scholarly journals Identification of Cyanobacterial Strains with Potential for the Treatment of Obesity-Related Co-Morbidities by Bioactivity, Toxicity Evaluation and Metabolite Profiling

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 280 ◽  
Author(s):  
Margarida Costa ◽  
Filipa Rosa ◽  
Tiago Ribeiro ◽  
Rene Hernandez-Bautista ◽  
Marco Bonaldo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolite Profiling ◽  
Metabolic Regulation ◽  
Complex Disease ◽  
Metabolic Diseases ◽  
Small Animal ◽  
Pheophorbide A ◽  
In Vivo Models

Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future.

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

scholarly journals Metabolite profiling and wound-healing activity of Boerhavia diffusa leaf extracts using in vitro and in vivo models

2020 ◽  
Vol 10 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Kriti Juneja ◽  
Rutusmita Mishra ◽  
Samrat Chauhan ◽  
Sumeet Gupta ◽  
Partha Roy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Metabolite Profiling ◽  
Leaf Extracts ◽  
In Vivo Models ◽  
Boerhavia Diffusa ◽  
Wound Healing Activity

scholarly journals PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Tesse ◽  
Ramaroson Andriantsitohaina ◽  
Thierry Ragot
Keyword(s):  
Metabolic Diseases ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Pharmacological Target ◽  
Cardiovascular Cells ◽  
Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

scholarly journals Genistein Induces Adipogenic and Autophagic Effects in Rainbow Trout (Oncorhynchus mykiss) Adipose Tissue: In Vitro and In Vivo Models

2020 ◽  
Vol 21 (16) ◽  
pp. 5884
Author(s):  
Sara Balbuena-Pecino ◽  
Esmail Lutfi ◽  
Natàlia Riera-Heredia ◽  
Esther Gasch-Navalón ◽  
Emilio J. Vélez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Rainbow Trout ◽  
Lipid Metabolism ◽  
Oncorhynchus Mykiss ◽  
Fatty Acid Synthase ◽  
Hormone Sensitive Lipase ◽  
In Vivo Models ◽  
Rainbow Trout Oncorhynchus Mykiss

Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.

scholarly journals Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3731
Author(s):  
Suji Baek ◽  
Jisu Kim ◽  
Byung Seok Moon ◽  
Sun Mi Park ◽  
Da Eun Jung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Muscle Atrophy ◽  
Gas Analysis ◽  
Skeletal Muscle Atrophy ◽  
Ros Scavenging ◽  
In Vivo Models

Sarcopenia- or cachexia-related muscle atrophy is due to imbalanced energy metabolism and oxidative stress-induced muscle dysfunction. Monoterpenes play biological and pharmacological reactive oxygen species (ROS) scavenging roles. Hence, we explored the effects of camphene, a bicyclic monoterpene, on skeletal muscle atrophy in vitro and in vivo. We treated L6 myoblast cells with camphene and then examined the ROS-related oxidative stress using Mito TrackerTM Red FM and anti-8-oxoguanine antibody staining. To investigate lipid metabolism, we performed real-time polymerase chain reactions, holotomographic microscopy, and respiratory gas analysis. Rat muscle atrophy in in vivo models was observed using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and immunocytochemistry. Camphene reversed the aberrant cell size and muscle morphology of L6 myoblasts under starvation and in in vivo models. Camphene also attenuated E3 ubiquitin ligase muscle RING-finger protein-1, mitochondrial fission, and 8-oxoguanine nuclear expression in starved myotubes and hydrogen peroxide (H2O2)-treated cells. Moreover, camphene significantly regulated lipid metabolism in H2O2-treated cells and in vivo models. These findings suggest that camphene may potentially affect skeletal muscle atrophy by regulating oxidative stress and lipid metabolism.

scholarly journals The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota

2021 ◽  
pp. 1-19
Author(s):  
Ya-Xin Zhang ◽  
Shan-Shan Qu ◽  
Li-Hua Zhang ◽  
Yu-Yan Gu ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Structural Changes ◽  
Metabolic Diseases ◽  
Cholesterol Metabolism ◽  
Control Group ◽  
Oral Glucose ◽  
Model Group

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

Photodynamic Therapy of Pheophorbide a Inhibits the Proliferation of Human Breast Tumour via Both Caspase-dependent and -independent Apoptotic Pathways in In Vitro and In Vivo Models

2011 ◽  
Vol 26 (5) ◽  
pp. 734-742 ◽  
Author(s):  
Sandy Wan-Heng Hoi ◽  
Hoi Ming Wong ◽  
Judy Yuet-Wa Chan ◽  
Grace Gar Lee Yue ◽  
Gary Man-Kit Tse ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Breast Tumour ◽  
Human Breast ◽  
Pheophorbide A ◽  
In Vivo Models ◽  
Human Breast Tumour ◽  
Apoptotic Pathways

scholarly journals Preclinical models as patients’ avatars for precision medicine in colorectal cancer: past and future challenges

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Erika Durinikova ◽  
Kristi Buzo ◽  
Sabrina Arena
Keyword(s):  
Colorectal Cancer ◽  
Precision Medicine ◽  
Complex Disease ◽  
Medical Decision ◽  
Preclinical Model ◽  
Preclinical Models ◽  
In Vivo Models ◽  
Dismal Prognosis

AbstractColorectal cancer (CRC) is a complex and heterogeneous disease, characterized by dismal prognosis and low survival rate in the advanced (metastatic) stage. During the last decade, the establishment of novel preclinical models, leading to the generation of translational discovery and validation platforms, has opened up a new scenario for the clinical practice of CRC patients. To bridge the results developed at the bench with the medical decision process, the ideal model should be easily scalable, reliable to predict treatment responses, and flexibly adapted for various applications in the research. As such, the improved benefit of novel therapies being tested initially on valuable and reproducible preclinical models would lie in personalized treatment recommendations based on the biology and genomics of the patient’s tumor with the overall aim to avoid overtreatment and unnecessary toxicity. In this review, we summarize different in vitro and in vivo models, which proved efficacy in detection of novel CRC culprits and shed light into the biology and therapy of this complex disease. Even though cell lines and patient-derived xenografts remain the mainstay of colorectal cancer research, the field has been confidently shifting to the use of organoids as the most relevant preclinical model. Prioritization of organoids is supported by increasing body of evidence that these represent excellent tools worth further therapeutic explorations. In addition, novel preclinical models such as zebrafish avatars are emerging as useful tools for pharmacological interrogation. Finally, all available models represent complementary tools that can be utilized for precision medicine applications.

scholarly journals Effect ofCentella asiaticaon Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yun Zhao ◽  
Ping Shu ◽  
Youzhi Zhang ◽  
Limin Lin ◽  
Haihong Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Centella Asiatica ◽  
Ethanol Extract ◽  
Hypolipidemic Effect ◽  
Mice Model ◽  
Hamster Model

Hyperlipidemia and many other metabolic diseases are related to oxidative stress.Centella asiaticais a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) ofCentella asiaticahad a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction ofCentella asiaticahas antioxidant and hypolipidemic properties.

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