scholarly journals Therapeutic Potential ofDioscoreaExtract (DA-9801) in Comparison with Alpha Lipoic Acid on the Peripheral Nerves in Experimental Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Heung Yong Jin ◽  
Sun Hee Kim ◽  
Hea Min Yu ◽  
Hong Sun Baek ◽  
Tae Sun Park
Keyword(s):  
Lipoic Acid ◽  
Peripheral Nerves ◽  
Experimental Diabetes ◽  
Therapeutic Potential ◽  
Alpha Lipoic Acid ◽  
Experimental Animals ◽  
Neurotrophic Activity ◽  
Response Thresholds ◽  
Sciatic Nerves ◽  
Thermal Stimuli

DA-9801, a mixture of extracts fromDioscorea japonicaThunb. andDioscorea nipponicaMakino, was reported to have neurotrophic activity. Therefore, we investigated the therapeutic potential of DA-9801, in comparison with alpha lipoic acid (ALA), for peripheral nerves preservation in experimental diabetes. Experimental animals were divided into 4 groups, and each group was designated according to the type of treatment administered as follows: normal, DM, DM+DA-9801, and DM+ALA. After 16 weeks, response thresholds to tactile and thermal stimuli were higher in DM+DA-9801 group than in nontreated DM group. This degree of increase in DM+DA-9801 group indicates more therapeutic potency of DA-9801 than ALA. Western blot analysis showed more significant increase in NGF and decrease in TNF-αand IL-6 in DM+DA-9801 group than in DM or DM+ALA groups (P<0.05). IENF density was reduced less significantly in the DM+DA-9801 group than in other DM groups (7.61 ± 0.32, 4.2 ± 0.26, and 6.5 ± 0.30 in DM+DA-9801, DM, and DM+ALA, resp.,P<0.05). Mean myelinated axonal area in the sciatic nerves was significantly greater in DM+DA-9801 group than in other DM groups (69.2 ± 5.76, 54.0 ± 6.32, and 63.1 ± 5.41 in DM+DA-9801, DM, and DM+ALA, resp.,P<0.05). Results of this study demonstrated potential therapeutic applications of DA-9801 for the treatment of diabetic peripheral neuropathy.

scholarly journals A Novel Model of Cancer-Induced Peripheral Neuropathy and the Role of TRPA1 in Pain Transduction

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Ahmad Maqboul ◽  
Bakheet Elsadek
Keyword(s):  
Immune Cells ◽  
Peripheral Nerves ◽  
Morphological Changes ◽  
Nerve Fibres ◽  
Cold Allodynia ◽  
Sciatic Nerves ◽  
Pain Transduction ◽  
Thermal Stimuli ◽  
Novel Model

Background. Models of cancer-induced neuropathy are designed by injecting cancer cells near the peripheral nerves. The interference of tissue-resident immune cells does not allow a direct contact with nerve fibres which affects the tumor microenvironment and the invasion process. Methods. Anaplastic tumor-1 (AT-1) cells were inoculated within the sciatic nerves (SNs) of male Copenhagen rats. Lumbar dorsal root ganglia (DRGs) and the SNs were collected on days 3, 7, 14, and 21. SN tissues were examined for morphological changes and DRG tissues for immunofluorescence, electrophoretic tendency, and mRNA quantification. Hypersensitivities to cold, mechanical, and thermal stimuli were determined. HC-030031, a selective TRPA1 antagonist, was used to treat cold allodynia. Results. Nociception thresholds were identified on day 6. Immunofluorescent micrographs showed overexpression of TRPA1 on days 7 and 14 and of CGRP on day 14 until day 21. Both TRPA1 and CGRP were coexpressed on the same cells. Immunoblots exhibited an increase in TRPA1 expression on day 14. TRPA1 mRNA underwent an increase on day 7 (normalized to 18S). Injection of HC-030031 transiently reversed the cold allodynia. Conclusion. A novel and a promising model of cancer-induced neuropathy was established, and the role of TRPA1 and CGRP in pain transduction was examined.

Abstract 440: Activation of Hepatic CREBH-Insig-2a Signaling in the Triglyceride-Lowering Mechanism of R-Alpha-Lipoic Acid

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Xuedong Tong ◽  
Regis Moreau ◽  
Qiaozhu Su
Keyword(s):  
Lipoic Acid ◽  
De Novo ◽  
Therapeutic Potential ◽  
Regulatory Element ◽  
Ldl Receptor ◽  
De Novo Lipogenesis ◽  
Alpha Lipoic Acid ◽  
Very Low Density Lipoproteins ◽  
Expression Of Genes

Activation of the sterol regulatory element-binding proteins (SREBPs), a step regulated by a cluster of ER-resident proteins, Insig-1, Insig-2 and SCAP, is rate limiting in hepatic de novo lipogenesis. We previously reported that feeding R-alpha-lipoic acid (LA) to ZDF (fa/fa) rats improves severe hypertriglyceridemia and lowers abdominal fat mass by inhibiting expression of genes involved in hepatic long-chain fatty acids and triacylglycerol syntheses. In this study, we characterized a novel mechanism of action of LA that explains its triacylglycerol lowering properties. Dietary LA activates liver specific transcription factor cAMP responsive element binding protein H (CREBH), which in turn enhances transcription and translation of Insig-1 and Insig-2. Chromatin immunoprecipitation (ChIP) assay demonstrated interaction between CREBH and the promoter of Insig-2 but not Insig-1. The increased abundance of Insig-1 and Insig-2 proteins contributes to sequester SREBP-1c and SREBP-2 in the ER and prevents their translocation to the Golgi apparatus where they would become activated. As a consequence, mRNA expression of genes involved in fatty acid and cholesterol synthesis, including FASN, ACC, SCD-1, HMGCR and LDL receptor, were significantly decreased in LA-fed animals versus pair-fed controls. Concomitantly, the assembly and secretion of very-low-density lipoproteins (VLDL) by primary hepatocytes were suppressed in the LA-fed ZDF rats as indicated by the decrease in VLDL-associated apolipoprotein B and apolipoprotein E. In vitro, treating a rat McA-RH7777 hepatoma cells with LA (200 micromole) activated CREBH, induced expression of Insig-1 and Insig-2, and hindered the palmitic acid-induced synthesis of triacylglycerol. This study provides new mechanistic insight into the triacylglycerol lowering properties of LA and supports the therapeutic potential of LA against hypertriglyceridemia.

Alpha Lipoic Acid as a Potential Treatment for COVID-19 - A Hypothesis

2020 ◽  
Vol 19 (2) ◽  
pp. 172-175
Author(s):  
Serkan Sayıner ◽  
Ahmet Özer Şehirli ◽  
Nedime Serakıncı
Keyword(s):  
T Cell Activation ◽  
Lipoic Acid ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Antiviral Drug ◽  
Alpha Lipoic Acid ◽  
Cytokine Storm ◽  
And Control ◽  
Antioxidant Molecule

SARS-CoV-2 infection has led to COVID-19 outbreak worldwide. To date, a specific antiviral drug does not exist to treat the disease and control the virus. In this paper, we have explored the potential utility of alpha lipoic acid, an anti-inflammatory and antioxidant molecule, for treatment. Alpha lipoic acid exhibits strong antioxidant properties and modulates the immune system by regulating T cell activation making it a useful therapeutic candidate for cytokine storm triggering SARS-CoV-2 infection. In the present communication, we focused on the therapeutic potential of ALA with respect to its potential role on reducing the severity of symptoms and the adverse effects of other antiviral drugs used. We consider different mechanisms by which modulating ACE2 levels after virus replication and preventing cytokine storm and also focus on a new therapeutic venue that utilizes ALA.

Alpha-Lipoic Acid: A Dietary Supplement With Therapeutic Potential for Obesity and Related Metabolic Diseases

2019 ◽  
pp. 85-92 ◽  
Author(s):  
Ana E. Huerta ◽  
Marta Fernández-Galilea ◽  
Pedro L. Prieto-Hontoria ◽  
J. Alfredo Martínez ◽  
María J. Moreno-Aliaga
Keyword(s):  
Dietary Supplement ◽  
Lipoic Acid ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Alpha Lipoic Acid

scholarly journals Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes

2015 ◽  
Vol 93 (12) ◽  
pp. 1021-1027 ◽  
Author(s):  
Luc Rochette ◽  
Steliana Ghibu ◽  
Adriana Muresan ◽  
Catherine Vergely
Keyword(s):  
Oxidative Stress ◽  
Lipoic Acid ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Vascular Diseases ◽  
Alpha Lipoic Acid ◽  
Insulin Mimetic ◽  
Beneficial Effects ◽  
Intracellular Compartments ◽  
Endothelial Nitric Oxide

Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.

scholarly journals Biochemical and clinical relevance of alpha lipoic acid: antioxidant and anti-inflammatory activity, molecular pathways and therapeutic potential

2017 ◽  
Vol 66 (11) ◽  
pp. 947-959 ◽  
Author(s):  
Daniele Tibullo ◽  
Giovanni Li Volti ◽  
Cesarina Giallongo ◽  
Sonia Grasso ◽  
Daniele Tomassoni ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Clinical Relevance ◽  
Therapeutic Potential ◽  
Inflammatory Activity ◽  
Molecular Pathways ◽  
Alpha Lipoic Acid ◽  
Anti Inflammatory

scholarly journals Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer’s Disease?

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Sávio Monteiro dos Santos ◽  
Camila Fernanda Rodrigues Romeiro ◽  
Caroline Azulay Rodrigues ◽  
Alícia Renata Lima Cerqueira ◽  
Marta Chagas Monteiro
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipoic Acid ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
In Vivo Studies ◽  
Alpha Lipoic Acid ◽  
Amyloid A

Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by impairments in the cognitive domains associated with orientation, recording, and memory. This pathology results from an abnormal deposition of the β-amyloid (Aβ) peptide and the intracellular accumulation of neurofibrillary tangles. Mitochondrial dysfunctions play an important role in the pathogenesis of AD, due to disturbances in the bioenergetic properties of cells. To date, the usual therapeutic drugs are limited because of the diversity of cellular routes in AD and the toxic potential of these agents. In this context, alpha-lipoic acid (α-LA) is a well-known fatty acid used as a supplement in several health conditions and diseases, such as periphery neuropathies and neurodegenerative disorders. It is produced in several cell types, eukaryotes, and prokaryotes, showing antioxidant and anti-inflammatory properties. α-LA acts as an enzymatic cofactor able to regulate metabolism, energy production, and mitochondrial biogenesis. In addition, the antioxidant capacity of α-LA is associated with two thiol groups that can be oxidised or reduced, prevent excess free radical formation, and act on improvement of mitochondrial performance. Moreover, α-LA has mechanisms of epigenetic regulation in genes related to the expression of various inflammatory mediators, such PGE2, COX-2, iNOS, TNF-α, IL-1β, and IL-6. Regarding the pharmacokinetic profile, α-LA has rapid uptake and low bioavailability and the metabolism is primarily hepatic. However, α-LA has low risk in prolonged use, although its therapeutic potential, interactions with other substances, and adverse reactions have not been well established in clinical trials with populations at higher risk for diseases of aging. Thus, this review aimed to describe the pharmacokinetic profile, bioavailability, therapeutic efficacy, safety, and effects of combined use with centrally acting drugs, as well as report in vitro and in vivo studies that demonstrate the mitochondrial mechanisms of α-LA involved in AD protection.

scholarly journals Therapeutic Potential of Alpha-Lipoic Acid in Viral Infections, including COVID-19

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1294
Author(s):  
Stela Dragomanova ◽  
Simona Miteva ◽  
Ferdinando Nicoletti ◽  
Katia Mangano ◽  
Paolo Fagone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Metabolic Syndrome ◽  
Lipoic Acid ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Alpha Lipoic Acid ◽  
Pathogenetic Role ◽  
Potential Use

Oxidative stress (OS), resulting from a disrupted balance between reactive oxygen species (ROS) and protective antioxidants, is thought to play an important pathogenetic role in several diseases, including viral infections. Alpha-lipoic acid (LA) is one of the most-studied and used natural compounds, as it is endowed with a well-defined antioxidant and immunomodulatory profile. Owing to these properties, LA has been tested in several chronic immunoinflammatory conditions, such as diabetic neuropathy and metabolic syndrome. In addition, a pharmacological antiviral profile of LA is emerging, that has attracted attention on the possible use of this compound for the cotreatment of several viral infections. Here, we will review the emerging literature on the potential use of LA in viral infections, including COVID-19.

scholarly journals Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

2009 ◽  
Vol 1790 (10) ◽  
pp. 1149-1160 ◽  
Author(s):  
Kate Petersen Shay ◽  
Régis F. Moreau ◽  
Eric J. Smith ◽  
Anthony R. Smith ◽  
Tory M. Hagen
Keyword(s):  
Dietary Supplement ◽  
Lipoic Acid ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Alpha Lipoic Acid
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