Two New Chromane Meroditerpenoids with Anti-Neuroinflammatory Potential from a Chinese Collection of the Brown Alga Sargassum siliquastrum

Abstract

Objectives: This study focused on the isolation, structural elucidation, and anti-neuroinflammatory activities of meroditerpenoids from a Chinese collection of the brown alga Sargassum siliquastrum. Methods: A variety of chromatographic methods were applied to isolate compounds from the EtOAc-soluble extract of S. siliquastrum. Their chemical structures were determined by extensive spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS data. The compounds were evaluated for their anti-neuroinflammatory activities against lipopolysaccharide (LPS)-induced inflammatory response in murine BV-2 microglial cells. Results: Two new chromane-type meroditerpenoids, namely 9′-deoxysargachromanol E (1) and 3′,4′-dihydro-4′-hydroxysargachromanol I (2), were isolated from the EtOAc-soluble extract of S. siliquastrum, along with three known analogues (3–5). Compounds 1–4 showed inhibition against LPS-induced nitric oxide (NO) production in BV-2 cells with IC₅₀ values of 19.5, 8.0, 15.1, and 14.3 μM, respectively. Conclusions: Two new chromane meroditerpenoids were identified from the brown alga S. siliquastrum. These meroditerpenoids had promising anti-neuroinflammatory effects in vitro.

Keywords

Brown alga chromane meroditerpenoid structural elucidation anti-neuroinflammatory activity

Introduction

Chromane-type meroterpenoids are a group of natural products consisting of a polyprenyl chain attached to a hydroquinone ring. These metabolites are widely distributed in marine brown algae¹ and particularly abundant in the genus Sargassum (family Sargassaceae).^2–7 Up to now, dozens of chromane meroterpenoids have been obtained from the Sargassum algae, some of these chromanes showed a variety of pharmaceutical functions, such as alleviation of inflammatory response, scavenging of free radicals, and inhibition of Na⁺/K⁺ ATPase and acetylcholinesterase (AChE).^4,8–17 The species S. siliquastrum is frequently encountered in the South-East Asia coastal waters. Previously, antioxidant sargachromanols and analogues have been reported from this species collected in Korea.^4–7 In addition, anti-neuroinflammatory meroditerpenoids named sargasilols A–N have been identified by our group from this species of China Sea.^18,19 Our continuing interest on the chemical diversity of this specimen led to the isolation of another two previously undescribed chromane-type meroditerpenoids, 9′-deoxysargachromanol E (1) and 3′,4′-dihydro-4′-hydroxysargachromanol I (2), along with three known analogues (3–5) (Figure 1). These chromane meroditerpenoids were evaluated for their inhibition against lipopolysaccharide (LPS)-induced inflammatory response in murine BV-2 microglial cells. Herein, we report the isolation, structural elucidation, and biological evaluation of these meroterpenoids.

Figure 1.

Chemical structures of compounds 1–5.

Materials and Methods

General

IR spectra were recorded on an FTIR-850 spectrometer. UV spectra were recorded on a TU 1901 spectrometer. Optical rotations were determined on a PoLAAR 3005 digital polarimeter. NMR spectra (500 or 600 MHz for ¹H and 125 or 150 MHz for ¹³C) were acquired on Bruker Avance Ⅲ NMR spectrometers using tetramethylsilane as an internal standard. (+)-HRESIMS spectra were measured with a Thermo Scientific Q Exactive hybrid quadrupole-Orbitrap mass spectrometer. Column chromatography was performed with Silica gel (200–300 mesh, Qingdao Marine Chemistry Co. Ltd), Sephadex LH-20 (GE Healthcare Biosciences AB), and ODS (50 μm, YMC). Reversed-phase high-performance liquid chromatography (HPLC) was performed using an Agilent 1100 series instrument equipped with a YMC-Pack C₁₈ (10 μm, 250 × 10 mm) column.

Plant Material

The brown alga Sargassum siliquastrum were collected off the coast of Changdao Island, Yantai, China, in August 2019. The species identification was carried out by one of the authors (Zhongmin Sun). A voucher specimen (SY201901) is deposited at the Laboratory of Marine Natural Products Chemistry, Wenzhou Medical University, China.

Extraction and Isolation

The protocols for the extraction and prefractionation were described in the previous work.¹⁸ The air-dried algal material (540 g) was extracted with 95% EtOH at room temperature. The concentrated extract was partitioned between H₂O and EtOAc. Evaporation of EtOAc in vacuo yielded a dark residue of 12.3 g. The EtOAc fraction (12.0 g) was subjected to silica gel vacuum column chromatography, eluted with a stepwise gradient of EtOAc/petroleum ether (PE) (1:15, 1:10, 1:5, 1:3, 1:2, and 1:1), to afford seven fractions (A–G). Fraction C (1.0 g) was separated on a Sephadex LH-20 column, eluting with CH₂Cl₂/MeOH (1:1), to obtain four fractions (C1–C4). Fraction C3 (670.0 mg) was further separated on a silica gel column, eluting with a stepwise gradient of EtOAc/PE (1:15, 1:10, and 1:5), to afford four fractions (C3a–C3d). Fraction C3c (18.6 mg) was purified by semipreparative HPLC, using MeOH/H₂O (75:25) as eluent, to obtain 5 (4.8 mg). Fraction D (2.6 g) was subjected to a Sephadex LH-20 column, eluting with CH₂Cl₂/MeOH (1:1), to afford three fractions (D1–C3). Fraction D2 (612.2 mg) was further separated on an ODS column, eluting with MeOH/H₂O (75:25, 80:20, 85:15, and 90:10), to obtain six fractions (D2a–D2f). Fraction D2d (78.2 mg) was purified by HPLC (MeOH/H₂O, 76:24) to yield 4 (14.2 mg). Fraction D2e (54.7 mg) was purified by HPLC (MeOH/H₂O, 85:15) to afford 1 (5.2 mg). Fraction F (1.2 g) was separated on a Sephadex LH-20 column, eluting with CH₂Cl₂/MeOH (1:1), to afford three fractions (F1–F3). Fraction F2 (450.0 mg) was separated on an ODS column, eluting with MeOH/H₂O (70:30, 75:25, and 80:20), to obtain seven fractions (F2a–F2g). Fraction F2c (23.1 mg) was purified by HPLC (MeOH/H₂O, 73:27) to yield 2 (2.3 mg). Fraction F2e (34.0 mg) was purified by HPLC (MeOH/H₂O, 77:23) to obtain 3 (1.8 mg).

9′-Deoxysargachromanol E (1). Colorless oil; [α]25 D + 14.0 (c 0.1, MeOH); UV (MeOH) λ_max (log ε) 204 (4.60), 296 (3.49) nm; IR (KBr) ν_max 3381, 2926, 2869, 1610, 1472, 1371, 1221, 1099, 997, 850 cm⁻¹; HR-ESI-MS m/z 435.2851 [M + Na]⁺ (Calcd. for C₂₇H₄₀O₃Na, 435.2870); ¹H- and ¹³C-NMR data (CDCl₃): see Table 1.

Table 1.

¹H- and ¹³C-NMR Spectroscopic Data for 1 and 2 (CDCl₃).

	1^a		2^b
Pos.	δ_C (type)	δ_H (J in Hz)	δ_C (type)	δ_H (J in Hz)
2	75.3 (C)		75.4 (C)
3	31.4 (CH₂)	1.79 m; 1.74 m	31.4 (CH₂)	1.78 m; 1.73 m
4	22.5 (CH₂)	2.69 m	22.5 (CH₂)	2.68 m
4a	121.2 (C)		121.2 (C)
5	112.6 (CH)	6.37 d (2.4)	112.6 (CH)	6.38 d (2.5)
6	148.1 (C)		147.8 (C)
7	115.7 (CH)	6.47 d (2.4)	115.7 (CH)	6.48 d (2.5)
8	127.3 (C)		127.3 (C)
8a	145.7 (C)		145.9 (C)
1′	39.5 (CH₂)	1.62 m; 1.54 m	40.1 (CH₂)	1.60 m; 1.54 m
2′	22.1 (CH₂)	2.11 m	17.9 (CH₂)	1.41 m
3′	124.8 (CH)	5.13 t (7.2)	42.3 (CH₂)	1.43 m
4′	134.8 (C)		72.6 (C)
5′	39.5 (CH₂)	2.00 m	41.7 (CH₂)	1.43 m
6′	26.5 (CH₂)	2.11 m	21.5 (CH₂)	1.26 m
7′	128.6 (CH)	5.20 t (6.6)	34.5 (CH₂)	1.64 m; 1.37 m
8′	131.6 (C)		41.4 (CH)	2.69 m
9′	48.1 (CH₂)	2.12 m	214.6 (C)
10′	65.8 (CH)	4.40 dd (13.8, 7.8)	74.3 (CH)	4.87 d (9.5)
11′	127.3 (CH)	5.14 d (7.8)	121.1 (CH)	4.98 d (9.5)
12′	135.0 (C)		140.0 (C)
13′	25.8 (CH₃)	1.72 s	26.0 (CH₃)	1.80 s
14′	18.2 (CH₃)	1.69 s	18.7 (CH₃)	1.86 s
15′	16.1 (CH₃)	1.64 s	16.2 (CH₃)	1.06 d (7.0)
16′	15.7 (CH₃)	1.58 s	27.0 (CH₃)	1.15 s
17′	24.1 (CH₃)	1.25 s	24.1 (CH₃)	1.25 s
18′	16.1 (CH₃)	2.12 s	16.1 (CH₃)	2.11 s

600 MHz for ¹H and 150 MHz for ¹³C

500 MHz for ¹H and 125 MHz for ¹³C.

3′,4′-Dihydro-4′-hydroxysargachromanol I (2). colorless oil; [α]25 D −14.3 (c 0.1, MeOH); UV (MeOH) λ_max (log ε) 203 (4.25), 294 (3.38) nm; IR (KBr) ν_max 3330, 2935, 2868, 1707, 1610, 1468, 1371, 1221 cm⁻¹; HR-ESI-MS m/z 469.2906 [M + Na]⁺ (Calcd. for C₂₇H₄₂O₅Na, 469.2924); ¹H- and ¹³C-NMR data (CDCl₃): see Table 1.

Cell Culture

Murine BV-2 microglia cells were purchased from Cell Culture Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. BV-2 cells were cultured at 37°C with 5% CO₂, in Dulbecco's modified Eagle's medium (DMEM, Gibco) complemented with 10% (v/v) fetal bovine serum (Gibco) and 1% penicillin (Gibco).

MTT Assay

Cell viability was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT; 0.5 mg/mL; Sigma) method. BV-2 cells were seeded in 96-well plates and treated with different compounds for 24 h. MTT solution was added and cultured at 37°C for another 4 h. Then, MTT solution was discarded and dimethyl sulfoxide (DMSO, Sigma) was added to dissolve the formazan crystals. The absorbance at 490 nm was determined on a microplate reader (Thermo Fisher Scientific). The cell viability was calculated using the following formula: cell viability (%) = [OD₄₉₀ (experiment group)/OD₄₉₀ (control group)] × 100%.

Assay for Inhibition Against Nitric Oxide Production

A previously established protocol¹⁸ was employed. BV-2 cells were seeded in 96-well plates (1 × 10⁴ cells/well) and cultured with or without compounds at different concentrations for 4 h. Then, cells were stimulated with LPS (1 μg/mL) for another 24 h. The NO level in the supernatant was detected using the Griess reaction following the manufacturer's instruction (Nanjing Jiancheng Bioengineering Institute). The absorbance value at 540 nm was determined on a microplate reader (Thermo Fisher Scientific).

Statistical Analysis

All bioassays were replicated for three times. The SPSS 20.0 software was used for statistical analysis. Statistical significances were analyzed using a Student's t-test or one-way analysis of variance (ANOVA) for multiple comparisons. P value less than 0.05 (P < 0.05) was considered as statistical significance.

Results

Compound 1 was isolated as a colorless oil. It had a molecular formula of C₂₇H₄₀O₃ as determined by high-resolution electrospray ionization-mass spectrometry (HRESIMS) data (m/z 435.2851 [M + Na]⁺) (Figure S1), requiring eight degrees of unsaturation. The ¹H-NMR spectrum (Figure S2) of 1 showed two aromatic proton signals at δ_H 6.47 (1H, d, J = 2.4 Hz, H-7) and 6.37 (1H, d, J = 2.4 Hz, H-5); three olefinic proton signals at δ_H 5.20 (1H, t, J = 6.6 Hz, H-7′), 5.14 (1H, d, J = 7.8 Hz, H-11′), and 5.13 (1H, t, J = 7.2 Hz, H-3′); an oxygenated methine proton at δ_H 4.40 (1H, dd, J = 13.8, 7.8 Hz, H-10′); and six methyl signals at δ_H 2.12 (3H, s, H₃-18′), 1.72 (3H, s, H₃-13′), 1.69 (3H, s, H₃-14′), 1.64 (3H, s, H₃-15′), 1.58 (3H, s, H₃-16′), and 1.25 (3H, s, H₃-17′). The ¹³C-NMR spectrum (Figure S3) exhibited 27 carbon signals including 12 sp² carbons attributed to a benzene and three double bonds. The assignment of protonated carbons and corresponding protons was based on heteronuclear single quantum coherence (HSQC) spectrum (Figure S4). These NMR data (Table 1) were indicative of a chromane-type meroterpenoid, represented by sargachromanols⁴ and sargasilols^18,19 isolated from the title species. A 2,8-dimethylchroman-6-ol moiety was established by ¹H–¹H correlation spectroscopy (COSY, Figure S5) relationships of H₂-3 (δ_H 1.79, m; 1.74, m) and H₂-4 (δ_H 2.69, m) and heteronuclear multiple bond correlations (HMBC, Figure S6) from the methyl singlet H₃-18′ to C-7 (δ_C 115.7, CH), C-8 (δ_C 127.3, C), and C-8a (δ_C 145.7, C), from H-5 to C-6 (δ_C 148.1, C), C-7 (δ_C 115.7, CH), and C-8a, from H₂-4 to C-5 (δ_C 112.6, CH), C-4a (δ_C 121.2, C), and C-8a, and from the methyl H₃-17′ to an oxygenated nonprotonated carbon C-2 (δ_C 75.3, C), an aliphatic methylene carbon C-3 (δ_C 31.4, CH₂), and a key four-bond correlation to C-8a (Figure 2). The NMR data of the polyprenyl chain were found to be similar to those of the co-occurring analogue sargachromanol E (3).⁴ The only notable difference was the replacement of signals for a secondary alcohol in 3 by signals for an aliphatic methylene in 1. COSY correlation between the oxygenated methine proton (δ_H 4.40, dd, J = 13.8, 7.8 Hz, H-10′) and an olefinic proton (δ_H 5.14, d, J = 7.8 Hz, H-11′) suggested an allylic alcohol. COSY correlations between the oxygenated methine proton H-10′ and a methylene (δ_H 2.12, m, H₂-9′) in combination with HMBC correlations from the olefinic methyls H₃-13′ and H₃-14′ to an olefinic methine carbon C-11′ (δ_C 127.3, CH), from H₃-15′ to an aliphatic methylene carbon C-9′ (δ_C 48.1, CH₂), and from H-10′ to two olefinic nonprotonated carbons C-8′ (δ_C 131.6, C) and C-12′ (δ_C 135.0, C) further assigned the hydroxy group to C-10′ (δ_C 65.8, CH). In addition, the polyprenyl chain was attached to C-2 by HMBC correlations from H₃-17′ to an aliphatic methylene carbon C-1′ (δ_C 39.5, CH₂) and from H₂-2′ (δ_H 2.11, m) to C-2. The configurations at C-2 and C-3′/C-4′ and C-7′/C-8′ double bonds were suggested to be identical to those of 3 based on biogenetic considerations and the similar NMR data, including nuclear Overhauser effect spectroscopy (NOESY, Figure S7) correlations of H₃-16′/H₂-2′ and H₃-15′/H₂-6′, while the configuration at C-10′ remains to be determined. Thus, compound 1 was established as 9′-deoxysargachromanol E (Figure 1).

Figure 2.

COSY and HMBC correlations of 1 and 2.

Compound 2 had a molecular formula of C₂₇H₄₂O₅ as determined by HRESIMS data (m/z 469.2906 [M + Na]⁺) (Figure S8), implying seven degrees of molecular unsaturation. Detailed analysis of 1D- and 2D-NMR spectroscopic data (Figures S9–S14) revealed that 2 had a structure closely related to that of the co-occurring meroterpenoid sargachromanol I (4).⁴ The only difference was loss of signals for a trisubstituted olefinic double bond and the appearance of signals for an oxygenated nonprotonated carbon (δ_C 72.6, C-4′) and an additional methylene (δ_C 42.3, CH₂, C-3′; δ_H 1.43, m, H₂-3′) (Table 1). HMBC correlations from the methyl singlet H₃-16′ (δ_H 1.15, s) to the oxygenated nonprotonated carbon C-4′ and two methylene carbons C-3′ and C-5′ (δ_C 41.7, CH₂) and from the methylene protons H₂-1′ (δ_H 1.60, m; 1.54, m) to the methylene carbon C-3′ revealed that C-4′ in 2 was hydroxylated (Figure 2). The 9′-oxo-10′-hydroxy moiety was confirmed by COSY correlation between the hydroxylated methine proton H-10′ (δ_H 4.87, d, J = 9.5 Hz) and olefinic proton H-11′ (δ_H 4.98, d, J = 9.5 Hz) (Figure 2), as well as HMBC correlations from the methyl doublet H₃-15′ (δ_H 1.06, d, J = 7.0 Hz) and hydroxylated methine H-10′ to the carbonyl carbon C-9′ (δ_C 214.6) and from H₃-13′ (δ_H 1.80, s) and H₃-14′ (δ_H 1.86, s) to the olefinic carbon C-11′ (δ_C 121.1, CH). The configurations at C-2 was suggested to be the same as that of sargachromanol I (4)⁴ based on biogenetic considerations, while the configurations at C-4′, C-8′, and C-10′ remain to be determined. Thus, compound 2 was defined as 3′,4′-dihydro-4′-hydroxysargachromanol I (Figure 1).

In addition, three known meroterpenoids were co-isolated and identified as sargachromanols E (3) and I (4)⁴ and apo-9′-sargachromanol I acid (5)⁶ (Figure 1) by comparison of their spectroscopic data (Figures S15–S20) with literature values.

All compounds were assayed for their inhibitory activities against LPS-stimulated inflammation response in murine BV-2 microglial cells.^20,21 Prior to the bioassay, the cytotoxic effects of 1–5 on BV-2 cells were evaluated by the MTT method. All compounds showed no significant effects on cell viability at a high concentration of 50 μM. At nontoxic concentrations, compounds 1–4 showed inhibition against LPS-induced nitric oxide (NO) production in BV-2 cells with IC₅₀ values of 19.5, 8.0, 15.1, and 14.3 μM, respectively, indicating the promising anti-neuroinflammatory effects, while 5 was weak (IC₅₀> 25 μM) in this assay. Most of the chromane meroterpenoids showed anti-neuroinflammatory activities in the LPS-induced BV2 cells, implying that the conservative 2,8-dimethylchroman-6-ol scaffold is essential and the changes on the polyprenyl chain can affect the activity.

Discussion

Previous studies have reported tens of chromane meroterpenoids, incuding sargachromanols^4–7 and sargasilols,^18,19 from the brown alga S. siliquastrum mainly collected in Korea and China. The present study yielded another two previously undescribed chromane meroditerpenoids, 9′-deoxysargachromanol E (1) and 3′,4′-dihydro-4′-hydroxysargachromanol I (2). By extensive spectroscopic analyses, the chemical structures of 1 and 2 were established to be closely related to those of the known chromanes sargachromanol E (3) and sargachromanol I (4),⁴ respectively, with difference in the oxidation of the polyprenyl chain. This study suggests that the alga S. siliquastrum of China Sea has the potential to produce structurally diverse chromane meroditerpenoids, and thus merits continuous attention to obtain more novel metabolites for drug discovery efforts.

Several previous reports have shown that the marine algae-derived chromane meroterpenoids have significant antioxidant and anti-inflammatory activities.^4–7 However, the potential of these chromanes against neuroinflammatory responses is rarely studied, except our recent reports.^18,19 The present study is another example showing the anti-neuroinflammatory activities of these chromanes in LPS-induced BV-2 microglia cells. In combination with our previous studies,^18,19 the conservative 2,8-dimethylchroman-6-ol scaffold is suggested to be essential for the anti-neuroinflammatory activity, meanwhile, the different polyprenyl chain can affect the activity. This result suggests that the polyprenyl chain can be modified for structural optimization based on chromane scaffold. Since abnormal neuroinflammation has been proved to play a key role in the pathologenesis of various neurodegenerative disorders, such as Alzheimer's and Parkinson's disease,²² the present findings provide a new perspective on the development of therapeutic agents based on chromane meroterpenoids for the treatments of neurodegenerative disorders.

There are some limitations on this study. First, the stereochemistry of two new compounds 1 and 2 could not be established thoroughly, the absolute configuration at C-2 of 1 and 2 was suggested to be R based on biogenetic considerations, while the relative configuration of C-2 to the other stereogenic centers had not been assigned due to the limited amounts of obtained materials. Second, the anti-neuroinflammatory potential of the active compounds 1–4 needs to be confirmed by determination of their effects on other pro-inflammatory factors.

Conclusion

In summary, further phytochemical investigation on the EtOAc-soluble extract of the brown alga S. siliquastrum led to the isolation of another two new chromane meroditerpenoids, 9′-deoxysargachromanol E (1) and 3′,4′-dihydro-4′-hydroxysargachromanol I (2), together with three known analogues including sargachromanols E (3) and I (4) and apo-9′-sargachromanol I acid (5). Compounds 1–4 showed potent inhibitory activities against LPS-induced NO production in BV-2 cells with IC₅₀ values of 8.0–19.5 μM, indicating the promising anti-neuroinflammatory effects. This study enriches the chemical diversity of the alga S. siliquastrum and suggests drug discovery efforts on identification of neuroprotective lead compounds from brown algae resource. These findings also warrant further investigations on the the anti-neuroinflammatory potential of chromane meroterpenoids both in vitro and in vivo and molecular mechanisms after large amounts of materials are available.

Supplemental Material

sj-docx-1-npx-10.1177_1934578X251321614 - Supplemental material for Two New Chromane Meroditerpenoids with Anti-Neuroinflammatory Potential from a Chinese Collection of the Brown Alga Sargassum siliquastrum

Supplemental material, sj-docx-1-npx-10.1177_1934578X251321614 for Two New Chromane Meroditerpenoids with Anti-Neuroinflammatory Potential from a Chinese Collection of the Brown Alga Sargassum siliquastrum by Junzhi Pan, Huayuan Liu, Xiaofeng Xu, Feijing Lv, Yu Qi, Chaojie Wang, Changle Wu, Zhongmin Sun, Gang Xu and Pengcheng Yan in Natural Product Communications

Footnotes

Acknowledgments

We acknowledge the support received from the Wenzhou Key Laboratory of Research and Transformation of Chinese Medicine.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Approval

Ethical approval is not applicable to this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Jinhua City Science and Technology Project, (grant number 2023-3-061).

Statement of Human and Animal Rights

This article does not contain any studies with human or animal subjects.

Statement of Informed Consent

There are no human subjects in this article and informed consent is not applicable.

ORCID iD

Pengcheng Yan

Supplemental Material

Supplemental material for this article is available online.

References

Blunt

Copp

Munro

MHG

, et al. Marine natural products. Nat Prod Rep. 2010;27(2):165–237.

Giriwono

Iskandriati

Tan

, et al. Sargassum seaweed as a source of anti-inflammatory substances and the potential insight of the tropical species: a review. Mar Drugs. 2019;17(10):590. doi:https://doi.org/10.3390/md17100590

Liu

Heinrich

Myers

, et al. Towards a better understanding of medicinal uses of the brown seaweed Sargassum in traditional Chinese medicine: a phytochemical and pharmacological review. J Ethnopharmacol. 2012;142(3):591–619.

Jang

Lee

Choi

, et al. Chromenes from the brown alga Sargassum siliquastrum. J Nat Prod. 2005;68(5):716–723.

Jung

Jang

Kim

, et al. Meroditerpenoids from the brown alga Sargassum siliquastrum. J Nat Prod. 2008;71(10):1714–1719.

Lee

Seo

. Chromanols from Sargassum siliquastrum and their antioxidant activity in HT 1080 cells. Chem Pharm Bull. 2011;59(6):757–761.

Lee

Park

Kim

, et al. Isolation of two new meroterpenoids from Sargassum siliquastrum. Bull Korean Chem Soc. 2014;35(9):2867–2869.

Herath

Kim

Jang

, et al. Mojabanchromanol isolated from Sargassum horneri attenuates particulate matter induced inflammatory responses via suppressing TLR2/4/7-MAPK signaling in MLE-12 cells. Mar Drugs. 2020;18(7):355.

Chung

Jang

Park

, et al. Sargachromanols as inhibitors of Na⁺/K⁺ ATPase and isocitrate lyase. Bioorg Med Chem Lett. 2011;21(7):1958–1961.

10.

Seong

Ali

Kim

, et al. BACE1 Inhibitory activity and molecular docking analysis of meroterpenoids from Sargassum serratifolium. Bioorg Med Chem. 2017;25(15):3964–3970.

11.

Cho

Kang

, et al. Antioxidant activity of mojabanchromanol, a novel chromene, isolated from brown alga Sargassum siliquastrum. J Environ Biol. 2008;29(4):479–484.

12.

Choi

Shin

Chun

, et al. Sargahydroquinoic acid isolated from Sargassum serratifolium as inhibitor of cellular basophils activation and passive cutaneous anaphylaxis in mice. Int Immunopharmacol. 2022;105:108567. doi:https://doi.org/10.1016/j.intimp.2022.108567

13.

Lee

Kang

Lee

, et al. Potent inhibition of acetylcholinesterase by sargachromanol I from Sargassum siliquastrum and by selected natural compounds. Bioorg Chem. 2019;89:103043.

14.

Farrokhnia

. Density functional theory studies on the antioxidant mechanism and electronic properties of some bioactive marine meroterpenoids: sargahydroquionic acid and sargachromanol. ACS Omega. 2020;5(32):20382–20390.

15.

Yoon

Heo

Han

, et al. Anti-inflammatory effect of sargachromanol G isolated from Sargassum siliquastrum in RAW 264.7 cells. Arch Pharm Res. 2012;35(8):1421–1430.

16.

Heo

Jang

, et al. Chromene suppresses the activation of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells. Food Chem Toxicol. 2014;67:169–175.

17.

Lee

Samarakoon

, et al. Preparative isolation of sargachromanol E from Sargassum siliquastrum by centrifugal partition chromatography and its anti-inflammatory activity. Food Chem Toxicol. 2013;62:54–60.

18.

Wang

Zhang

, et al. Anti-neuroinflammatory meroterpenoids from a Chinese collection of the brown alga Sargassum siliquastrum. J Nat Prod. 2023;86(5):1284–1293.

19.

Pan

Liu

, et al. Five new chromane meroterpenoids from the brown alga Sargassum siliquastrum of China sea. Phytochem Lett. 2024;64:133–137.

20.

Chen

Zhang

, et al. Sinusiaetone A, an anti-inflammatory norditerpenoid with a bicyclo[11.3.0]hexadecane nucleus from the Hainan soft coral Sinularia siaesensis. Org Lett. 2021;23(15):5621–5625.

21.

Guo

Meng

Niu

, et al. Epigenetic manipulation to trigger production of guaiane-type sesquiterpenes from a marine-derived Spiromastix sp. Fungus with antineuroinflammatory effects. J Nat Prod. 2021;84(7):1993–2003.

22.

Kaur

Chugh

Sakharkar

, et al. Neuroinflammation mechanisms and phytotherapeutic intervention: a systematic review. ACS Chem Neurosci. 2020;11(22):3707–3731.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

1.32 MB