Triple Action of Lignosulfonic Acid Sodium: Anti-protease, Antioxidant, and Anti-inflammatory Effects of a Polymeric Heparin Mimetic.

BACKGROUND: Heparins are sulfated glycosaminoglycans that are used as anticoagulants to treat thrombosis. Heparins exhibit other potential therapeutic effects, such as anti-inflammatory, anti-viral, and anti-malarial effects. However, the strong anticoagulant activity of heparins poses a risk of life-threatening bleeding, limiting their therapeutic use for other diseases beyond thrombosis. To exploit the other effects of heparins and eliminate the bleeding risk, we explored an alternative polymer called lignosulfonic acid sodium (LSAS), which acts as a sulfonated heparin mimetic. LSAS targets factor XIa to exert an anticoagulant effect, and thus, unlike heparins, it is unlikely to cause bleeding. METHODS: This study investigated the multiple effects of LSAS to identify potential leads for complex pathologies treatment. A series of chromogenic substrate hydrolysis assays were used to evaluate the inhibition of three inflammation-related proteases by LSAS. Its chemical antioxidant activity against the system of ABTS/hydrogen peroxide/metmyoglobin was also determined. Lastly, the effect of LSAS on TNFα-induced activation of the NF-κB pathway in HEK-293 cells was also tested to determine its cellular anti-inflammatory activity. RESULTS: The results showed that LSAS effectively inhibited human neutrophil elastase, cathepsin G, and plasmin, with IC50 values ranging from 0.73 to 212.5 µg/mL. Additionally, LSAS demonstrated a significant chemical antioxidant effect, with an IC50 value of 44.1 µg/mL. Furthermore, at a concentration of approximately 530 µg/mL, LSAS inhibited the TNFα-induced activation of the NF-κB pathway in HEK-293 cells, indicating a substantial anti-inflammatory effect. An essential advantage of LSAS is its high water solubility and virtual non-toxicity, making it a safe and readily available polymer. CONCLUSION: Based on these findings, LSAS is put forward as a polymeric heparin mimetic with multiple functions, serving as a potential platform for developing novel therapeutics to treat complex pathologies.

Micro Area Interface Wetting Structure with Tailored Li+-Solvation and Fast Transport Properties in Composite Polymer Electrolytes for Enhanced Performance in Solid-State Lithium Batteries.

To satisfy the demand for high safety and energy density in energy storage devices, all-solid-state lithium metal batteries with solid polymer electrolytes (SPE) replacing traditional liquid electrolytes and separators have been proposed and are increasingly regarded as one of the most promising candidates as next-generation energy storage systems. In this study, poly(vinylidene fluoride)-hexafluoropropylene/lignosulfonic acid (PVDF-HFP/LSA) composite polymer electrolyte (CPE) membranes with a micro area interface wetting structure were successfully prepared by incorporating LSA into the PVDF-HFP polymer matrix. The enhanced interaction between the polar functional group in LSA and the C═O in N-methylpyrrolidone (NMP) hinders the evaporation of solvent NMP, thus creating a micro area wetting structure, which offers a flexible region for the chain segment movement and enlarging the area of the amorphous zone in PVDF-HFP. From the results of IR and Raman spectroscopy, it was found that the presence of LSA induced unique ion transport channels created by the massive aggregated ion pair (AGG) and contact ion pair (CIP) of ion cluster structures composed of Li+ and multiple TFSI- and, at the same time, effectively reduced the crystallinity of the polymer electrolyte, hence further contributing to the Li+ diffusion. As a result, at a rate of 2 C, the Li|CPE-15|LiFePO4 solid-state battery delivers an initial discharge-specific capacity of 134.9 mAh g-1 and maintains stability with a retention of 84% during 400 charge-discharge cycles while the Li|CPE-0|LiFePO4 battery fails after only a few cycles at the same rate.

Wood-inspired strategy to toughen transparent cellulose nanofibril films.

The simultaneous attainment of high strength and high toughness of transparent cellulose nanofibril (CNF) film can expedite its uses in advanced applications. In this work, a wood-inspired strategy is proposed to address the conflict between strength and toughness by using natural derived lignosulfonic acid (LA) as a reinforcing additive. Only 1 wt% LA addition can double the toughness (11.0±1.3 MJ/m3) of pure CNF film. Consequently, the as-prepared CNF/LA-1 nanocomposite film not only exhibits superior mechanical properties (23.6±1.3 MJ/m3 toughness, 249±6 MPa strength, and 15.4±1.4 % strain), but also maintains an excellent optical transparency of 91.2 % (550 nm). Furthermore, the mechanism for simultaneously enhancing strength and toughness is essentially attributed to the improved hydrogen bonding between CNF-OH and LA-SO3H and effective energy dissipation system. This work provides a green and effective approach to prepare strong yet tough and transparent biodegradable CNF film for high-end applications.

Lignosulfonic acid attenuates NF-κB activation and intestinal epithelial barrier dysfunction induced by TNF-α/IFN-γ in Caco-2 cells.

Lentinula edodes mycelia solid culture extract (MSCE) is used as a medical food ingredient and provides beneficial effects to patients with cancer and chronic type C hepatitis. Low molecular weight lignin (LM-lignin), which is an active component of MSCE, exhibits hepatoprotective, antitumor, antiviral, and immunomodulatory effects. In this study, we investigated the effect of LM-lignin/lignosulfonic acid on intestinal barrier function. Lignosulfonic acid enhanced transepithelial membrane electrical resistance in human intestinal Caco-2 cell monolayers. In Caco-2 cells treated with lignosulfonic acid, expression of claudin-2, which forms high conductive cation pores in tight junctions (TJs), was decreased. Lignosulfonic acid also attenuated the barrier dysfunction that is caused by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in Caco-2 cells. TNF-α- and IFN-γ-induced activation of NF-κB, such as translocation of NF-κB p65 into the nucleus and induction of gene expression, was inhibited by lignosulfonic acid treatment. Furthermore, lignosulfonic acid decreased the TNF-α- and IFN-γ-induced increase in interleukin (IL)-1ß and IL-6 expression in Caco-2 cells. These results suggest that lignosulfonic acid not only enhances TJ barrier function but also restores TJ barrier integrity impaired by inflammatory cytokines. Therefore, lignosulfonic acid may be beneficial for the treatment of inflammation-induced intestinal barrier dysfunction observed in inflammatory bowel disease.

Lignosulfonic acid promotes hypertrophy in 3T3-L1 cells without increasing lipid content and increases their 2-deoxyglucose uptake.

OBJECTIVE: Adipose tissue plays a key role in the development of obesity and diabetes. We previously reported that lignosulfonic acid suppresses the rise in blood glucose levels through the inhibition of α-glucosidase activity and intestinal glucose absorption. The purpose of this study is to examine further biological activities of lignosulfonic acid. METHODS: In this study, we examined the effect of lignosulfonic acid on differentiation of 3T3-L1 cells. RESULTS: While lignosulfonic acid inhibited proliferation (mitotic clonal expansion) after induction of differentiation, lignosulfonic acid significantly increased the size of accumulated lipid droplets in the cells. Semi-quantitative reverse transcription polymerase chain reaction analysis showed that lignosulfonic acid increased the expression of the adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), leading to increased glucose transporter 4 (Glut-4) expression and 2-deoxyglucose uptake in differentiated 3T3-L1 cells. Additionally, feeding lignosulfonic acid to diabetic KK-Ay mice suppressed increase of blood glucose level. CONCLUSION: Lignosulfonic acid may be useful as a functional anti-diabetic component of food.

Degradation of lignosulfonic and tannic acids by ligninolytic soil fungi cultivated under icroaerobic conditions

Soil fungi were evaluated regarding their ability to degrade lignin-related compounds by producing the ligninolytic enzymes. Lignosulfonic and tannic acids were used as sole carbon sources during 30 days under microaerobic and very-low-oxygen conditions. The fungi produced lignin-peroxidase, manganese-peroxidase and laccase . Expressive degradations was observed by C18 reversed-phase HPLC, indicating the biodegradation potential of these fungi, showing more advantages than obligate anaerobes to decontaminate the environment when present naturally.

Fungos isolados de solo foram avaliados quanto à habilidade em degradarem compostos derivados de lignina pela produção de enzimas ligninolíticas. Os ácidos lignosulfônicos e tânico foram usados separadamente como única fonte de carobono para cultivo dos fungos em 30 dias sob condições microaeróbias. Os fungos foram capazes de crescer e usar tais compostos como fonte de carbono e mostraram produção de lignina-peroxidase, manganês-peroxidase e lacase. Degradações expressivas dos ácidos lignosulfônico e tânico foram verificadas por Cromatografia Liquida de Alta Eficiência (CLAE), indicando grande potencial de uso em processos de biorremediação de macromoléculas aromáticas similares à lignina em ambientes naturais sob condições baixas de oxigenação.