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8 pages, 563 KiB

Open AccessArticle

Evaluation of the Immunomodulatory Effects of Fucoidan Derived from Cladosiphon Okamuranus Tokida in Mice

by Makoto Tomori, Takeaki Nagamine, Tomofumi Miyamoto and Masahiko Iha

Mar. Drugs 2019, 17(10), 547; https://doi.org/10.3390/md17100547 - 24 Sep 2019

Cited by 42 | Viewed by 4998

Abstract

Okinawa mozuku (Cladosiphon okamuranus Tokida) is an edible seaweed classified as brown algae and is a native species of the Ryukyu Islands in Japan. In recent years, the genomic decoding of Okinawa mozuku has been completed. Previous studies on the anti-inflammatory, antiviral, [...] Read more.

Okinawa mozuku (Cladosiphon okamuranus Tokida) is an edible seaweed classified as brown algae and is a native species of the Ryukyu Islands in Japan. In recent years, the genomic decoding of Okinawa mozuku has been completed. Previous studies on the anti-inflammatory, antiviral, and antitumor properties of Okinawa mozuku have suggested that it affects the regulation of cellular and humoral immunity. The aim of the present study was to examine the immunoregulatory effect of fucoidan derived from Okinawa mozuku in mice. A product containing fucoidan (purity, 88.3%; molecular weight, 49.8 kDa) was developed from Okinawa mozuku and tested for its immunoregulatory effects in mice. The experimental animals were 8-week-old female BALB/c mice to which fucoidan (0, 102.5, 205.0, 410.0, and 1025.0 mg/kg) was administered orally continuously for six weeks. Immune cell proliferation, cytokine production, macrophage phagocytosis, and serum antibody concentration were measured. We found that immune cell proliferation, interleukin (IL)-2, macrophage phagocytes, and serum antibodies (IgM, -G, -A) increased significantly, but IL-4, -5, and IgE decreased significantly. These results indicated that fucoidan modulated cellular and humoral immunity. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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11 pages, 1680 KiB

Open AccessArticle

Bioactive Capnosanes and Cembranes from the Soft Coral Klyxum flaccidum

by Wan-Ru Tseng, Atallah F. Ahmed, Chiung-Yao Huang, Yi-Ying Tsai, Chi-Jen Tai, Raha S. Orfali, Tsong-Long Hwang, Yi-Hsuan Wang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2019, 17(8), 461; https://doi.org/10.3390/md17080461 - 7 Aug 2019

Cited by 15 | Viewed by 3712

Abstract

Two new capnosane-based diterpenoids, flaccidenol A (1) and 7-epi-pavidolide D (2), two new cembranoids, flaccidodioxide (3) and flaccidodiol (4), and three known compounds 5 to 7 were characterized from the marine soft coral [...] Read more.

Two new capnosane-based diterpenoids, flaccidenol A (1) and 7-epi-pavidolide D (2), two new cembranoids, flaccidodioxide (3) and flaccidodiol (4), and three known compounds 5 to 7 were characterized from the marine soft coral Klyxum flaccidum, collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus Klyxum for the first time. The cytotoxicity of compounds 1 to 7 against the proliferation of a limited panel of cancer cell lines was assayed. The isolated diterpenoids also exhibited anti-inflammatory activity through suppression of superoxide anion generation and elastase release in the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-stimulated human neutrophils. Furthermore, 1 and 7 also exhibited cytotoxicity toward the tested cancer cells, and 7 could effectively inhibit elastase release. It is worth noting that the biological activities of 7 are reported for the first time in this paper. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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9 pages, 1500 KiB

Open AccessArticle

Kabirimine, a New Cyclic Imine from an Okinawan Dinoflagellate

by Idam Hermawan, Mikako Higa, Philipus Uli Basa Hutabarat, Takeshi Fujiwara, Kiyotaka Akiyama, Akihiko Kanamoto, Takahiro Haruyama, Nobuyuki Kobayashi, Masahiro Higashi, Shoichiro Suda and Junichi Tanaka

Mar. Drugs 2019, 17(6), 353; https://doi.org/10.3390/md17060353 - 13 Jun 2019

Cited by 23 | Viewed by 4516

Abstract

On our quest for new bioactive molecules from marine sources, two cyclic imines (1, 2) were isolated from a dinoflagellate extract, inhibiting the growth of the respiratory syncytial virus (RSV). Compound 1 was identified as a known molecule portimine, while [...] Read more.

On our quest for new bioactive molecules from marine sources, two cyclic imines (1, 2) were isolated from a dinoflagellate extract, inhibiting the growth of the respiratory syncytial virus (RSV). Compound 1 was identified as a known molecule portimine, while 2 was elucidated to be a new cyclic imine, named kabirimine. The absolute stereochemistry of 1 was determined by crystallographic work and chiral derivatization, whereas the structure of 2 was elucidated by means of spectroscopic analysis and computational study on all the possible isomers. Compound 1 showed potent cytotoxicity (CC₅₀ < 0.097 µM) against HEp2 cells, while 2 exhibited moderate antiviral activity against RSV with IC₅₀ = 4.20 µM (95% CI 3.31–5.33). Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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15 pages, 3318 KiB

Open AccessArticle

Soritesidine, a Novel Proteinous Toxin from the Okinawan Marine Sponge Spongosorites sp.

by Ryuichi Sakai, Kota Tanano, Takumi Ono, Masaya Kitano, Yusuke Iida, Koji Nakano and Mitsuru Jimbo

Mar. Drugs 2019, 17(4), 216; https://doi.org/10.3390/md17040216 - 8 Apr 2019

Cited by 3 | Viewed by 4248

Abstract

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, [...] Read more.

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N-terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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10 pages, 1626 KiB

Open AccessArticle

Briarenones A‒C, New Briarellin Diterpenoids from the Gorgonian Briareum violaceum

by Yang Cheng, Atallah F. Ahmed, Raha S. Orfali, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2019, 17(2), 120; https://doi.org/10.3390/md17020120 - 17 Feb 2019

Cited by 7 | Viewed by 3659

Abstract

Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C (1‒3), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The [...] Read more.

Three new eunicellin-derived diterpenoids of briarellin type, briarenones A‒C (1‒3), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The absolute configuration of 1 was further confirmed by a single crystal X-ray diffraction analysis. The in vitro cytotoxic and anti-inflammatory potentialities of the isolated metabolites were tested against the growth of a limited panel of cancer cell lines and against the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenyl-alanine and cytochalasin B (fMLF/CB)-stimulated human neutrophils, respectively. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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17 pages, 4080 KiB

Open AccessArticle

Cacolides: Sesterterpene Butenolides from a Southern Australian Marine Sponge, Cacospongia sp.

by Shamsunnahar Khushi, Laizuman Nahar, Angela A. Salim and Robert J. Capon

Mar. Drugs 2018, 16(11), 456; https://doi.org/10.3390/md16110456 - 20 Nov 2018

Cited by 15 | Viewed by 4938

Abstract

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A–L (1–12), together with biosynthetically related norsesterterpene carboxylic acids, [...] Read more.

Chemical analysis of a marine sponge, Cacospongia sp. (CMB-03404), obtained during deep sea commercial fishing activities off the southern coast of Australia, yielded an unprecedented family of sesterterpene α-methyl-γ-hydroxybutenolides, cacolides A–L (1–12), together with biosynthetically related norsesterterpene carboxylic acids, cacolic acids A–C (13–15). Structures were assigned on the basis of detailed spectroscopic analysis with comparisons to known natural products and biosynthetic considerations. In addition to revealing new chemical diversity, this study provided a valuable platform for comparing and contrasting the capabilities of the traditional dereplication technologies of HPLC-DAD, HPLC-MS and NMR, with those of the emerging HPLC-MS/MS approach known as global natural products social molecular networking (GNPS), as applied to marine sponge sesterterpene tetronic acids. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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10 pages, 852 KiB

Open AccessArticle

Benderamide A, a Cyclic Depsipeptide from a Singapore Collection of Marine Cyanobacterium cf. Lyngbya sp.

by Chi Ying Gary Ding, Ji Fa Marshall Ong, Hui Chin Goh, Cynthia R. Coffill and Lik Tong Tan

Mar. Drugs 2018, 16(11), 409; https://doi.org/10.3390/md16110409 - 26 Oct 2018

Cited by 9 | Viewed by 4219

Abstract

Benderamide A (1), a (S)-2,2-dimethyl-3-hydroxy-7-octynoic acid (S-Dhoya)-containing cyclic depsipeptide that belongs to the kulolide superfamily, was isolated from a Singapore collection of cf. Lyngbya sp. marine cyanobacterium using a bioassay-guided approach. While the planar structure of 1 [...] Read more.

Benderamide A (1), a (S)-2,2-dimethyl-3-hydroxy-7-octynoic acid (S-Dhoya)-containing cyclic depsipeptide that belongs to the kulolide superfamily, was isolated from a Singapore collection of cf. Lyngbya sp. marine cyanobacterium using a bioassay-guided approach. While the planar structure of 1 was elucidated using a combination of 1D and 2D NMR experiments and MS analysis, the absolute configuration was subsequently achieved using the results obtained from Marfey’s analysis, comparative analysis of nuclear overhauser effect spectroscopy (NOESY) with the known compound 3, and one dimensional-nuclear overhauser effect (1D-NOE). Although 1 did not display antiproliferative activity against MCF7 breast cancer cells, the presence of an Ala instead of Gly suggests a possible mechanistic pathway to explain the consequential decrease in cytotoxicity compared to the closely related 2. In addition, results obtained from an LC–MS/MS-based molecular networking algorithm revealed two other closely related compounds encouraging further identification and isolation from the same marine cyanobacterium extract. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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8 pages, 2288 KiB

Open AccessArticle

Marine Peroxy Sesquiterpenoids Induce Apoptosis by Modulation of Nrf2-ARE Signaling in HCT116 Colon Cancer Cells

by Junsei Taira, Haruna Miyazato and Katsuhiro Ueda

Mar. Drugs 2018, 16(10), 347; https://doi.org/10.3390/md16100347 - 23 Sep 2018

Cited by 9 | Viewed by 3602

Abstract

Our current study demonstrated that the marine peroxy sesquiterpenoids isolated from the Okinawan soft coral Sinularia sp. have an antitumor activity in human colon cancer cell (HCT) 116 colon cancer cells with their induction of apoptosis due to H₂O₂ production [...] Read more.

Our current study demonstrated that the marine peroxy sesquiterpenoids isolated from the Okinawan soft coral Sinularia sp. have an antitumor activity in human colon cancer cell (HCT) 116 colon cancer cells with their induction of apoptosis due to H₂O₂ production derived from the compounds. This study clarified that peroxy sesquiterpenoids (1 and 2) inhibited anti-apoptosis proteins, such as B-cell lymphoma-extra large (Bcl-xL) and phosphoAkt (pAkt). In addition, the heme oxygenase-1 (HO-1), nuclear factor-erythroid-2-related factor (Nrf2), and phosphoNrf2 (pNrf2) proteins related to the cell survival regulation signal of Nrf2-ARE (antioxidant response element) were also suppressed in the presence of these compounds. While the cells treated with the compounds and trolox as an antioxidant expressed the inhibited proteins, such as HO-1, Nrf2, and Bcl-xL, it was suggested that the H₂O₂ involving free radical reactions derived from the molecule would be a trigger of apoptosis with the modulation of Nrf2-ARE signaling in the cells. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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12 pages, 1720 KiB

Open AccessArticle

Cloning of the Bisucaberin B Biosynthetic Gene Cluster from the Marine Bacterium Tenacibaculum mesophilum, and Heterologous Production of Bisucaberin B

by Masaki J. Fujita, Yusuke Goto and Ryuichi Sakai

Mar. Drugs 2018, 16(9), 342; https://doi.org/10.3390/md16090342 - 19 Sep 2018

Cited by 6 | Viewed by 5654

Abstract

The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N-hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene cluster consists of six open [...] Read more.

The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N-hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene cluster consists of six open reading frames (ORFs), in contrast to the four ORFs typically seen in biosynthetic gene clusters of the related molecules. Heterologous expression of the key enzyme, BsbD2, which is responsible for the final biosynthetic step of 1 resulted in production of bisucaberin B (1), but not bisucaberin (2) a macrocyclic counterpart of 1. To date, numbers of related enzymes producing macrocyclic analogues have been reported, but this work represents the first example of the HSD-based siderophore biosynthetic enzyme which exclusively produces a linear molecule rather than macrocyclic counterparts. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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13 pages, 2605 KiB

Open AccessArticle

by Chia-Hua Wu, Chih-Hua Chao, Tzu-Zin Huang, Chiung-Yao Huang, Tsong-Long Hwang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2018, 16(8), 278; https://doi.org/10.3390/md16080278 - 9 Aug 2018

Cited by 25 | Viewed by 5266

Abstract

Five new cembranoid-related diterpenoids, namely, flexibilisins D and E (1 and 2), secoflexibilisolides A and B (3 and 4), and flexibilisolide H (5), along with nine known compounds (6–14), were isolated from the [...] Read more.

Five new cembranoid-related diterpenoids, namely, flexibilisins D and E (1 and 2), secoflexibilisolides A and B (3 and 4), and flexibilisolide H (5), along with nine known compounds (6–14), were isolated from the soft coral Sinularia flexibilis. Their structures were established by extensive spectral analysis. Compound 3 possesses an unusual skeleton that could be biogenetically derived from cembranoids. The cytotoxicity and anti-inflammatory activities of the isolates were investigated, and the results showed that dehydrosinulariolide (7) and 11-epi-sinulariolide acetate (8) exhibited cytotoxicity toward a limited panel of cancer cell lines and 14-deoxycrassin (9) displayed anti-inflammatory activity by inhibition of superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophils. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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10 pages, 625 KiB

Open AccessArticle

Absorption Study of Mozuku Fucoidan in Japanese Volunteers

by Kizuku Kadena, Makoto Tomori, Masahiko Iha and Takeaki Nagamine

Mar. Drugs 2018, 16(8), 254; https://doi.org/10.3390/md16080254 - 30 Jul 2018

Cited by 40 | Viewed by 5498

Abstract

We performed an oral administration study of fucoidan in 396 Japanese volunteers and investigated significant factors concerning the absorption of fucoidan. Urine samples were collected at 0, 3, 6, and 9 h after ingestion of 3 g of fucoidan. Fucoidan was detected in [...] Read more.

We performed an oral administration study of fucoidan in 396 Japanese volunteers and investigated significant factors concerning the absorption of fucoidan. Urine samples were collected at 0, 3, 6, and 9 h after ingestion of 3 g of fucoidan. Fucoidan was detected in urine after ingestion in 385 out of 396 subjects. The maximum value (mean ± standard deviation (SD)) of urinary fucoidan was 332.3 ± 357.6 μg/gCr in subjects living in Okinawa prefecture, compared with 240.1 ± 302.4 μg/gCr in subjects living outside Okinawa. Compared with the estimated urinary excretion of fucoidan by place of residence, those of subjects living in Okinawa prefecture were significantly higher than those living outside Okinawa prefecture (p < 0.01). In addition, subjects living in Okinawa prefecture consumed significantly greater amounts of mozuku compared with those living outside Okinawa prefecture (p < 0.01). Multiple regression analysis showed that having Okinawa prefecture as a place of residence was a significant factor (p < 0.01) contributing to the estimated urinary excretion of fucoidan. Because the habit of eating mozuku was significantly higher (p < 0.01) in subjects living in Okinawa prefecture than in those living outside Okinawa prefecture, the habit of eating mozuku was speculated to be a factor in the absorption of fucoidan. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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15 pages, 5268 KiB

Open AccessArticle

Isolation and Structure Elucidation of Cembranoids from a Dongsha Atoll Soft Coral Sarcophyton stellatum

by Atallah F. Ahmed, Yi-Wei Chen, Chiung-Yao Huang, Yen-Ju Tseng, Chi-Chen Lin, Chang-Feng Dai, Yang-Chang Wu and Jyh-Horng Sheu

Mar. Drugs 2018, 16(6), 210; https://doi.org/10.3390/md16060210 - 14 Jun 2018

Cited by 24 | Viewed by 5145

Abstract

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (1–3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7–16) from the ethyl acetate [...] Read more.

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (1–3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7–16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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Review

Jump to: Research

69 pages, 19533 KiB

Open AccessFeature PaperReview

Marine Natural Products from Indonesian Waters

by Novriyandi Hanif, Anggia Murni, Chiaki Tanaka and Junichi Tanaka

Mar. Drugs 2019, 17(6), 364; https://doi.org/10.3390/md17060364 - 19 Jun 2019

Cited by 44 | Viewed by 15710

Abstract

Natural products are primal and have been a driver in the evolution of organic chemistry and ultimately in science. The chemical structures obtained from marine organisms are diverse, reflecting biodiversity of genes, species and ecosystems. Biodiversity is an extraordinary feature of life and [...] Read more.

Natural products are primal and have been a driver in the evolution of organic chemistry and ultimately in science. The chemical structures obtained from marine organisms are diverse, reflecting biodiversity of genes, species and ecosystems. Biodiversity is an extraordinary feature of life and provides benefits to humanity while promoting the importance of environment conservation. This review covers the literature on marine natural products (MNPs) discovered in Indonesian waters published from January 1970 to December 2017, and includes 732 original MNPs, 4 structures isolated for the first time but known to be synthetic entities, 34 structural revisions, 9 artifacts, and 4 proposed MNPs. Indonesian MNPs were found in 270 papers from 94 species, 106 genera, 64 families, 32 orders, 14 classes, 10 phyla, and 5 kingdoms. The emphasis is placed on the structures of organic molecules (original and revised), relevant biological activities, structure elucidation, chemical ecology aspects, biosynthesis, and bioorganic studies. Through the synthesis of past and future data, huge and partly undescribed biodiversity of marine tropical invertebrates and their importance for crucial societal benefits should greatly be appreciated. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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