scholarly journals The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents

2022 ◽  
Vol 23 (2) ◽  
pp. 736
Author(s):  
Alexandra Prodea ◽  
Alexandra Mioc ◽  
Christian Banciu ◽  
Cristina Trandafirescu ◽  
Andreea Milan ◽  
...  
Keyword(s):  
Water Solubility ◽  
Therapeutic Potential ◽  
Underlying Mechanism ◽  
Biological Behavior ◽  
Therapeutic Effects ◽  
Practical Applications ◽  
Starch Derivatives ◽  
Solubility Enhancers ◽  
Low Solubility

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.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

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 ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Water Solubility ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Liver Injuries ◽  
Repeated Consumption ◽  
Histopathologic Findings ◽  
Poor Stability

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.

scholarly journals Extracellular vesicles in diagnosis and therapy of kidney diseases

2016 ◽  
Vol 311 (5) ◽  
pp. F844-F851 ◽  
Author(s):  
Wei Zhang ◽  
Xiangjun Zhou ◽  
Hao Zhang ◽  
Qisheng Yao ◽  
Yutao Liu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cross Talk ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Cell Communication ◽  
Therapeutic Effects ◽  
Glomerular Diseases ◽  
The Cross

Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.

The role of caspase family in acute brain injury: the potential therapeutic targets in the future

2021 ◽  
Vol 19 ◽  
Author(s):  
Anke Zhang ◽  
Zeyu Zhang ◽  
Yibo Liu ◽  
Cameron Lenahan ◽  
Houshi Xu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Biological Function ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Acute Brain Injury ◽  
Therapeutic Effects ◽  
Caspase Inhibitors ◽  
Caspase Family ◽  
Translational Strategies

: The caspase family is commonly involved in the pathophysiology of acute brain injury (ABI) through complex apoptotic, pyroptotic, and inflammatory pathways. Current translational strategies for caspase modulation in ABI primarily focus on caspase inhibitors. Because there are no caspase-inhibiting drugs approved for clinical use on the market, the development of caspase inhibitors remains an attractive challenge for researchers and clinicians. Therefore, we conducted the present review with the aim of providing a comprehensive introduction of caspases in ABI. In this review, we summarized the available evidence and potential mechanisms regarding the biological function of caspases. We also reviewed the therapeutic effects of caspase inhibitors on ABI and its subsequent complications. However, various important issues remain unclear, prompting further verification of the efficacy and safety regarding clinical application of caspase inhibitors. We believe that our work will be helpful to further understand the critical role of the caspase family, and will provide novel therapeutic potential for ABI treatment.

scholarly journals Mesenchymal stromal cells attenuate alveolar type 2 cells senescence through regulating NAMPT-mediated NAD metabolism

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaofan Lai ◽  
Shaojie Huang ◽  
Sijia Lin ◽  
Lvya Pu ◽  
Yaqing Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Alveolar Type ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Nad Metabolism

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.

scholarly journals Recent advances in Nanocrystal

2020 ◽  
Vol 11 (4) ◽  
pp. 5791-5796
Author(s):  
Nikhil S Bhujbal ◽  
Binoy Varghese Cheriyan
Keyword(s):  
Spray Drying ◽  
Water Solubility ◽  
Aqueous Solubility ◽  
Therapeutic Effects ◽  
New Techniques ◽  
Rate Of Dissolution ◽  
New Chemical Entities ◽  
Particulate Size ◽  
Low Solubility ◽  
Nano Size

The biggest challenge in the discovery and fabrication of drugs nowadays is low solubility. Many new chemical entities have major therapeutic effects, increased performance, but due to poor water solubility their clinical applications are limited. This is why Nanocrystal technology to solve the issue of low aqueous solubility was established. Nanocrystal technology improves the rate of dissolution according to the surface area of the active medicinal substance by reducing its particulate size to the nano size level, maintaining the pharmaceutical crystal morphology and enhancing pharmacokinetic and pharmacodynamic properties of different types of pharmaceuticals. Nanocrystals are prepared using the method down, up and down, spray drying and thus new techniques. Nanocrystals loaded as tablet or capsule. The obtained nanocrystal can be managed in different ways. Using freeze-drying or spray-drying to produce powder, which then is used for tabletting or other oral product, may usually be dried with nanocrystal.

scholarly journals Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 427 ◽  
Author(s):  
Kyungtae Kim ◽  
Ki Hong Nam ◽  
Sang Ah Yi ◽  
Jong Woo Park ◽  
Jeung-Whan Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Panax Ginseng ◽  
Lipid Droplets ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Ginsenoside Rg3 ◽  
White Adipocytes

Ginsenoside Rg3, one of the major components in Panax ginseng, has been reported to possess several therapeutic effects including anti-obesity properties. However, its effect on the browning of mature white adipocytes as well as the underlying mechanism remains poorly understood. In this study, we suggested a novel role of Rg3 in the browning of mature 3T3-L1 adipocytes by upregulating browning-related gene expression. The browning effects of Rg3 on differentiated 3T3-L1 adipocytes were evaluated by analyzing browning-related markers using quantitative PCR, immunoblotting, and immunostaining. In addition, the size and sum area of lipid droplets in differentiated 3T3-L1 adipocytes were measured using Oil-Red-O staining. In mature 3T3-L1 adipocytes, Rg3 dose-dependently induced the expression of browning-related genes such as Ucp1, Prdm16, Pgc1α, Cidea, and Dio2. Moreover, Rg3 induced the expression of beige fat-specific genes (CD137 and TMEM26) and lipid metabolism-associated genes (FASN, SREBP1, and MCAD), which indicated the activation of lipid metabolism by Rg3. We also demonstrated that activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) is required for Rg3-mediated up-regulation of browning gene expression. Moreover, Rg3 inhibited the accumulation of lipid droplets and reduced the droplet size in mature 3T3-L1 adipocytes. Taken together, this study identifies a novel role of Rg3 in browning of white adipocytes, as well as suggesting a potential mechanism of an anti-obesity effect of Panax ginseng.

scholarly journals Therapeutic Potential of Neu1 in Alzheimer’s Disease Via the Immune System

2021 ◽  
Vol 36 ◽  
pp. 153331752199614
Author(s):  
Aiza Khan ◽  
Sumit Das ◽  
Consolato Sergi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaques ◽  
Beta Amyloid ◽  
Underlying Mechanism ◽  
Amyloid Deposits ◽  
Potential Therapeutic Role

Alzheimer’s Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.

scholarly journals Minimising The Counter-Therapeutic Effects Of Coronial Investigations: In Search Of Balance

2016 ◽  
Vol 16 (3) ◽  
pp. 4 ◽  
Author(s):  
Ian Freckelton
Keyword(s):  
Therapeutic Potential ◽  
Empirical Studies ◽  
Family Members ◽  
Therapeutic Jurisprudence ◽  
Therapeutic Effects ◽  
Counselling Services ◽  
Therapeutic Outcomes ◽  
Fact Finding ◽  
The Impact

<p><em><span style="font-size: medium;">For more than a decade analyses of coronial processes inspired by both therapeutic jurisprudence and restorative justice have identified the potential for maximising the therapeutic and public health benefits of the investigative functions of coroners’ courts and minimising their counter-therapeutic potential. The focus of both scholarly literature and law reform proposals has been upon addressing deficits in respect of the role of families in coronial investigations and especially coroners’ inquests. This has been a constructive contribution and has improved sensitivity to the risk that family members will be disenfranchised and alienated at a highly vulnerable time after they have been bereaved. This article chronicles the development in awareness of such issues. However, the potential for adv­erse effects on parties other than family members has been inadequately recognised in the literature, save for empirical studies conducted in 2011 for the Coronial Council of Victoria and another study published in 2014 in New Zealand. This article seeks to redress that imbalance. It argues that it is appropriate also to have regard to such potential in endeavouring to provide an approach to the work of coroners that is influenced by the sensibilities of therapeutic jurisprudence and seeks to reduce, so far as possible, counter-therapeutic outcomes for all parties, at the same time prioritising accurate and robust fact-finding and formulation of constructive recommendations to avoid avoidable deaths. It calls for further empirical research on the impact of coroners’ investigations on all affected parties and argues in favour of extension of improved funding to enable approaches to be informed by therapeutic jurisprudence and in particular to enhance eligibility for the services of counselling services attached to coroners’ courts.</span></em></p>

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