture Hs68 subjected to tumor necrosis factor (TNF)-α challenge or UVB irradiation. Our findings reveal that both TNF-α (20 ng/mL) and UVB (10 mJ/cm2) induced mRNA expression and extracellular activity of MMP-2 and MMP-9, which was significantly inhibited by SHQA. While SHQA reduced the MMP-1 mRNA level, its impact on MMP-1 protein levels, both intracellular and extracellular, was not significant. Furthermore, SHQA mitigated the TNF-α-induced reduction in collagen type I alpha 1 (COL1A1), whereas low-dose UVB did not significantly affect COL1A1 protein expression. The inhibition of Akt and p38 signaling pathways by SHQA is implicated in this process. In summary, our findings demonstrate that SHQA effectively attenuates skin aging induced by both TNF-α and low-dose UV irradiation in dermal fibroblasts, through attenuating MMP hyperactivation and maintaining the level of COL1A1. This suggests that SHQA has the potential to serves as a natural skin-protective cosmeceutical ingredient.

Sargahydroquinoic acid isolated from Sargassum serratifolium as inhibitor of cellular basophils activation and passive cutaneous anaphylaxis in mice

Basophils and mast cells are characteristic effector cells in allergic reactions. Sargahydorquinoic acid (SHQA), a compound isolated from Sargassum serratifolium (marine alga), possesses various biochemical properties, including potent antioxidant activities. The objective of the present study was to investigate inhibitory effects of SHQA on the activation of human basophilic KU812F cells induced by phorbol myristate acetate and A23187 (PMACI), a calcium ionophore. Furthermore, we confirmed the inhibitory effects of SHQA on the activation of rat basophilic leukemia (RBL)–2H3 cells induced by compound 48/80 (com 48/80), bone marrow-derived mast cells (BMCMCs) induced by anti-dinitrophenyl(DNP)-immunoglobulin E (IgE)/DNP-bovine serum albumin (BSA), DNP/IgE and on the reaction of passive cutaneous anaphylaxis (PCA) mediated by IgE. SHQA reduced PMACI-induced intracellular reactive oxygen species (ROS) and calcium levels. Western blot analysis revealed that SHQA downregulated the activation of ERK, p38, and NF-κB in a dose-dependent manner. Moreover, SHQA suppressed the production and gene expression of various cytokines, including interleukin (IL)-1 β, IL-4, IL-6, and IL-8 in PMACI-induced KU812F cells and IL-4 and tumor necrosis factor (TNF)- α in com 48/80-induced RBL-2H3 cells. It also determined the inhibition of PMACI, com 48/80- and IgE/DNP-induced degranulation by reducing the release of β -hexosaminidase. Furthermore, it attenuated the IgE/DNP-induced PCA reaction in the ears of BALB/c mice. These results suggest that SHQA isolated from S. serratifolium is a potential therapeutic functional food material for inhibiting effector cell activation in allergic reactions and anaphylaxis in animal model.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

Protective effect of sargahydroquinoic acid against Aβ25–35-evoked damage via PI3K/Akt mediated Nrf2 antioxidant defense system

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. β-Amyloid (Aβ) is widely accepted as the main neurotoxin that triggers mitochondrial-associated oxidative stress, leading to neuronal death in AD. Following our preliminary research on the neuroprotective effects of the brown alga Sargassum serratifolium, its major compounds, including sargaquinoic acid, sargahydroquinoic acid (SHQA), and sargachromenol, were investigated to elucidate the antioxidant and anti-apoptotic properties of Aβ25–35-stimulated PC12 cells. SHQA exhibited the most potent effect on Aβ-induced mitochondrial-associated oxidative stress and apoptosis. In addition, the compound enhanced the expression and translocation of nuclear factor-E2-related factor 2 (Nrf2), while reducing the expression of cytoplasmic Kelch-like ECH-associated protein 1 (Keap1). Furthermore, the compound upregulated the expression of Nrf2-regulated antioxidant enzymes, including HO-1, NQO1, GCLc, GCLm, and TrxR1. Co-treatment with SHQA and LY294002, a specific PI3K inhibitor, inhibited nuclear Nrf2 expression and Akt phosphorylation, demonstrating that SHQA-mediated Nrf2 activation was directly associated with the PI3K/Akt signaling pathway. Mechanistic studies indicate that activation of the PI3K/Akt/Nrf2 pathway is the molecular basis for the neuroprotective effects of SHQA. In silico docking simulation revealed that SHQA established specific interactions with the key amino acid residues of PI3K, Akt, and Nrf2-Keap1 via hydrogen bonding and van der Waals interactions, which may affect the biological capacities of target markers. Overall, this is the first report of this novel mechanism of SHQA as a Nrf2 activator against Aβ-mediated oxidative damage, suggesting that the compound might be a potential agent for the prevention of AD.

Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells.

Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.

Sargahydroquinoic Acid, a Cyclooxygenase-2 Inhibitor, Attenuates Inflammatory Responses by Regulating NF-κB Inactivation and Nrf2 Activation in Lipopolysaccharide-Stimulated Cells.

Sargahydroquinoic acid (SHQA) is a major plastoquinone in Sargassum macrocarpum and has shown the capacity to prevent inflammation and oxidative stress. However, the protective mechanisms were unclear. The molecular mechanisms of SHQA on ameliorating inflammation and oxidative stress have been investigated, using lipopolysaccharide (LPS)-stimulated macrophages. SHQA was isolated and purified from S. macrocarpum and the anti-inflammatory mechanisms were explored using LPS-stimulated murine macrophage RAW 264.7 cells. SHQA did not change the expression of cyclooxygenase-2 (COX-2) but inhibited the activity of COX-2. As a result, SHQA significantly diminished the secretions of nitric oxide (NO), prostaglandin E2 (PGE2), and multiple pro-inflammatory cytokines. LPS-induced activation of nuclear factor-κB (NF-κB) was inhibited by SHQA by preventing the degradation of inhibitor κB-α (IκBα). NF-κB activation was also downregulated by the inhibition of Akt phosphorylation in LPS-stimulated cells. Furthermore, SHQA induced the expression of heme oxygenase 1 via Nrf2 activation. These results indicated that SHQA inhibited LPS-induced expressions of inflammatory mediators via suppressing the Akt-mediated NF-κB pathway as well as upregulating the Nrf2/HO-1 pathway. Our findings suggest that SHQA might be a potential therapeutic agent in various inflammatory diseases.

Sargahydroquinoic acid (SHQA) suppresses cellular senescence through Akt/mTOR signaling pathway.

The effects of sargahydroquinoic acid (SHQA) on cellular senescence and the underlying mechanisms were investigated using human umbilical vascular endothelial cells (HUVECs). SHQA or DMSO was supplemented into the medium. Low dose of H2O2 was used to induce premature senescence. Replicative senescence was achieved by continuously culturing cells until they reached a plateau phase. Senescence biomarkers, including p53, p21, and p16 proteins, and SA-β-Gal activity were measured. Pretreatment of SHQA significantly suppressed the oxidative stress-induced protein expression of p53, p21, and p16, as well as the activity of SA-β-Gal. Additionally, SHQA also delayed the replicative senescence as indicated by an increased population doubling number, reduced protein expression of p53, p21, and p16, as well as a decreased SA-β-Gal activity. SHQA inhibited the phosphorylation of Akt, mTOR, and downstream targets of mTOR, such as p-S6K, which was elevated by premature senescence and replicative senescence. In the absence of senescence stimuli, SHQA also inhibited the Akt/mTOR signaling pathway and promoted autophagy. SHQA suppressed senescence induced by oxidative stress and replication through inhibiting the Akt/mTOR pathway. With the potential of acting as an Akt/mTOR inhibitor, SHQA might be useful for developing anti-ageing therapy.

Density Functional Theory Studies on the Antioxidant Mechanism and Electronic Properties of Some Bioactive Marine Meroterpenoids: Sargahydroquionic Acid and Sargachromanol.

Certain meroterpenoids isolated from brown alga of the genus Sargassum are known to be antioxidant agents. Herein, density functional theory has been performed to analyze the preferred antioxidant mechanism of the two reactive antioxidant compounds derived from the Sargassum genus, that is, Sargahydroquinoic acid and Sargachromanol and some of their derivatives. Their global reactivity descriptors have been calculated to reveal their reactivity as an antioxidant. Molecule 1 is the most reactive antioxidant according to calculated descriptors. The results of molecule 1 are comparable to that of Trolox, suggesting their similar activity. The calculated descriptors are closely matched with experimental pieces of evidence. It has been found that hydrogen atom transfer (HAT) is more favored in gas media. Also, the effect of solvent polarity on the antioxidant activity has been explored for molecule 1. The results disclose that the polarity of the solvent increases the contribution of two other mechanisms, that is, single-electron transfer, followed by proton transfer and sequential proton loss electron transfer.

Sargahydroquinoic Acid in Sargassum Serratifolium Activates Lipid Catabolic Pathways in 3T3-L1 Preadipocytes by Inducing White Adipocyte Browning (P06-108-19)

ObjectivesSargassum serratifolium, a marine brown alga consumed in Asian countries, has shown anti-obesity effect by stimulating white adipose tissue browning. Therefore, the purpose of this study was to investigate lipid catabolic effects of sargahydroquinoic acid (SHQA), which is one of the major bioactive compounds of S. serratifolium by white adipocyte browning effect. MethodsIsolated and purified SHQA from S. serratifolium was used to treat 3T3-L1 preadipocytes to see the effects of lipid catabolism and white adipocyte browning. Glycerol concentration measurement, Oil Red O lipid staining, and triglyceride quantification were conducted to examine the lipid catabolism by SHQA in the 3T3-L1 cells. In addition, real-time PCR and Western Blot assays were used to examine the expressions of genes related with lipid catabolic pathway, mitochondria biogenesis and white adipocyte browning. ResultsSHQA significantly upregulated non-shivering thermogenic gene expressions in 3T3-L1 cells including uncoupling protein 1, peroxisome proliferator-activated receptor γ and PR domain containing 16. SHQA also notably reduced cellular lipid accumulation. Interestingly, peroxisome proliferator-activated receptor (PPAR)γ, which is involved in lipid uptake and adipogenesis was upregulated by SHQA treatment. However, Western Blotting and protein-ligand docking simulation revealed that SHQA activates not only PPARγ but also PPARα and AMP-activated protein kinase (AMPK) α, which are lipid-catabolic proteins. In addition, SHQA treatment markedly elevated lipolysis and the amounts of mitochondria in 3T3-L1 cells. ConclusionsOur results indicate that SHQA may combat obesity and associated metabolic syndromes through lipid catabolic pathways, mitochondria biogenesis and adipocyte browning by activating PPARγ, PPARα, and AMPKα pathways. Funding SourcesThis study was a part of the project, “Development of functional food products with natural materials derived from marine resources” funded by the Ministry of Oceans and Fisheries, Republic of Korea.

Sargahydroquinoic acid, a major compound in Sargassum serratifolium (C. Agardh) C. Agardh, widely activates lipid catabolic pathways, contributing to the formation of beige-like adipocytes

Abstract Sargassum serratifolium (C. Agardh) C. Agardh, a marine brown alga, has been consumed as food and traditional medicine in Asia. Previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (C. Agardh) C. Agardh (MES) stimulated adipose tissue browning and inhibited diet-induced obesity and metabolic syndrome. Sargahydroquinoic acid (SHQA) is a major component in MES. It is investigated whether SHQA is a contributor for the anti-obesity effect of MES and whether SHQA directly acts on adipocytes using 3T3-L1 differentiated under the classical and beige adipocyte-inducing conditions. Interestingly, SHQA notably reduced lipid accumulation despite the upregulation of adipogenic transcription factor PPARγ in adipocytes differentiated under both conditions. Western blotting and protein-ligand docking simulation further revealed that SHQA also activates PPARα and AMPKα, lipid-catabolic proteins. Thus, it is further focused on the signaling pathways mediated by these proteins. SHQA markedly elevated lipolysis and mitochondria number, but paradoxically reduced ATP production. When uncoupled metabolic signaling was examined, SHQA significantly increased UCP1-positive adipocytes as well as beige adipocyte markers. In conclusion, SHQA may activate PPARγ, PPARα, and AMPKα, contributing to the stimulation of lipid catabolic pathways and adipocyte browning. Therefore, SHQA may be used as a novel pharmaceutical agent to combat obesity and associated metabolic syndrome.

In Vitro Evaluation of the Phytopharmacological Potential of Sargassum incisifolium for the Treatment of Inflammatory Bowel Diseases.

Background: Comprised of Crohn’s disease and ulcerative colitis, inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastro-intestinal tract, which often results in severe damage to the intestinal mucosa. This study investigated metabolites from the South African endemic alga, Sargassum incisifolium, as potential treatments for IBD. Phytochemical evaluation of S. incisifolium yielded prenylated toluhydroquinones and toluquinones, from which semi-synthetic analogs were derived, and a carotenoid metabolite. The bioactivities of S. incisifolium fractions, natural products, and semi-synthetic derivatives were evaluated using various in vitro assays. Methods: Sargahydroquinoic acid isolated from S. incisifolium was converted to several structural derivatives by semi-synthetic modification. Potential modulation of IBD by S. incisifolium crude fractions, natural compounds, and sargahydroquinoic acid analogs was evaluated through in vitro anti-inflammatory activity, anti-oxidant activity, cytotoxicity against HT-29 and Caco-2 colorectal cancer cells, and PPAR-γ activation. Results: Sargahydroquinoic acid acts on various therapeutic targets relevant to IBD treatment. Conclusions: Conversion of sargahydroquinoic acid to sarganaphthoquinoic acid increases peroxisome proliferator activated receptor gamma (PPAR-γ) activity, compromises anti-oxidant activity, and has no effect on cytotoxicity against the tested cell lines.

Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents.

Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.

Evaluation of antioxidant activities of various solvent extract from Sargassum serratifolium and its major antioxidant components.

Sargassum serratifolium has been known to contain a high level of meroterpenoids as antioxidant components. We investigated antioxidant activities and active components in various solvent extracts from S. serratifolium. Ethyl acetate, ethanol, and methanol extracts showed relatively strong DPPH, ABTs, and superoxide radical scavenging activities. Hexane and ethyl acetate extract showed the strongest hydroxyl radical and reactive oxygen species (ROS), respectively, scavenging activities. Sargahydroquinoic acid (SHQA), sargachromanol (SCM) and sargaquinoic acid (SQA) were main antioxidant components in S. serratifolium. Ethanol extract showed the highest levels of SHQA, SCM, and SQA which comprised to be 227 ± 6.31 mg/g. SHQA and SCM exhibited stronger antioxidant capacities than SQA based on lower IC50 values in ROS, DPPH, ABTs, and superoxide radical scavenging assays. The result showed that ethanol is the most efficient extracting solvent for the active components from S. serratifolium and the plant has the potential as a natural antioxidant.

Meroterpinoid-rich fraction of the ethanol extract from Sargassum serratifolium suppresses TNF-α-induced monocytes adhesion to vascular endothelium and vascular inflammation in high cholesterol-fed C57BL/6J mice

Sargassum serratifolium has been known to contain high concentration of meroterpinoids as anti-inflammatory compounds. We investigated the protective effects of the meroterpinoid-rich fraction of the ethanol extract from S. serratifolium (MES) on vascular inflammation using tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVECs) and high cholesterol diet (HCD)-fed C57BL/6J mice. The in vitro results showed that MES inhibited the adhesion of monocytes to TNF-α-stimulated HUVECs by reduced levels of cell adhesion molecules, monocyte chemoattractant protein-1, and matrix metalloproteinase-9. Decreased levels of these proteins by MES were associated with down-regulated translocation of nuclear factor kappa B. Active compounds in MES were identified as sargahydroquinoic acid, sargacromenol and sargaquinoic acid based on the inhibition of adhesion molecules. In vivo study, MES supplementation remarkably decreased levels of vascular inflammatory proteins in serum and aorta tissue in HCD-fed mice. These results suggest that MES could be a potential supplement as an anti-atherogenic dietary agent for the prevention of atherosclerosis.

α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitory Activity of Plastoquinones from Marine Brown Alga Sargassum serratifolium.

Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO−-mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid) were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14–14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO−-mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes.

BACE1 inhibitory activity and molecular docking analysis of meroterpenoids from Sargassum serratifolium

A wide range of pharmacological properties of Sargassum spp. extracts and isolated components have been recognized. Although individual meroterpenoids of Sargassum species have been reported to possess strong activity against Alzheimer’s disease (AD), the active compounds of Sargassum serratifolium have not been fully explored. Therefore, we evaluated the anti-AD activity of S. serratifolium extract through enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Three meroterpenoids (sargahydroquinoic acid (1), sargachromenol (2) and sargaquinoic acid (3)) were isolated from S. serratifolium. These compounds showed moderate AChE inhibitory activity, but exhibited potent inhibitory activity against BChE and BACE1 (15.1, 9.4, and 10.4µM for BChE; 4.3, 6.9, and 12.5µM for BACE1, respectively). Kinetic study and molecular docking simulation of these compounds demonstrated that 1 and 3 interacted with both catalytic aspartyl residues and allosteric sites of BACE1, whereas 2 interacted with the allosteric site of BACE1. The results of the present study demonstrate that meroterpenoids from S. serratifolium might be beneficial in the treatment of AD.

Ethanolic extract from Sargassum serratifolium attenuates hyperpigmentation through CREB/ERK signaling pathways in α-MSH-stimulated B16F10 melanoma cells

Hyperpigmentation is an increased deposition of melanin in the skin. The effects of ethanolic extract from the brown alga Sargassum serratifolium (ESS) on melanogenic protein expressions in B16F10 mouse melanoma cells were examined to elucidate its hypopigmenting properties. ESS remarkably reduced melanin synthesis in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. Western blot analysis revealed that ESS attenuated the expression of melanogenic enzymes, tyrosinase, and tyrosinase-related protein 1, by cyclic adenosine monophosphate (cAMP)-responsive element-binding protein (CREB)-mediated downregulation of microphthalmia-associated transcription factor (MITF). ESS inhibited accumulation of cellular cAMP that leads to inhibition of CREB phosphorylation. Moreover, ESS activated extracellular signal-regulated kinase (ERK), but not Akt and other mitogen-activated protein kinases, which is responsible for posttranslational downregulation of MITF. Therefore, ESS attenuated α-MSH-stimulated hyperpigmentation in B16F10 cells through modulation of CREB/ERK signaling pathways. Three antimelanogenic compounds such as sargahydroquinoic acid, sargachromenol, and sargaquinoic acid were identified in ESS depending on inhibition of melanin synthesis. These findings suggest that ESS could be a potential agent in the treatment of hyperpigmentation-related skin disorders.