Lipoic Acid Research Articles

The effects of alpha-lipoic acid transdermal patch for local subcutaneous fat reduction: A randomized, placebo-controlled, clinical trial in overweight volunteers

BackgroundCombating obesity is challenging, as anti-obesity compounds lose effectiveness or cause severe side effects when delivered via conventional routes. Thus, there is a need for new, effective treatment routes that are home-based and safe for long-term use. This double-blind, placebo-controlled clinical trial aimed to investigate the efficacy of a biocellulose transdermal patch containing α-lipoic acid (ALA), an anti-obesity compound, in reducing subcutaneous fat accumulation. MethodsOne hundred and sixteen overweight participants (average age 37.96 ± 7.80 years) were recruited for the study. They were randomly assigned to apply either the calcium citrate nanoparticle-encapsulated ALA transdermal patch or a placebo on their arm. The participants’ body weight, height, blood lipid profile (cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein), arm circumference, triceps skin fold, and subcutaneous fat thickness were recorded at baseline and at the 2-week follow-up. ResultsThe mean arm circumference did not show any significant difference from baseline, whereas the triceps skinfold and subcutaneous fat thickness showed a significant reduction. The 2-week treatment did not significantly alter the plasma LDL, HDL, and triglyceride levels of the participants, but it significantly reduced the total cholesterol level. ConclusionThis study reports the successful reduction of subcutaneous fat of the calcium citrate nanoparticle-encapsulated ALA transdermal patches. The transdermal patches could be used as a safe and effective home-based solution for combating obesity.

Poly(thioctic acid) Hydrogels Integrated with Self-Healing, Bioadhesion, Antioxidation, and Antibiosis for Infected Wound Treatment.

Bacterial infections pose significant challenges in wound healing and are a serious threat to human health. Hydrogels have emerged as an ideal wound dressing due to their three-dimensional network, which facilitates exudate absorption and maintains a moist environment conducive to healing. Herein, we developed integrated hydrogels composed of poly(thioctic acid) (PTA), polydopamine (PDA), and curcumin (Cur). The formation of covalent and hydrogen bonds among PTA, PDA, and Cur endowed the hydrogels with excellent self-healing and bioadhesion properties. These hydrogels were utilized as dressings for healing Staphylococcus aureus-infected wounds. The PDA-PTA-Cur 16 hydrogel showed the best overall performance in stability, bioadhesion, antioxidant activity, and antibacterial effectiveness. The in vivo results revealed that the PDA-PTA-Cur 16 hydrogel accelerated infected wound healing by inhibiting bacterial growth, alleviating inflammation, promoting collagen deposition, and inducing angiogenesis. This multifunctional hydrogel not only enhances wound healing but also presents a promising strategy for combating bacterial infections in clinical settings.

Amelioration of Neuronal Deficits in Aged Rats Via Ganoderma Lucidum Extract Alone and Combination with Alpha Lipoic Acid

Amelioration of Neuronal Deficits in Aged Rats Via Ganoderma Lucidum Extract Alone and Combination with Alpha Lipoic Acid

An advanced chitosan based sponges dressing system with antioxidative, immunoregulation, angiogenesis and neurogenesis for promoting diabetic wound healing

Promoting wound nerve regeneration and synchronously initiating angiogenesis are critical factors in the healing process of diabetic wounds. However, existing research on diabetic wounds mainly focuses on angiogenesis, bacterial infection and reactive oxygen species, often failing to coordinate neurogenesis and angiogenesis. To coordinate the symbiosis of nerves and blood vessels in the diabetic wounds, we successfully designed a multifunctional chitosan (CS)-based sponges by regulating the structure of CS specifically for diabetic wound healing. This sponge, which facilitates effective exudate transfer and modulates the wound microenvironment, was constructed using hydroxybutyl CS grafted with thioctic acid (TA), named as HCT sponge. When applied in a humid environment, the hydrophobic side chains of the HCT sponge interact with self-assembled hydrophobic domains, forming gel-sponge composite. Experimental results showed that the adhesion strength of the HCT sponge to wet porcine skin was 70.3 kPa. Additionally, the sponge exhibited favorable degradability, cytocompatibility and antioxidant properties. As it is shown in the experiments in vitro, sponge can not only promote cell proliferation, migration, and blood vessel formation, but also promote M2 macrophage polarization. Moreover, the rat liver and femoral artery injury model validated that the HCT sponge can effectively treat heavy bleeding from wounds efficacy through quickly sealing wounds and the formation of multiple hemostatic dams. In vivo studies indicated that the HCT sponge significantly accelerated the diabetic wound healing process compared to the recombinant bovine basic fibroblast growth factor gel, achieving a better recovery from the HCT sponge after 15 days. Pathological results show that the designed novel sponge holds considerable promise for treating diabetic wound, allowing regenerative neurogenesis and angiogenesis at the wound site, which provides a significant potential for further improving clinical applications.

Exploring α-Lipoic Acid Based Thermoplastic Silicone Adhesive: Towards Sustainable and Green Recycling

Exploring α-Lipoic Acid Based Thermoplastic Silicone Adhesive: Towards Sustainable and Green Recycling

Effects of alpha-lipoic acid and sildenafil citrate on sperm quality in asthenozoospermic men during freezing-thawing processes

We aimed to investigate the combined effects of alpha-lipoic acid (ALA) and sildenafil citrate (SC) on sperm quality during freeze-thawing in asthenozoospermic men. We categorized thirty semen samples from asthenozoospermic into five different groups for analysis: Control (fresh), Freeze, Freeze + SC, Freeze + ALA, and Freeze + SC + ALA. We evaluated sperm parameters in each group, including motility, viability, morphology, plasma membrane integrity, DNA fragmentation, mitochondrial membrane potential, protamine deficiency, acrosome integrity, malondialdehyde, tumor necrosis factor-alpha (TNF-α), antioxidants (Superoxide dismutase, Glutathione, Catalase), and gene expression of HSP70 and Bcl-2. The Freeze group showed significant declines in viability, motility, morphology, membrane integrity, antioxidants, and mitochondrial membrane potential, with increases in protamine deficiency, abnormalities, DNA fragmentation, TNF-α, and malondialdehyde compared to control (p = 0.000). These effects were significantly reversed in all treatment groups (p = 0.000). Bcl-2 and HSP70 expression increased significantly in all groups (p = 0.000). Acrosomal integrity decreased significantly (p = 0.000) in the Freeze group compared to controls and in the Freeze + SC group compared to the Freeze group. However, acrosomal integrity significantly increased (p = 0.000) in the Freeze + SC + ALA group compared to the Freeze + SC group and in the Freeze + ALA group compared to other treatments. Our findings indicate that the simultaneous addition of SC and ALA in the freezing media yielded increased sperm quality. This enhancement was evidenced by reductions in oxidative stress, inflammation, and apoptosis, along with partial prevention of premature acrosome reactions induced by SC.

Alpha-lipoic acid, as an effective agent against toxic elements: a review

Alpha-lipoic acid, as an effective agent against toxic elements: a review

Effects of Short-Term Treatment with α-Lipoic Acid on Neuropathic Pain and Biomarkers of DNA Damage in Patients with Diabetes Mellitus.

Diabetes mellitus (DM) is a complex and heterogenous disease classified as a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. It leads to various complications, some of which are macrovascular or microvascular complications, like diabetic polyneuropathy (DPN), having a profound impact on patients' quality of life. Oxidative stress (OS) is one of the significant mechanisms in the development and progression of DPN. Thus, targeting OS pathways by antioxidants, such as α-lipoic acid (ALA), could represent a promising therapeutic strategy for alleviating neuropathic symptoms. The aim of our study was to evaluate whether short-term (from 4 to 9 days) intravenous administration of ALA could cause any measurable improvement in subjects with DM. Sixteen subjects with DM (six type 1 and ten type 2) and sixteen nondiabetic subjects matched by sex and age were recruited to this study. Only subjects with DM received treatment with ALA (600 mg daily). Pain intensity and biomarkers of DNA damage including plasma concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), frequency of micronucleated lymphocytes (MN), and frequency of sister-chromatid exchanges (SCEs), were measured before and after the treatment with ALA. Pain intensity and 8-OHdG levels were significantly lower in DM subjects after the ALA treatment than before the treatment. However, no changes in the frequency of SCEs and MN were observed. Our results show some evidence that even a short-term intravenous treatment with ALA could be beneficial for diabetic subjects, reducing pain intensity and concentration of 8-OHdG in blood plasma.

Nuclear PD-L1 compartmentalization suppresses tumorigenesis and overcomes immunocheckpoint therapy resistance in mice via histone macroH2A1.

Canonically PD-L1 functions as the inhibitory immune checkpoint on cell surface. Recent studies have observed PD-L1 expression in the nucleus of cancer cells. But the biological function of nuclear PD-L1 (nPD-L1) in tumor growth and antitumor immunity is unclear. Here we enforced nPD-L1 expression and established stable cells. nPD-L1 suppressed tumorigenesis and aggressiveness in vitro and in vivo. Compared with PD-L1 deletion, nPD-L1 expression repressed tumor growth and improved survival more markedly in immunocompetent mice. Phosphorylated AMPKα (p-AMPKα) facilitated nuclear PD-L1 compartmentalization and then cooperated with it to directly phosphorylate S146 of histone variant macroH2A1 (mH2A1) to epigenetically activate expression of genes of cellular senescence, JAK/STAT, and Hippo signaling pathways. Lipoic acid (LA) that induced nuclear PD-L1 translocation suppressed tumorigenesis and boosted antitumor immunity. Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.

Transcriptomic and Metabolomic Insight into the Roles of α-Lipoic Acid in the Antioxidant Mechanisms of Sheep

Transcriptomic and Metabolomic Insight into the Roles of α-Lipoic Acid in the Antioxidant Mechanisms of Sheep

Ocular motor mononeuropathies in diabetes mellitus: A brief review.

Ocular motor mononeuropathies affect cranial nerves III, IV and VI and are more frequent in diabetes mellitus, with oculomotor nerve involvement being predominant. The aim of this narrative brief review was to discuss the clinical manifestations, diagnosis and management of ocular motor nerve palsies in subjects with diabetes. Clinical manifestations often include ptosis, diplopia, and periorbital pain. A characteristic of third nerve palsy is pupillary sparing. Differential diagnosis may be challenging due to overlapping symptoms with nerve palsies of other aetiologies. Treatment includes optimised glycaemic control and management of vascular risk factors. Neuroprotective agents, mainly alpha-lipoic acid and botulinum toxin A have been occasionally used, as well. Spontaneous recovery is also seen in many cases.

THERAPEUTIC USE OF ALPHA-LIPOIC ACID SUPPLEMENTATION: A REVIEW ON CURRENT USE AND FUTURE PROSPECTIVE

Alpha-lipoic acid (ALA, thioctic acid, 5-(1,2-dithiolan-3-yl) pentanoic acid) is an organosulfur compound produced by plants, humans, and animals. ALA plays a crucial role in mitochondrial bioenergetics reactions. It is a natural antioxidant and a dithiol compound. ALA is a coenzyme that plays a crucial role in the function of pyruvate and Alpha-ketoglutarate dehydrogenase complexes found in mitochondria. ALA has cytotoxic and antiproliferative effects on several cancers, including Polycystic Ovarian Syndrome (PCOS). Most of ALA's clinical applications come from its antioxidant properties, but it also shows potential in treating female and male infertility. Although ALA can potentially be a therapeutic agent, its pharmacokinetic profile limits its effectiveness. Research suggests that ALA has a short half-life and low bioavailability (around 30%) because it gets broken down in the liver, has reduced solubility, and is unstable in the stomach. Liquid formulations have higher bioavailability and plasma concentration than solid dose forms. This review covers the current clinical evidence on using ALA to prevent, manage, and cure numerous disorders, including diabetic neuropathy, obesity, central nervous system-related ailments, and pregnancy abnormalities.

Rhomboid-like 2 correlated with TME infiltration inhibits cuproptosis-related genes and drives malignant phenotype in clear cell renal cell carcinoma

The crosstalk between cuproptosis and the tumor immune microenvironment (TIME) is vital during clear cell renal cell carcinoma (ccRCC) malignant progression. However, the underlying molecular mechanisms regulate this cross-talk remain elusive. Through tailored machine learning, we analyze clinical ccRCC data from The Cancer Genome Atlas (TCGA) to explore the critical factors that regulate the interaction among cuproptosis, TIME, and tumor progression. We found that rhomboid-like 2 (RHBDL2), critical gene affecting this process, might inhibit cuproptosis-related genes (CRGs) and promotes ccRCC progression through the Wnt/β-catenin pathway. Next, knocking down RHBDL2 expression increased the cuproptosis-related genes ferredoxin 1 (FDX1) and lipoic acid synthase (LIAS) levels but reduced forkhead box P3 (FOXP3) levels and tumor growth in vivo and in vitro models. By employing HLY78, Wnt/β-catenin pathway activator, we rescued the expression of CRGs and the malignant proliferation and metastasis capacity in ccRCC cells with RHBDL2 knockdown. Mechanistically, RHBDL2 inhibits cuproptosis and promotes malignant progression of ccRCC through the Wnt/β-catenin pathway. Abnormal RHBDL2 expression may cause the suppressive TIME formation by regulating Treg-cell infiltration, thus triggering immune escape. In summary, our results indicated that RHBDL2 is an oncogene that induces tumorigenesis and targeting RHBDL2 may be novel therapeutic direction for metastatic ccRCC.

Highly Elastic, Fatigue-Resistant, and Antifreezing MXene Functionalized Organohydrogels as Flexible Pressure Sensors for Human Motion Monitoring.

Conductive organohydrogels-based flexible pressure sensors have gained considerable attention in health monitoring, artificial skin, and human-computer interaction due to their excellent biocompatibility, wearability, and versatility. However, hydrogels' unsatisfactory mechanical and unstable electrical properties hinder their comprehensive application. Herein, an elastic, fatigue-resistant, and antifreezing poly(vinyl alcohol) (PVA)/lipoic acid (LA) organohydrogel with a double-network structure and reversible cross-linking interactions has been designed, and MXene as a conductive filler is functionalized into organohydrogel to further enhance the diverse sensing performance of flexible pressure sensors. The as-fabricated MXene-based PVA/LA organohydrogels (PLBM) exhibit stable fatigue resistance for over 450 cycles under 40% compressive strain, excellent elasticity, antifreezing properties (<-20 °C), and degradability. Furthermore, the pressure sensors based on the PLBM organohydrogels show a fast response time (62 ms), high sensitivity (S = 0.0402 kPa-1), and excellent stability (over 1000 cycles). The exceptional performance enables the sensors to monitor human movements, such as joint flexion and throat swallowing. Moreover, the sensors integrating with the one-dimensional convolutional neural networks and the long-short-term memory networks deep learning algorithms have been developed to recognize letters with a 93.75% accuracy, representing enormous potential in monitoring human motion and human-computer interaction.

Comparative efficacy and safety of Chinese patent medicines as an adjunctive therapy for diabetic peripheral neuropathy: systematic review and network meta-analysis of randomized controlled trials

Context Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN. Objective This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN. Materials and methods We conducted searches for randomized controlled trials (RCTs) evaluating CPMs in conjunction with mecobalamin (Mec) or alpha-lipoic acid (αLA) across eight databases up to July 2024. The surface under the cumulative ranking area (SUCRA) was utilized to assess the clinical efficacy rate (CER), the peroneal motor nerve conduction velocity (pMNCV), the peroneal sensory nerve conduction velocity (pSNCV), the median motor nerve conduction velocity (mMNCV), and the median sensory nerve conduction velocity (mSNCV). Results The search yielded 128 eligible studies with 31 CPMs with Mec and 39 eligible studies with 17 CPMs with αLA. SUCRA rankings indicated that, when combined with Mec, Mailuoning liquid (lMLN) was the most effective regimen for CER, Honghua injection (iHH) for pMNCV, Maixuekang capsule (cMXK) for pSNCV, Dengzhanxixin injection (iDZXX) for mMNCV, and Tongxinluo capsule (cTXL) for mSNCV. Combined with αLA, Danhong injection (iDH) showed the highest efficacy for CER, pSNCV, and mSNCV, while Xueshuantong injection (iXShT) was the most effective for pMNCV and mMNCV. Conclusion This network meta-analysis confirms the efficacy and safety of 37 CPMs combined with Mec or αLA for treating DPN. However, given the potential risk of bias and the very low certainty of the evidence, these recommendations should be adopted with caution.

Enhanced Asymmetric Circularly Polarized Luminescence in Self-Organized Helical Superstructures Enabled by Macro-Chiral Liquid Crystal Quantum Dots.

Circularly polarized luminescent (CPL) materials have garnered considerable interest for a variety of advanced optical applications including 3D imaging, data encryption, and asymmetric catalysis. However, the development of high-performance CPL has been hindered by the absence of simple synthetic methods for chiral luminescent emitters that exhibit both high quantum yields and dissymmetry factors. In this study, we present an innovative approach for the synthesis of macro-chiral liquid crystal quantum dots (Ch-QDs/LC) and their CPL performance enhancement through doping with 4-cyano-4'-pentylbiphenyl (5CB), thus yielding a CPL-emitting generator (CEG). The Ch-QDs/LCs were synthesized, and their surfaces functionalized with a chiral mesogenic ligand, specifically cholesteryl benzoate, anchored via a lipoic acid linker. Under the regulation of chiral 2S-Zn2+ coordination complexes, the chiral LC encapsulation process promotes coordinated ligand substitution, resulting in an exceptional quantum yield of 56.3%. This is accompanied by high absorption dissymmetry factor (gabs) and luminescence dissymmetry factor (glum) values ranging from 10-3 to 10-2, surpassing most reported dissymmetry factors by at least an order of magnitude. The modular Ch-QDs/LCs demonstrate the ability to transfer chirality to the surrounding medium efficiently and manifest macro-chiral characteristics within a nematic LC matrix. Utilizing Ch-QDs/LC as an effective CPL emitter within achiral 5CB matrices enabled the system to achieve a maximum glum value of 0.35. The resultant CEG device acted as a direct CPL source, initiating enantioselective photopolymerization.

Alpha-lipoic acid-mediated inhibition of LTB4 synthesis suppresses epithelial-mesenchymal transition, modulating functional and tumorigenic capacities in non-small cell lung cancer A549 cells

BackgroundLeukotriene B4 (LTB4) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB4 is mediated by leukotriene A4 hydrolase (LTA4H), and it binds to the receptors BLT1 and BLT2. Dysregulation in LTB4 production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB4 synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA4H. The objective of this study was to evaluate the effect of ALA on the expression of canonical EMT markers and the functional and tumorigenic capacities induced by LTB4 in A549 cells. MethodsThe expression of cPLA2, 5LOX, FLAP, LTA4H, BLT1, and LTB4 production in human adenocarcinomic alveolar basal epithelial A549 cells was assessed using Western blot, RT-qPCR, and ELISA, respectively. Subsequently, the expression of canonical EMT markers was evaluated by Western blot. Functional assays were performed to assess cell viability, proliferation, invasion, migration, and clonogenicity using MTT, Western blot, Transwell assays, and colony formation assays, respectively. Results were expressed as median with interquartile range (n≥3) and analyzed using the Kruskal-Wallis or Tukey multiple comparisons tests. ResultsA549 cells express key proteins involved in LTB4 synthesis and receptor binding, including LTA4H and BLT1, and ALA inhibits the production of LTB4. Additionally, LTA4H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB4 was found to induce EMT, whereas ALA treatment enhanced the expression of epithelial markers and reduced the expression of mesenchymal markers. Furthermore, ALA treatment resulted in a decrease in LTB4 levels and attenuated the functional and tumorigenic capacities of A549 cells, including their viability, migration, invasion, and clonogenic potential. ConclusionsThese findings suggest that ALA may offer therapeutic potential in the context of lung cancer, as it could be integrated into conventional pharmacological therapies to enhance treatment efficacy and mitigate the adverse effects associated with chemotherapy. Further studies are warranted to confirm the clinical applicability of ALA as an adjunctive treatment in lung cancer.

Antioxidant and antiplatelet effect of nanodispersions with conjugate of glutathione and lipoic acid

To increase the therapeutic effectiveness of antioxidants (lipoic acid and glutathione) and improve their transport to target cells, various methods of modifying its substances are used. In this work, the synthesis of an amide derivative of lipoic acid and glutathione (GSH–LA) is performed, and GSH–LA nanodispersions based on Pluronic F68 are obtained. The most pronounced antioxidant and antiplatelet effects are exhibited by nanoparticles containing GSH–LA at the maximum tested concentration.

Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency

Protein lipoylation, a vital lysine posttranslational modification (PTM), plays a crucial role in the function of key mitochondrial TCA cycle enzymatic complexes. In eukaryotes, lipoyl PTM synthesis occurs exclusively through de novo pathways, relying on lipoyl synthesis/transfer enzymes, dependent upon mitochondrial fatty acid and Fe-S cluster biosynthesis. Dysregulation in any of these pathways leads to diminished cellular lipoylation. Efficient restoration of lipoylation in lipoylation deficiency cell states using either chemical or genetic approaches has been challenging due to pathway complexity and multiple upstream regulators. To address this challenge, we explored the possibility that a bacterial lipoate protein ligase (lplA) enzyme, that can salvage free lipoic acid bypassing the dependency on de novo synthesis, could be engineered to be functional in human cells. Overexpression of the engineered lplA in lipoylation null cells restored lipoylation levels, cellular respiration, and growth in low glucose conditions. Engineered lplA restored lipoylation in all tested lipoylation null cell models, mimicking defects in mitochondrial fatty acid synthesis (MECR KO), Fe-S cluster biosynthesis (BOLA3 KO), and specific lipoylation regulating enzymes (FDX1, LIAS and LIPT1 KOs). Furthermore, we describe a patient with a homozygous c.212C>T variant LIPT1 with a previously uncharacterized syndromic congenital sideroblastic anemia. K562 erythroleukemia cells engineered to harbor this missense LIPT1 allele recapitulate the lipoylation deficient phenotype and exhibit impaired proliferation in low glucose that is completely restored by engineered lplA. This synthetic approach offers a potential therapeutic strategy for treating lipoylation disorders.

Synthesis, Structure, and In Vitro Biological Evaluation of Semi-Synthetic Derivatives of Betulin

Betulin and α-lipoic acid are naturally occurring substances with different biological properties. Combining two phytochemical units into a conjugate is a frequently used method to obtain new compounds with better pharmacokinetic parameters. This research concerned the preparation of lipoate derivatives of betulin using the Steglich method. Experimental lipophilicity values were determined for target compounds 6–10 by reversed-phase thin-layer chromatography. In silico methods were used to calculate the physicochemical parameters and lipophilicity of new derivatives and to determine the probable directions of biological activity. α-Lipoic acid, betulin, and lipoate derivatives 6–10 were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, HCT116, MiaPaca-2, and Hs294T cancer cells. 3-(5-(1,2-Dithiolan-3-yl)pentanoyl))betulin 10 showed moderate anticancer activity against MV4-11, PC-3, and HCT116, with IC50 values in the range of 39.8–76.7 µM. The introduction of a dithiolate substituent at the C3 position in 28-acetylbetulin gave compound 9 the highest activity (IC50 = 37.9 µM), in the ratio of biphenotypic B myelomonocytic leukemia cells (MV4-11). All lipoate derivatives were inactive towards normal cells.