Search Results (157)

Alpha-lipoic acid (ALA) is a naturally occurring organosulfur compound with antioxidant and anti-inflammatory activities. The time-dependent effects of ALA and mechanism of interaction with cystathionine-γ-lyase (CSE—an enzyme responsible for hydrogen sulfide—H₂S synthesis) in RAW 264.7 macrophages remain unknown. In this study, we report results supporting the hypothesis that anti-inflammatory effects of ALA are associated with the reduction in CSE expression. To investigate the temporal effect of ALA in lipopolysaccharide (LPS—a potent stimulator of inflammation) treated RAW 264.7 macrophages, ALA was administered 1 h before LPS stimulation and 1, 3, and 6 h post LPS stimulation. Effects of ALA on different inflammatory and oxidative stress biomarkers including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), catalase activity (CAT), and malondialdehyde (MDA) levels were investigated. LPS stimulation significantly increased TNF- α, IL-6, MCP-1, MDA levels, and CSE expression and decreased CAT activity compared with the control group (p < 0.05 to 0.0001). ALA treatment at 1000 µM significantly attenuated LPS-stimulated inflammatory response in the macrophages across different time points (p < 0.05 to 0.0001). Furthermore, we found that ALA treatment reduced the expression of CSE in both pre- and post-treated LPS-stimulated macrophages in a time-dependent manner. In conclusion, this study demonstrated for the first time that the protective effects of ALA are dependent on the reduction in CSE expression in LPS-stimulated RAW 264.7 macrophages. Full article

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration. Full article

Background: Neuropathic pain is a complex condition often resistant to current therapies due to limited efficacy and adverse effects. Nutraceuticals offer promising alternatives, combining antioxidant and anti-inflammatory properties with good tolerability. This study aimed to compare the effects of a commercial nutraceutical formulation, SUPERALA CARNITINE^® (Pharma Suisse Laboratories SpA, Milan, Italy), containing Alpha-Lipoic Acid (ALA), with a novel formulation, called SUPERALA CARNITINE^® Forte, where ALA and vitamin B6 were replaced by N-acetylcysteine (NAC), Glutathione (GSH), and Uridine monophosphate (UMP). Methods: An indirect gut–peripheral nerve axis was employed to simulate oral absorption, metabolism, and effect on nervous tissues using 3D in vitro models. Both formulations and their individual components were assessed for cytotoxicity and permeability in the gut model (Caco-2 cells in Transwell^®) and, after gut metabolism, for antioxidant capacity, anti-inflammatory activity, and neuroprotective potential in the peripheral nerve model. Results: SUPERALA CARNITINE^® Forte improved cell viability and favoured the maintenance of intestinal integrity, showing enhanced permeability, and significantly reduced oxidative stress (OS) and pro-inflammatory cytokines (TNF-α, IL-2) at the peripheral nervous system. In addition, it increased levels of neuronal markers (p75, MPZ, NRG1, ERβ) and decreased NaV1.7 and NaV1.8 activity, indicating greater neuroprotection and analgesic modulation than the ALA-based formula. Conclusions: The replacement of ALA and vitamin B6 with NAC, GSH, and UMP produced favorable responses in vitro on neuronal cells, supporting a hypothetical potential interest in this nutraceutical combination and justifying further future in vivo investigations. Full article

Background/Objective: Electromagnetic radiation (EMR) from wireless technologies has raised concerns about male reproductive health. We aimed to evaluate the protective role of alpha-lipoic acid (ALA), a potent antioxidant, against testicular alterations induced by 2.45 GHz EMR. Methods: Twenty-eight adult male rats were randomly divided into four groups: control, EMR, ALA, and ALA+EMR. Animals in the EMR and ALA+EMR groups were exposed to EMR for 2 h/day for 1 month. Testicular tissues were examined histologically, stereologically, and immunohistochemically, while serum samples were analysed biochemically. Results: EMR exposure caused marked structural damage, including disruption of seminiferous tubule architecture, increased collagen deposition, and expansion of tubular and interstitial volumes. These pathological changes were primarily prevented in the ALA+EMR group. Immunohistochemical analyses revealed increased IL-6 and TNF-α expression following EMR exposure, whereas ALA supplementation significantly reduced these inflammatory markers and restored AR, ZO-1, and ZO-2 expression. Biochemically, EMR reduced antioxidant enzyme activities (SOD, GSH, GPx) and elevated MDA levels, indicating oxidative stress; these parameters were reversed by ALA treatment. Conclusions: Collectively, our findings demonstrate that 2.45 GHz EMR induces oxidative stress, inflammation, and testicular injury, while ALA provides significant protection. These results highlight the therapeutic potential of ALA as a protective agent against EMR-related reproductive toxicity and infertility risk. Full article

Background: Melasma is a chronic hyperpigmentation disorder, often therapy-resistant. Minimally invasive combinations of chemical stimulators and serums show promise. This study evaluated trichloroacetic acid stabilized with hydrogen peroxide and kojic acid, plus a serum with niacinamide, tranexamic acid, lactoferrin, ferulic acid, alpha-lipoic acid, and physic acid. Methods: Ten female volunteers with clinically diagnosed melasma underwent six treatment sessions. Each procedure involved application of the chemical stimulator followed by the serum, with strict photoprotection advised. Clinical improvement was assessed using the modified Melasma Area and Severity Index (mMASI) by three independent experts. Objective analysis of pigmentation and texture was performed with photographic documentation processed by the Grey Level Co-Occurrence Matrix (GLCM), measuring contrast and homogeneity in selected facial regions. Results: After six treatments, significant improvement was observed. Mean mMASI scores decreased by 62.3% after 2 weeks and 62.9% after 8 weeks. GLCM confirmed pigmentation reduction, showing decreased contrast and increased homogeneity across all regions, with the chin responding best. Correlation analysis indicated a positive trend between mMASI reduction and contrast changes. No serious adverse events or post-inflammatory hyperpigmentation were reported. Conclusions: The combined protocol significantly reduced melasma hyperpigmentation both clinically and objectively. GLCM analysis complements traditional scales and may provide a valuable quantitative tool for future research. Full article

Alpha-lipoic acid (ALA) is well-known for its antioxidant and anti-inflammatory functions in various disease models. Here, we tested whether pre-exposure to ALA can protect the testes from cellular damage caused by scrotal heat shock (HS) in mice. Methods: Thirty-six Swiss albino mice were divided into control (CTRL, n = 6), HS (n = 10), and two ALA dose (HS + ALA 200 mg/kg, n = 10; and HS + ALA 400 mg/kg, n = 10) groups. ALA supplementation was administered orally for 30 days. Subsequently, the animals, except the controls, were subjected to an HS water bath at 43 °C for 20 min. Two days later, they were euthanized, and biometric data from gonads and accessory sexual glands, testicular samples for histomorphometric and immunohistochemical analyses, and sperm from the epididymis cauda were obtained for evaluation. Results: Animals submitted to HS had a lower body weight, decreased relative mass of testes and prostate, reduced seminiferous epithelium height and tubular diameter, and increased degeneration in seminiferous tubules. Additionally, sperm analysis showed a reduced linear progressive velocity (VSL) and straightness (STR), increased midpiece defects, and fewer sperm with functional membranes. Immunohistochemical evaluation revealed a reduced superoxide dismutase (SOD1) staining intensity in the testes. Preventive exposure to ALA at 200 mg/kg did not normalize the relative testicular mass, but it reduced the number of giant cells, decreased midpiece defects, normalized the number of sperm with functional membranes, and partially preserved SOD1 expression. Although animals treated with ALA 400 mg/kg showed an improvement in relative testicular mass, this dose was less efficient in other parameters. Conclusions: This study showed that while 30 days of oral ingestion of ALA before the induction of acute degenerative injury did not fully protect male mouse gonads at the tissue level, some parameters related to testicular function and sperm quality showed a partial improvement. Full article

Readily degradable low-dose hydrate inhibitors are of great significance for flow assurance in the petroleum industry. Recently, α-lipoic acid (LA) was shown to undergo ring-opening reaction via reversible addition–fragmentation chain-transfer copolymerization with acrylamides to introduce labile disulfide bonds into the stable vinyl polymer backbone. Here, LA was copolymerized with acryloyl morpholine (AM) to evaluate their performance as kinetic hydrate inhibitors. Degradability was confirmed for the copolymers with 20 mol.% LA (AM/LA20, M_n = 19 → 9 kDa) after disulfide reduction. Thermogravimetric analysis also indicated faster thermal degradation of AM/LA due to the incorporation of weaker S-S and S-C linkages. Increasing LA content reduced hydrophilicity, and the copolymers were treated with NaOH to ensure water solubility. However, at 700 ppm, poly(AM) homopolymer reduced methane consumption during hydrate growth to 54% with respect to the uninhibited system, while gas consumption for the carboxylate AM/LA20 reached 78%. An advantageous feature of LA is its carboxylic acid, allowing desired functionalities to be grafted onto the degradable copolymer. Isopropyl amine (IPAm) was coupled with LA to form an amide known to be effective during hydrate inhibition (LA(IPAm)). The copolymer AM/LA(IPAm)20 demonstrated better water solubility compared to the original AM/LA20. Furthermore, the desirable IPAm functionality allowed the hydrate inhibition to be re-established at 54%, nearly recovering the performance of the poly(AM) homopolymer. This article assesses the application of LA and LA derivatives as building blocks for degradable amide-based kinetic hydrate inhibitors by validating their degradability with material characterizations and their inhibition performance during structure I hydrate growth. Full article

Pain remains a major clinical challenge due to its complex physiopathology and limited treatment options. In this context, several supplements based on palmitoylethanolamide (PEA) and alpha-lipoic acid (ALA) are known for their neuroprotective properties. ALA-based supplements have shown potential, but concerns about adverse effects persist. This study examines the formulations of two commercial products based on ALA and PEA, IperALA^® and IperALA^® Forte, in which ALA and vitamin D3 are replaced with Coriandrum sativum extract (C. sativum e.s.), N-acetylcysteine (NAC) and glutathione (GSH), assessing improvement of neuroprotective, anti-inflammatory and analgesic properties of the new formulation. Intestinal, blood–brain barrier (BBB), and central nervous system (CNS) models were sequentially stimulated with the test compounds. Both formulations were assessed for cytotoxicity, barrier integrity, permeability, oxidative stress, inflammation, and neuroprotection-related biomarkers. IperALA^® Forte demonstrated superior performance compared to IperALA^® and individual agents. It enhanced cell viability, preserved intestinal and BBB integrity, and improved compound permeability. Notably, it reduced ROS and pro-inflammatory cytokines (TNFα, IL-1), while increasing analgesic markers (CB2R, GABA) in the central system. The replacement of ALA and vitamin D3 with C. sativum, NAC, and GSH in IperALA^® Forte significantly improved the neuroprotective, antioxidant, and anti-inflammatory profile of the supplement. These results indicate a possible connection between the observed neuroprotective properties and the pathways involved in nociception and pain regulation, stating the hypothetical potential relevance of this approach for the treatment of pain-related conditions. Full article

Alcohol misuse can lead to alcohol-related brain damage (ARBD), a condition linked to long-term cognitive impairment and considerable disease burden. The pharmacological characteristics of alpha-lipoic acid (ALA) make it a promising candidate for the treatment of ARBD. In this study, adult male Wistar rats were divided into eight experimental groups. Four groups received a 20% (v/v) ethanol–tap water solution ad libitum for 15 weeks to induce early-stage ARBD, while the remaining received only tap water. After 14 weeks, all groups were administered daily injections for one week with either ALA, rivastigmine, or memantine. Behavioral testing included the step-through passive avoidance and rotarod performance tests. Whole-brain biochemical analyses assessed acetylcholinesterase activity, brain-derived neurotrophic factor, and oxidative stress biomarkers. Brain weight, relative brain weight, and brain histopathological changes were also evaluated. Results showed that, similar to memantine and rivastigmine, ALA improved STL at both 24 h and 8 days and reduced ethanol-induced Purkinje cell damage. It also decreased lipid peroxidation levels by 44%, unlike the reference drugs, and superoxide dismutase activity by 33%, similar to them. No other significant changes were detected. Albeit several limitations, this is the first study comparing ALA with rivastigmine and memantine in this experimental context. Full article

Background/Objectives: This systematic review and meta-analysis evaluated the effectiveness of olfactory training (OT) using standardized protocols in patients with post-COVID-19 olfactory dysfunction. The objective was to assess whether OT, compared to no treatment, placebo, or alternative therapies, improved olfactory function as measured using validated smell tests, including UPSIT, Sniffin’ Sticks (TDI score), CCCRC, and B-SIT. Methods: A systematic search of PubMed, Web of Science, and Ovid Medline was conducted through February 2025 in accordance with PRISMA guidelines. Eight randomized controlled trials (RCTs) met the inclusion criteria. Data were extracted on study characteristics (author, year, country, design, sample size), population details (age, sex, post-COVID-19 cause), intervention type (training method, frequency, duration), comparators, outcome measures (baseline and post-intervention olfactory scores), follow-up duration, and reported adverse effects. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analyses were performed using RevMan and Open Meta-Analyst. Results: Olfactory training significantly improved the olfactory scores compared to those of the controls. The greatest improvement was observed when OT was combined with PEA-luteolin (MD = 4.62, 95% CI: 2.17–7.06, p = 0.0002), followed by EDTA (MD = 2.33, 95% CI: 0.58–4.08, p = 0.009). Corticosteroids showed a borderline benefit (MD = 1.34, 95% CI: 0.01–2.67, p = 0.05), while alpha-lipoic acid had no significant effect. Combination therapies were associated with higher recovery rates (RR = 1.65, 95% CI: 1.13–2.42, p = 0.01). Conclusions: Olfactory training is an effective treatment for post-COVID-19 smell dysfunction. When paired with specific adjunct therapies, particularly PEA-luteolin, it may yield superior recovery outcomes. Further large-scale, standardized RCTs are needed to define optimal treatment protocols. Full article

In the context of expanding research on the development of compounds with multiple therapeutic actions, this study aims to consolidate findings from the last decade on new synthetic sulfonamide therapies for managing type 2 diabetes mellitus (T2DM) associated with oxidative stress (OS). The novelty of this synthesis study lies in the synergistic approach of antidiabetic molecular targets with those against oxidative stress, having the sulfonylurea class as a common point. By utilizing international databases, we identified and selected conclusive studies for this review. Promising results have been achieved through dual therapies that combine antioxidants (such as sesame oil, naringin, alpha-lipoic acid, resveratrol, and quercetin) with sulfonylureas (including glipizide, glibenclamide, gliclazide, and glimepiride). Additionally, triple therapies that associated sulfonylureas with other classes of antidiabetic medications have also shown encouraging outcomes. These findings are supported by in vivo tests conducted on experimental laboratory models as well as on human subjects. These recent advancements in synthetic sulfonamide research point to a promising future in diabetes management, especially considering the dual functionalities demonstrated by in vivo studies—specifically, their antidiabetic and antioxidant effects. Moreover, the synergy between sulfonamides and other antioxidant agents represents a beneficial strategy for optimizing future chemical structures, potentially allowing for their integration into personalized treatments aimed at combating T2DM. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

Diabetic encephalopathy affects over 40% of diabetic patients globally, yet effective treatments remain critically limited. This study investigated the synergistic neuroprotective potential of alpha-lipoic acid (ALA) and metformin through the coordinated activation of Nrf2 and AMPK signaling pathways in type 2 diabetes mellitus (T2DM)-induced encephalopathy. Using a clinically relevant streptozotocin-nicotinamide-induced T2DM rat model, sixty male Sprague–Dawley rats were randomly assigned to five groups: control, diabetic, ALA-treated (300 mg/kg), metformin-treated (50 mg/kg), and combination-treated groups over eight weeks. Combination therapy produced statistically validated synergistic effects with significant interaction terms (p < 0.01) across all evaluated parameters. Nuclear Nrf2 translocation increased 3.9-fold and AMPK phosphorylation rose 3.2-fold compared to monotherapies, surpassing mathematical additivity. Mitochondrial function was remarkably restored, with ATP production increasing to 92% of control levels. Cognitive performance was normalized, with spatial memory approaching control values. Combination index analysis (CI < 1.0) confirmed true synergistic interactions across molecular, cellular, and behavioral endpoints. These findings establish a novel convergent mechanism providing compelling evidence for combination ALA–metformin therapy as an innovative treatment strategy for diabetes-associated neurodegeneration. Full article

Background/Objectives: This study aimed to evaluate the effects of four weeks of combined Acetyl-l-Carnitine and alpha-lipoic acid (ALA) supplementation on anaerobic and aerobic performance and fatigue resistance in trained cyclists, hypothesizing improvements in maximal aerobic power (MAP), Wingate test performance, and reduced lactate accumulation. Methods: In a double-blind, randomized trial, 41 male trained cyclists (age: 36 ± 12 years; MAP: 4.35 ± 0.60 W·kg⁻¹) were assigned to a supplement group (SUP, n = 19; 1200 mg/day Acetyl-l-Carnitine, 300 mg/day ALA, 1.1 mg Vitamin B1, 2.5 µg Vitamin B12) or placebo group (PLA, n = 22) for four weeks. Performance was assessed pre- and post-intervention via counter-movement jumps (CMJs), Wingate tests (WG₁, WG₂), and a graded exercise test (GXT). Blood lactate ([La⁻]) was measured post-Wingate. A three-way mixed ANOVA analyzed Wingate performance (session, order, and group), and a two-way ANOVA assessed MAP and fatigue effects. Results: MAP increased by 3.4% (314 ± 32 W to 324 ± 37 W; p = 0.005) with no group interaction (p = 0.457). Wingate peak power showed main effects for order (p < 0.001) and session (p = 0.011) but no group interaction (p = 0.676). SUP reduced [La⁻] by 1.5 mmol·L⁻¹ post-WG₂ in POST (p = 0.049). No significant group differences were found for CMJ or fatigue metrics. Conclusions: Four weeks of Acetyl-l-Carnitine and ALA supplementation did not enhance aerobic or anaerobic performance in trained cyclists, despite reducing blood lactate after high-intensity exercise, suggesting no ergogenic benefits. Full article