AQUACULTURE
·
2025
·
IF 3.9
Shenye Qu,Yihang Liu,Kaiyuan Lu,Yunlong Qin,Jiacheng Qin,Jietao Liu,Xiaohu Wu,Gaoxue Wang,Fei Ling
Ichthyophthirius multifiliis infections constitute a critical challenge demanding urgent resolution in global aquaculture systems. Although over 20 chemicals and natural products have demonstrated efficacy against I. multifiliis in the past two decades, the translation of these findings into clinically viable antiparasitic agents has progressed slowly, with the development of novel potent therapeutics remaining a major challenge. In this study, six novel magnolol-derived compounds were rationally designed through structural optimization of the magnolol scaffold. All synthesized compounds exhibited potent antiparasitic activity against both theront and tomont stages of I. multifiliis . Compound C1 showed superior efficacy to magnolol, with 18-fold and 26-fold lower EC 50 values against theronts (0.035 mg/L) and tomonts (0.024 mg/L) in vitro, respectively. Notably, these activity surpassed the potency of malachite green. Moreover, compound C1 showed lower toxicity than malachite green. ADMET and Density functional theory (DFT) calculations revealed that compound C1 had a favorable electrostatic potential (ESP) distribution and a lower energy gap between Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), indicating good druggability. Integrated in silico strategy identified Mapk3 (mitogen-activated protein kinase 3) as the primary therapeutic target mediating C1's antiparasitic effects. Protein-Protein Interaction (PPI) network analysis, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, suggested that compound C1 might disrupt lipid metabolism and lipoxygenases pathways by modulating Mapk3 expression, thereby exerting potent antiparasitic effects. These findings establish compound C1 as the most potent anti- I. multifiliis agent reported to date. Its potential application in aquaculture may provide valuable insights for addressing this critical bottleneck issue.
研究领域:
药理学
·
水产养殖学
·
计算化学
✓ 已验证
DOI
高影响因子
AQUACULTURE
·
2023
·
IF 4.5
Jietao Liu,Shenye Qu,Tao Wang,Bin Yang,Xiang Liu,Gaoxue Wang,Pengfei Li,Qing Yu,Fei Ling
Natural products have gained recognition as a valuable resource and have significant implications in the field of aquaculture. Nevertheless, the limited water solubility of drugs, leading to compromised bioavailability, has been a persistent challenge in the realm of pharmaceutical research. Magnolol as a natural product, the low solubility leads to limited activity against Ichthyophthirius multifiliis , which severely limits the application of magnolol. Nanosuspensions are considered to be an important strategy to improve the solubility and bioavailability of insoluble drugs. The purpose of this study is to fabricate nanosuspensions that can effectively improve the solubility and antiparasitic activity of magnolol. Magnolol nanosuspensions (MNs) containg Pluronic F68 as a stabilizer was prepared by the solvent-antisolvent precipitation method. The results of TEM , DSC and FTIR analysis showed that the surfactant attached to the surface of magnolol, and the nanosuspensions process significantly reduced the crystallinity and improved the solubility and dissolution rate of magnolol. The Central Composite Design was adopted to investigate the effects of independent variables viz. amount of temperature (A), the ratio of pluronic F68 to magnolol ( w /w) (B), and churning time (C) on particle size (Y), obtaining optimum nanosuspensions with a size of 32.03 nm. Compared with free magnolol, the release rate of magnolol in 119 nm and 35 nm MNs was significantly improved, and the release rate of magnolol was increased from 28.13% to 58.45% and 85.70% within 60 min. Further, the antiparasitic activity of MNs was measured. The results showed the reduction in drug particle size leads to an enhancement in the insecticidal activity of magnolol. Altogether, this study proposes a promising strategy to enhance activity by increasing the solubility of natural products.
研究领域:
水产养殖
·
药剂学
·
天然产物研究
✓ 已验证
产品关联
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Senyue Liu,Ming Xu,Baipeng Chen,Fulong Li,Yongqiang Deng,Yufan Zhang,Gang Lin,Defang Chen,Yi Geng,Yangping Ou,Xiaoli Huang
Because of the low host specificity , Ichthyophthirius multifiliis ( Ich ) can widely cause white spot disease in aquatic animals, which is extremely difficult to treat. Prior research has demonstrated a considerable impact of concentrated mannan-oligosaccharide (cMOS) on the prevention of white spot disease in goldfish , but the specific mechanism is still unknown. In this study, transcriptome sequencing, histological analysis, immunofluorescence analysis, phagocytosis activity assay and qRT-PCR assay were used to systematically reveal the potential mechanism of cMOS in supporting the resistance of goldfish ( Carrasius auratus ) to Ich invasion. According to the transcriptome analysis, the gill tissue of goldfish receiving the cMOS diet showed greater expression of mannose-receptor (MRC) related genes, higher phagocytosis activity, up-regulated expression of phagocytosis-related genes and inflammatory-related genes compared with the control, indicating that cMOS can have an effect on phagocytosis and non-specific immunity of goldfish. After the Ich challenge, transcriptome analysis revealed that cMOS fed goldfish displayed a higher level of phagocytic response, whereas non-cMOS fed goldfish displayed a greater inflammatory reaction. Besides, after Ich infection, cMOS-fed goldfish displayed greater phagocytosis activity, a stronger MRC positive signal, higher expression of genes associated with phagocytosis ( ABCB2 , C3 , MRC ), and lower expression of genes associated with inflammation ( IL-1β, IL-17, IL-8, TNF-α, NFKB ). In conclusion, our experimental results suggest that cMOS may support phagocytosis by binding to MRC on the macrophage cell membrane and change the non-specific immunity of goldfish by stimulating cytokine expression. The results of this study provide new insights for the mechanism of cMOS on parasitic infection, and also suggest phagocytosis-related pathways may be potential targets for prevention of Ich infection.
研究领域:
水产养殖
·
免疫学
·
寄生虫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2022
·
IF 4.622
Xiaoli Huang,Senyue Liu,Fengyuan Zuo,Lin Luo,Defang Chen,Yangping Ou,Yi Geng,Yufan Zhang,Gang Lin,Shiyong Yang,Wei Luo,Lizi Yin,Zhi He
Methods of supporting mucosal immune barrier integrity and prevention of some pathogenic infections in aquatic species , are key areas of active study, often focusing on feed additives . The objectives of this study were to explore the effects of feeding cMOS (concentrated mannan oligosaccharide) on the gill and skin mucosal barriers of goldfish ( Carassius auratus Linnaeus ) and evaluate health status during Ichthyophthirius multifiliis infection. After feeding the cMOS-containing diet for 60 days, Hematoxylin and eosin (H&E) staining showed greater length of gill lamella and thicker dermal dense layer, while Alcian Blue and Periodic acid–Schiff (AB-PAS) staining showed higher numbers of mucin cells in cMOS fed fish. Chemical analysis showed that fish fed cMOS had greater enzyme activity of lysozyme (LZM) and alkaline phosphatase (AKP) in gill and skin tissues, while qRT-PCR revealed higher expression of Muc-2 and IL-1β , as well as lower expression of IL-10 . After Ichthyophthirius multifiliis challenge, goldfish fed the cMOS diet had lower mortality and infection rates, as well as fewer visible white spots on the body surfaces. Histologically, the gill and skin of these fish presented less tissue damage and fewer parasites, and had a greater number of mucus cells. In addition, the expression of Muc-2 and IL-10 were notably higher while the expression of IL-1β was significantly lower in cMOS fed goldfish than control fed fish. In this study, cMOS fed goldfish had stronger immune barrier function of skin and gill mucous, and better survival following Ichthyophthirius multifiliis infection.
研究领域:
水生生物学
·
免疫学
·
渔业科学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2026
·
IF 4.4
Jietao Liu,Shenye Qu,Yihang Liu,Yunlong Qin,Jiacheng Qin,Xiaofa Luan,Qing Yu,Gaoxue Wang,Fei Ling
Ichthyophthirius multifiliis , a ciliate pathogen causing White Spot Disease in freshwater aquaculture, is responsible for substantial economic losses globally. This study establishes a machine learning (ML)-driven workflow for the efficient discovery of novel antiparasitic agents. The antiparasitic efficacy of 24 quinoline derivatives was evaluated against the theront and tomont life stages. Halogenated 8-hydroxyquinolines were identified as the most potent class, with 5,7-dichloro-2-methyl-8-quinolinol (Compound 13) emerging as the lead compound, demonstrating EC₅₀ values of 0.271 mg/L against theronts and 0.184 mg/L against tomonts. A predictive Quantitative Structure-Activity Relationship (QSAR) framework was established, with the Random Forest (RF) model showing superior predictive performance (test set R 2 = 0.761 for theronts and 0.703 for tomonts). Subsequently, the validated model was applied to screen a virtual compound library, identifying four novel quinoline candidates. Experimental validation of these ML-prioritized compounds confirmed their high potency, demonstrating the model's robust capability to identify new active scaffolds beyond the training set chemical space. Interpretation of molecular descriptors revealed that halogen-mediated electronic effects, molecular topological symmetry, and balanced hydrophobicity are critical factors governing antiparasitic activity. This work not only identifies highly promising candidates for the control of White Spot Disease but also provides a scalable, ML-accelerated paradigm for antiparasitic drug discovery in aquaculture.
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Shenye Qu,Yihang Liu,Jietao Liu,Xiaohu Wu,Pengfei Li,Qing Yu,Gaoxue Wang,Fei Ling
Aquaculture is a rapidly growing sector of global food production, playing a vital role in poverty alleviation, food security, and income generation. However, it faces substantial challenges, particularly due to infections caused by the protozoan Ichthyophthirius multifiliis, leading to reduced yields and economic losses. In this study, two classes of magnolol derivatives (M1–M26) were synthesized and evaluated for their parasiticidal activity against I. multifiliis theronts and tomonts. Based on the determined EC50 values, two significant convolutional neural networks (CNNs) and pharmacophore models were developed, guiding the design and synthesis of three new compounds. Among these, compound new-1 exhibited superior parasiticidal efficacy both in vitro and in vivo compared to magnolol and the commercial parasiticide methylene blue, with EC50 values of 0.197 and 0.252 mg/L, respectively. Toxicity assays demonstrated that compound new-1 showed no significant harmful effects on goldfish and zebrafish embryos at effective concentrations. Further, in silico and experimental analyses identified CDK2 as a molecular target for compound new-1, which disrupted the reproduction and exerts parasiticidal activity against I. multifiliis. Additionally, compound new-1 exhibited antifungal activity against Aspergillus flavus with a MIC of ∼0.8 mg/mL, suggesting its potential application in food preservation. This study provides valuable insights into the development of magnolol-based agents for aquaculture.
研究领域:
水产养殖
·
药物化学
·
计算生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Fulong Li,Ming Xu,Baipeng Chen,Senyue Liu,Yanhao Cao,Yufan Zhang,Gang Lin,Ping Ouyang,Defang Chen,Yi Geng,Xiaoli Huang
Ichthyophthirius multifiliis is a highly pathogenic ciliate parasite that infects nearly all freshwater teleost fish and causes significant economic losses. However, none of the current treatments for ichthyophthiriasis are effective. Therefore, it is necessary to explore new effective, alternative, and environmentally friendly products for the control of I. multifiliis infection. Concentrated mannan oligosaccharide (cMOS) is widely used in aquaculture as a functional additive to enhance fish immunity and disease resistance. In this study, 1 ‰, 2 ‰, and 4 ‰ cMOS were included into the diet of grass carp ( Ctenopharyngodon idellus ) for 6 weeks while observing growth performance and immune response in order to evaluate the concentration and time of cMOS supplementation needed to support I. multifiliis infected grass carp. The results showed that feeding 2 ‰ and 4 ‰ cMOS significantly increased the body weight of grass carp ( P < 0.05), and feeding 4 ‰ cMOS increased the total length and specific growth rate ( P < 0.05). The histological results showed that grass carp fed with 4 ‰ cMOS for three weeks and 2 ‰ cMOS for four weeks had more mucous cells and T/NK cells in their gills ( P < 0.05). Further qRT-PCR revealed higher expression of Muc-2 , TCR and IL-1β , as well as lower expression of IL-10 in cMOS fish ( P < 0.05). After the I. multifiliis challenge, feeding 4 ‰ cMOS for 3 weeks and 2 ‰ cMOS for 4 weeks resulted in significantly less severity of I. multifiliis infection, lower mortality, and lessened pathological damage to gill tissue ( P < 0.05). In addition, qRT-PCR revealed the expression of IL-1β , Muc-2 , MHC-II , IgM , and TCR in cMOS groups was significantly lower than that of the control-infection group, while the expression of IL-10 was significantly higher ( P < 0.05). The results of this study contribute new knowledge for the formulation of commercial feed for grass carp and provide both theoretical support and practical guidance for research on the prevention and control of fish ichthyophthiriasis.
✓ 已验证
产品关联
DOI
高影响因子
Pathogens
·
2025
·Vol. 14
·期 10
·1069
·
IF 3.3
Xianqi Peng,Xialian Bu,Weisong Ma,Jinbiao Jiao,Xiaohong Huang,Yu Zhao,Jian Zhu,Lei Huang,Jing Chen,A’qin Zheng,Huantao Qu,Jiayun Yao
White spot disease, caused by the parasiticIchthyophthirius multifiliis, induces mortality exceeding 80% in intensive aquaculture systems, resulting in global annual losses of >$1 billion. Current chemical controls (e.g., formaldehyde) face environmental persistence and drug resistance challenges. This study developed a synthetic isoquinoline derivative, BHTCA (s)-2-tert-butoxycarbonyl-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), as a biodegradable alternative againstI. multifiliisin grass carp (Ctenopharyngodon idella). In vitro assays revealed stage-selective efficacy: theronts exhibited higher susceptibility (EC50= 0.10 mg/L at 4 h) than tomonts (EC50= 0.40 mg/L at 24 h), with BHTCA disrupting ciliary structures and compromising cyst integrity. In vivo trials (0.6 mg/L) reduced parasite loads by 78.1% and host mortality by 66.7% versus untreated controls. Acute toxicity tests confirmed a high therapeutic index (LC50= 16.75 mg/L; >167× effective concentration). With demonstrated efficacy, low production cost, and minimal eco-toxicity, BHTCA presents a sustainable strategy for Ichthyophthiriasis management in aquaculture.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）