scholarly journals Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis

2019 ◽  
Vol 20 (16) ◽  
pp. 4057 ◽  
Author(s):  
Yu Chiuan Wu ◽  
Han Hsiang Huang ◽  
Yi Jhen Wu ◽  
Ioannis Manousakas ◽  
Chin Chang Yang ◽  
...  

Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 ± 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.

2022 ◽  
Vol 23 (2) ◽  
pp. 736
Author(s):  
Alexandra Prodea ◽  
Alexandra Mioc ◽  
Christian Banciu ◽  
Cristina Trandafirescu ◽  
Andreea Milan ◽  
...  

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes’ therapeutic effects and the development of new topical formulations.


2021 ◽  
Vol 21 (3) ◽  
pp. 80-89
Author(s):  
Adamcakova Jana ◽  
Mokra Daniela

Abstract Lung silicosis is a serious pulmonary disease caused by an exposure of lung to inhaled silicon dioxide (SiO2) or silica. Although pathomechanisms of the disease have not been fully elucidated, oxidative stress has been recognized as a fundamental factor triggering a fibrotizing inflammation leading to irreversible changes in lung tissue. Based on this knowledge, therapeutic potential of various antioxidants has been intensively discussed. Among them, N-acetylcysteine with its multiple anti-inflammatory and antioxidant actions and a long-term experience with its clinical use in various diseases appears as a very promising choice. The purpose of this article is to review the therapeutic effects of N-acetylcysteine particularly in relation to a lung injury and to point out a potential of N-acetylcysteine in the treatment of lung silicosis.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Tsung-Hsun Hsieh ◽  
Xiao-Kuo He ◽  
Hui-Hua Liu ◽  
Jia-Jin J. Chen ◽  
Chih-Wei Peng ◽  
...  

Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson’s disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.


1994 ◽  
Vol 22 (01) ◽  
pp. 29-42 ◽  
Author(s):  
Song-chow Lin ◽  
Chun-ching Lin ◽  
Yun-ho Lin ◽  
Ching-hsein Chen

The hepatoprotective effect of Ban-zhi-lian was investigated in three kinds of experimental models. The animals were treated with Ban-zhi-lian (300 mg/kg, p.o.) at 2, 4, and 10 hours after carbon tetrachloride (32l/kg, i.p.), acetaminophen (600 mg/kg, i.p.), and β-D-galactosamine (188 mg/kg, i.p.) administration. Significant protective effects from these hepatotoxins were expressed. This protection was evidenced by comparing the serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and histopathologic examination in animals treated and untreated with Ban-zhi-lian. Serum enzyme activities were significantly lower in Ban-zhi-lian-treated groups. In the histopathologic observation, liver damage induced by three hepatotoxins was markedly improved in Ban-zhi-lian treated animals. These results demonstrated that Ban-zhi-lian has a protective effect against experimental liver damage induced by various hepatotoxins.


2021 ◽  
Vol 22 (9) ◽  
pp. 4815
Author(s):  
Vilde Yuli Stenberg ◽  
Roy Hartvig Larsen ◽  
Li-Wei Ma ◽  
Qian Peng ◽  
Petras Juzenas ◽  
...  

Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Zhu ◽  
Bingwu Huang ◽  
Wenbing Jiang

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaofan Lai ◽  
Shaojie Huang ◽  
Sijia Lin ◽  
Lvya Pu ◽  
Yaqing Wang ◽  
...  

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive deadly fibrotic lung disease with high prevalence and mortality worldwide. The therapeutic potential of mesenchymal stem cells (MSCs) in pulmonary fibrosis may be attributed to the strong paracrine, anti-inflammatory, anti-apoptosis and immunoregulatory effects. However, the mechanisms underlying the therapeutic effects of MSCs in IPF, especially in terms of alveolar type 2 (AT2) cells senescence, are not well understood. The purpose of this study was to evaluate the role of MSCs in NAD metabolism and senescence of AT2 cells in vitro and in vivo. Methods MSCs were isolated from human bone marrow. The protective effects of MSCs injection in pulmonary fibrosis were assessed via bleomycin mouse models. The senescence of AT2 cells co-cultured with MSCs was evaluated by SA-β-galactosidase assay, immunofluorescence staining and Western blotting. NAD+ level and NAMPT expression in AT2 cells affected by MSCs were determined in vitro and in vivo. FK866 and NAMPT shRNA vectors were used to determine the role of NAMPT in MSCs inhibiting AT2 cells senescence. Results We proved that MSCs attenuate bleomycin-induced pulmonary fibrosis in mice. Senescence of AT2 cells was alleviated in MSCs-treated pulmonary fibrosis mice and when co-cultured with MSCs in vitro. Mechanistic studies showed that NAD+ and NAMPT levels were rescued in AT2 cells co-cultured with MSCs and MSCs could suppress AT2 cells senescence mainly via suppressing lysosome-mediated NAMPT degradation. Conclusions MSCs attenuate AT2 cells senescence by upregulating NAMPT expression and NAD+ levels, thus exerting protective effects in pulmonary fibrosis.


Author(s):  
Claire Galea ◽  
Nicoletta Riva ◽  
Jean Calleja-Agius

Menstrual-derived Stem Cells (MenSC) are a potential novel source of mesenchymal stem cells. There is an increased interest in investigating the therapeutic potential of MenSC due to the various advantages they exhibit, when compared to other types of stem cells. MenSC are obtained non-invasively from menstrual blood. Thus, collection of MenSC is simple, reproducible and can be carried out periodically, with minimal complications. MenSC are present in abundance, are highly proliferative, exhibit a low immunogenicity and lack ethical issues. MenSC have shown the ability to differentiate into several lineages. The therapeutic potential of MenSC in non-gynaecological applications has been investigated in wound healing, neurological, musculo-skeletal,  cardiovascular, respiratory, and liver disorders, as well as in diabetes and cancer. Human clinical trials are limited. To date, therapeutic efficacy and safety have been reported in patients with Avian influenza A subtype H7N9, COVID-19, congestive heart failure, multiple sclerosis and Duchene muscular dystrophy. However, further clinical trials in humans should be conducted, to study the long-term therapeutic effects of these stem cells in various diseases and to further explore their mechanism of action. This systematic review focuses on the application of MenSC in non-gynaecological diseases.


2017 ◽  
Vol 22 (4-5) ◽  
pp. 303-310 ◽  
Author(s):  
Hao Xiong ◽  
Yongkang Ou ◽  
Yaodong Xu ◽  
Qiuhong Huang ◽  
Jiaqi Pang ◽  
...  

The sirtuin SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase known to have protective effects against a wide range of neurological disorders. In the present study, we discovered that C57BL/6 mice fed a long-term diet supplemented with high-dose resveratrol exhibited increased cochlear SIRT1 activity and presented a better recovery of hearing and less loss of hair cells after intense noise exposure compared with those fed a standard chew. Moreover, resveratrol attenuated cochlear SIRT1 decrease and reduced oxidative stress in the cochlea after noise exposure. These results suggest a considerable therapeutic potential of resveratrol for the treatment of noise-induced hearing loss.


2009 ◽  
Vol 90 (7) ◽  
pp. 1775-1780 ◽  
Author(s):  
Vito Vetrugno ◽  
Michele Angelo Di Bari ◽  
Romolo Nonno ◽  
Maria Puopolo ◽  
Claudia D'Agostino ◽  
...  

Statins are potent inhibitors of HMG–CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase in the cholesterol-biosynthesis pathway. They are either lipophilic (e.g. simvastatin) or hydrophilic [e.g. pravastatin (PRV)] compounds, considered mainly for long-term treatment of hypercholesterolaemic individuals. Beneficial effects of statins are not related exclusively to their lipid-lowering action; they also possess cholesterol-independent, pleiotropic effects (e.g. anti-inflammatory and antioxidant). Recent studies revealed that simvastatin treatment increased survival significantly in scrapie-infected mice. Although PRV treatment results in measurable drug levels in the mouse brain, the anti-prion effect of this compound has not been investigated. Therefore, we aimed to test the potential therapeutic action of PRV in a murine scrapie model. Our study showed that high-dose and long-term oral PRV treatment prolonged survival times of strain 139A scrapie-infected mice significantly (194 versus 177 days) in the absence of any obvious toxicity, suggesting that protective effects of statins may be independent of absolute solvent or water solubility of the drug.


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