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16 pages, 4839 KiB

Open AccessArticle

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet–Endothelium Interaction

by Yao-Sheng Liu, Wen-Liang Chen, Yu-Wei Zeng, Zhi-Hong Li, Hao-Lin Zheng, Ni Pan, Li-Yan Zhao, Shu Wang, Sen-Hua Chen, Ming-Hua Jiang, Chen-Chen Jin, Yu-Chen Mi, Zhao-Hui Cai, Xin-Zhe Fang, Yong-Jun Liu, Lan Liu and Guan-Lei Wang

Mar. Drugs 2024, 22(6), 283; https://doi.org/10.3390/md22060283 - 16 Jun 2024

Viewed by 1639

Abstract

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. [...] Read more.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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13 pages, 6278 KiB

Open AccessArticle

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

by Chang Xu, Guangping Cao, Hong Zhang, Meng Bai, Xiangxi Yi and Xinjian Qu

Mar. Drugs 2024, 22(6), 275; https://doi.org/10.3390/md22060275 - 13 Jun 2024

Viewed by 1155

Abstract

Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province [...] Read more.

Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21^WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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15 pages, 11095 KiB

Open AccessEditor’s ChoiceArticle

Study on the Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives

by Qian-Qian Jing, Jun-Na Yin, Ya-Jie Cheng, Qun Zhang, Xi-Zhen Cao, Wei-Feng Xu, Chang-Lun Shao and Mei-Yan Wei

Mar. Drugs 2024, 22(3), 135; https://doi.org/10.3390/md22030135 - 16 Mar 2024

Cited by 2 | Viewed by 2052

Abstract

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid [...] Read more.

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC₉₀ values of 80, 90, 80 and 80 μM, respectively. The preliminary structure–activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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14 pages, 3139 KiB

Open AccessArticle

A SIRT6 Inhibitor, Marine-Derived Pyrrole-Pyridinimidazole Derivative 8a, Suppresses Angiogenesis

by Nannan Song, Yanfei Tang, Yangui Wang, Xian Guan, Wengong Yu, Tao Jiang, Ling Lu and Yuchao Gu

Mar. Drugs 2023, 21(10), 517; https://doi.org/10.3390/md21100517 - 28 Sep 2023

Cited by 2 | Viewed by 1698

Abstract

Angiogenesis refers to the process of growing new blood vessels from pre-existing capillaries or post-capillary veins. This process plays a critical role in promoting tumorigenesis and metastasis. As a result, developing antiangiogenic agents has become an attractive strategy for tumor treatment. Sirtuin6 (SIRT6), [...] Read more.

Angiogenesis refers to the process of growing new blood vessels from pre-existing capillaries or post-capillary veins. This process plays a critical role in promoting tumorigenesis and metastasis. As a result, developing antiangiogenic agents has become an attractive strategy for tumor treatment. Sirtuin6 (SIRT6), a member of nicotinamide adenine (NAD⁺)-dependent histone deacetylases, regulates various biological processes, including metabolism, oxidative stress, angiogenesis, and DNA damage and repair. Some SIRT6 inhibitors have been identified, but the effects of SIRT6 inhibitors on anti-angiogenesis have not been reported. We have identified a pyrrole-pyridinimidazole derivative 8a as a highly effective inhibitor of SIRT6 and clarified its anti-pancreatic-cancer roles. This study investigated the antiangiogenic roles of 8a. We found that 8a was able to inhibit the migration and tube formation of HUVECs and downregulate the expression of angiogenesis-related proteins, including VEGF, HIF-1α, p-VEGFR2, and N-cadherin, and suppress the activation of AKT and ERK pathways. Additionally, 8a significantly blocked angiogenesis in intersegmental vessels in zebrafish embryos. Notably, in a pancreatic cancer xenograft mouse model, 8a down-regulated the expression of CD31, a marker protein of angiogenesis. These findings suggest that 8a could be a promising antiangiogenic and cancer therapeutic agent. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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16 pages, 3960 KiB

Open AccessArticle

A Terphenyllin Derivative CHNQD-00824 from the Marine Compound Library Induced DNA Damage as a Potential Anticancer Agent

by Xi-Zhen Cao, Bo-Qi Zhang, Cui-Fang Wang, Jun-Na Yin, Waqas Haider, Gulab Said, Mei-Yan Wei and Ling Lu

Mar. Drugs 2023, 21(10), 512; https://doi.org/10.3390/md21100512 - 27 Sep 2023

Cited by 1 | Viewed by 1844

Abstract

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls—a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core—has [...] Read more.

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls—a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core—has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative—CHNQD-00824—derived from the marine compound library as a potential anticancer agent. The cytotoxic activities of the CHNQD-00824 compound were evaluated against 13 different cell lines with IC₅₀ values from 0.16 to 7.64 μM. Further study showed that CHNQD-00824 inhibited the proliferation and migration of cancer cells, possibly by inducing DNA damage. Acridine orange staining demonstrated that CHNQD-00824 promoted apoptosis in zebrafish embryos. Notably, the anti-cancer effectiveness was verified in a doxycin hydrochloride (DOX)-induced liver-specific enlargement model in zebrafish. With Solafinib as a positive control, CHNQD-00824 markedly suppressed tumor growth at concentrations of 2.5 and 5 μM, further highlighting its potential as an effective anticancer agent. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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21 pages, 17892 KiB

Open AccessArticle

Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway

by Islam Ahmed Abdelmawgood, Noha Ahmed Mahana, Abeer Mahmoud Badr, Ayman Saber Mohamed, Abdeljalil Mohamed Al Shawoush, Tarek Atia, Amir Elhadi Abdelrazak and Hader I. Sakr

Mar. Drugs 2023, 21(8), 455; https://doi.org/10.3390/md21080455 - 18 Aug 2023

Cited by 6 | Viewed by 3201

Abstract

Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative [...] Read more.

Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1β (IL-1β). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome’s therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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15 pages, 4393 KiB

Open AccessArticle

Anti-Atopic Dermatitis Activity of Epi-Oxyzoanthamine Isolated from Zoanthid

by Chieh-Chen Huang, Yuan-Hsin Lo, Yu-Jou Hsu, Yuan-Bin Cheng, Chia-Chi Kung, Cher-Wei Liang, Der-Chen Chang, Kang-Ling Wang and Chi-Feng Hung

Mar. Drugs 2023, 21(8), 447; https://doi.org/10.3390/md21080447 - 12 Aug 2023

Cited by 2 | Viewed by 2337

Abstract

Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop [...] Read more.

Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. Epi-oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of epi-oxyzoanthamine on the skin. In this paper, epi-oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that epi-oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that epi-oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that epi-oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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10 pages, 1389 KiB

Open AccessArticle

New Sorbicillinoids from the Mangrove Endophytic Fungus Trichoderma reesei SCNU-F0042

by Jialin Li, Tao Chen, Jianchen Yu, Hao Jia, Chen Chen and Yuhua Long

Mar. Drugs 2023, 21(8), 442; https://doi.org/10.3390/md21080442 - 5 Aug 2023

Cited by 4 | Viewed by 1890

Abstract

Three new dimeric sorbicillinoids (1–3) and one new 3,4,6-trisubstituted α-pyrone (5), along with seven analogues (4 and 6–11), were isolated from the mangrove endophytic fungus Trichoderma reesei SCNU-F0042 under the guidance of molecular [...] Read more.

Three new dimeric sorbicillinoids (1–3) and one new 3,4,6-trisubstituted α-pyrone (5), along with seven analogues (4 and 6–11), were isolated from the mangrove endophytic fungus Trichoderma reesei SCNU-F0042 under the guidance of molecular networking approach. Their chemical structures were established by 1D and 2D NMR HR-ESI-MS and ECD analysis. In a bioassay, compound 2 exhibited moderate SARS-CoV-2 inhibitory activity with an EC₅₀ value of 29.0 μM. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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22 pages, 3341 KiB

Open AccessArticle

Anti-Diabetic Activity of a Novel Exopolysaccharide Produced by the Mangrove Endophytic Fungus Penicillium janthinellum N29

by Zhuling Shao, Yingying Tian, Shan Liu, Xiao Chu and Wenjun Mao

Mar. Drugs 2023, 21(5), 270; https://doi.org/10.3390/md21050270 - 26 Apr 2023

Cited by 8 | Viewed by 2258

Abstract

Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present [...] Read more.

Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present study, a homogeneous exopolysaccharide from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ1-1, was obtained. The results of chemical and spectroscopic analyses showed that PJ1-1 was a novel galactomannan with a molecular weight of about 10.24 kDa. The backbone of PJ1-1 was composed of →2)-α-d-Manp-(1→, →4)-α-d-Manp-(1→, →3)-β-d-Galf-(1→ and →2)-β-d-Galf-(1→ units with partial glycosylation at C-3 of →2)-β-d-Galf-(1→ unit. PJ1-1 had a strong hypoglycemic activity in vitro, evaluated using the assay of α-glucosidase inhibition. The anti-diabetic effect of PJ1-1 in vivo was further investigated using mice with type 2 diabetes mellitus induced by a high-fat diet and streptozotocin. The results indicated that PJ1-1 markedly reduced blood glucose level and improved glucose tolerance. Notably, PJ1-1 increased insulin sensitivity and ameliorated insulin resistance. Moreover, PJ1-1 significantly decreased the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, enhanced the level of serum high-density lipoprotein cholesterol and alleviated dyslipidemia. These results revealed that PJ1-1 could be a potential source of anti-diabetic agent. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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13 pages, 1492 KiB

Open AccessArticle

Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3β,5α-Dihydroxycholest-6-One

by Mireguli Maimaitiming, Ling Lv, Xuetao Zhang, Shuli Xia, Xin Li, Pingyuan Wang, Zhiqing Liu and Chang-Yun Wang

Mar. Drugs 2023, 21(3), 191; https://doi.org/10.3390/md21030191 - 20 Mar 2023

Cited by 2 | Viewed by 2301

Abstract

Previously, we identified a series of steroids (1–6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC₅₀ values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer [...] Read more.

Previously, we identified a series of steroids (1–6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC₅₀ values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3β,5α-dihydroxycholest-6-one, named as (25R)-5, in seven steps from a commercially available compound diosgenin (7), with a total yield of 2.8%. Unfortunately, compound (25R)-5 and the intermediates only showed slight inhibitions against RSV replication at the concentration of 10 µM, but they possessed potent cytotoxicity activities against human bladder cancer 5637 (HTB-9) and hepatic cancer HepG2, with IC₅₀ values ranging from 3.0 to 15.5 µM without any impression of normal liver cell proliferation at 20 µM. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC₅₀ values of 4.8 µM and 15.5 µM, respectively. Further studies indicated that compound (25R)-5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25R-isomer of compound 5; the biological results suggested that compound (25R)-5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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10 pages, 542 KiB

Open AccessArticle

Antioxidative Indenone and Benzophenone Derivatives from the Mangrove-Derived Fungus Cytospora heveae NSHSJ-2

by Ge Zou, Taobo Li, Wencong Yang, Bing Sun, Yan Chen, Bo Wang, Yanghui Ou, Huijuan Yu and Zhigang She

Mar. Drugs 2023, 21(3), 181; https://doi.org/10.3390/md21030181 - 14 Mar 2023

Cited by 4 | Viewed by 2014

Abstract

Seven new polyketides, including four indenone derivatives, cytoindenones A–C (1, 3–4), 3′-methoxycytoindenone A (2), a benzophenone derivative, cytorhizophin J (6), and a pair of tetralone enantiomers, (±)-4,6-dihydroxy-5-methoxy-α-tetralone (7), together with [...] Read more.

Seven new polyketides, including four indenone derivatives, cytoindenones A–C (1, 3–4), 3′-methoxycytoindenone A (2), a benzophenone derivative, cytorhizophin J (6), and a pair of tetralone enantiomers, (±)-4,6-dihydroxy-5-methoxy-α-tetralone (7), together with a known compound (5) were obtained from the endophytic fungus Cytospora heveae NSHSJ-2 isolated from the fresh stem of the mangrove plant Sonneratia caseolaris. Compound 3 represented the first natural indenone monomer substituted by two benzene moieties at C-2 and C-3. Their structures were determined by the analysis of 1D and 2D NMR, as well as mass spectroscopic data, and the absolute configurations of (±)-7 were determined on the basis of the observed specific rotation value compared with those of the tetralone derivatives previously reported. In bioactivity assays, compounds 1, 4–6 showed potent DPPH· scavenging activities, with EC₅₀ values ranging from 9.5 to 16.6 µM, better than the positive control ascorbic acid (21.9 µM); compounds 2–3 also exhibited DPPH· scavenging activities comparable to ascorbic acid. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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19 pages, 17326 KiB

Open AccessEditor’s ChoiceArticle

Botryllin, a Novel Antimicrobial Peptide from the Colonial Ascidian Botryllus schlosseri

by Nicola Franchi, Loriano Ballarin and Francesca Cima

Mar. Drugs 2023, 21(2), 74; https://doi.org/10.3390/md21020074 - 21 Jan 2023

Cited by 6 | Viewed by 3473

Abstract

By mining the transcriptome of the colonial ascidian Botryllus schlosseri, we identified a transcript for a novel styelin-like antimicrobial peptide, which we named botryllin. The gene is constitutively transcribed by circulating cytotoxic morula cells (MCs) as a pre-propeptide that is then cleaved [...] Read more.

By mining the transcriptome of the colonial ascidian Botryllus schlosseri, we identified a transcript for a novel styelin-like antimicrobial peptide, which we named botryllin. The gene is constitutively transcribed by circulating cytotoxic morula cells (MCs) as a pre-propeptide that is then cleaved to mature peptide. The synthetic peptide, obtained from in silico translation of the transcript, shows robust killing activity of bacterial and unicellular yeast cells, causing breakages of both the plasma membrane and the cell wall. Specific monoclonal antibodies were raised against the epitopes of the putative amino acid sequence of the propeptide and the mature peptide; in both cases, they label the MC granular content. Upon MC degranulation induced by the presence of nonself, the antibodies recognise the extracellular nets with entrapped bacteria nearby MC remains. The obtained results suggest that the botryllin gene carries the information for the synthesis of an AMP involved in the protection of B. schlosseri from invading foreign cells. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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35 pages, 1776 KiB

Open AccessReview

Marine Microorganism Molecules as Potential Anti-Inflammatory Therapeutics

by Malia Lasalo, Thierry Jauffrais, Philippe Georgel and Mariko Matsui

Mar. Drugs 2024, 22(9), 405; https://doi.org/10.3390/md22090405 - 3 Sep 2024

Viewed by 3453

Abstract

The marine environment represents a formidable source of biodiversity, is still largely unexplored, and has high pharmacological potential. Indeed, several bioactive marine natural products (MNPs), including immunomodulators, have been identified in the past decades. Here, we review how this reservoir of bioactive molecules [...] Read more.

The marine environment represents a formidable source of biodiversity, is still largely unexplored, and has high pharmacological potential. Indeed, several bioactive marine natural products (MNPs), including immunomodulators, have been identified in the past decades. Here, we review how this reservoir of bioactive molecules could be mobilized to develop novel anti-inflammatory compounds specially produced by or derived from marine microorganisms. After a detailed description of the MNPs exerting immunomodulatory potential and their biological target, we will briefly discuss the challenges associated with discovering anti-inflammatory compounds from marine microorganisms. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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