Publications by authors named "Kechun Liu"

80 Publications

Treatment of Parkinson's disease in Zebrafish model with a berberine derivative capable of crossing blood brain barrier, targeting mitochondria, and convenient for bioimaging experiments.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jul 31:109151. Epub 2021 Jul 31.

Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250103, Shandong Province, China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan 250103, Shandong Province, China. Electronic address:

Berberine is a famous alkaloid extracted from Berberis plants and has been widely used as medications and functional food additives. Recent studies reveal that berberine exhibits neuroprotective activity in animal models of Parkinson's disease (PD), the second most prevalent neurodegenerative disorders all over the world. However, the actual site of anti-PD action of berberine remains largely unknown. To this end, we employed a fluorescently labeled berberine derivative BBRP to investigate the subcellular localization and blood brain barrier (BBB) permeability in a cellular model of PD and zebrafish PD model. Biological investigations revealed that BBRP retained the neuroprotective activity of berberine against PD-like symptoms in PC12 cells and zebrafish, such as protecting 6-OHDA induced cell death, relieving MPTP induced PD-like behavior and increasing dopaminergic neuron loss in zebrafish. We also found that BBRP could readily penetrate BBB and function in the brain of zebrafish suffering from PD. Subcellular localization study indicated that BBRP could rapidly and specifically accumulate in mitochondria of PC12 cells when it exerted anti-PD effect. In addition, BBRP could suppress accumulation of Pink1 protein and inhibit the overexpression of LC3 protein in 6-OHDA damaged cells. All these results suggested that the potential site of action of berberine is mitochondria in the brain under the PD condition. Therefore, the findings described herein would be useful for further development of berberine as an anti-PD drug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbpc.2021.109151DOI Listing
July 2021

A novel -dimethylaminophenylether-based fluorescent probe for the detection of native ONOO in cells and zebrafish.

Analyst 2021 Aug 2. Epub 2021 Aug 2.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

Peroxynitrite (ONOO-) is a highly reactive substance, and plays an essential part in maintaining cellular homeostasis. It is crucial to monitor the ONOO- level in cells in normal and abnormal states. We introduced a p-dimethylaminophenylether-based fluorescent probe PDPE-PN, which could be synthesized readily. The new probe had prominent sensitivity and specificity, and a fast response towards ONOO-. The spectral performance of probe PDPE-PN was outstanding and the limit of detection was 69 nM. Probe PDPE-PN with low toxicity was applied to detect endogenous/exogenous ONOO- in RAW 264.7 macrophages and zebrafish. Importantly, successful application of the new receptor opens up new ideas for the design of ONOO- probes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1an00608hDOI Listing
August 2021

Anti-inflammatory peptides and metabolomics-driven biomarkers discovery from sea cucumber protein hydrolysates.

J Food Sci 2021 Jul 15. Epub 2021 Jul 15.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

The hydrolysates from Apostichopus japonicus sea cucumber are an important source of nitrogen that may be added to foods. We evaluated the effect of A. japonicus hydrolysates on inflammation-associated leukocyte recruitment. The results revealed that leukocyte migration to the site of injury was significantly blocked by AJH-1 (<10 kDa), suggesting a protective effect against CuSO -induced neuromast damage in a zebrafish model. Based on liquid chromatography/time-of-flight/mass spectrometry, and metabolomic analysis, the nine biomarker candidates in AJH-1 were Val, Ala-Pro-Arg, Gly-Lys, Asp propyl ester, Glu methyl ester, His butyl ester, Ile-Ala-Ala-Lys, Tyr-Lys, and Asn-Pro-Gly-Lys. We used molecular docking to predict the binding affinity and docked position of the peptides onto the angiotensin converting enzyme (ACE). All the identified peptides had adequate binding affinity toward ACE, especially peptides Ala-Pro-Arg and Gly-Lys. These peptides may be used in the development of therapeutic foods. PRACTICAL APPLICATION: The study revealed the anti-inflammatory properties of the fractionated sea cucumber protein hydrolysate (<10 kDa). The characteristic peptides may be used as functional ingredients in nutraceutical foods and beverages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1750-3841.15834DOI Listing
July 2021

Characterization and bioactivities of phospholipids from squid viscera and gonads using ultra-performance liquid chromatography-Q-exactive orbitrap/mass spectrometry-based lipidomics and zebrafish models.

Food Funct 2021 Jul 14. Epub 2021 Jul 14.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

There has been great interest in phospholipids (PLs) from marine by-products due to their long-chain polyunsaturated fatty acids with unique health and functional properties. Here, marine PLs from squid viscera and gonads were comprehensively characterized and compared by UPLC-Q-Exactive Orbitrap/MS-based lipidomics analysis. A total of thirteen phospholipid classes including 1223 molecular species were identified and quantified in both resources. PC, PE and SM were further isolated from the total PLs of squid viscera and gonads, respectively. All isolated squid PL components were first evaluated for anti-inflammatory, antioxidant and cardiovascular effects using in vivo zebrafish models. Our results showed the diversity, content and physiological functions of PLs from squid by-products, which provided a basis for their future application in the nutritional and pharmaceutical industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1fo00796cDOI Listing
July 2021

Developmental toxicity caused by sanguinarine in zebrafish embryos via regulating oxidative stress, apoptosis and wnt pathways.

Toxicol Lett 2021 Jul 9;350:71-80. Epub 2021 Jul 9.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan, 250103, Shandong Province, PR China. Electronic address:

Sanguinarine, derived from the root of Sanguinaria canadensis, have multiple biological activities, such as antimicrobial, insecticidal, antitumor, anti-inflammatory and anti-angiogenesis effect, but little is known about its toxicity on normal embryonic development. Here, we study the developmental toxicity using zebrafish model. Notably, sanguinarine caused a significant increase of the malformation rate and decrease of hatching rates and body length of zebrafish embryos. Sanguinarine also impaired the normal development of heart, liver and nerve system of zebrafish embryos. Further, the ROS level and MDA concentrations were remarkably increased, while the activity of T-SOD was decreased. In addition, obvious increase of apoptosis were observed by AO staining or TUNEL assay. Further studies showed that the oxidative stress-, apoptosis-related genes were changed, while genes of nrf2 and wnt pathways were inhibited by sangunarine. To sum up, our study will be helpful to understand the adverse effect of sanguinarine on embryonic development and the underlying molecular mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2021.07.001DOI Listing
July 2021

Protective Effect of Chlorogenic Acid and Its Analogues on Lead-Induced Developmental Neurotoxicity Through Modulating Oxidative Stress and Autophagy.

Front Mol Biosci 2021 11;8:655549. Epub 2021 Jun 11.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

Lead (Pb) is among the deleterious heavy metal and has caused global health concerns due to its tendency to cause a detrimental effect on the development of the central nervous system (CNS). Despite being a serious health concern, treatment of Pb poisoning is not yet available, reflecting the pressing need for compounds that can relieve Pb-induced toxicity, especially neurotoxicity. In the quest of exploring protective strategies against Pb-induced developmental neurotoxicity, compounds from natural resources have gained increased attention. Chlorogenic acid (CGA) and its analogues neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) are the important phenolic compounds widely distributed in plants. Herein, utilizing zebrafish as a model organism, we modeled Pb-induced developmental neurotoxicity and investigated the protective effect of CGA, NCGA, and CCGA co-treatment. In zebrafish, Pb exposure (1,000 μg/L) for 5 days causes developmental malformation, loss of dopaminergic (DA) neurons, and brain vasculature, as well as disrupted neuron differentiation in the CNS. Additionally, Pb-treated zebrafish exhibited abnormal locomotion. Notably, co-treatment with CGA (100 µM), NCGA (100 µM), and CCGA (50 µM) alleviated these developmental malformation and neurotoxicity induced by Pb. Further underlying mechanism investigation revealed that these dietary phenolic acid compounds may ameliorate Pb-induced oxidative stress and autophagy in zebrafish, therefore protecting against Pb-induced developmental neurotoxicity. In general, our study indicates that CGA, NCGA, and CCGA could be promising agents for treating neurotoxicity induced by Pb, and CCGA shows the strongest detoxifying activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.655549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226318PMC
June 2021

Schaftoside Suppresses Pentylenetetrazol-Induced Seizures in Zebrafish via Suppressing Apoptosis, Modulating Inflammation, and Oxidative Stress.

ACS Chem Neurosci 2021 07 15;12(13):2542-2552. Epub 2021 Jun 15.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, People's Republic of China.

The lack of disease-modifying therapeutic strategies against epileptic seizures has caused a surge in preclinical research focused on exploring and developing novel therapeutic candidates for epilepsy. Compounds from traditional Chinese medicines (TCMs) have gained much attention for a plethora of neurological diseases, including epilepsy. Herein, for the first time, we evaluated the anticonvulsive effects of schaftoside (SS), a TCM, on pentylenetetrazol (PTZ)-induced epileptic seizures in zebrafish and examined the underlying mechanisms. We observed that SS pretreatments significantly suppressed seizure-like behavior and prolonged the onset of seizures. Zebrafish larvae pretreated with SS demonstrated downregulation of expression during seizures. PTZ-induced upregulation of apoptotic cells was decreased upon pretreatment with SS. Inflammatory phenomena during seizure progression including the upregulation of interleukin 6 (), interleukin 1 beta (), and nuclear factor kappa-light-chain-enhancer of activated B cells () were downregulated upon pretreatment with SS. The PTZ-induced recruitment of immunocytes was in turn reduced upon SS pretreatment. Moreover, SS pretreatment modulated oxidative stress, as demonstrated by decreased levels of catalase () and increased levels of glutathione peroxidase-1a () and manganese superoxide dismutase (). However, pretreatment with SS modulated the PTZ-induced downregulation of the relative enzyme activity of CAT, GPx, and SOD. Hence, our findings suggest that SS pretreatment ameliorates PTZ-induced seizures, suppresses apoptosis, and downregulates the inflammatory response and oxidative stress, which potentially protect against further seizures in zebrafish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschemneuro.1c00314DOI Listing
July 2021

Study on the Mechanism of the Danggui-Chuanxiong Herb Pair on Treating Thrombus through Network Pharmacology and Zebrafish Models.

ACS Omega 2021 Jun 25;6(22):14677-14691. Epub 2021 May 25.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250103, China.

Danggui-Chuanxiong (DC) is a commonly used nourishing and activating blood medicine pair in many gynecological prescriptions and modern Chinese medicine. However, its activating blood mechanism has not been clearly elucidated. Our research aimed at investigating the activating blood mechanisms of DC using network pharmacology and zebrafish experiments. Network pharmacology was used to excavate the potential targets and mechanisms of DC in treating thrombus. The antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities of DC and the main components of DC, ferulic acid (DC2), ligustilide (DC7), and levistilide A (DC17), were evaluated by zebrafish models in vivo. A total of 24 compounds were selected as the active ingredients with favorable pharmacological parameters for this herb pair. A total of 89 targets and 18 pathways related to the thrombus process were gathered for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A, CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets for this herb pair to exert cardiovascular activity from the analysis of protein-protein interaction and KEGG pathway results, which were mainly related to inflammation, vasculogenesis, immunity, hormones, and so forth. The zebrafish experiment results showed that DC had antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities. The main compounds had different effects of zebrafish activities. Especially, the antithrombotic activity of the DC17H group, anti-inflammatory activities of DCH and DC2H groups, antioxidant activities of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities of DCM, DCH, and DC2 groups were stronger than those of the positive group. The integrated method coupled zebrafish models with network pharmacology provided the insights into the mechanisms of DC in treating thrombus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c01847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190889PMC
June 2021

Anti-angiogenesis and anti-metastasis effects of Polyphyllin VII on Hepatocellular carcinoma cells in vitro and in vivo.

Chin Med 2021 May 31;16(1):41. Epub 2021 May 31.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China.

Background: Polyphyllin VII (PP7), a steroidal saponin from P. polyphylla has been found to exert strong anticancer activity. Little is known about the anti-angiogenesis and anti-metastasis properties of PP7. In this study, the anti-angiogenic and anti-metastatic effects of PP7 on HCC and the molecular mechanisms were evaluated.

Methods: Effect of PP7 on angiogenesis was assessed by tube formation assay and applied a transgenic Tg(fli1:EGFP) zebrafish model. Effects of PP7 on tumor metastasis and invasion were examined in cell migration and invasion assay, zebrafish tumor xenograft models and lung metastasis mouse models. The protein levels were examined by Western blotting.

Results: PP7 significantly decreased the tube formation of human umbilical vein endothelial cells, the number and length of ISVs and SIVs of transgenic zebrafish, and the metastasis and invasion of cancer cells in vitro and in vivo. The anti-angiogenic and anti-metastatic effects of PP7 in HepG2 cells were attributable, at least partially, to downregulated NF-κB/MMP-9/VEGF signaling pathway.

Conclusion: This study demonstrates that PP7 possesses strong anti-angiogenesis and anti-metastasis activities, suggesting that PP7 could be a potential candidate agent for HCC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13020-021-00447-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166003PMC
May 2021

Involvement of Nrf2-HO-1/JNK-Erk Signaling Pathways in Aconitine-Induced Developmental Toxicity, Oxidative Stress, and ROS-Mitochondrial Apoptosis in Zebrafish Embryos.

Front Pharmacol 2021 21;12:642480. Epub 2021 Apr 21.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 μM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 μM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (, , , and ) and were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (, , , , and ) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.642480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097150PMC
April 2021

Role of atmospheric particulate matter exposure in COVID-19 and other health risks in human: A review.

Environ Res 2021 07 5;198:111281. Epub 2021 May 5.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, Shandong Province, PR China. Electronic address:

Due to intense industrialization and urbanization, air pollution has become a serious global concern as a hazard to human health. Epidemiological studies found that exposure to atmospheric particulate matter (PM) causes severe health problems in human and significant damage to the physiological systems. In recent days, PM exposure could be related as a carrier for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus transmission and Coronavirus disease 2019 (COVID-19) infection. Hence, it is important to understand the adverse effects of PM in human health. This review aims to provide insights on the detrimental effects of PM in various human health problems including respiratory, circulatory, nervous, and immune system along with their possible toxicity mechanisms. Overall, this review highlights the potential relationship of PM with several life-limiting human diseases and their significance for better management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2021.111281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096764PMC
July 2021

Novel Quercetin Derivative of 3,7-Dioleylquercetin Shows Less Toxicity and Highly Potent Tyrosinase Inhibition Activity.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

Quercetin is a well-known plant flavonol and antioxidant; however, there has been some debate regarding the efficacy and safety of native quercetin as a skin-whitening agent via tyrosinase inhibition. Several researchers have synthesized quercetin derivatives as low-toxicity antioxidants and whitening agents. However, no suitable quercetin derivatives have been reported to date. In this study, a novel quercetin derivative was synthesized by the S2 reaction using quercetin and oleyl bromide. The relationship between the structures and activities of quercetin derivatives as anti-melanogenic agents was assessed using in vitro enzyme kinetics, molecular docking, and quenching studies; cell line experiments; and in vivo zebrafish model studies. Novel 3,7-dioleylquercetin (OQ) exhibited a low cytotoxic concentration level at >100 µg/mL (125 µM), which is five times less toxic than native quercetin. The inhibition mechanism showed that OQ is a competitive inhibitor, similar to native quercetin. Expression of tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2), and microphthalmia-associated transcription factor was inhibited in B16F10 melanoma cell lines. mRNA transcription levels of tyrosinase, TRP-1, and TRP-2 decreased in a dose-dependent manner. Melanin formation was confirmed in the zebrafish model using quercetin derivatives. Therefore, OQ might be a valuable asset for the development of novel skin-whitening agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22084264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072539PMC
April 2021

Preparation and characterization of young fruit fraction and its anti-inflammatory effect on a transgenic zebrafish model.

Nat Prod Res 2021 Apr 16:1-6. Epub 2021 Apr 16.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, P.R.China.

Young fruits (YPF) contain substances that are distinct from those found in the mature fruits. Response surface methodology was used to explore the influences of extraction conditions including ultrasonic time (X), ethanol proportion (X), liquid-to-solid ratio (X) and temperature (X) on UV-absorbing components from YPF. To purify the extract, the adsorption/desorption properties of 280 nm-absorbing components on AB-8 resin were investigated. A total of 11 metabolites (amino acids, glycosylated amino acids and phenolics) were identified in the UV-absorbing fraction of YPF (YPF-F) based on LC-MS/MS assays. In a study of anti-inflammatory activity, YPF-F significantly decreased the number of inflammatory cells that migrated to the lateral line location in CuSO-induced transgenic fluorescent zebrafish. YPF should be utilized as a high value resource of functional foods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1912748DOI Listing
April 2021

Investigating the anti-angiogenic effects of Fufang Kushen Injection in combination with cisplatin using a zebrafish model.

Pak J Pharm Sci 2020 Sep;33(5):1955-1960

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

The Traditional Chinese Medicine formula Fufang Kushen Injection (FKI) has demonstrated potential to enhance the efficacy and reduce the toxicity of the chemotherapeutic drug cisplatin. However, there is insufficient evidence to determine whether the combination of matrine and cisplatin were linked to the angiogenesis pathway. In this study, we selected two zebrafish lines, AB and Tg (vegfr2: GFP), as in vivo models to rapidly assess the anti-angiogenesis effects. KFI and cisplatin had no obvious effects when used individually, but combined KFI (5 and 10 μL/mL) and cisplatin (50μg/mL) significantly inhibited the zebrafish intersegmental vessel (ISV) formation and growth. Matrine at 50 μg/mL also showed synergetic anti-angiogenesis activity with cisplatin (50μg/mL) in 48hpf zebrafish larvae. This study has shown the potential of FKI to enhance cisplatin efficacy and reduce its toxicity by inhibiting angiogenesis. These results contribute to the scientific evidence supporting the use of KFI in combination with cisplatin to treat cancer in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2020

The possible hormetic effects of fluorene-9-bisphenol on regulating hypothalamic-pituitary-thyroid axis in zebrafish.

Sci Total Environ 2021 Jul 19;776:145963. Epub 2021 Feb 19.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China. Electronic address:

Fluorene-9-bisphenol (BHPF) is a bisphenol A substitute, which has been introduced for the production of so-called 'bisphenol A (BPA)-free' plastics. However, it has been reported that BHPF can enter living organisms through using commercial plastic bottles and cause adverse effects. To date, the majority of the toxicologic study of BHPF focused on investigating its doses above the toxicological threshold. Here, we studied the effects of BHPF on development, locomotion, neuron differentiation of the central nervous system (CNS), and the expression of genes in the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish exposed to different doses of BHPF ranging from 1/5 of LD1 to LD50 (300, 500, 750, 1500, 3000, and 4500 nM). As a result, the possible hormetic effects of BHPF on regulating the HPT axis were revealed, in which low-dose BHPF positively affected the HPT axis while this regulation was inhibited as the dose increased. Underlying mechanism investigation suggested that BHPF disrupted myelination through affecting HPT axis including related genes expression and TH levels, thus causing neurotoxic characteristics. Collectively, this study provides the full understanding of the environmental impact of BHPF and its toxicity on living organisms, highlighting a substantial and generalized ongoing dose-response relationship with great implications for the usage and risk assessment of BHPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.145963DOI Listing
July 2021

Separation, identification and cardiovascular activities of phospholipid classes from the head of by lipidomics and zebrafish models.

Food Funct 2021 Mar;12(5):2282-2291

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250103, China. and Bioengineering Technology Innovation Center of Shandong Province, Heze, 274000, China.

Phospholipids not only have high nutritional value, but also have a positive effect on cardiovascular disease, cancer and nervous system diseases. However, the activity of individual phospholipid classes of shrimp phospholipids is rarely studied. This paper researched phospholipids in the by-products of Penaeus vannamei processing. The phospholipid classes of the head from P. vannamei (PV) were separated by column chromatography, analyzed with UHPLC-Q-Exactive HF/MS, and quantified using ammonium ferrothiocyarate spectrophometry. In addition, their cardiovascular activities in zebrafish models were evaluated. A total of 5 phospholipid classes were obtained, including PV-PC, PV-PE, PV-PI, PV-PS and PV-SM, and identified as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and sphingomyelin (SM), respectively. In the phospholipid profiling analysis, PV-PC (308 molecules) had the highest proportion with 85.24%, followed by PV-PE (139 types) with 9.32%, PV-SM (41 structures) with 4.75%, PV-PS (24 types) with 0.16%, and PV-PI (6 molecules) with 0.03%. In the quantitative analysis, the content of PV was 45.7%, and the purity of phospholipid classes was 75.5-88.1%. In the cardiovascular activity assays, the effects of different phospholipid classes were different. For example, PV-PC groups had strong angiogenesis activity, but PV-PE groups showed the opposite property. Our comprehensive profiling analysis and in vivo bioactivity evaluation of phospholipids from the head of P. vannamei can provide evidence for their targeted applications in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo03017aDOI Listing
March 2021

Immunohistological Localization of Mel1a Melatonin Receptor in Pigeon Retina.

Nat Sci Sleep 2021 5;13:113-121. Epub 2021 Feb 5.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, People's Republic of China.

Background: Melatonin (N-acetyl-5-methoxytryptamine), a significant indoleamine neuromodulator implicated in circadian rhythms and sleep patterns, regulates diverse rhythmic functions via activating its high-affinity G-protein-coupled receptors. However, the detailed cellular expression of the Mel1a receptor in the retina is still a research gap.

Methods: The expression of the Mel1a receptor in pigeon retina was assessed using Western blot analysis and immunofluorescent staining. The cellular localization of the Mel1a receptor was studied using double immunofluorescent staining and laser-scanning confocal microscopy.

Results: Our data suggested that the Mel1a receptor was extensively expressed in the outer segment of Rho4D2-labeled rod and L/M-opsin-labeled red/green cone and in the somata of the CB-labeled horizontal cell, TH-labeled dopaminergic amacrine cell, ChAT-labeled cholinergic amacrine cell, PV-labeled AII amacrine cell, Brn3a-labeled conventional ganglion cell, melanopsin-containing ganglion cell and CRALBP-labeled Müller glial cell. In addition, the Mel1a receptor was diffusely distributed throughout the full thickness of the inner plexiform layer. However, the outer segment of S-opsin-labeled blue cone, the somata of ChX-10-labeled bipolar cell and outer plexiform layer seemed to lack immunoreactivity of the Mel1a receptor.

Conclusion: The finding that multiple types of retinal cells express the Mel1a receptor provides a new neurobiological basis for the participation of melatonin in the regulation of retinal functions through activating the Mel1a receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NSS.S290757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872906PMC
February 2021

New Prenylated Indole Homodimeric and Pteridine Alkaloids from the Marine-Derived Fungus Y32-2.

Mar Drugs 2021 Feb 9;19(2). Epub 2021 Feb 9.

Key Laboratory of Marine Bioactive Substances, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China.

Chemical investigation of secondary metabolites from the marine-derived fungus Y32-2 resulted in the isolation of two new prenylated indole alkaloid homodimers, di-6-hydroxydeoxybrevianamide E () and dinotoamide J (), one new pteridine alkaloid asperpteridinate A (), with eleven known compounds (-). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, while their absolute configurations were determined by ECD calculations. Each compound was evaluated for pro-angiogenic, anti-inflammatory effects in zebrafish models and cytotoxicity for HepG2 human liver carcinoma cells. As a result, compounds , , , , exhibited pro-angiogenic activity in a PTK787-induced vascular injury zebrafish model in a dose-dependent manner, compounds , , , displayed anti-inflammatory activity in a CuSO-induced zebrafish inflammation model, and compound showed significant cytotoxicity against HepG2 cells with an IC value of 30 µg/mL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19020098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916005PMC
February 2021

An ultrasensitive ratiometric fluorescent probe for the detection of Hg and its application in cell and zebrafish.

Anal Methods 2021 03;13(8):1043-1048

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

Mercury is a highly toxic metal element, and the accumulation of mercury in the human body can cause great harm, including but not limited to brain damage, kidney damage and behavioral disorders. Therefore, an effective way to detect mercury ions in the environment is urgently needed. In this study, a novel fluorescent probe (CP-Hg) was synthesized with coumarin as the fluorophore and propanethiol as the recognition receptor. The probe was characterized with high sensitivity (detection limit is approximately 0.5 nM) and selectivity. Note that the probe can react with mercury ions with a distinct color change. In addition, it has been proved to have low toxicity and successfully applied to detect mercury in water samples, macrophages and zebrafish model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ay00063bDOI Listing
March 2021

Clozapine Induced Developmental and Cardiac Toxicity on Zebrafish Embryos by Elevating Oxidative Stress.

Cardiovasc Toxicol 2021 May 24;21(5):399-409. Epub 2021 Jan 24.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 Jingshi Dong Road, Licheng District, Jinan, 250103, Shandong, China.

Clozapine is one of the antipsychotic drugs for treating schizophrenia, but its cardiotoxicity was the primary obstacle for its clinical use, due to the unknown mechanism of clozapine-induced cardiotoxicity. In this study, we studied the cardiotoxicity of clozapine by employing zebrafish embryos. Acute clozapine exposure showed dose-dependent mortality with the LC at 59.36 μmol L and 49.60 μmol L when determined at 48 and 72 h post exposure, respectively. Morphological abnormalities like pericardial edema, incompletely heart looping, and bradycardia were detected after clozapine exposure in a time- and dose-dependent manner. Clozapine treatment also resulted in a slower heart rate and disturbed rhythm in zebrafish embryos. Also, oxidative stress was observed after clozapine exposure by measurement of ROS (reactive oxygen species), MDA (a lipid peroxidation marker), antioxidant enzyme activities, and oxidative stress-related gene expression. The elevation of inflammation coincided with oxidative stress by the assay of inflammation-related genes expression accompanied by clozapine incubation. Collectively, the data indicate that clozapine might achieve cardiotoxic effect in zebrafish larva through increasing oxidative stress, attenuation in antioxidant defense, and up-regulation of inflammatory cytokines. The data could provide experimental explanations for myocarditis and pericarditis induced by clozapine in clinics, and help find an effective solution to reduce its cardiotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12012-021-09632-7DOI Listing
May 2021

Lemnardosinanes A-I: New Bioactive Sesquiterpenoids from Soft Coral sp.

J Org Chem 2021 01 15;86(1):970-979. Epub 2020 Dec 15.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

Two rearranged nardosinane sesquiterpenoids with novel carbon skeletons, lemnardosinanes A () and B (), and seven new nardosinane-related sesquiterpeniod lemnardosinanes C-I (), together with a known compound 6,7-seco-13-nornardosinan (), were isolated from the soft coral sp. collected from Xisha Islands of the South China Sea. Their structures were elucidated by comprehensive spectroscopic analyses, Mosher's method, Mo(OAc)-induced circular dichroism experiment, and quantum chemical calculations. Plausible biosynthetic pathways of - were proposed. Compounds and displayed angiogenesis promoting activity in a zebrafish model. Compounds and exhibited antiviral activity against the H1N1 virus with IC values of 10.9 and 41.5 μM, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.0c02463DOI Listing
January 2021

Nano-titanium nitride causes developmental toxicity in zebrafish through oxidative stress.

Drug Chem Toxicol 2020 Dec 9:1-10. Epub 2020 Dec 9.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

Nano-titanium nitride (Nano-TiN) has strong resistance to wear and corrosion, good biocompatibility, and an attractive metallic luster. Nano-TiN is widely used in medical devices, such as orthopedic implants, syringe needles, coronary stents, and long-term dental implants, and also in imitation gold jewelry. Despite its widespread use, there are few reports describing safety evaluations of Nano-TiN. Here, we exposed healthy zebrafish embryos to different concentrations of Nano-TiN solution for five days, starting at about four hours post fertilization, and found that Nano-TiN caused dose- and time-dependent developmental toxicity. With increasing Nano-TiN concentration and length of exposure, mortality, and deformities gradually increased; body length shortened and hatching rate and motility were significantly reduced. We also found that exposure to Nano-TiN affected development of the heart, liver, nerves, and other organs, and led to elevated levels of reactive oxygen species and reduced antioxidant capacity. Exposure to Nano-TiN resulted in downregulation of expression of antioxidant genes, such as , , , , and . Our results showed that exposure to Nano-TiN caused developmental and organ toxicity in zebrafish embryos and that the toxic effects may be mediated through oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01480545.2020.1853765DOI Listing
December 2020

Toxicity of different zinc oxide nanomaterials and dose-dependent onset and development of Parkinson's disease-like symptoms induced by zinc oxide nanorods.

Environ Int 2021 01 21;146:106179. Epub 2020 Oct 21.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan 250103, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Jinan 250103, PR China. Electronic address:

With the increasing applications in various fields, the release and accumulation of zinc oxide (ZnO) nanomaterials ultimately lead to unexpected consequences to environment and human health. Therefore, toxicity comparison among ZnO nanomaterials with different shape/size and their adverse effects need better characterization. Here, we utilized zebrafish larvae and human neuroblastoma cells SH-SY5Y to compare the toxic effects of ZnO nanoparticles (ZnO NPs), short ZnO nanorods (s-ZnO NRs), and long ZnO NRs (l-ZnO NRs). We found their developmental- and neuro-toxicity levels were similar, where the smaller sizes showed slightly higher toxicity than the larger sizes. The developmental neurotoxicity of l-ZnO NRs (0.1, 1, 10, 50, and 100 μg/mL) was further investigated since they had the lowest toxicity. Our results indicated that l-ZnO NRs induced developmental neurotoxicity with hallmarks linked to Parkinson's disease (PD)-like symptoms at relatively high doses, including the disruption of locomotor activity as well as neurodevelopmental and PD responsive genes expression, and the induction of dopaminergic neuronal loss and apoptosis in zebrafish brain. l-ZnO NRs activated reactive oxygen species production, whose excessive accumulation triggered mitochondrial damage and mitochondrial apoptosis, eventually leading to PD-like symptoms. Collectively, the developmental- and neuro-toxicity of ZnO nanomaterials was identified, in which l-ZnO NRs harbors a remarkably potential risk for the onset and development of PD at relatively high doses, stressing the discretion of safe range in view of nano-ZnO exposure to ecosystem and human beings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.106179DOI Listing
January 2021

Developmental neurotoxicity fingerprint of silica nanoparticles at environmentally relevant level on larval zebrafish using a neurobehavioral-phenomics-based biological warning method.

Sci Total Environ 2021 Jan 21;752:141878. Epub 2020 Aug 21.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, 28789 East Jingshi Road, Ji'nan 250103, Shandong Province, PR China. Electronic address:

Background: Larval zebrafish (Danio rerio) is not only an ideal vertebrate applied in Fish Embryos Toxicity (FET) test but also a well-accepted model in behavioral neurotoxicity research. By applying the commercial standard behavioral tracking system (Zebrabox), the locomotion profiles (neurobehavioral-phenomics) of larval zebrafish can be comprehensively monitored and systematically analyzed to probe ecotoxicological neurotoxicity of nano-pollutants at environmental relevant concentration level.

Results: Herein, the potential toxicity of at environment relevant concentration level on embryonic zebrafish was evaluated by FET and neurobehavioral-phenomics (NBP). The embryos were exposed to the environmental relevant concentration (0.05, 0.1,1, 5, 10, 100 μg/L). The FET criteria were utilized to evaluate the ecotoxicological effect induced by silica NPs. Subsequently, behavioral neurotoxicity of silica NPs was further quantified via locomotion response (LMR). Specifically, the alteration of Light/Dark challenge (LDC) evoked by light/dark stimulation was detected and analyzed by commercially standard behavioral protocols using zebrabox. We revealed that the exposures of silica NPs at environmental relevant concentration (0.05, 0.1, 1, 5, 10,100 μg/L) significantly disturbed locomotion profiles of larval zebrafish. Additionally, it was obviously noted that low, environmentally relevant silica concentrations might result in altering the total behavioral profiles in developing zebrafish.

Conclusions: In sum, neurobehavior phenomics profiling based on LMR and LDC is a potent methodology for the evaluation of sub-lethal or sub-teratogenic toxicity. Compared with the FET tests characterized by the detection of embryonic teratogenicity, the neurobehavior phenomics based method can be more sensitive to determine sub-teratogenic toxicity of silica NPs at environmental concentrations. With the combination of multivariate data analysis, this approach would offer effective technical reference for environmental nano-toxicology research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.141878DOI Listing
January 2021

ERN1 knockdown modifies the effect of glucose deprivation on homeobox gene expressions in U87 glioma cells.

Endocr Regul 2020 Jul;54(3):196-206

Department of Molecular Biology, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine.

Objective: The aim of the present investigation was to study the expression of genes encoding homeobox proteins ZEB2 (zinc finger E-box binding homeobox 2), TGIF1 (TGFB induced factor homeobox 1), SPAG4 (sperm associated antigen 4), LHX1 (LIM homeobox 1), LHX2, LHX6, NKX3-1 (NK3 homeobox 1), and PRRX1 (paired related homeobox 1) in U87 glioma cells in response to glucose deprivation in control glioma cells and cells with knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), the major pathway of the endoplasmic reticulum stress signaling, for evaluation of it possible significance in the control of glioma growth through ERN1 signaling and chemoresistance.

Methods: The expression level of homeobox family genes was studied in control (transfected by vector) and ERN1 knockdown U87 glioma cells under glucose deprivation condition by real-time quantitative polymerase chain reaction.

Results: It was shown that the expression level of ZEB2, TGIF1, PRRX1, and LHX6 genes was up-regulated in control glioma cells treated by glucose deprivation. At the same time, the expression level of three other genes (NKX3-1, LHX1, and LHX2) was down-regulated. Furthermore, ERN1 knockdown of glioma cells significantly modified the effect glucose deprivation condition on the expression almost all studied genes. Thus, treatment of glioma cells without ERN1 enzymatic activity by glucose deprivation condition lead to down-regulation of the expression level of ZEB2 and SPAG4 as well as to more significant up-regulation of PRRX1 and TGIF1 genes. Moreover, the expression of LHX6 and NKX3-1 genes lost their sensitivity to glucose deprivation but LHX1 and LHX2 genes did not change it significantly.

Conclusions: The results of this investigation demonstrate that ERN1 knockdown significantly modifies the sensitivity of most studied homeobox gene expressions to glucose deprivation condition and that these changes are a result of complex interaction of variable endoplasmic reticulum stress related and unrelated regulatory factors and contributed to glioma cell growth and possibly to their chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/enr-2020-0022DOI Listing
July 2020

Corrigendum to 'Zebrafish neurobehavioral phenomics applied as the behavioral warning methods for fingerprinting endocrine disrupting effect by lead exposure at environmentally relevant level'[(2019) 315-325/231].

Chemosphere 2020 Nov 28;258:127783. Epub 2020 Jul 28.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.127783DOI Listing
November 2020

Synthesis of a novel fluorescent berberine derivative convenient for its subcellular localization study.

Bioorg Chem 2020 08 17;101:104021. Epub 2020 Jun 17.

Biological Engineering College, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250056, Shandong Province, China.

Berberine is a naturally occurred isoquinoline alkaloid that shows great potential for developing anticancer drugs. However, the problem stays of poor understanding of the mechanisms of anticancer action of berberine. It depends on evaluation of berberine's pharmacokinetics, namely monitoring of its uptake and distribution in cells, tissues and organs. In order to address these problems, we have designed and synthesized a novel berberine derivative BBR-BODIPY bearing a fluorescent tag that allows screening its interaction with the targeted cells. It was shown that the synthesized fluorescent derivative could penetrate into human breast carcinoma MCF7 cells, and then induced apoptosis detected by the Western Blot analysis as changed expression of apoptosis-related proteins, including Bax, Bcl2, and Cyto C released from mitochondria, Cleaved Caspase 9, Cleaved PARP, Pro-Caspase 3, and Cleaved Caspase 3. The results of MitoTracker analysis followed by the confocal microscopy of sub-cellular localization of BBR-BODIPY in the MCF7 cells demonstrated excellent cell-penetrating ability of this compound even at low concentrations, and mitochondria was the main site of its accumulation. Together with the results of Western Blot analysis, these data indicated that the mitochondria pathway might be involved in berberine-induced apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.104021DOI Listing
August 2020

Possible involvement of TGF‑β‑SMAD‑mediated epithelial‑mesenchymal transition in pro‑metastatic property of PAX6.

Oncol Rep 2020 Aug 11;44(2):555-564. Epub 2020 Jun 11.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250103, P.R. China.

Paired box 6 (PAX6) is a transcription factor that has oncogenic features. In breast cancer, PAX6 facilitates tumor progression; however, the underlying mechanism is largely unknown. The majority of breast cancer‑related mortalities are associated with metastasis of cancer cells. Therefore, the present study aimed to investigate the role of PAX6 in breast tumor metastasis. PAX6 was stably overexpressed in breast cancer cells to perform tumor migration and metastasis assays in vitro and in vivo. In addition, the expression of PAX6 and transforming growth factor β (TGF‑β)‑SMAD signaling associated proteins on human breast cancer tissue array, as well as key factors involved in epithelial‑mesenchymal transition (EMT) were assayed to explore the mechanism underlying metastasis of breast cancer cells. The expression levels of PAX6 were demonstrated to be increased in human breast cancer tissues and associated with poor clinical outcomes. Overexpression of PAX6 markedly promoted metastasis. Further investigation revealed that PAX6 overexpression increased TGF‑β‑SMAD signaling pathway and induced EMT. These results suggested that highly expressed PAX6 led to EMT through TGF‑β‑SMAD signaling pathway, thereby promoting cell metastasis and ultimately affecting survival in patients with breast cancer. Taken together, findings indicated that PAX6 may serve as a therapeutic target for the clinical treatment of breast cancer and the underlying mechanism could be used to overcome metastasis of cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2020.7644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336511PMC
August 2020

Isolation and Identification of Three New Sterigmatocystin Derivatives from the Fungus Aspergillus versicolor Guided by Molecular Networking Approach.

Chem Biodivers 2020 Jun 19;17(6):e2000208. Epub 2020 May 19.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, P. R. China.

Molecular networking approach was applied for the targeted isolation of new sterigmatocystin derivatives, sterigmatocystins A-C, from the marine sponge-derived fungus Aspergillus versicolor. Sterigmatocystin A features a rare 6/6/6/6/5 polycyclic system. The structures of sterigmatocystins A-C, including absolute configurations, were determined on the basis of spectroscopic data and ECD calculations. Sterigmatocystin A showed more stronger promoting angiogenesis activity than the positive control at 1.25 μM level in transgenic fluorescent zebrafish. Sterigmatocystins A-C also exhibited moderate antiviral activity by the inhibition of HSV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbdv.202000208DOI Listing
June 2020

Synthesis of disaccharide modified berberine derivatives and their anti-diabetic investigation in zebrafish using a fluorescence-based technology.

Org Biomol Chem 2020 05;18(18):3563-3574

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, Shandong Province, China.

Berberine is a naturally occurring isoquinoline alkaloid and has been used as an important functional food additive in China due to its various pharmacological activities. Berberine exhibits great potential for developing anti-diabetic agents against type 2 diabetes mellitus (T2DM), as it can reduce the blood glucose level in many animal models. However, the low anti-diabetic activity and poor bioavailability of berberine (below 5%) by oral administration significantly limit its practical applications. To solve these problems, this article focuses on the structural modification of berberine using some disaccharide groups, because the carbohydrate moiety has been proved to improve the bioavailability and enhance the receptor-binding affinity of drugs. Anti-diabetic investigation of the synthesized compounds was performed in a zebrafish model using a fluorescently labelled glucose analog 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a glucose tracker. The results indicated that the modification of berberine with carbohydrate groups could give derivatives with improved anti-diabetic activity, in particular the diglucose modified berberine derivative 1 which could dramatically promote the uptake of 2-NBDG in both zebrafish larvae and their eyes even at very low concentrations. Furthermore, the fluorescence-based anti-diabetic investigation method in zebrafish shows great potential for anti-diabetic drug screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0ob00327aDOI Listing
May 2020
-->