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Pre-Clinical Marine Drug Discovery

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (17 May 2019) | Viewed by 60958

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Prof. Dr. Jun Lu

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Auckland Bioengineering Institute, University of Auckland, Auckland 1142, New Zealand
Interests: diabetes; obesity; cancer; non-communicalbe diseases; marine natural compounds; fucoidan; seaweed; clams; food chemistry; pharmacology; drug metabolism; pharmacokinetics; pre-clinical pharmacology; natural compound extraction; polyamine metabolism; marine bioactives
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Assoc. Prof. Yu Zhao

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College of Life Sciences, Shanghai Normal University, Shanghai, China

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Dear Colleagues,

Marine products provide ample opportunities for us to find bioactive compounds. To identify and confirm their bioactivities, pre-clinical studies are necessary before they can be developed further, either as health products or ultimately as medicine. There are plenty of pre-clinical tools and models for marine drug discovery. Through pre-clinical screening, many marine compounds have demonstrated important biological properties in the prevention and treatment of various diseases, including cancer, neurodegenerative diseases, obesity, diabetes, etc. Pre-clinical screening is a crucial step for discovering new lead compounds from marine products, therefore, this "Pre-Clinical Marine Drugs Discovery” Special Issue aims to gather the most relevant and new research articles in the field. We hope to capture the progress and development in this important field. It is also a chance for scientists who are working on pre-clinical marine drug discovery to showcase their recent findings and attract the attention of marine drug developers.

Assoc. Prof. Jun Lu
Assoc. Prof. Yu Zhao
Guest Editor

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Keywords

marine products
natural compounds
pre-clinical screening
mechanism of action
extraction and analysis
bioactive extracts and fractions
pre-clinical models
pre-clinical pharmacology
molecular target

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Published Papers (9 papers)

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16 pages, 3060 KiB

Open AccessArticle

In Vitro Studies Reveal Antiurolithic Effect of Antioxidant Sulfated Polysaccharides from the Green Seaweed Caulerpa cupressoides var flabellata

by Dayanne Lopes Gomes^1,2, Karoline Rachel Teodosio Melo¹, Moacir Fernandes Queiroz¹, Lucas Alighieri Neves Costa Batista¹, Pablo Castro Santos³, Mariana Santana Santos Pereira Costa⁴, Jailma Almeida-Lima¹, Rafael Barros Gomes Camara¹, Leandro Silva Costa⁵ and Hugo Alexandre Oliveira Rocha^1,2,*

¹ Laboratory of Natural Polymer Biotechnology (BIOPOL), Department of Biochemistry, Center of Biosciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte- RN 59078-970, Brazil

² Federal Institute of Education, Science and Technology of Piauí (IFPI), São Raimundo Nonato Campus, São Raimundo Nonato-PI 64.770-000, Brazil

³ State University of Rio Grande do Norte (UERN), Mossoró-RN 59.610-210, Brazil

⁴ Federal Institute of Education, Science and Technology of Rio Grande do Norte (IFRN), João Câmara-RN 59.550-000, Brazil

⁵ Federal Institute of Education, Science and Technology of Rio Grande do Norte (IFRN), Canguaretama-RN 59.190-000, Brazil

Mar. Drugs 2019, 17(6), 326; https://doi.org/10.3390/md17060326 - 1 Jun 2019

Cited by 27 | Viewed by 4522

Abstract

Urolithiasis affects approximately 10% of the world population and is strongly associated with calcium oxalate (CaOx) crystals. Currently, there is no efficient compound that can be used to prevent this disease. However, seaweeds’ sulfated polysaccharides (SPs) can change the CaOx crystals surface’s charge and thus modify the crystallization dynamics, due to the interaction of the negative charges of these polymers with the crystal surface during their synthesis. We observed that the SPs of Caulerpa cupressoides modified the morphology, size and surface charge of CaOx crystals. Thus, these crystals became similar to those found in healthy persons. In the presence of SPs, dihydrate CaOx crystals showed rounded or dumbbell morphology. Infrared analysis, fluorescence microscopy, flow cytometry (FITC-conjugated SPs) and atomic composition analysis (EDS) allowed us to propose the mode of action between the Caulerpa’s SPs and the CaOx crystals. This study is the first step in understanding the interactions between SPs, which are promising molecules for the treatment of urolithiasis, and CaOx crystals, which are the main cause of kidney stones. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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9 pages, 1362 KiB

Open AccessArticle

Biosynthesis and Secretion of Human Tissue Kallikrein in Transgenic Chlamydomonas reinhardtii

by Jun Chen^1,†, Jinxia Wu^1,†, Qingyu Wu² and Zhangli Hu^1,2,*

¹ Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Key Laboratory of Plant Epigenetic, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China

² Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Science and Oceanography, Shenzhen University, Shenzhen 518060, China

^† These authors contributed equally to this work

Mar. Drugs 2018, 16(12), 493; https://doi.org/10.3390/md16120493 - 7 Dec 2018

Cited by 5 | Viewed by 4186

Abstract

The green alga Chlamydomonas reinhardtii was recently been shown to be an effective bio-manufacturing platform for the production of recombinant proteins. The advantage of using C. reinhardtii is that it is fast to grow, inexpensive to culture, and relatively safe. However, the expression of foreign proteins is always low and difficult to purify in C. reinhardtii. Human kallikrein has the potential to be developed into certain drugs, like insulin. Therefore, its biosynthesis is important to drug development. In this study, we synthesized the sg gene, a signal peptide sequence of alkaline phosphatase, and inserted it into a pH124 plasmid, which contains a HSP70A-RBCS2 promoter and a RBCS2 terminator. Then, we inserted the human kallikrein gene klk1 behind the sg sequence to make a pHsgk124 vector. The pHsgk124 were transferred into a cell-wall deficient strain of C. reinhardtii, cc-503, by using the glass bead method. Southern blot analysis showed that sg and klk1 were incorporated into genes of the transgenic C. reinhardtii. RT-PCR analysis showed that it had an active transcription and its expression increased three times under heat stress. Western blot analyses of proteins inside and outside cells (in the culture medium) showed that klk1 was expressed in the cell and the resulting protein was secreted into medium. An enzyme activity assay showed that the recombinant protein had the ability to hydrolyze the specific substrate H-D-Val-Leu-Arg-Pna. In conclusion, we successfully bioengineered C. reinhardtii to produce and secrete human kallikrein protein, which has important biomedical implications. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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25 pages, 4605 KiB

Open AccessArticle

Fucoidan Extracted from the New Zealand Undaria pinnatifida—Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines

by Jun Lu^1,2,3,4,5,*

, Keyu Kally Shi², Shuping Chen⁶, Junqiao Wang⁶, Amira Hassouna^4,7, Loretta Nicole White²

, Fabrice Merien^2,8

, Mingyong Xie⁶, Qingjun Kong^2,3, Jinyao Li⁹, Tianlei Ying¹⁰, William Lindsey White² and Shaoping Nie^6,*

¹ College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518071, China

² School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

³ College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710119, China

⁴ School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

⁵ Institute of Biomedical Technology, Auckland University of Technology, Auckland 1010, New Zealand

⁶ State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China

⁷ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 12613, Egypt

⁸ AUT-Roche Diagnostics Laboratory, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

⁹ Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, Xinjiang, China

¹⁰ Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Road, Shanghai 200032, China

Mar. Drugs 2018, 16(12), 461; https://doi.org/10.3390/md16120461 - 22 Nov 2018

Cited by 57 | Viewed by 9757

Abstract

Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines—MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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14 pages, 1701 KiB

Open AccessArticle

Investigation of Different Molecular Weight Fucoidan Fractions Derived from New Zealand Undaria pinnatifida in Combination with GroA Therapy in Prostate Cancer Cell Lines

by Xu Yang¹, Sheng Wang¹, Sari Schokoroy Trangle², Yan Li^1,3, William Lindsey White¹, Jinyao Li⁴, Tianlei Ying⁵, Qingjun Kong⁶, Yu Zhao⁷ and Jun Lu^{1,3,6,7,8,9,*}

¹ School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

² Department of Neurobiology, Tel-Aviv University, Ramat-Aviv 69978, Israel

³ School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

⁴ Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, Xinjiang, China

⁵ Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Road, Shanghai 200032, China

⁶ College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710119, Shaanxi, China

⁷ College of Life Sciences, Shanghai Normal University, 100 Guilin Road, Shanghai 200234, China

⁸ Institute of Biomedical Technology, Auckland University of Technology, Auckland 1010, New Zealand

⁹ College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518071, China

Mar. Drugs 2018, 16(11), 454; https://doi.org/10.3390/md16110454 - 18 Nov 2018

Cited by 19 | Viewed by 5058

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has been shown to possess various antioxidant, anticoagulant, antiviral, and anticancer functions. In this study, we focused on low molecular weight fucoidan (LMWF) which was extracted from New Zealand Undaria pinnatifida, and investigated its anti-proliferative effects, combined with a quadruplex-forming oligonucleotide aptamer (GroA, AS1411), a powerful cell surface Nucleolin inhibitor, in prostate cancer cells. We examined LMWF (<10 kDa) and compared it with laboratory grade Fucoidan purchased from Sigma (FS), all extracted from the same seaweed species U. pinnatifida. We found that LMWF significantly improved the anti-proliferative effect of GroA, as it decreased cancer cell growth and viability and increased cell death. This research may provide the foundation for LMWF to be used against prostate cancers as a supplement therapy in combination with other therapeutic agents. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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17 pages, 1953 KiB

Open AccessArticle

Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional Foods

by Yu Zhao^1,*, Yizhou Zheng¹, Jie Wang¹, Shuyi Ma¹, Yiming Yu¹, William Lindsey White², Shiping Yang¹, Fan Yang^1,3 and Jun Lu^{1,2,4,5,6,7,*}

¹ Life and Environment Science College, Shanghai Normal University, 100 Guilin Road, Shanghai 200234, China

² School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

³ State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China

⁴ School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand

⁵ Institute for Biomedical Technology, Auckland University of Technology, Auckland 1010, New Zealand

⁶ College of Life and Marine Sciences, Shenzhen University, Shenzhen 518060, China

⁷ College of Food Engineering and Nutrition Sciences, Shaanxi Normal University, Xi’an 710119, China

Mar. Drugs 2018, 16(9), 321; https://doi.org/10.3390/md16090321 - 9 Sep 2018

Cited by 151 | Viewed by 14718

Abstract

The importance of fucoidan as a functional ingredient in food, health products, and pharmaceutics is well-recognized due to its beneficial biological effects. Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida. Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and anticoagulant properties. This review focuses on the biological activity of U. pinnatifida-derived fucoidan and investigates its structure–activity or fraction–activity relationship. It also describes several fucoidan extracts, along with their claimed anticancer effects. It aims to provide information and thoughts for future research such as the development of fucoidan into functional foods or nutraceuticals. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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12 pages, 2259 KiB

Open AccessArticle

Protective Effect of Eckol against Acute Hepatic Injury Induced by Carbon Tetrachloride in Mice

by Shulan Li, Juan Liu, Mengya Zhang, Yuan Chen, Tianxing Zhu and Jun Wang^*

Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China

Mar. Drugs 2018, 16(9), 300; https://doi.org/10.3390/md16090300 - 27 Aug 2018

Cited by 26 | Viewed by 4392

Abstract

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl₄)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl₄-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl₄ model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl₄-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl₄-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c⁺ dendritic cells into the liver tissues of CCl₄-treated mice. These results indicated that eckol has the protective effect on CCl₄-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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14 pages, 1722 KiB

Open AccessArticle

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

by Bihong Hong^1,2,*, Jipeng Sun², Hongzhi Zheng³, Qingqing Le², Changsen Wang^2,4, Kaikai Bai², Jianlin He²

, Huanghuang He² and Yanming Dong^1,*

¹ Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005, China

² Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, China

³ School of pharmaceutical Sciences, Xiamen University, Xiamen 361102, China

⁴ College of Chemical Engineering, Huaqiao University, Xiamen 361021, China

Mar. Drugs 2018, 16(6), 195; https://doi.org/10.3390/md16060195 - 5 Jun 2018

Cited by 27 | Viewed by 5622

Abstract

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (C_max) at around 2 h, with an elimination half-life time (t_1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD₅₀) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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10 pages, 8683 KiB

Open AccessArticle

Marine Longilenes, Oxasqualenoids with Ser-Thr Protein Phosphatase 2A Inhibition Activity

by Francisco Cen-Pacheco^1,2

, Claudia Pérez Manríquez^1,3, María Luisa Souto^1,4, Manuel Norte^1,4, José Javier Fernández^1,4,* and Antonio Hernández Daranas^1,5,*

¹ Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez 2, 38206 Tenerife, Spain

² Facultad de Bioanálisis, Campus-Veracruz, Universidad Veracruzana, Veracruz 91700, Mexico

³ Departamento de Botánica, Facultad de Ciencias Naturales y Oceanográficas, Universidad de Concepción, Barrio Universitario, Concepción, Región del Biobío 4030000, Chile

⁴ Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez 2, 38206 Tenerife, Spain

⁵ Instituto de Productos Naturales y Agrobiología (IPNA), Consejo Superior de Investigaciones Científicas (CSIC), Avenida Astrofísico Francisco Sánchez 2, 38206 Tenerife, Spain

Mar. Drugs 2018, 16(4), 131; https://doi.org/10.3390/md16040131 - 17 Apr 2018

Cited by 9 | Viewed by 3971

Abstract

The red seaweed Laurencia viridis is a rich source of oxygenated secondary metabolites that were derived from squalene. We report here the structures of three novel compounds, (+)-longilene peroxide (1), longilene (2), and (+)-prelongilene (3) that were isolated from this alga, in addition to other substances, 4 and 5, resulting from their acid-mediated degradation. The effect of compounds 1 and 3 against Ser-Thr protein phosphatase type 2A (PP2A) was evaluated, showing that (+)-longilene peroxide (1) inhibited PP2A (IC₅₀ 11.3 μM). In order to explain the interaction between PP2A and compounds 1 and 3, molecular docking simulations onto the PP2A enzyme-binding region were used. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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21 pages, 4188 KiB

Open AccessArticle

Nanocomposite of Half-Fin Anchovy Hydrolysates/Zinc Oxide Nanoparticles Exhibits Actual Non-Toxicity and Regulates Intestinal Microbiota, Short-Chain Fatty Acids Production and Oxidative Status in Mice

by Ru Song^1,*, Jianbin Yao¹, Qingqing Shi¹ and Rongbian Wei^2,*

¹ Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, College of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan 316000, China

² College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316000, China

Mar. Drugs 2018, 16(1), 23; https://doi.org/10.3390/md16010023 - 11 Jan 2018

Cited by 32 | Viewed by 7405

Abstract

The nanocomposite of half-fin anchovy hydrolysates (HAHp) and zinc oxide nanoparticles (ZnO NPs) (named as HAHp(3.0)/ZnO NPs) demonstrated increased antibacterial activity compared to either HAHp(3.0) or ZnO NPs as per our previous studies. Also, reactive oxygen species (ROS) formation was detected in Escherichia coli cells after treatment with HAHp(3.0)/ZnO NPs. The aim of the present study was to evaluate the acute toxicity of this nanocomposite and to investigate its effect on intestinal microbiota composition, short-chain fatty acids (SCFAs) production, and oxidative status in healthy mice. The limit test studies show that this nanoparticle is non-toxic at the doses tested. The administration of HAHp(3.0)/ZnO NPs, daily dose of 1.0 g/kg body weight for 14 days, increased the number of goblet cells in jejunum. High-throughput 16S ribosomal RNA gene sequencing of fecal samples revealed that HAHp(3.0)/ZnO NPs increased Firmicutes and reduced Bacteriodetes abundances in female mice. Furthermore, the microbiota for probiotic-type bacteria, including Lactobacillus and Bifidobacterium, and SCFAs-producing bacteria in the Clostridia class, e.g., Lachnospiraceae_unclassified and Lachnospiraceae_UCG-001, were enriched in the feces of female mice. Increases of SCFAs, especially statistically increased propionic and butyric acids, indicated the up-regulated anti-inflammatory activity of HAHp(3.0)/ZnO NPs. Additionally, some positive responses in liver, like markedly increased glutathione and decreased malonaldehyde contents, indicated the improved oxidative status. Therefore, our results suggest that HAHp(3.0)/ZnO NPs could have potential applications as a safe regulator of intestinal microbiota or also can be used as an antioxidant used in food products. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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