Lipoic Acid Research Articles

Bioactive Compounds in Meat: Their Roles in Modulating Palatability and Nutritional Value

Meat’s global appeal, driven by its nutritional richness and sensory attributes, encompasses high-quality proteins, bioavailable iron, and various bioactive compounds, especially B12 and iron. Palatability, assessed via juiciness,tenderness, and flavor, enhances its desirability. Despite these merits, meat is susceptible to lipid and protein oxidation by generating secondary metabolites aldehydes and carbonyls. Endogenous carnosine and anserine act as scavengers of these metabolites, thus enhancing meat’s palatability. Additionally, meat houses an array of other bioactive compounds,including L-carnitine, taurine, conjugated linoleic acid, glutathione, alpha-lipoic acid, and bioactive peptides, each contributing to nutritional value of meat and exerting diverse physiological roles. This comprehensive review explores the various aspects of these bioactive compounds. Special emphasis is placed on carnosine and anserine, which exemplify the synergy of nutrition and palatability in the meat matrix. Insights into their pivotal roles in augmenting palatability and mitigating lipid oxidation offer a deeper understanding of the multifaceted benefits of bioactive compounds in meat

A silk-based hydrogel containing dexamethasone and lipoic acid microcrystals for local delivery to the inner ear

Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.

Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.

Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

Phytochemical analysis underlying membrane stabilization and anti-oxidant promising potentials of Acacia nilotica seed extract

Gentamicin induces gonadotoxicity in animal models, accompanied by oxidative stress. This study evaluated the histopathological protective effect of alpha-lipoic acid against gentamicin-induced gonadotoxicity. A parallel experimental study included 50 albino Wister rats, which were divided into 5 groups of ten according to the intraperitoneal intervention: group I received gentamicin, group II received gentamicin plus alpha-lipoic (100 mg/kg), group III received gentamicin plus a double dose of alpha-lipoic acid, group III received gentamicin plus oral vitamin E, and group IV received NaCl 0.9% (control). The animals were equally euthanized on days 15 and 16. Tests were dissected, prepared, and stained using a light microscope for histopathological examination. Rats exposed to gentamicin showed degeneration of seminiferous tubules, characterized by a significant decrease in germinal epithelial cells, impaired Spermatogenesis, and a lack of spermatozoa in the lumen. An improvement in testes of animals co-treated with alpha-lipoic acid or vitamin E, including restoration of Spermatogenesis and epithelial thickness. The histometric analysis also showed that the tubule epithelial thickness decreased when gentamicin was used, but this did not happen when alpha-lipoic acid or vitamin E was added simultaneously. The detrimental effects of gentamicin on testicular architecture are preventable through alpha-lipoic acid or vitamin E co-treatment. Keywords: Alpha-lipoic acid, Gonads, Histometric, Gentamicin, Seminiferous tubule, Spermatogenesis

Evaluating the protective effect of alpha-lipoic acid against gentamicin-induced gonadal toxicity indicated by histopathology.

Gentamicin induces gonadotoxicity in animal models, accompanied by oxidative stress. This study evaluated the histopathological protective effect of alpha-lipoic acid against gentamicin-induced gonadotoxicity. A parallel experimental study included 50 albino Wister rats, which were divided into 5 groups of ten according to the intraperitoneal intervention: group I received gentamicin, group II received gentamicin plus alpha-lipoic (100 mg/kg), group III received gentamicin plus a double dose of alpha-lipoic acid, group III received gentamicin plus oral vitamin E, and group IV received NaCl 0.9% (control). The animals were equally euthanized on days 15 and 16. Tests were dissected, prepared, and stained using a light microscope for histopathological examination. Rats exposed to gentamicin showed degeneration of seminiferous tubules, characterized by a significant decrease in germinal epithelial cells, impaired spermatogenesis, and a lack of spermatozoa in the lumen. An improvement in testes of animals co-treated with alpha-lipoic acid or vitamin E, including restoration of spermatogenesis and epithelial thickness. The histometric analysis also showed that the tubule epithelial thickness decreased when gentamicin was used, but this did not happen when alpha-lipoic acid or vitamin E was added simultaneously. The detrimental effects of gentamicin on testicular architecture are preventable through alpha-lipoic acid or vitamin E co-treatment. Keywords: Alpha-lipoic acid; Gonads; Histometric; Gentamicin; Seminiferous tubule; Spermatogenesis.

Nanodrug Hijacking Blood Transferrin for Ferroptosis-Mediated Cancer Treatment.

Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T10 on the surface of cross-linked lipoic acid vesicles (T10@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe2+ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe2+ to further boost the ferroptosis. The results disclosed that T10@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.

Enhancing healthy aging with small molecules: Amitochondrial perspective.

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5'-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Wearable and Recyclable Water-Toleration Sensor Derived from Lipoic Acid.

Flexible wearable sensors recently have made significant progress in human motion detection and health monitoring. However, most sensors still face challenges in terms of single detection targets, single application environments, and non-recyclability. Lipoic acid (LA) shows a great application prospect in soft materials due to its unique properties. Herein, ionic conducting elastomers (ICEs) based on polymerizable deep eutectic solvents consisting of LA and choline chloride are prepared. In addition to the good mechanical strength, high transparency, ionic conductivity, and self-healing efficiency, the ICEs exhibit swelling-strengthening behavior and enhanced adhesion strength in underwater environments due to the moisture-induced association of poly(LA) hydrophobic chains, thus making it possible for underwater sensing applications, such as underwater communication. As a strain sensor, it exhibits highly sensitive strain response with repeatability and durability, enabling the monitoring of both large and fine human motions, including joint movements, facial expressions, and pulse waves. Furthermore, due to the enhancement of ion mobility at higher temperatures, it also possesses excellent temperature-sensing performance. Notably, the ICEs can be fully recycled and reused as a new strain/temperature sensor through heating. This study provides a novel strategy for enhancing the mechanical strength of poly(LA) and the fabrication of multifunctional sensors.

Polysaccharides as Protective Agents against Heavy Metal Toxicity.

Polysaccharides are functional foods or drugs that can be used to alleviate heavy metal poisoning by cadmium, lead, mercury, and arsenic. Industries generate substantial quantities of toxic heavy metal wastes, such as wastewater discharges, paints, electronic waste, batteries, pigments, and plastics, into the environment that pose a risk to human health. Therefore, it is imperative to eliminate accumulated heavy metal ions from the body and the environment. Heavy metal toxicity can lead to decreased energy levels and impair the functioning of vital organs, such as the brain, lungs, kidneys, liver, and blood. Prolonged exposure can result in progressive physical, muscular, and neurological degeneration that resembles conditions such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, and muscular dystrophy. Polysaccharides operate through mechanisms such as chelation, antioxidant defense, immunomodulation, and tissue repair. Polysaccharides involved in heavy metal removal include methionine and cysteine, together with N-acetylcysteine, an acetylated form of cysteine, S-adenosylmethionine, a metabolite of methionine, α-lipoic acid, and the tripeptide glutathione (GSH). These compounds effectively bind with harmful heavy metals to create a stable complex and defend biological targets from metal ions, thus decreasing their harmful effects and causing them to be excreted from the body. This review also highlights the importance of polysaccharides' ability to mitigate oxidative stress, enhance immune responses, and support tissue repair processes. Polysaccharides are ubiquitous in nature and take part in diverse processes, making them potential natural therapies for heavy metal-related diseases. This review discusses the effectiveness of natural polysaccharides and the mechanisms that allow them to bind with heavy metals to alleviate their effects from the body and the environment. Polysaccharides have inherent features that enable them to function as pharmacological agents and regulate the immune response.

Protective effect of alpha‑lipoic acid against in utero cytarabine exposure-induced hepatotoxicity in rat female neonates.

Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA's protective effects against prenatal cytarabine-induced hepatotoxicity.

Purpald-functionalized biosensor for simultaneous electrochemical detection of ascorbic acid, uric acid, L-cysteine and lipoic acid

The polymer purpald (4-amino-3-hydrazino-5-mercapto-1,2,4-triazole) film on glassy carbon electrode (p-Purpald@GCE) was fabricated using purpald monomer by electropolymerization method, and the modified electrode was applied as a probe for the simultaneous sensing of ascorbic acid (AA), uric acid (UA), L-cysteine (L-Cys) and lipoic acid (LA). The modified p-Purpald@GCE was well characterized by Scanning electrode microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Cyclic Voltammetry (CV), Electrochemical impedance spectroscopy (EIS) and Differential Pulse Voltammetry (DPV) techniques. CV, EIS results were confirmed the good electrocatayst nature of p-Purpald@GCE. Independent and simultaneous detection of AA, UA, L-Cys, and LA ware performed by DPV method. For Independent detection, based on the oxidation current changes, we have calculated the limit of detection (LOD) of 392, 137, 341 and 200 nM (LOD) = 3S/m) for AA, UA, L-Cys and LA, respectively. The simultaneous detection of AA, UA, L-Cys, and LA executed and LOD found to be 364, 132, 275 and 192 nM, respectively. The modified electrode shows the high selectivity towards AA, UA, L-Cys and LA even in the presence of high concentration of other interferences. The developed sensor technique will be useful for the sensitive and simultaneous detection of AA, UA, L-Cys, and LA in food and clinical samples.

Citrus aurantifolia (Chrism.) Swingle peel extract attenuate nephrotoxicity induced by doxorubicin

BackgroundDoxorubicin (DOX) is an anthracycline antibiotic primarily utilized in the treatment of various solid tumors, including those affecting the cervix, ovaries, breasts, uterus, lungs, as well as certain blood cancers. However, the nephrotoxicity connected to DOX therapy restricts its clinical use. In an Ancient Chinese Medicine used Lime (Citrus. aurantifolia) Peel was employed to address cramps, colic pain, cold, and as an appetite stimulant. Lime is known as "Zhi qiao" in Traditional Chinese Medicine (TCM), in addition to its nephroprotective, antioxidant and immunostimulatory properties the peel had been noted for its effectiveness in regulating vital energy, used to treat cough, abdominal distention and constipation. ObjectiveThe purpose of this research is to evaluate the potential protective effect of Citrus aurantifolia peel extract (CAPE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. MethodsThirty Wister albino rats were randomly and equally separated into six groups (n = 5), and they were treated as follows: group I received distilled water only (baseline), toxicant groups administered with 15 mg/kg, i.p. DOX, 24 h after, groups II, III IV, V and VI were treated with distilled water (negative control), Alpha lipoic acid, 150 mg/kg (positive control) and 100, 200 and 400 mg/kg of CAPE respectively, orally for seven days. ResultsDOX caused kidney injury after a single intraperitoneal injection, as shown by substantial changes in kidney biomarkers, histological irregularities, and the reduction of antioxidant defense mechanisms (reduced glutathione, superoxide dismutase and catalase). CAPE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, albumin and uric acid), haematological parameters, antioxidative markers, and malondialdehyde. The present findings indicated that CAPE could reduce lipid peroxidation (LPO) and reactive oxygen species production, and observable histological improvements supported this result. ConclusionOur results point out that CAPE is a potential therapeutic alternative for the prevention of DOX-related nephrotoxicity.

Dendrobium officinale regulate lipid metabolism in diabetic mouse liver via PPAR-RXR signaling pathway: Evidence from an integrated multi-omics analysis

Dendrobium officinale (DEN) is recognized as a kind of functional food that can effectively ameliorate endocrine and metabolic disruptions. This study delved into the pharmacological mechanism of DEN on hepatic lipotoxicity associated with Type II diabetes mellitus (T2DM). In vivo study experiments on db/db mice indicated that DEN treatment notably enhanced liver function, decreased blood lipid levels, and improved insulin sensitivity. Non-targeted metabolomics analysis revealed that DEN significantly ameliorated metabolism pathways, including lipoic acid, linoleic acid, bile secretion, and the alanine/aspartate/glutamate metabolism, as well as taurine and hypotaurine metabolism. Transcriptomics analysis demonstrated DEN treatment could modulate the expression of genes such as Cpt1b, Scd1, G6pc2, Fos, Adrb2, Atp2a1, Ppp1r1b, and Cyp7a1. Furthermore, Proteomics analysis indicated that the beneficial effect of DEN on lipid metabolism was linked to pathways like AMPK and PPAR signaling. The integrative analysis of multi-omics revealed that the PPAR-RXR signaling was critical to the therapeutic effect of DEN on T2DM-induced fatty liver. Additionally, in vitro study on AML-12 cells confirmed that DEN counteract PA-induced lipid accumulation by activating the PPAR-RXR pathway. Overall, these findings suggested that DEN exhibited the potential to mitigate T2DM-induced hepatic lipo-toxicity and manage lipid imbalances in T2DM.

Alpha-lipoic acid improves cryopreservation of rooster semen by reducing oxidative stress

Inhibiting oxidative stress is key for ensuring sperm motility during semen cryopreservation. The aim of this study was to investigate the effect of adding alpha-lipoic acid (ALA) as an extender in rooster semen cryopreservation. Different concentrations of ALA were added to the frozen diluent of rooster semen; subsequently, computer-aided semen analysis was used to determine membrane functional integrity, acrosome integrity, antioxidant capacity (based on T-AOC, GSH-Px, SOD, CAT, and MDA contents), and mitochondrial integrity. The frozen sperm ultrastructure was observed using transmission electron microscopy. The results showed that the addition of different concentrations of ALA partially to greatly improved the quality of frozen sperm; in particular, 8 μg/mL ALA significantly improved multiple parameters of sperm quality, including sperm motility and antioxidant enzyme activity, after freeze-thaw. The results of this study provide empirical and theoretical support for effective rooster semen cryopreservation and can inform the development of new protective agents in the field of livestock reproduction.

Novel 1,3,4-thiadiazol derivatives including α-lipoic acid: Synthesis, characterization, and antioxidant properties

In this study, new 1,3,4-thiadiazole-2-amine derivatives containing different substitution groups were synthesized in order to increase the free radical quenching ability of α-lipoic acid. The target thiadiazole amines were derived from thiosemicarbazide reagent. Structural analysis for the synthesized compounds (1–8) was carried out using modern spectroscopic techniques including FTIR, NMR, EIMS spectral analyses. The antioxidant properties of each molecule were elucidated by calculating% inhibition as well as significant IC50 values using the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging method. The antioxidant activities of the compounds were compared against ascorbic acid, a water-soluble antioxidant, and against α-lipoic acid, the starting molecule of the synthesis step, which actually showed a low DPPH quenching activity. While lipoic acid had a reference standard value of 15,625.02±0.96 µM, compound 8 was the compound with the highest antioxidant activity with an IC50 value of 433.69±0.04 µM. The obtained data suggested that the (NH) proton in the thiadiazole structure bound to lipoic acid plays an important role in binding to the DPPH radical. This study may provide a source for the synthesis of α-lipoic acid-based thiadiazole derivatives, new compounds with antioxidant properties that can be used in medicine and pharmacy.

Melatonin supplementation enhances browning suppression and improves transformation efficiency and regeneration of transgenic rough lemon plants (Citrus × jambhiri).

Enzymatic browning poses a significant challenge that limits in vitro propagation and genetic transformation of plant tissues. This research focuses on investigating how adding antioxidant substances can suppress browning, leading to improved efficiency in transforming plant tissues using Agrobacterium and subsequent plant regeneration from rough lemon (Citrus × jambhiri). When epicotyl segments of rough lemon were exposed to Agrobacterium, they displayed excessive browning and tissue decay. This was notably different from the 'Hamlin' explants, which did not exhibit the same issue. The regeneration process failed completely in rough lemon explants, and they accumulated high levels of total phenolic compounds (TPC) and polyphenol oxidase (PPO), which contribute to browning. To overcome these challenges, several antioxidant and osmoprotectant compounds, including lipoic acid, melatonin, glycine betaine, and proline were added to the tissue culture medium to reduce the oxidation of phenolic compounds and mitigate browning. Treating epicotyl segments with 100 or 200 μM melatonin led to a significant reduction in browning and phenolic compound accumulation. This resulted in enhanced shoot regeneration, increased transformation efficiency, and reduced tissue decay. Importantly, melatonin supplementation effectively lowered the levels of TPC and PPO in the cultured explants. Molecular and physiological analyses also confirmed the successful overexpression of the CcNHX1 transcription factor, which plays a key role in imparting tolerance to salinity stress. This study emphasizes the noteworthy impact of supplementing antioxidants in achieving successful genetic transformation and plant regeneration in rough lemon. These findings provide valuable insights for developing strategies to address enzymatic browning and enhance the effectiveness of plant tissue culture and genetic engineering methods with potential applications across diverse plant species.

(206) Strategies of Nitric Oxide Augmentation for PDE5 Inhibitors

Abstract Introduction Erectile function and endothelial functions are closely related entities. Nitric oxide NO regulates circulation and microcirculation involved in erection.NO concentration is reduced with aging, diabetes, environment pollution smoking, obesity, inflammation, high prolactin, low testosterone oxidative stress and atherosclerosis. Many of erectile dysfunction patients are PDE5 inhibitor resistant. Strategies to enhance NO expression, can be employed to convert treatment resistant patient into responder. Objective Employ every possible mechanism to augment nitric oxide expression. Greater base line nitric oxide better would be PDE5 inhibitor respose. Methods Internet search was made on various website including pub med, science direct, google scholars using key words like erection, erectile dysfunction, nitric oxide, l arginine, oxidative stress, antioxidant, NOS, endothelial dysfunction, atherosclerosis and etc. This was followed by literature study on given topic. Results Efficacy of PDE 5 inhibitor in ED treatment is 70%. NO concentration decline to 50% by age of 40 and is only 15% at age 60. Humming can increase nasal NO level up to 15 time. Conclusions NO regulates endothelial function, vasodilatation, platelet aggregation inhibition, free radical scavenging, testosterone synthesis and neuronal protection. Study of mechanism of NO production provides, strategies for its enhancement. L arginine, L citrulline, serve as substrate and vitamin C, tetrahydrobiopterin (BH4) act as co factors in production of NO. Endothelial nitric oxide synthase e NOS, neuronal nitric oxide synthase n NOS are major enzymes act involved in synthesis. Oxygen is required for NO synthesis process. Supplementation of substrate and cofactors help increase NO levels. Oxygen availability can be increased through exercise and raising hemoglobin level. Reactive oxygen species ROS convert NO into bioinactive peroxynitrite which itself is ROS. Oxidative stress can cause endothelial nitric oxide synthase uncoupling. Consequently eNOS start producing ROS. This causes oxidation of NOS and as well as of cofactor like BH4 and vitamin C. ROS also increase level of methylarginines. Antioxidant used to neutralize ROS include Co Q10, alpha lipoic acid, flavonoids, bioflavonoids poly phenols, pycnogenol, resveterol, fulvic acid and etc. Second mechanism NO production is from dietary nitrates. Nutritional nitrates are converted into nitrite by oral anaerobic bacteria’s. Nitrate rich foods like beet root or spinach are added to enhance nitrate based NO. Nitric oxide thus produced is used for vasodilatation of penile vessels as well sinuses of corpus cavernousm. Apart from that it inhibits uncoupling of NOS. This support L arginine based mechanism of NO production. Nitroglycerin or minoxidal act as NO donors. These agents can be used locally at glans penis to augment NO availability. Bee breathing is maneuver in which humming sound vibrates nasal sinus increasing NO production up to 15 folds. Inhaled NO act as bronchodilator which increase lung capacity leading to higher blood oxygen concentration. Various NO enhancement strategies thus applied, may convert non responder PDE5 inhibitor to responders. Disclosure No.

Orally fast dissolving α-lipoic acid electrospun nanofibers mitigates lipopolysaccharide induced inflammation in RAW 264.7 macrophages

α-Lipoic acid (LA), a dietary supplement known for its strong antioxidant and anti-inflammatory potential, faces challenges due to its poor aqueous solubility and thermal instability. To address these issues, herein methyl-beta-cyclodextrin (M-β-CD) was utilized to create inclusion complex (IC) of LA in 1:1 M stoichiometric ratio of M-β-CD to LA. The LA-M-β-CD-IC was further combined with pullulan (PUL), a non-toxic and water-soluble biopolymer, for the development of electrospun nanofibers (NF) by green and sustainable approach. The resulting PUL/LA/M-β-CD NF formed as a self-standing and flexible material with an average diameter of 569 ± 129 nm and encapsulation efficiency of ∼86.90 %. The developed NF demonstrated an accelerated release, quick dissolution, and disintegration when exposed to artificial saliva replicating the conditions of oral cavity. PUL/LA/M-β-CD NF attenuated the production of ROS and NO by downregulating pro-inflammatory enzymes (iNOS and COX-2) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Moreover, PUL/LA/M-β-CD NF also significantly downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β along with suppression of NF-ĸB nuclear translocation in comparison to LA (at 250 μM). In nutshell, PUL/LA/M-β-CD NF demonstrated great potential as a rapid disintegrating delivery system for oral anti-inflammatory treatment due to the enhanced physicochemical characteristics of LA.

Comparing the effects of developmental exposure to alpha lipoic acid (ALA) and perfluorooctanesulfonic acid (PFOS) in zebrafish (Danio rerio)

Alpha lipoic acid (ALA) is a dietary supplement that has been used to treat a wide range of diseases, including obesity and diabetes, and have lipid-lowering effects, making it a potential candidate for mitigating dyslipidemia resulting from exposures to the per- and polyfluoroalkyl substance (PFAS) family member perfluorooctanesulfonic acid (PFOS). ALA can be considered a non-fluorinated structural analog to PFOS due to their similar 8-carbon chain and amphipathic structure, but, unlike PFOS, is rapidly metabolized. PFOS has been shown to reduce pancreatic islet area and induce β-cell lipotoxicity, indicating that changes in β-cell lipid microenvironment is a mechanism contributing to hypomorphic islets. Due to structural similarities, we hypothesized that ALA may compete with PFOS for binding to proteins and distribution throughout the body to mitigate the effects of PFOS exposure. However, ALA alone reduced islet area and fish length, with several morphological endpoints indicating additive toxicity in the co-exposures. Individually, ALA and PFOS increased fatty acid uptake from the yolk. ALA alone increased liver lipid accumulation, altered fatty acid profiling and modulated PPARɣ pathway signaling. Together, this work demonstrates that ALA and PFOS have similar effects on lipid uptake and metabolism during embryonic development in zebrafish.