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Antioxidant activity of low molecular weight hyaluronic acid
Abstract
Two polysaccharides, low molecular weight hyaluronic acid-1 (LMWHA-1) and LMWHA-2, with their molecular weight of 1.45×10(5) and 4.52×10(4)Da, respectively, were prepared from high molecular weight hyaluronic acid (HA,1.05×10(6)Da). LMWHA-1, LMWHA-2 and HA were studied for their antioxidant activities. In vitro antioxidant assay, LMWHA showed strong inhibition of lipid peroxidation and scavenging activities of hydroxyl radical, moderate 1,1-diphenyl-2-picryldydrazyl radical and superoxide anion scavenging activity. In addition, the LMWHA-1 exhibited much stronger antioxidant activity than LMWHA-2 and HA. For antioxidant testing in vivo, LMWHA-1, LMWHA-2 and HA were orally administrated over a period of 7days in a cyclophosphamide(CY) induced immunosuppressed mice model. As results, administration of LMWHA was able to overcome CY-induced immunosuppression and significantly raised the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (TAOC) in immunosuppressed mice. The results showed that the LMWHA, possessing pronounced free radical scavenging and antioxidant activities.
... The obtained blended coatings were investigated for their physicochemical and fruit preservation effectiveness using strawberries as a model fruit. Hyaluronic acid was selected for its natural antioxidant properties and biocompatibility [26,27] with the hypothesis that its (hyaluronic acid) inclusion will significantly enhance the properties of produced edible coatings. We observed a significant preservation and shelf-life of strawberries with increasing concentrations of hyaluronic acid in produced edible coatings. ...
... Similar to other antioxidant assays (TPC and ascorbic acid), drastic and significant reduction was observed in antioxidant amounts in uncoated strawberries compared to coated fruits. Further, in coated samples, hyaluronic acid containing coatings (7CS:2G:1HA, 6CS:2G:2HA and 5CS:2G:3HA) performed significantly better than the 1CS:1G coating control which could be explained by the strong intrinsic antioxidant properties of hyaluronic acid [26,27]. Also, hyaluronic acid concentration dependent response in terms of preventing loss of antioxidant activity during storage was obtained for hyaluronic acid containing coatings. ...
With the growing demand for extending the shelf-life of perishable goods such as fruits and vegetables, there is continued interest towards the development of edible coatings derived from natural sources. To avoid rapid dissolution, water insoluble polysaccharide such as chitosan has been widely explored. In this work, we developed robust hyaluronic acid-based edible polysaccharide-protein coatings by combining it (hyaluronic acid) with chitosan and gelatin to introduce additional antioxidant properties. This work is the first example of using hyaluronic acid in edible coatings for fruit preservation. The effect of developed edible composite coatings on the quality of coated strawberries was investigated over a 15 day storage period with 3-day examination intervals. The obtained results revealed hyaluronic acid dose-dependent improvement in intrinsic properties of coated strawberries including weight loss, pH, titratable acidity (TA) and total solids content (TSS). Furthermore, the inclusion of hyaluronic acid significantly enhanced the antioxidant properties of developed edible coatings as measured using total phenolic content, change in ascorbic acid content and DPPH assay prolonging the shelf-life of coated strawberries.
... In tissues, HA has also been shown to have antioxidant properties by suffering oxidative damage in lieu of other compounds [40][41][42][43]. Particularly, structural characteristics, such as decreased sulfation and β-linked structural units, make certain glycosaminoglycans (GAGs) more susceptible to be oxidized. ...
... This is supported by the fact that corneal epithelial progenitor cells, which are surrounded by an HA-rich niche, have been shown to be resistant to H 2 O 2 damage [73]. In fact, HA matrices have shown prominent antioxidant characteristics in various tissues [40][41][42][43]. It has been suggested that in tissues, the protective effect exerted by HA against oxidative damage comes mainly from HA undergoing chemical modifications by ROS in lieu of other molecules, and not by altering the production of ROS and/or the synthesis of antioxidant enzymes [74]. ...
A buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiological properties remain largely unknown. This study characterized the molecular weight (MW), structures, and physiological properties of oxHA. For this, high-molecular-weight HA (HMWHA) was oxidized using increasing molar ratios of hydrogen peroxide (H2O2) or hypochlorous acid (HOCl). ROS lead to the fragmentation of HA, with the oxHA products produced by HOCl exhibiting an altered chemical structure while those produced by H2O2 do not. HMWHA promotes the viability of human corneal epithelial cells (hTCEpi), while low MWHA (LMWHA), ultra-LMWHA (ULMWHA), and most forms of oxHA do not. HMWHA and LMWHA promote hTCEpi proliferation, while ULMWHA and all forms of oxHA do not. LMWHA and some forms of oxHA promote hTCEpi migration, while HMWHA does not. Finally, all native forms of HA and oxHA produced by HOCl promote in vivo corneal wound healing, while oxHA produced by H2O2 does not. Taken together, our results show that HA fragmentation by ROS can alter the physiological activity of HA by altering its MW and structure.
... The synthesis of HA is enzymatic controlled by hyaluronan synthetases (HASs) (HAS1, HAS2, HAS3, located on the inner surface of the cellular membrane), while hyaluronidase and oxidative stress are implicated in its degradation. The turnover is very fast (5 g/day), and the half-life is less than 24h [174]. ...
... In the inflammatory phase, HA with high molecular weight is degraded into fragments smaller than 120 kDa, with immunostimulatory properties and a proangiogenesis effect. These products stimulate the production of cytokines (IL-1 and IL-8, TNF-α) and, consequently, the infiltration, activation, and maturation of immune cells are accelerated [174,179,180]. During the proliferation phase, HA with low molecular weight is degraded to oligomers, which will interact with the CD44 and RHAMM receptors. ...
Wound management represents a well-known continuous challenge and concern of the global healthcare systems worldwide. The challenge is on the one hand related to the accurate diagnosis, and on the other hand to establishing an effective treatment plan and choosing appropriate wound care products in order to maximize the healing outcome and minimize the financial cost. The market of wound dressings is a dynamic field which grows and evolves continuously as a result of extensive research on developing versatile formulations with innovative properties. Hydrogels are one of the most attractive wound care products which, in many aspects, are considered ideal for wound treatment and are widely exploited for extension of their advantages in healing process. Smart hydrogels (SHs) offer the opportunities of the modulation physico-chemical properties of hydrogels in response to external stimuli (light, pressure, pH variations, magnetic/electric field, etc.) in order to achieve innovative behavior of their three-dimensional matrix (gel–sol transitions, self-healing and self-adapting abilities, controlled release of drugs). The SHs response to different triggers depends on their composition, cross-linking method, and manufacturing process approach. Both native or functionalized natural and synthetic polymers may be used to develop stimuli-responsive matrices, while the mandatory characteristics of hydrogels (biocompatibility, water permeability, bioadhesion) are preserved. In this review, we briefly present the physiopathology and healing mechanisms of chronic wounds, as well as current therapeutic approaches. The rational of using traditional hydrogels and SHs in wound healing, as well as the current research directions for developing SHs with innovative features, are addressed and discussed along with their limitations and perspectives in industrial-scale manufacturing.
... Due to the viscosity exhibited even at low concentrations, HMW HA can be difficult to work with depending on the application. For this reason, there has been a great deal of interest in using moderate molecular weight HA (50-500 kDa), which has the advantages of low molecular weight HA, such as penetration through skin, proliferation and migration of vascular endothelial cells, and wound healing abilities [4,15,16], whilst simultaneously proving more amenable to engineer. In this study, the molecular weight of HA chosen was 30-50 kDa to enable ease of modification, retain printability and the ability to pipette the polymer when in solution. ...
... Analysis was performed on Nexera-i system (Shimadzu Corp.) equipped with a LC-2040 pump, LC-2040 autosampler and a PDA detector model SPD-M40. The elution was performed in isocratic mode at a flowrate of 1 ml min − 1 with the mobile phase consisting of acetonitrile: water (15,85) adjusted to pH 2 with orthophosphoric acid. Peak areas from chromatograms obtained at 210 nm were analysed on LabSolutions software (Shimadzu Corp.) and subsequently used to quantify the degree of substitution of methacrylated hyaluronic acid. ...
Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that, due to its inherent bioactivity and extracellular matrix-like structure, has the potential to be utilised extensively in tissue engineering. However, this glycosaminoglycan lacks the properties required for cellular adhesion and photo-crosslinking by UV light, which significantly hinders this polymers applicability. This research presents a method for modifying hyaluronic acid via thiolation and methacrylation to generate a novel photo-crosslinkable polymer with improved physicochemical properties, biocompatibility and the potential to customize biodegradability according to the ratio of monomers used. A decrease in stiffness proportional to increasing thiol concentration was observed when testing the compressive strength of hydrogels. Conversely, it was noted that the storage moduli of hydrogels increased proportionally to thiol concentration indicating a greater degree of cross-linking with the addition of thiol. The addition of thiol to HA increased the biocompatibility of the material in both neuronal and glial cell lines and improved the degradability of methacrylated HA. Due to the enhanced physicochemical properties and biocompatibility imparted by the introduction of thiolated HA, this novel hydrogel system could have numerous bioengineering applications.
... The ability of hyaluronidase to scavenge DPPH could also reflect its ability to inhibit the formation of free radicals. The presence of carboxylic groups in hyaluronidase is most likely responsible for its anti-radical properties [58]. This will be defined by fact that; the antioxidants donate protons to the loose radicals to neutralize rate within the solution as a result of which the absorbance decreases at wavelength at 515 nm [59]. ...
... Superoxide anion is likewise known to initiate indirectly the fat peroxides as a result of the creation of H 2 O 2 in generating hydroxyl radical [61]. Many researchers have reported on the ability of hyaluronic acid to chelate sundry ions and transition metals [58]. The hydroxy radical is the most harmful. ...
This work studied the antioxidant and anti-breast cancer properties of hyaluronidase, extracted from a potential marine strain, Staphylococcus aureus (CASMTK1), isolated from Parangipettai coastal waters in southeast coast of India. The Staphylococcal enzyme production was tested under different carbon and nitrogen sources; and recorded the maximum production when the microbial strain was cultured with starch as the carbon source and ammonium sulphate as the inorganic nitrogen source with the enzyme production of 92.5 U/mL and 95.0 U/mL, respectively. The hyaluronidase enzyme production was also tested in different pH and temperature; and recorded the maximum yield of 102.5 U/mL in pH 5 and that of 95.5 U/mL in 45 °C. The partially purified enzyme was subjected to FTIR and FT Raman technique and found the presence of the amide- I and II, Carboxyl, N-H bending, C-H stretching and α-helices and β-sheet proteins between wave number 1500–1700 cm−1. The partially purified enzyme also exhibited strong antioxidant and in-vitro breast cancer properties. The enzyme showed the highest hydroxyl radical scavenging activity of 79% at the 50 µg/mL concentration, and this activity increased in a dose-dependent manner. The enzyme inhibited proliferation of the breast cancer cell line of MCF-7, and it caused 100% cell death at the concentration of 80 µg/mL. The enzyme generated capacity of producing free radicles that damage the cancer cells, and this effect was very nearer to the standard drug, paclitaxel. The enzyme damaged the cancer cells and induced apoptosis in 78% of cancer cells as evident by condensed or fragmented chromatin at 40 µg/mL. Further purification of the enzyme, analysis of its molecular aspects, and elucidation of exact mechanisms of its biological activities will throw new light on the utility of staphylococcal hyaluronidase in anticancer chemotherapy.
... We observed a significant difference (p < 0.001) between LMWHA and HA in antioxidation ability, which showed that the radical scavenging capacity of LMWHA is significantly stronger than that of HA per the results of the above four indicators. The antioxidant ability of LMWHA is better than that of HA [34][35][36]. However, the enhanced antioxidant capacity of the cleavage products of hyaluronic acid lyases was not clearly explained in terms of molecular properties. ...
... We observed a significant difference (p < 0.001) between LMWHA and HA in antioxidation ability, which showed that the radical scavenging capacity of LMWHA is significantly stronger than that of HA per the results of the above four indicators. The antioxidant ability of LMWHA is better than that of HA [34][35][36]. However, the enhanced antioxidant capacity of the cleavage products of hyaluronic acid lyases was not clearly explained in terms of molecular properties. . ...
The Gram-negative strain of Citrobacter freundii, YNLX, has the ability to degrade hyaluronic acid. In this study, we expressed a C. freundii hyaluronic acid lyase, from polysaccharide lyase family 8, in Escherichia coli. The purified recombinant enzyme (rHynACF8) showed a substantially higher cleavage activity of hyaluronic acid than chondroitin sulfate. We found that its optimal pH and temperature are 5.5 and 35 °C, respectively. In addition, the enzyme activity was not notably affected by most metal ions. Km and kcat of rHynACF8 towards HA were 1.5 ± 0.01 mg/mL and 30.9 ± 0.5 /s, respectively. rHynACF8 is an endo-acting enzyme. Its cleavage products had dramatically increased antioxidant activity than hyaluronic acid in vitro (p < 0.001). As the molecular weight of hyaluronic acid decreased, the intramolecular interactions among antioxidant functional groups were removed; in the process of the cracking reaction, new double bonds formed and conjugated with the carbonyl group. We presumed that the structural change is the critical factor influencing antioxidant capacity. Overall, we found that rHynACF8 from Gram-negative bacteria with metal ion resistance, indicated the relationship between the function and structure of its antioxidant cleavage product.
... In vitro and in vivo studies demonstrate that low-molecular-weight hyaluronic acid shows superior antioxidant properties to high-molecular-weight hyaluronic acid [59]. Likewise, low-molecular-weight hyaluronic acid does not favor inflammatory reactions mediated by macrophages [60]. ...
Background: Treatments for androgenetic alopecia (AGA) include different drugs, but a treatment based on stabilized hyaluronic acid has not been tested. The aim of this study is to clinically evaluate the effect of six sessions of injections using a hyaluronic acid compound supplemented with vitamins, ions, and amino acids (CH) on hair density and quality in volunteers. Methods: For this purpose, twenty-six healthy volunteers of both sexes with moderate AGA were injected with 3 mL of CH using the micro-papule technique. All received six CH sessions at two-week intervals. Hair loss, hair thickness, and shine were assessed using macro-photographs. A follow-up questionnaire was given to the volunteers at 40 days and at 90 days after the last treatment to determine their level of satisfaction. In addition, a dermatological control was carried out to assess the tolerance of the treatment applied. Results: The results indicate that, after treatment with CH, there is a significant improvement in the thickness, shine, and density of scalp hair, and that the treatment significantly reduces hair loss on the scalp. On a dermatological level, the tolerability of the treatment was excellent with no complications observed. In total, 88.5% of the volunteers indicated that CH treatment improved their appearance. In summary, it can be said that CH treatment reduces hair loss and promotes hair growth. Conclusions: It is suggested that this treatment is effective in reducing the signs and symptoms of alopecia.
... 6 LMW-HA exhibits antioxidant, antitumour, and angiogenic properties, and has shown potential benefit in a number of dermatologic and non-dermatologic conditions. [7][8][9] The purpose of this study was to explore the current and potential uses of LMW-HA, specifically in dermatology, as well as avenues for continued research. ...
Introduction: Hyaluronan, or hyaluronic acid (HA), is a naturally occurring glycosaminoglycan present in the skin, joints, and eyes that provides hydration, lubrication, protection, and other important benefits. HA in dermatology is commonly discussed in the context of its anti-ageing properties. However, both pre-clinical and clinical studies have shown numerous applications of HA, low-molecular-weight (LMW) HA, and hybrid LMW/high-molecular-weight HA in dermatology. LMW-HA exhibits antioxidant, anti-tumour, and angiogenic properties, and given its size, an ability to fully penetrate the skin. Aims: The purpose of this review was to explore the current science and utility of LMW-HA in clinical dermatology and provide an update on its use. Methods: A PubMed search from 2003–2023 on LMW-HA was conducted to evaluate LMW-HA’s utility in clinical dermatology. Results: Identified applications of LMW-HA in medical dermatology included treatment of acute and chronic wounds, rosacea, scars, and seborrhoeic dermatitis. Cosmetic applications of LMW and hybrid HA included treatment of skin ageing, enlarged pores, and skin laxity, as well as enhancement of skin hydration. Topical LMW-HA administration promoted healing after cosmetic procedures, chemical peels, and ingrown toenail surgery. Studies of topical and oral LMW-HA demonstrated adequate safety, and newer techniques of administration, such as needleless jet injection, are available. Conclusion: Exploration and understanding of the properties and benefits of LMW-HA are key to translating its usage in the clinical setting. Basic scientists and dermatologists have achieved substantial progress over the past two decades, and several applications of LMW-HA in dermatology were identified. Additional advantages of LMW-HA are worth exploring.
... This keeps cells safe from oxidative damage, which is linked to a number of illnesses and early ageing [4,5]. A multitude of disorders can arise from free radicals' great attraction for lipids, proteins, nucleic acids, and glycosaminoglycans found in the extracellular matrix, including hyaluronic acid [6]. Because polyunsaturated fatty acids are more susceptible to damage from free radicals, they may develop central nervous system problems and cerebral ischemia [7,8]. ...
Objective: The main objective of this work is to synthesize thiobarbituric acid based bis-Schiff base derivatives and to evaluate their ability to inhibit urease enzyme and DPPH free radical scavenging potential. Methods: Thiobarbituric acid derived bis-Schiff bases (IIIa-IIIi) were synthesized by treating 2,4-dihydroxy-benzaldehyde and the starting moiety 1,3-diethyl-2-thiobarbituric acid in ethanol through refluxed followed by treating chloro ethyl acetate in DMF solvent. Subsequently, hydrazine hydrate was added to compound (II), yielding bis-hydrazide in better yield, which was further reacted via refluxed with benzaldehydes in ethanol, catalyzed by acetic acid to yield compounds (IIIa-IIIi) in excellent yields. Results: The resulting compounds were tested to inhibit urease enzyme and DPPH free radical scavenging activity. Among the series, compound (IIId) (IC 50 = 16.11 ± 0.92 µM), (IIIc) (IC 50 = 19.11 ± 0.55 µM), and (IIIf) (IC 50 = 21.01 ± 1.42 µM) were found as promising lead urease inhibitors, stronger than the standard thiourea (IC 50 = 21.15 ± 0.32 µM). Moreover, compound (IIIa) (IC 50 = 40.21 ± 0.12 µM) was found as the excellent antioxidant agent comparing it with the standard ascorbic acid. Molecular docking study was performed to analyze the most potent compounds against urease enzyme. The results also shows that all compounds had good ADME properties there was no violation found in compounds ranges all are under druglikness criteria. Additional research combining in vivo, toxicological, and computational analyses can offer thorough understandings of the effectiveness, safety, and fundamental mechanisms of action of these potentially beneficial antioxidant substances. Conclusions: These compounds showed tremendous potential as DPPH free radical scavengers and urease enzyme inhibitors. Compound (IIId) demonstrated the greatest suppression of urease enzyme activity, however compound (IIIa) displayed superior antioxidant effects. Additional research, incorporating in vivo, toxicological, and computational examinations, is necessary to thoroughly assess the effectiveness, safety, and fundamental mechanisms of action of these intriguing antioxidant molecules.
... Glutathione, a potent antioxidant, is known for its skin-whitening properties and anti-melanogenic effects, which impact melanin production (10)(11)(12). Hyaluronic acid, with its biodegradability and non-toxicity, functions primarily as a hydrating agent by binding water to tissue, thus improving skin hydration (6,9,13). ...
Background
High-intensity focused ultrasound (HIFU) is well-documented for skin rejuvenation, lifting, and tightening. However, its synergistic effects with topical agents, enhanced by HIFU-induced vibration and heat, remain underexplored.
Objective
To evaluate clinical and photographic outcomes of HIFU combined with a topical agent versus the topical agent alone.
Method
This non-randomized controlled trial involved 20 female volunteers (ages 30–55) divided into two groups. Group A (n = 10) received two HIFU sessions combined with a topical agent containing glutathione and hyaluronic acid. Group B (n = 10) received the topical agent alone. Outcomes were assessed using digital photography, patient satisfaction surveys, and the A-One Smart™ system for fine wrinkles, hyperpigmentation, and hydration. Skin brightening was evaluated with the Global Esthetic Improvement Scale (GAIS).
Results
Group A showed significant reductions in fine wrinkles (6.25 ± 2.00 mm to 3.10 ± 1.62 mm), improved hyperpigmentation (3.50 ± 0.80 to 2.10 ± 1.05), and increased hydration (28 ± 10 to 55 ± 11) (all p < 0.05). Over two-thirds of Group A reported significant improvements, with no complications. Group B showed minimal, non-significant changes (p > 0.05), with only 30% reporting noticeable improvements.
Conclusion
Combining HIFU with a topical agent significantly enhances skin quality and brightness without adverse effects.
... Antimicrobial peptides are small, multifunctional peptides synthesized in ribosomes with a relatively low molecular weight [42]. Furthermore, it is already known that lowmolecular-weight substances have strong antioxidant activity [43]. Therefore, we speculate that the antiapoptotic effect of IsCT may be attributed to its strong antioxidant activity. ...
The objective of this research was to investigate how dietary antimicrobial peptides (AMP), namely, Isalo scorpion cytotoxic peptide (IsCT), affect the gill physical barrier function and immune function of grass carp challenged with Flavobacterium columnare (F. columnare). Five hundred forty grass carp were randomly allocated to six groups and fed to varying levels of IsCT in the diet (0, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg diet) for a duration of 60 days. Afterward, the grass carps faced a challenge from F. columnare. The results revealed that the use of optimal IsCT dramatically mitigated gill damage in grass carp that were infected with F. columnare. Additionally, IsCT exhibited a notable enhancement in gill antioxidant capabilities, as evidenced by a significant reduction in ROS, MDA, and PC levels, an elevation in antioxidant enzyme activities, and an upregulation of antioxidant-related genes and Nrf2 mRNA levels. Conversely, the expression of Keap1a and Keap1b mRNA was decreased. Besides, IsCT exhibited its capability to inhibit apoptosis via downregulating the mRNA levels of caspase-2, caspase-3, caspase-7, caspase-8, caspase-9, Apaf1, Fasl, Bax, and JNK while concurrently increasing the mRNA levels of Bcl-2, Mcl-1, and IAP in fish gills. Additionally, IsCT promoted the integrity of tight junction barrier by increasing the gene expression of claudin-b, claudin-c, claudin-3c, ZO-1, ZO-2b, occludin, and JAM while suppressing MLCK signaling. Additionally, optimal dietary IsCT improved antibacterial ability, as evidenced by heightened LZ, ACP activities, and elevated levels of C3, C4, and IgM. Additionally, there was an upregulation in β-defensin-1, LEAP-2A, LEAP-2B, hepcidin, and mucin-2 mRNA expression in the gills. Simultaneously, the inclusion of optimal dietary IsCT in the diet resulted in improved gill immunity barriers through the reduction of proinflammatory cytokine mRNA levels and the increase in the expression of anti-inflammatory cytokine mRNA levels. This was partly facilitated by the IκBa/NF-κB p65 signaling pathway and TOR/S6K1 signaling pathways in the gills of grass carp. Therefore, supplementing the diet with IsCT has potential advantages in enhancing gill health by improved physical barriers and immunity in grass carp. Based on LZ activity and against lipid peroxidation, optimum IsCT concentrations in on-growing grass carp (136.88 ± 0.72 g) were found to be 1.68 and 1.54 mg/kg diet, respectively.
... Returning to our data, the efficiency of counteracting oxidative stress could be due to the antioxidant activity of the components of the polymeric matrix of NGs, i.e., chitosan [57] and hyaluronic acid [58]. ...
The aim of this study was the investigation of biochemical and histological changes induced in different tissues, as a result of the subcutaneous administration of Gd nanohydrogels (GdDOTA⸦CS-TPP/HA) in a CD-1 mouse strain. The nanohydrogels were obtained by encapsulating contrast agents (GdDOTA) in a biocompatible polymer matrix composed of chitosan (CS) and hyaluronic acid (HA) through the ionic gelation process. The effects of Gd nanohydrogels on the redox status were evaluated by measuring specific activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as oxidative stress markers, such as reduced glutathione (GSH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and protein-reactive carbonyl groups (PRCG), in the liver, kidney, and heart tissues. The nitrosylated proteins expression were analyzed with Western Blot and the serum biochemical markers were measured with spectrophotometric methods. Also, a histological analysis of CD-1 mouse tissues was investigated. These results indicated that Gd nanohydrogels could potentially be an alternative to current MRI contrast agents thanks to their low toxicity in vivo.
... The present study evaluated the effectiveness of lotus seed-HA as a local drug delivery agent for the scavenging of free radicals as estimated by its antioxidant and anti-inflammatory ability (16). Ironically, in the present cosmetic era, use of natural remedies and herbal treatments has become increasingly popular for treating ailments such as cancer, skin diseases, poisoning, and periodontitis (16,17). The ethanolic extract of Nelumbo nucifera showed potent antioxidant and anti-inflammatory properties. ...
OBJECTIVE The plant species Nelumbo nucifera (lotus) is widely used in traditional medicine and is known to contain flavonoids, alkaloids, and other polyphenols which contribute to its potent antioxidant, anti-inflam- matory properties in addition to its being a remedy for cardiac diseases. Hyaluronic acid, present in skin and connective tissue, is well known for its tissue regeneration and wound healing properties. The present study aimed to determine the antioxidant and anti-inflammatory effect of the hyaluronic acid gel combined with lotus seed extract and how this com- bination could be used as an effective local drug delivery system for the treatment of periodontitis.
METHODS A 2% solution of hyaluronic acid gel was combined with increasing concentrations of prepared lotus seed extract. A DPPH test was conducted to determine the antioxidant activity of the resultant mixture at increasing concentrations. Additionally, anti-inflammatory activity was assessed using a UV spectrometer, and the spreadability of the gel was measured using the sliding glass slide method. The values obtained were plotted on graphs.
RESULTS The DPPH scavenging assay revealed that lotus seed extract with 2% hyaluronic acid gel exhibited increased antioxidant activity in a dose-dependent manner with IC50 at 76 μL. The lotus seed extract with 2% hyaluronic acid gel also showed increased anti-inflammatory properties in a dose-dependent manner with IC50 at 271 μL. Moreover, the spreadability of the lotus seed extract with 2% hyaluronic acid gel was found to be 42 mm.
CONCLUSIONS Lotus seed extract shows potent antioxidant and anti- inflammatory activities which vary with the concentration of the extract,
and can serve as an effective local drug delivery system.
... Due to its hygroscopic and viscoelastic properties, HA acts as a lubricant in body fluids, such as the vitreous [2] and synovial ones [3]. HA is also involved in cell proliferation, differentiation, adhesion and migration [4][5][6][7][8], inflammation [9], immunomodulation [10][11][12], antioxidant response [13][14][15], tissue regeneration [16][17][18], and angiogenesis [19][20][21]. Remarkably, the cytoprotective potential of HA is related to the polymer length; the higher the molecular mass, the stronger the protection from different stressors. ...
Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.
... The antoxidant ability of low molecular weight HA (LMWHA, 200-230 kDa) seems to be related to their ability to penetrate the skin preventing ROS damage in granulation tissue and promoting incisional wound healing in a rat experimental model [90,91]. The administration of LMWHA increased the activity of SOD, catalase, glutathione peroxidase, and total antioxidant capacity in cyclophosphamide-induced immunosuppressed mice [92]. The effect of oligosaccharides of HA (400-2000 Da) on epidermal stem cells was also studied. ...
Objective: Haemorrhoidal disease (HD) is a very diffuse anorectal condition that involves a large part of the population, both male and female of every age. Among the procedures proposed to treat HD, conventional excisional surgery remains one of the most performed. Milligan-Morgan (MM) technique is one of the most used haemorrhoidectomy techniques. In this technique, the wounds are left open and re-epithelialization requires almost 3-5 weeks, in which patients generally experience pain and intense discomfort improving over the weeks. Methods: The aim of this study was to evaluate the effect of topic administration of Benebeo Gel®, mainly composed by bergamot-derived flavonoids and hyaluronic acid, on post-operative wound healing after open MM haemorrhoidectomy. An observational prospective study was carried out, involving 205 patients aged between 18 and 75. Results and Conclusion: The results after 2 weeks of treatment seem to be promising with a very good clinical outcome and patient satisfaction within 1 month.
... Administration of LMWHA helped immunosuppressed mice recover from CY-induced immunosuppression. It dramatically increased their levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (TAOC) [33]. ...
Natural non-sulfated glycosaminoglycan hyaluronic acid (HA), a biopolymer, has a variety of functions in controlling different biological processes. However, articular cartilage and synovial fluid contain more HA than other tissues and fluids. Over the past few decades, HA has been employed as a pharmacotherapeutic for a variety of conditions, such as osteoarthritis, cartilage regeneration, and wound healing. HA is used to create scaffold materials appropriate for tissue engineering because of its unique physicochemical characteristics. Recent cutting-edge research has shown that the molecular weight (Mw) of HA affects its efficacy. This paper provided a summary of recent developments in several pharmacotherapeutic applications and recommended research areas in order to improve HA activity.
... Furthermore, HA is also known as a lubricant or support for other lubricants, such as lipids, in synovial joints [17]. Antioxidant activity and anti-inflammatory activity of HA have also been reported [18][19][20][21][22]. HA-based hydrogels have several advantages over other biomaterials for bone tissue engineering applications. ...
Hydrogel-based bone tissue engineering is a potential strategy for treating bone abnormalities and fractures. Hyaluronic acid (HA) is a natural polymer that is widely distributed in the human body and plays a significant role in numerous physiological processes such as cell migration, tissue hydration, and wound healing. Hydrogels based on HA and its derivatives have gained popularity as potential treatments for bone-related diseases. HA-based hydrogels have been extensively studied for their ability to mimic the natural extracellular matrix of bone tissue and provide a suitable microenvironment for cell support and tissue regeneration. The physical and chemical properties of HA can be modified to improve its mechanical strength, biocompatibility, and osteogenic potential. Moreover, HA-based hydrogels combined with other biomaterials in the presence or absence of bioactive agents have been investigated as a means of improving the mechanical properties and bioactivity of the hydrogel scaffold. Therefore, HA-based hydrogels have shown great promise in bone tissue engineering due to their biocompatibility, osteogenic activity, and ability to mimic the natural extracellular matrix of bone tissue. Overall, this review provides a comprehensive overview of the current state of the art in HA-based hydrogels for bone tissue engineering, highlighting the key advances, challenges, and future directions in this rapidly evolving field.
... Dermal fillers can attenuate aging-induced loss of soft tissue volume. HA injection has various biologic effects including tissue hydration [53] and antioxidant activity [54,55]. HA also decreases apoptosis and promotes cell migration during wound healing [56][57][58] and increases fibroblast proliferation and synthesis of type I collagen [53]. ...
Poly-D,L-lactic acid (PDLLA) filler corrects soft tissue volume loss by increasing collagen synthesis in the dermis; however, the mechanism is not fully understood. Adipose-derived stem cells (ASCs) are known to attenuate the decrease in fibroblast collagen synthesis that occurs during aging, and nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) increases ASCs survival by inducing M2 macrophage polarization and IL-10 expression. We evaluated the ability of PDLLA to induce collagen synthesis in fibroblasts by modulating macrophages and ASCs in a H2O2-induced cellular senescence model and aged animal skin. PDLLA increased M2 polarization and NRF2 and IL-10 expression in senescence-induced macrophages. Conditioned media from senescent macrophages treated with PDLLA (PDLLA-CMMΦ) reduced senescence and increased proliferation and expression of transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) 2 in senescence-induced ASCs. Conditioned media from senescent ASCs treated with PDLLA-CMMΦ (PDLLA-CMASCs) increased the expression of collagen 1a1 and collagen 3a1 and reduced the expression of NF-κB and MMP2/3/9 in senescence-induced fibroblasts. Injection of PDLLA in aged animal skin resulted in increased expression of NRF2, IL-10, collagen 1a1, and collagen 3a1 and increased ASCs proliferation in aged animal skin. These results suggest that PDLLA increases collagen synthesis by modulating macrophages to increase NRF2 expression, which stimulates ASCs proliferation and secretion of TGF-β and FGF2. This leads to increased collagen synthesis, which can attenuate aging-induced soft tissue volume loss.
... It has been reported that CS and HA can increase cellular antioxidant enzyme expression, such as superoxide dismutase and catalase, which convert ROS into less harmful substances, prevent DNA damage and protein oxidation, and reduce cell death (Abd El-Hack et al., 2020;Litwiniuk, Krejner, Speyrer, Gauto, & Grzela, 2016). In addition, the interaction capacity of carboxyl and hydroxyl groups in HA with ROS may also contribute to the ROS scavenging ability of HA (Ke, Sun, Qiao, Wang, & Zeng, 2011). ...
The management of infected diabetic wounds remains a major challenge in clinical practice. Recently, multifunctional hydrogels have attracted much attention in the area of wound healing. Herein, we developed the drug-free and non-crosslinked chitosan (CS)/hyaluronic acid (HA) hybrid hydrogel, so as to combine the multiple functions of CS and HA for synergistic healing of the methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wound. As a result, CS/HA hydrogel showed the broad-spectrum antibacterial activity, the great capacity for promoting fibroblasts proliferation and migration, the excellent reactive oxygen species (ROS) scavenging ability, and the great cell-protection effects under oxidative stress. In the MRSA-infected diabetic mouse wounds, CS/HA hydrogel significantly promoted the wound healing via eliminating MRSA infection and enhancing epidermal regeneration, collagen deposition and angiogenesis. Considering the drug-free feature, the ready availability, the great biocompatibility and the excellent wound healing efficacy, CS/HA hydrogel may have great potentials in clinical use for the management of chronic diabetic wounds.
... Despite its pro-inflammatory properties, LMW HA has also been postulated to exert an antioxidative capacity. Thus, antioxidant properties were shown for LMW HA against ROS and inhibition of lipid peroxidation [121], but as there is limited literature on this topic, the mechanisms by which LMW HA performs its antioxidant properties are still subject to research. The interactions of LMW HA/HMW HA and ROS in inflammation are summarized in Table 2. Table 2. LMW HA/HMW HA and ROS in inflammation. ...
Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.
... After SH treatment, nematode antioxidant enzyme activities were increased, and the levels of oxidative damage were reduced. Interestingly, Ke et al. indicated that in vivo antioxidant enzyme activities were increased by low molecular weight HA in immunosuppressed mice [29]. In summary, we can expect that SH has a good performance on antioxidant and anti-ageing effects in nematodes. ...
As an acidic polysaccharide, the formation of Hyaluronic acid (HA) is typically Sodium Hyaluronate (SH) for knee repair, oral treatment, skincare and as a food additive. Nevertheless, little information is available on the anti-ageing activity of SH as a food additive. Therefore, we treated C. elegans with SH, then inferred the anti-aging activity of SH by examining the lifespan physiological indicators and senescence-associated gene expression. Compared with the control group, SH (800 µg/mL) prolonged the C. elegans' lifespans in regular, 35 • C and H 2 O 2 environment by 0.27-fold, 0.25-fold and 1.17-fold. Simultaneously, glutathione peroxidase (GSH-Px), antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT) were increased by 8.6%, 0.36% and 167%. However, lipofuscin accumulation, reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased by 36%, 47.8-65.7% and 9.5-13.1%. After SH treatment, athletic ability was improved and no impairment of reproductive capacity was seen. In addition, SH inhibited the blocking effect of age-1 and up-regulated gene levels involving daf-16, sod-3, gst-4 and skn-1. In conclusion, SH provides potential applications in anti-ageing and anti-oxidation and regulates physiological function.
... The effects on the wound healing process depend on its molecular weight. HA with a low molecular weight has been demonstrated to be responsible for extracellular matrix regenerations through the stimulation of proteoglycans and fibronectin synthesis by fibroblasts [54][55][56]. Also, cytokine motility, angiogenesis, inflammatory effects, and oxidative stress may be modulated using products with HA with low molecular weight in wound treatments [57,58]. ...
Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels’ structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.
... Liang and colleagues showed that TQ played an inhibitory role in UVA-induced oxidative stress, inflammation and the mitochondrial apoptosis of human skin keratinocytes [64]. The antioxidant properties of HA are well known, as reported by Almalik and co-workers in 2018, where it was shown that HA is involved in inflammatory response, due to its antioxidant scavenging activity [65,66]. According to these data, in our work, HA-coated liposomes significantly reduced the mtROS levels induced by 450 mOsM for 5 h, and this could be explained by a possible synergistic effect of TQ with HA. ...
Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of Nigella sativa L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.
... HMWHA can prevent cells from undergoing apoptosis and modulate cell receptors including CD44, which plays a significant role in promoting cell migration and wound healing [16][17][18]. Both HMWHA and LMWHA have demonstrated strong antioxidant capability [19,20]. The level of HA cross-linking also affects the cosmetic effect. ...
Materials of different allogeneic or xenogeneic or autologous origins are widely used as soft-tissue fillers or structural scaffolds in the field of cosmetic surgery, while complications including prosthesis infection, donor site deformity and filler embolization have always been difficult problems for plastic surgeons. The application of novel biomaterials may bring in hopeful solutions for these problems. Recently, some advanced biomaterials, such as regenerative biomaterials can effectively promote the repair of defective tissues, which have been proven to have good therapeutic as well as cosmetic effects in cosmetic surgery. Therefore, biomaterials with active compunds have drawed significant attention for the tissue regeneration of reconstructive and aesthetic treatment. Some of these applications have achieved better clinical outcomes than traditional biological materials. This review summarized recent progress and clinical applications of advance biomaterials in cosmetic surgery.
... Oxidative damage protection provided by antioxidant and repair systems are typically insufficient. Because of that, too much attention has been focused on the role of hyaluronic acid as an antioxidant [6,19,23,25]. ...
O ácido hialurônico (AH), é um polissacarídeo que possui numerosas aplicações naturais devido às suas propriedades bioquímicas e, portanto, há grande interesse por parte das indústrias cosmética, médica e farmacêutica na sua obtenção. O AH pode ser extraído de tecidos animais ou obtido pelo cultivo de bactérias, sendo a última via mais vantajosa. Assim, a otimização do meio de cultivo para a produção do polímero procariótico é de grande importância. Este trabalho teve por objetivo avaliar o efeito da concentração de sacarose e extrato de levedura, bem como de arginina e glutamina na produção de ácido hialurônico por Streptococcus equi subsp. zooepidemicus. Foram realizadas fermentações de acordo com um planejamento fatorial completo 3² (com dois pontos centrais), utilizando concentrações de 20, 30 e 40 g.L-1 de sacarose e extrato de levedura. Encontrada a relação C:N ótima para produção de AH, testou-se o efeito da concentração de arginina e glutamina (0,0 a 3,0 g.L-1) através de planejamento fatorial completo 3² (com dois pontos centrais). Apenas o extrato de levedura mostrou efeito significativo, exibindo influência positiva na produção de AH. No entanto, observou-se um aumento na produção de AH com a adição dos aminoácidos. A maior produção do polímero (1,096 g.L-1) ocorreu em 30 g.L-1 de sacarose, 40 g.L-1 de extrato de levedura, 1,5 g.L-1 de arginina e sem adição de glutamina.
... 48 HA, as a macromolecular polysaccharide, also has the antioxidant capacity and has a role in scavenging ROS in vivo. 49 According to our experimental results, SIN-L-H had a good scavenging ability on DPPH and H 2 O 2 In vitro, and it also had an obvious inhibitory effect on MDA in organs. Therefore, in the treatment of oxidative stress, the combination of SIN, phospholipids, and HA will be an excellent choice, and SIN-L-H might be a good antioxidant for the clinic in the future. ...
Sinomenine (SIN), a natural product, has been used to treat rheumatoid arthritis (RA) in China for thousands of years. SIN has been developed for the treatment of RA by way of tablets and injections, but both dosage forms have been associated with severe adverse reactions. Making SIN into liposomes-in-hydrogel biomaterials for external use has a good slow-release effect and can play an important role in avoiding the first-pass effect, gastrointestinal reaction, and increasing the local action time of drugs. SIN-loaded liposomes were formed by the thin-film dispersion method, then SIN-loaded liposomes-in-hydrogels were prepared by combining the SIN-L with hyaluronic acid (HA) hydrogels. In this paper, the basic characteristics, In vitro and Ex vivo release, and antioxidant activity of SIN-loaded liposomes-in-hydrogels were studied. The results showed that SIN-loaded liposomes-in-hydrogels have good sustained-release and antioxidant effects, and the preparation is expected to be a good biomaterial.
... In this study, AKP activity was highest at 2.73% dietary Arg levels. Furthermore, antioxidant enzymes (e.g., SOD, CAT, and T-AOC) play a direct role in removing excess ROS and protecting cells from oxidative damage (Ke et al., 2011;Ighodaro and Akinloye, 2018). T-AOC can be used as a comprehensive index to assess the antioxidant capacity of the body. ...
This study investigated the effects of different dietary arginine (Arg) levels on the growth, protein synthesis, antioxidant capacity, and immunity of postlarval mud crab Scylla Paramamosain. Six isonitrogenous and isolipidic diets were formulated to contain 1.51%, 1.81%, 2.16%, 2.35%, 2.73%, and 3.07% dietary Arg levels (dry matter). There were four replicates for each diet treatment (26 crabs per replicate, initial body weight: 7.40 ± 0.15 mg). After eight weeks of feeding trial, the survival and molting frequency (MF) of crabs were not affected by the experimental treatment (P>0.05). Crabs fed the 2.50% Arg diet achieved the highest weight gain (WG) and specific growth rate (SGR) (P<0.05). The whole-body protein content of the 2.16% and 2.73% Arg groups were significantly higher than that of the 1.51% Arg group (P<0.05). Crabs in the 2.35% group obtained the highest levels of phenylalanine and leucine (P<0.05). Superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) activity in the 2.16%, 2.35% and 2.73% Arg groups were significantly higher than that in other treatments (P<0.05). Malondialdehyde (MDA) concentration and alkaline phosphatase (AKP) activity were not significantly affected by the treatments. The transcript levels of insulin-like growth factor 1 (igf-1), rapamycinin (TOR), S6 kinase-polypeptide 1 (s6k1) in crabs fed with 2.16% and 2.35% dietary Arg were significantly higher than those in crabs fed with 1.51% and 3.07% dietary Arg (P<0.05). The lowest prophenoloxidase (proPO), relish, and lysozyme transcript levels were observed in crabs fed the 1.51% dietary Arg. The current study founded that the Arg requirement for postlaval S.paramamosain was 2.34% (5.20% of the dietary protein), based on the second order polynomial regression analysis of WG.
... Scientists have found, that hyaluronic acid derivatives have antioxidant activity [61]. In a study conducted by Chunlin et al., it was found that low molecular weight hyaluronic acid derivatives exhibited antioxidant activity and that the compounds were able to reduce lipid peroxidation [62]. In this experiment, we investigated the antioxidant activity of 0.1% (~1.5-1.8 × 10 6 Da) hyaluronic acid in the formulations. ...
Phenolic compounds of natural origin have been valued for their beneficial effects on health since ancient times. During our study, we performed the extraction of phenolic compounds from balsam poplar buds using different concentrations of aqueous polyethylene glycol 400 solvents (10–30% PEG400). The aqueous 30% PEG400 extract showed the best phenolic yield. The stability of the extract during autoclave sterilization was evaluated. The extract remained stable under heat sterilization. Ophthalmic formulations are formed using different concentrations (8–15%) of poloxamer 407 (P407) together with hydroxypropyl methylcellulose (0.3%), sodium carboxymethyl cellulose (0.3%) or hyaluronic acid (0.1%). Physicochemical parameters of the formulations remained significantly unchanged after sterilization. Formulations based on 12% P407 exhibited properties characteristic of in situ gels, the gelation point of the formulations was close to the temperature of the cornea. After evaluating the amount of released compounds, it was found that, as the concentration of polymers increases, the amount of released compounds decreases. Formulations based on 15% P407 released the least biologically active compounds. Sterilized formulations remained stable for 30 days.
... HA was also found to enhance peripheral nerve regeneration in the frog (5). In addition, several reports showed that HA possessed free radical scavenging and antioxidant activities in vivo and in vitro settings (6)(7)(8). Reactive oxygen species (ROS) have been proven as endogenous mediators of muscle fatigue and possibly involved in chronic fatigue syndrome (9, 10). ...
Hyaluronan (HA) is a mucopolysaccharide that naturally exists in all living organisms as the main component of the extracellular matrix. Over the last 30 years, HA has been used as the main ingredient in cosmetic products, eye drops, and medicinal products. It is also taken orally as a health supplement. However, the physiological effect of the ingested HA is not clear. In the current study, the interaction between HA and gut microbiota, and the potential prebiotic effects were investigated. HA was used to treat the C57BL/6 mice for 15 consecutive days, then fecal genomic DNA was extracted from fecal samples for 16S rRNA amplicon sequencing. The results showed that HA could significantly change the composition of gut microbiota (GM), e.g., increased the relative abundance of beneficial bacteria, including short-chain fatty acids (SCFAs)-producing bacteria and xylan/cellulose-degrading bacteria, whereas decreased the relative abundance of potential pathogens including sulfate-reducing bacteria (SRB), inflammation and cancer-related bacteria. The rotarod test was used to evaluate the anti-fatigue effects of HA in C57BL/6 mice. The results showed that HA could lengthen the mice's retention time on the accelerating rotarod. HA increased the concentration of glycogen and superoxide dismutase (SOD) in mice's muscle and liver, whereas decreased the serum concentration of malondialdehyde (MDA). Moreover, the metabolic products of Desulfovibrio vulgaris (MPDV), the model SRB bacteria, showed cytotoxic effects on H9c2 cardiomyocytes in a dosage-dependent manner. MPDV also caused mitochondrial damage by inducing mitochondrial fragmentation, depolarization, and powerless ATP production. Taken together, we show that HA possesses significant prebiotic and anti-fatigue effects in C57BL/6 mice.
... HA conjugation with different drugs such as paclitaxel, 5-fluro uracil, doxorubicin and methotrexate has been well-documented in previous literature [26][27][28][29] with drug liberation by the intracellular cleavage of HA-drug bonds [30]. In addition, HA by its antioxidant potential would decrease oxidation response, preventing hepatic stellate cells activation and decreasing the possibility of liver fibrosis [31,32]. ...
Drug covalently bound to polymers had formed, lately, platforms with great promise in drug delivery. These drug polymer conjugates (DPC) boosted drug loading and controlled medicine release with targeting ability. Herein, the ability of entecavir (E) conjugated to hyaluronic acid (HA) forming the core of vitamin E coated lipid nanohybrids (EE-HA LPH), to target Kupffer cells and hepatocyte had been proved. The drug was associated to HA with efficiency of 93.48 ± 3.14 % and nanohybrids loading of 22.02 ± 2.3 %. DiI labelled lipidic nanohybrids improved the macrophage uptake in J774 cells with a 21 day hepatocytes retention post intramuscular injection. Finally, in vivo biocompatibility and safety with respect to body weight, organs indices and histopathological alterations were demonstrated. Coating with vitamin E and conjugation of E to HA (a CD44 ligand), could give grounds for prospective application for vectored nano-platform in hepatitis B.
This study aimed to develop hyaluronan (HA)-based hydrogel microparticles (MPs) loaded with hemin to address the limitations of traditional macroscale hydrogels. The objective is to design MPs such that they can modulate their physicochemical properties. Given the widespread use of ultraviolet C (UVC) light in various industries and the need for protective measures against accidental exposure, this study evaluated the potential of hemin-loaded MPs to protect human dermal fibroblasts from oxidative stress and cell death caused by UVC exposure. Multiple MP formulations were developed and analysed for size, surface charge, swelling behaviour, degradation rate, and radical scavenging capabilities, both with and without hemin loading. The most promising formulations were tested against UVC-exposed cells to assess cell viability, intracellular nitric oxide (˙NO) and reactive oxygen species levels, and protein carbonylation. The fabricated particles were in the form of microneedles, and the degree of their crosslinking and the role of hemin in the chemical crosslinking reaction were found to influence the surface charge and hydrodynamic diameter of the MPs. Increased crosslinking resulted in reduced swelling, slower degradation, and decreased hemin release rate. MPs with a higher degree of swelling were capable of releasing hemin into the culture medium, leading to enhanced bilirubin generation in dermal fibroblasts following cellular uptake. Pre-treatment with these MPs protected the cells from UVC-induced cell death, nitrosative stress, and protein carbonylation. These findings highlight the potential of the studied MPs to release hemin and to minimise the harmful effects of UVC on dermal fibroblasts.
MXene‐based thermal camouflage materials have gained increasing attention due to their low emissivity, however, the poor anti‐oxidation restricts their potential applications under complex environments. Various modification methods and strategies, e.g., the addition of antioxidant molecules and fillers have been developed to overcome this, but the realization of long‐term, reliable thermal camouflage using MXene network (coating) with excellent comprehensive performance remains a great challenge. Here, a MXene‐based hybrid network comodified with hyaluronic acid (HA) and hyperbranched polysiloxane (HSi) molecules is designed and fabricated. Notably, the presence of appreciated HA molecules restricts the oxidation of MXene sheets without altering infrared stealth performance, superior to other water‐soluble polymers; while the HSi molecules can act as efficient cross‐linking agents to generate strong interactions between MXene sheets and HA molecules. The optimized MXene/HA/HSi composites exhibit excellent mechanical flexibility (folded into crane structure), good water/solvent resistance, and long‐term stable thermal camouflage capability (with low infrared emissivity of ≈0.29). The long‐term thermal camouflage reliability (≈8 months) under various outdoor weathers and the scalable coating capability of the MXene‐coated textile enable them to disguise the IR signal of various targets in complex environments, indicating the great promise of achieved material for thermal camouflage, IR stealth, and counter surveillance.
A medicinal biopolymer with high economic value, hyaluronic acid (HA), is increasingly synthesized through microbial fermentation. Research and development have focused on enhancing hyaluronic acid’s crucial quality characteristics, purity, and molecular weight. Due to its adaptability, hyaluronic acid has played a significant role in biomedical research and has been used in numerous sectors, including tissue engineering and cancer treatment, in various forms. Micelles, polymersomes, hydrogels, and other hyaluronic acid-based nanomaterials are essential for effective drug administration and cancer treatment. Modern hyaluronic acid encapsulation techniques can adequately prevent probiotics and nutraceuticals from the severe conditions of food processing. Hyaluronic acid can also create a wide range of vaccinations as an efficient and biocompatible adjuvant. Also, developing nasal vaccinations against infectious diseases is a promising application for hyaluronic acid-coated micelles. This chapter examines the benefits and drawbacks of microbial hyaluronic acid generation and its diverse applicability in various industries.KeywordsHyaluronic acidFermentationBiomedicineNutraceuticalsVaccine adjuvant
A total of forty-two bacterial isolates from different samples of yoghurt and shnina purchased form local markets in Basrah Governorate. The preliminary screening was carried out all bacterial isolates by carbazol staining. The twenty-one isolates were selected based on the intensity of colour variation in the fermentation medium and were identified according to phenotypic, microscopic, and biochemical examinations, which included twelve isolates of Streptococcus thermophilus, four isolates of Pediococcus pentosaceus, and five isolates of Entirococcus faecuim. Vitek II Compact instrument was used with all isolates to confirm the initial identification. The secondary screening was performed for isolates of S. thermophilus species. Given the amount of the produced hyaluronic acid, the St15 had the highest hyaluronic acid production, which was 0.231 g/L. The 16S rRNA test allowed the identification of this isolate.
The results showed that the best conditions for acid production were 0.598 g/L and the amount of biomass was 6.08 g/L after the S. thermophilus (ABST) strain grown on the alternative medium containing 450 ml/L whey, 7.5 g/L yeast extract, 3% an inoculum volume and pH 6.8, incubated on an orbital shaker at 40°C for 18 hours, and agitated at 150 rpm.
HPLC, FTIR, and NMR techniques were used to identify the nucleus of the hydrogen atom (proton) 1H and the carbon atoms 13C in the presence of standard hyaluronic acid for comparison. The results revealed the peaks and bands of the produced acid were similar to that of the standard acid.
The produced hyaluronic acid was characterized by a viscosity of 595 g/ml and a molecular weight of 6.83×106 Daltons. Its gravimetric decomposition temperature was 220 °C. The differential calorimetric decomposition results displayed three peaks, one of which is endothermic at a temperature of 103°C and two peaks are endothermic at 220°C and 238°C.
By assessing the antioxidant activity of hyaluronic acid at concentrations between 50-1300 g/ml, assays were conducted on free radical scavenging ability, reducing power, ability of hydrogen peroxide (H2O2) capture, and the binding of ferrous ion, which were 69.18%, 1.1 nm, 78.42, and 73.74% at the highest antioxidant activity, respectively.
The hyaluronic acid produced was used as a natural antioxidant to inhibit oxidation in crude sunflower oil by estimating the peroxide value, pH, thiobarbituric acid, and iodine number in two types of opaque and transparent containers and at different storage periods of 0, 30, 60, and 90 days. The concentration of 600 mg/kg of oil gave the best inhibitory activity to hinder oxidation in the oil filled in opaque packages during all storage periods. The inhibitory activity during 90 days of storage reached low values for peroxide number 32.81 mEq/kg oil, the acidity number 6.01 mg potassium hydroxide/kg oil, and thiobarbituric acid 0.43. The amount of malonaldehyde was 0.43 mg/kg oil, and high values for the iodine number 118.8 mg/100 g oil compared to the control sample.
The impact of feeding using oil supplemented with hyaluronic acid as an antioxidant was studied in the diet of experimental animals for 42 days. The animals were allocated into three treatments (T): The T1 fed on oil free of antioxidants, T2 fed on oil supplemented with synthetic antioxidants (BHT), and T3 fed on oil supplemented with hyaluronic acid. The results indicated that the cumulative weight increase rate for T1, T2 and T3 was 14.85, 21.14, and 24.48 gm, respectively. The average feed consumption was 679, 698, and 725 gm, respectively. The feed conversion efficiency (FCE) was 2.18, 3.02, and 3.37, respectively, while the feed conversion rate (FCR) was 45.72, 33.01, and 29.61, respectively.
After 42 days, the haematological parameters of experimental animals under T2 and T3 treatment showed that they were within the normal range of blood parameters where there was no harmful effect on liver function as measured through enzyme activity indicators in blood serum and on immune cells as compared to treatment T1.
The microbial characteristics were studied in the faeces of experimental animals fed for T1, T2, and T3 for 42 days. The results also pointed to a decrease in the number of Streptococci bacteria for T2 and T3 compared to T1 which counted to log 4.12 and 4.15 and 5.09 CFU/gm, respectively. The numbers of Lactic acid bacteria for T2 and T3 excelled which were log 9.55 and 9.15 CFU/gm, respectively, compared to the T1, which amounted to 9.05 CFU/gm. As for the intestinal bacteria group, it was noticed that their numbers decreased for groups T2 and T3, which amounted to 6.39 and 6.29 CFU/gm, respectively, while their numbers increased for T1, which amounted to log 7.95 CFU/gm.
Hyaluronic acid (HA), an anionic and nonsulfated glycosaminoglycan, is the main structural component of various tissues and plays an important role in various biological processes. Given the promising properties of HA, such as high cellular compatibility, moisture retention, antiaging, proper interaction with cells, and CD44 targeting, HA can be widely used extensively in drug delivery, tissue engineering, wound healing, and cancer therapy. HA can obtain from animal tissues and microbial fermentation, but its applications depend on its molecular weight. Microbial fermentation is a common method for HA production on an industrial scale and S. zooepidemicus is the most frequently used strain in HA production. Culture conditions including pH, temperature, agitation rate, aeration speed, shear stress, dissolved oxygen, and bioreactor type significantly affect HA biosynthesis properties. In this review, all the HA production methods and purification techniques to improve its physicochemical and biological properties for various biomedical applications are discussed in detail. In addition, we showed how HA molecular weight can significantly affect its properties and applications.
Increasing studies focus on chondroitin sulfate (CS) degradation to improve its biological activity. The review mainly introduces the degradation methods of CS and their mechanisms. Studies have shown that different degradation methods can lead to different structures of low molecular weight chondroitin sulfate (LMCS). LMCS were prepared through β-elimination reaction, hydrolysis reaction, hydrogen abstraction reaction, and deamination reaction. The degradation of CS is affected by two aspects: the structure of CS (disaccharide composition and molecular weight) and the influence of degradation conditions (temperature, pH, degradation promoters, auxiliary conditions, and time). LMCS with different structures have different biological activities. In addition, degradation could also change CS's metabolism, such as absorption effects and gut microbiota. Thus, choosing the appropriate degradation method for CS development and utilization is very important.
This work investigated the potential of amoxicillin-doped hyaluronic acid/fucoidan multifunctional coatings on medical grade stainless steel as biocompatible, osteointegration enhancing, antimicrobial, and bacterial biofilm inhibiting coatings for orthopedic implants. The coatings were prepared by layer-by-layer spin coating and confirmed by optical contact angle goniometry and infrared spectroscopy. Time-of-flight secondary ion mass spectrometry showed a homogeneous distribution of the individual layers. In contrast, thermal diffusivity, and thermal conductivity measurements by photothermal beam deflection spectrometry showed diffusion of the amoxicillin into the hyaluronic acid and fucoidan layers. In vitro release of amoxicillin showed complete release within one hour, as reflected by the formation of inhibition zones against Staphylococcus aureus and Escherichia coli. Synergistic effects were observed between the hyaluronic acid and amoxicillin in inhibiting S.Aureus biofilm, and between the fucoidan and amoxicillin in improving the antioxidant properties by an ABTS radical scavenging assay. Biocompatibility was determined with human osteoblasts, confirming the potential of such multifunctional coatings to enhance the bioactivity of steel-based orthop edic implants.
Advanced technologies for producing high-quality low molecular weight hyaluronic acid (LMW-HA) are required from the perspective of cost-efficiency and biosafety. Here, we report a new LMW-HA production system from high molecular weight HA (HMW-HA) using vacuum ultraviolet TiO2 photocatalysis with an oxygen nanobubble system (VUV-TP-NB). The VUV-TP-NB treatment for 3 h resulted in a satisfactory LMW-HA (approximately 50 kDa measured by GPC) yield with a low endotoxin level. Further, there were no inherent structural changes in the LMW-HA during the oxidative degradation process. Compared with conventional acid and enzyme hydrolysis methods, VUV-TP-NB showed similar degradation degree with viscosity though reduced process time by at least 8-fold. In terms of endotoxin and antioxidant effects, degradation using VUV-TP-NB demonstrated the lowest endotoxin level (0.21 EU/mL) and highest radical scavenging activity. This nanobubble-based photocatalysis system can thus be used to produce biosafe LMW-HA cost-effectively for food, medical, and cosmetics applications.
The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction - oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC --> TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, beta-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed.
Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, aging, and cancer. The superoxide anion O(2)(-) is the main ROS. Increased ROS production leads to tissue damage associated with inflammation. Superoxide dismutases (SODs) convert superoxide to hydrogen peroxide, which is then removed by glutathione peroxidase or catalase. Thus, SODs prevent the formation of highly aggressive ROS, such as peroxynitrite or the hydroxyl radical. Experimental models involving SOD knockout or overexpression are beginning to shed light on the pathophysiological role of SOD in humans. Although the antiinflammatory effects of exogenous native SOD (orgotein) are modest, synthetic SOD mimetics hold considerable promise for modulating the inflammatory response. In this review, we discuss new knowledge about the role of the superoxide anion and its derivates as mediators of inflammation and the role of SODs and SOD mimetics as antioxidant treatments in joint diseases such as rheumatoid arthritis, osteoarthritis, and crystal-induced arthropathies.
Hyaluronan is being used increasingly as a component of artificial matrices and in bioengineering for tissue scaffolding. The length of hyaluronan polymer chains is now recognized as informational, involving a wide variety of size-specific functions. Inadvertent scission of hyaluronan can occur during the process of preparation. On the other hand, certain size-specific hyaluronan fragments may be desirable, endowing the finished bioengineered product with specific properties. In this review, the vast arrays of reactions that cause scission of hyaluronan polymers is presented, including those on an enzymatic, free radical, and chemical basis.
CD8 + T cells respond to antigen stimulation through a process of activation, division, and differentiation generating a large pool of activated effector cytolytic T lymphocytes (CTLs). Many cancer patients harbor the accordant precursor CTLs capable of responding to various tumor‐associated antigens (TAA). In selected cases, vaccination with these TAA can elicit detectable antitumor responses. Presently, the clinical outcome of cancer vaccination remains inadequate. The lack of clinical efficacy may be attributed to various molecular and cellular mechanisms developed by tumors to successfully evade the host immune system. Some of these mechanisms have been identified. It is becoming increasingly apparent that immunotherapy with the sole objective of inducing immune activation is in itself not sufficient to fully overcome the mechanisms averting efficient antitumor responses. Strategies to neutralize tumor‐induced immune suppression have to be developed in parallel to antigenic stimulation. Our data show that both oxidative stress‐ and antigen‐mediated preferential cell death of antigen‐experienced memory CTLs may be a major contributor to tumor‐induced immune dysfunction. The persistence of functional CTLs is a key element for an efficient antitumor response and affects the outcome of any immunotherapy protocol. We therefore propose that protecting CTLs from premature death by identifying and targeting the responsible pathway can lead to substantial enhancement in antitumor response. In this review, we discuss some of the fundamental factors that may be involved in the modulation of the different lymphocyte subsets towards sensitization or resistance to tumor‐induced stress.
Hyaluronate lyase cleaves hyaluronan chains at a β-d-GalNAc-(1→4)-β-d-GlcA bond, ultimately breaking the polysaccharide down to 3-(4-deoxy-β-d-gluc-4-enuronosyl)-N-acetyl-d-glucosamine. In the present paper, the recombinant hyaluronate lyase (EC 4.2.2.1, HA lyase) of Streptococcus pyogenes bacteriophage H4489A was produced, purified and applied to digest hyaluronan producing unsaturated hyaluronan oligomers. The resulted unsaturated hyaluronan oligomers were purified and subjected to anion-exchange high performance chromatography. The cytotoxic activities of naturally hyaluronan, hyaluronate lyase and unsaturated hyaluronan oligomers were tested and evaluated against HEp-2 (human laryngeal carcinoma), Daoy (human medulloblastoma), MCF-7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma) tumor cell lines. Also, their antioxidant activities have been examined by the inhibition of lipid oxidation and free radical scavenging assays.
The antioxidant activities of crude Hyriopsis cumingii polysaccharides (HCPS) were evaluated both in vitro and in vivo. In vitro antioxidant assay, HCPS (crude and its purified fraction) could scavenge hydrogen peroxide, free radicals of superoxide anion and 2,2-diphenyl-1-picryl-hydrazyl, chelate ferrous ion and reduce ferric ion. Except for metal ion chelating activity, HCPS-3 exhibited much higher antioxidant activities than crude HCPS, HCPS-1 and HCPS-2. For antioxidant testing in vivo, different doses of crude HCPS were orally administrated over a period of 15 days in a d-galactose induced aged mice model. As results, administration of crude HCPS inhibited significantly the formation of malondialdehyde in mice livers and serums and raised the activities of antioxidant enzymes and total antioxidant capacity in a dose-dependent manner. The results suggested that HCPS had direct and potent antioxidant activities.
Crude capsule polysaccharides (CCP) were prepared from the culture of Streptococcus equi subsp. zooepidemicus C55129 and were partially purified through an anion-exchange column chromatography to afford partially purified capsule polysaccharides (PCP). The main component of CCP and PCP was hyaluronic acid. In vitro antioxidant assay, the capsule polysaccharides showed strong inhibition of lipid peroxidation and hydroxyl radical scavenging activity and moderate 1,1-diphenyl-2-picryldydrazyl radical scavenging activity. In addition, CCP exhibited much stronger reductive power than PCP. For antioxidant testing in vivo, CCP and PCP were orally administrated over a period of 15 days in a d-galactose induced aged mice model. As results, administration of capsule polysaccharides inhibited significantly the formation of malondialdehyde in mice livers and serums and raised the activities of antioxidant enzymes and total antioxidant capacity in a dose-dependent manner. However, the antioxidant activity of CCP was lower than that of PCP. The results suggest that the capsule polysaccharides from Streptococcus equi subsp. zooepidemicus C55129 have direct and potent antioxidant activities.
Hyaluronic acid (Hyaluronan, HA) was depolymerised by gamma irradiation and its structural changes and antioxidant activities were investigated. The structural changes of gamma irradiated HA were studied by gel-permeation chromatography (GPC), viscosity, pH, Hunter colour measurement, UV spectrophotometry, and FT-IR spectroscopy. The results demonstrated that gamma irradiation decreased molecular weight size, viscosity and pH of the hyaluronic acid and its colour turned to intense yellow. UV spectra of the irradiated HA showed a change at 265nm, which indicates the formation of double bonds. Differences in the height and shape of certain absorption bonds of FT-IR spectra in the range 1700-1750cm(-1) were also observed, which is associated with the formation of carboxylic acid. From these structural changes of the HA, gamma irradiation may have a role in the formation of pyrancarboxylic acid rings. DPPH radical scavenging ability and the reducing power of gamma irradiated HA were significantly higher than that of non-irradiated HA. However, non-irradiated and irradiated HA did not show significant differences in the Rancimat test.
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The effectiveness of mint leaves, a common herb used in Indian cuisine, as a natural antioxidant for radiation-processed lamb meat was investigated. Mint extract (ME) had good total phenolic and flavonoid contents. It exhibited excellent antioxidant activity, as measured by β-carotene bleaching and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. It also showed a high superoxide- and hydroxyl-scavenging activity but low iron-chelating ability. A positive correlation was found between the reducing power and the antioxidant activity. The antioxidant activity of ME was found to be comparable to the synthetic antioxidant, butylated hydroxytoluene (BHT). The suitability of ME as an antioxidant was determined during radiation processing of lamb meat. ME retarded lipid oxidation, monitored as thiobarbituric acid-reactive substances (TBARS), in radiation-processed lamb meat. TBARS values of ME containing irradiated meat stored at chilled temperatures were significantly lower (p < 0.05) than samples without ME. After 4 weeks of chilled storage, TBARS in irradiated meat containing ME (0.1%) was half of that in untreated irradiated meat.
In this study, high molecular weight hyaluronic acid in powder form (HMW-HA, with average molecular weight of 1042 kDa) was degraded to low molecular (LMW-HA, 200–230 kDa) by several methods, and the changes in molecular structure and antioxidative activities brought about by each degradation method were compared. The degradation methods used were electron beam irradiation (EB), gamma ray irradiation (GM), microwave irradiation (MW), and thermal treatment (TH). The FT-IR spectra showed no substantial changes of the spectral pattern between HMW and LMW-HAs. However, the UV absorbance of LMW-HA by MW was considerably greater at 265 nm indicating the formation of more double bonds. The antioxidative activities of all LMW-HA samples were found to have risen, but the MW-treated LMW-HA showed the most significant increase due to a newly formed double bond. EB- and GM-treated LMW-HA showed the lowest polydispersity and little change in UV spectra from those of HMW-HA.
Two polysaccharides, GAPS-1 and SAPS-1, were isolated from the gel and the skin of Aloe barbadensis Miller irrigated with sea water for 3.5 years through a combination of anion-exchange column chromatography and repeated gel chromatography and their chemical characterization and antioxidant activities in vitro were investigated. GAPS-1 and SAPS-1 were composed of Man:Glc:Gal in a ratio of 120:2:3 and 296:36:1 with their molecular weight 1.74 × 105 and 3.97 × 104 Da, respectively. IR and 13C NMR study of GAPS-1 and SAPS-1 demonstrated that the main skeletons of GAPS-1 was β-(1 → 4)-D linkaged mannose with acetylation at C-6 and C-3 of manopyranosyl and SAPS-1 was β-(1 → 4)-D linkaged galactoglucomannan with acetylation at C-6 of pyranosyl. In a concentration-dependent manner, GAPS-1 and SAPS-1 were demonstrated to have strong scavenging activities against superoxide radical, moderate ferrous chelating effect, moderate scavenging activities of hydroxyl radical, moderate reductive power and moderate inhibition of lipid peroxidation. Furthermore, GAPS-1 exhibited moderate scavenging activity of hydrogen peroxide, while SAPS-1 exhibited weak scavenging activity of hydrogen peroxide. GAPS-1 demonstrated more effective antioxidant activities than SAPS-1. The more acetyl group in GAPS-1 molecules probably contributes to the activities.
A thermal dissociation initiator, potassium persulfate (KPS), is added to the chitosan solution at 70 °C; immediately, the solution viscosity and the molecular weight of chitosan decrease in a very short time. Size exclusion chromatography, nuclear magnetic resonance and electron spin resonance were used to study the degradation mechanism. A free radical degradation mechanism of chitosan by KPS is then proposed. When KPS is thermally dissociated into anionic radicals, they are attracted to the cationic amino group in the chitosan ring. Subsequently, the anionic radical attacks the C-4 carbon and transfers the radical to the C-4 carbon by subtracting the hydrogen from it. The presence of free radical at C-4 carbon eventually results in the breakage of the glycosidic C–O–C bond in the chitosan main chain. According to this mechanism, the concentrations of KPS, total free radicals and the degraded chitosan chain at different degradation times are all calculated by solving the rate equations. Finally, the calculated average molecular weights of the degraded chitosan chains at different reaction times agree with the experimental values.
Hyaluronan (HA) is a naturally occurring, biocompatible polysaccharide with unique viscoelastic and hygroscopic properties. Its role as a natural lubricant and its excellent water-retaining properties make it well-suited for use in ophthalmic products. Many reports have been written describing the various uses of HA. The purpose of this report is to review the uses of HA in the anterior segment of the eye, more specifically, its use in the treatment of dry eye syndrome, and in contact lenses and contact lens care systems.
The present study aims to investigate whether Lycium barbarum polysaccharides (LBP) could protect against acute doxorubicin (DOX)-induced cardiotoxicity. Rats received daily treatment of either distilled water (4 ml/kg) or LBP (200mg/kg) for 10 days and then followed by an intravenous injection at day 7 of either saline (10 ml/kg) or DOX (10 mg/kg). DOX induced significantly myocardial damage in rats, which were characterized as conduction abnormalities, decreased heart-to-body weight ratio, increased serum CK, and myofibrillar disarrangement. DOX treatment also increased MDA and decreased SOD and GSH-Px activity in cardiac tissues. Pretreatment with LBP significantly reduced DOX-induced oxidative injury in cardiac tissue, suggesting by the fact that LBP significantly attenuated DOX-induced cardiac myofibrillar disarrangement and LBP was effective in decreasing the levels of serum CK and thus improving conduction abnormalities caused by DOX. LBP treatment significantly increased SOD and GSH-Px activity and decreased the MDA level of heart tissues damaged by DOX exposure in rats. Furthermore, the cytotoxic study showed that LBP protect against cytotoxicity of DOX in cardiac myoblasts H9c2 but dose not attenuate the anti-tumor activity of DOX. In summary, our evidence indicates that LBP elicited a typical protective effect on DOX-induced acute cardiotoxicity via suppressing oxidative stress.
Polygonum cillinerve (Nakai) Ohwi is commonly used in China for over 2000 years. Previous research has shown that the crude polysaccharides extracted from Polygonum cillinerve (Nakai) Ohwi (PCCP) have the scavenging free radicals and anti-tumor activities in vitro. In present study, PCCP were further approached the perspective of their anti-oxidation in immunosuppressed mice.
ICR mice were treated firstly with cyclophosphamide (CY, 150 mg/kg), 1 day later, treated with different dosages of PCCP or saline solution once daily for 21 days. Twenty-four hours later for the last drug administration, the animals were weighed, and then killed by decapitation. The liver, spleen, and thymus indices were investigated, and the biochemical parameters were evaluated for various tissues (liver, heart, and kidney).
The administration of PCCP with gavage was able to overcome the cyclophosphamide-induced immunosuppression, and significantly to raise the TOC, CAT, SOD, and GSH-Px level. It also raised the liver, spleen, and thymus indices, and decreased the MDA level in mice.
PCCP possess the pronounced free radical-scavenging and antioxidant activities, and could play an important role in the prevention of oxidative damage in immunological system.
CD8(+) T cells respond to antigen stimulation through a process of activation, division, and differentiation generating a large pool of activated effector cytolytic T lymphocytes (CTLs). Many cancer patients harbor the accordant precursor CTLs capable of responding to various tumor-associated antigens (TAA). In selected cases, vaccination with these TAA can elicit detectable antitumor responses. Presently, the clinical outcome of cancer vaccination remains inadequate. The lack of clinical efficacy may be attributed to various molecular and cellular mechanisms developed by tumors to successfully evade the host immune system. Some of these mechanisms have been identified. It is becoming increasingly apparent that immunotherapy with the sole objective of inducing immune activation is in itself not sufficient to fully overcome the mechanisms averting efficient antitumor responses. Strategies to neutralize tumor-induced immune suppression have to be developed in parallel to antigenic stimulation. Our data show that both oxidative stress- and antigen-mediated preferential cell death of antigen-experienced memory CTLs may be a major contributor to tumor-induced immune dysfunction. The persistence of functional CTLs is a key element for an efficient antitumor response and affects the outcome of any immunotherapy protocol. We therefore propose that protecting CTLs from premature death by identifying and targeting the responsible pathway can lead to substantial enhancement in antitumor response. In this review, we discuss some of the fundamental factors that may be involved in the modulation of the different lymphocyte subsets towards sensitization or resistance to tumor-induced stress.
Hyaluronan (HA), a component of the extracellular matrix, may regulate immune cell functions through its interactions with cellular receptors. Besides its effect on cytokine and chemokine production, its antioxidant properties have been described. However, the mechanisms of this are not fully elucidated. The aim of this study was to evaluate the relationship between HA concentration and molecular weight and its antioxidant properties towards human neutrophils. Also assessed was whether the antioxidant effect of HA is connected with a reduction in intracellular oxygen potential, which could indicate its direct effect on neutrophil respiratory burst.
The relationship between HA's antioxidant properties and its concentration and molecular weight was assessed by the luminol-enhanced chemiluminescence method (CL). To evaluate the effect of HA on intracellular oxygen potential selectively, the dihydrorhodamine 123 (DHR123) flow cytometric method was used.
Reduction of both HA molecular weight and its concentration decreased its antioxidant properties in the CL method. A selective effect of HA on intracellular oxygen potential measured by the DHR123 method was not shown.
The antioxidant properties of HA are related to both its molecular weight and its concentration. The lack of an antioxidant effect of HA in the DHR123 test compared with a significant reduction in CL values at the same HA concentration suggests that HA acts mainly as a chemical ROI scavenger in the extracellular space.
Cyclophosphamide (Cy) could induce immuno-suppression such as thymus atrophy and inhibition of lymphocyte proliferation response in mice. But, the mechanism of its effect is still not clear. Polysaccharides isolated from spore of Ganoderma lucidum (GL-SP) could, at least partly, restore the immunological effects against Cy-induced immuno-suppression. In the present study, a two-dimensional gel electrophoresis (2-DE)-based comparative proteomic method was conducted to identify the possible target-related proteins of Cy in mice thymus including those could be influenced by GL-SP. Fifteen proteins differentially expressed in Cy-treated mice compared with control were identified. Among the fifteen proteins, combined use of GL-SP with Cy could not affect Cy-induced expression change of three proteins, totally prevented Cy-induced expression change of six proteins, partly prevented Cy-induced expression change of four proteins and further enhanced Cy-induced expression change of two proteins. Results of the present study shed light on the mechanism of Cy-induced immuno-suppression as well as the protective effect of GL-SP against toxicity of Cy.
Oxidative burst provides the mechanism for specialized phagocytes, such as granulocytes or monocytes, to kill invading microorganisms through generation of superoxide anions. However, the oxidants generated during the burst damage DNA of the phagocytes and neighboring cells. Human blood leukocytes treated with phorbol myristate acetate (PMA) are considered to represent the experimental model of induction of oxidative burst. We recently reported that DNA damage in PMA-treated leukocytes is assessed by cytometric analysis of the induction of histone H2AX phosphorylation and Ataxia Telangiectasia Mutated (ATM) activation. In the present study we observed that hyaluronic acid (HA) of average molecular weight (MW) 5.4x10(6) and 2x10(6) at 0.1% (w/v) concentration significantly attenuated H2AX phosphorylation and ATM activation induced in leukocytes during oxidative burst. HA also reduced the intracellular level of PMA-induced reactive oxidants as measured by the ability of cells to oxidize 2',7'-dihydro-dichlorofluorescein-diacetate. No such effect was seen with HA of 6x10(4) MW. The data are consistent with earlier observations that HA of high MW protects DNA from oxidative damage induced by endo- or exogenous oxidants. The anti-oxidant effect of HA seen during oxidative burst also explains its anti-inflammatory effect when used to treat arthritic joints.
Several types of compound exert their cytotoxicity by generating reactive oxygen species, notably the superoxide anion radical. These include quinoid and nitroaromatic compounds serving as redox cyclers, i.e. producing superoxide at the expense of NADPH and oxygen catalyzed by cellular reductases. In specialized cell-types employed in defense such as granulocytes, eosinophils and macrophages, myeloperoxidase, NADPH oxidase and nitric oxide synthase have been identified as major sources of reactive oxygen species in cell toxicity. These include hypochlorite, singlet oxygen, superoxide, nitric oxide and hydrogen peroxide. The interaction of superoxide and nitric oxide generates further oxidants such as peroxynitrite. Lumino-amplified chemiluminescence generated by Kupffer cells is partially sensitive to inhibitors of NO synthase. Superoxide dismutase has been found to catalyze a novel reaction, the reversible conversion of nitric oxide to the nitroxyl anion, the latter being viewed as another form of EDRF. In the defense against oxidative damage, there are enzymatic and nonenzymatic antioxidants. Regarding compounds used pharmacologically, we have been interested in ebselen, a seleno-organic compound exhibiting GSH peroxidase activity, which protects against reactive oxygen species generated, for example, at reoxygenation following a period of hypoxia. Further, we have studied lipoate and dihydrolipoate as antioxidant redox system and as singlet oxygen quencher, e.g. protecting against damage of deoxyguanosines in plasmid DNA generated by singlet oxygen.
Manganese superoxide dismutase (MnSOD), an inductive antioxidant enzyme, can protect cells from oxidative injury to the mitochondria. The elevation of MnSOD activity in cells can effectively prevent many diseases associated with oxidative stress. Polysaccharide Krestin (PSK), a kind of protein-bound polysaccharide extracted from Coriolus versicolor, is used as an immune response modifier in anti-tumor therapy. We have previously found that PSK could alleviate the oxidative injury that oxidized low density lipoprotein (Ox-LDL) brought to monocytes/macrophages, and therefore had some preventive or therapeutic effect on atherosclerosis. In order to find out if the effects of PSK were associated with the alteration ofantioxidant enzymes, we investigated its effect on MnSOD activity and gene expression in mouse peritoneal macrophages. The results showed that PSK could enhance SOD activity and increase the contents ofMnSOD mRNA in mouse peritoneal macrophages. Furthermore, the induction of MnSOD by PSK could be blocked by cycloheximide and actinomycin D.
Fructans are polysaccharides consisting of one glucose unit and two or more fructose units. It was hypothesized that fructans play a role in drought tolerance in plants by interacting directly with the membrane. In this paper we investigated this hypothesis by studying fructan-membrane interactions in hydrated mono- and bilayer systems. It was found that fructans inserted between the headgroups of different kinds of phospholipids with some preference for phosphatidylethanolamine. Insertion occurred even under conditions of very tight lipid packing. The presence of a surface associated layer of fructan was observed in both model systems. This layer was able to reduce the ability of a surface-active protein to interact with the lipids. Fructans showed a much stronger effect on the different lipid systems than other (poly)saccharides, which appears to be related to their hydrophobic properties. Fructans were able to stabilize the liquid-crystalline lamellar phase, which is consistent with a drought protecting role in plants.
Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.
Degradation and the antioxidative effect of Na-, Zn-, Co-, Cu-, and Mn-hyaluronic acid (HA) associates were studied. Our findings revealed the protective effect of certain counterions against ROS-induced HA degradation. We could also separate the antioxidative effect of certain counterions from that of the HA by examining the effect of the counterions in their free ionic forms. The result showed that metal ions with altering oxidative status (Co(2+), Cu(2+), Mn(2+)) proved to be effective in themselves or their effect added to that of HA when HA was also effective. Moreover, the effects of Co-HA against z.rad;O(2)(-) and of Mn-HA against ONOO(-) as well as the synergic effect of Zn-HA associates where Zn(2+) is of fixed oxidative status were attributed to the structure-stabilizing complex formed between certain counterions and HA. Our examination also concerned the influence of HA associates on the indirect antioxidation related to Fe(2+) chelating. The individual effects of Zn(2+), Co(2+), and Cu(2+) were only detectable, which could be explained by the competitive displacement of ferrous from its binding site.
A modification of Dische's carbazole reaction for uronic acid in the presence of borate is described. The advantages of the procedure are: 1.(1) There is an approximately twofold increase of sensitivity. The OD is a linear function of concentration between 4 and 40 μg/ml.2.(2) Maximum color develops immediately.3.(3) The color is stable for at least 16 hr.4.(4) There is greater reproducibility and reduction of interference by chloride ion and oxidants.It has been found possible to distinguish between heparin, heparin derivatives, and other polyuronides of connective tissue by comparing the effect of chlorides on the color yield in both procedures.
The free radical scavenging activity of the 80% methanolic extracts from fresh leaves of 300 Chinese medical woody plants was assessed with the aid of the stable DPPH radical. Among the plants screened, 56 species had strong free radical scavenging capacities, with IC50 values lower than 0.5 mg leaves per milliliter. Analysis of the medical uses of these plants showed that most of them are employed for their effects on hemostasis, as anti-inflammatory, antimicrobial or for treatment of dysentery. These uses may be directly linked to the content in tannins and flavonoids and consequently to their free radical scavenging activities.
Hepatic fibrosis involves the interplay of many factors including reactive oxygen species. Recent reports described antioxidant properties of glycosaminoglycans (GAGs). Since several findings have shown that hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S) may act as antioxidant molecules, the aim of this research was to evaluate the antioxidant effects of HYA and C4S treatment in a rat model of liver fibrosis. The effect on tissue inhibitors of metalloproteinases (TIMPs) was also studied.
Recently, intense interest has focused on the antioxidant properties of natural products. In particular, Chinese herbal medicines (CHM) have become hot topics for life science researchers since many are reported to possess cardioprotective compounds, many of which remain to be identified. Indeed, the exact mechanisms by which CHM work remain unknown. Although many of these herbal remedies are undoubtedly efficacious, few have been scientifically investigated for their active chemical constituents and biological activities. We have previously reported higher activities of antioxidant defence enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferases in the liver of rats treated with the herb Salvia miltiorrhiza in a model of acute myocardial infarction. Using well established in vitro antioxidant assays employing 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and diphenyl-l-picrylhydrazyl (DPPH) we have shown that in addition to elevating endogenous antioxidant enzyme activity, Salvia miltiorrhiza and other CHM traditionally used for cardiovascular disorders (such as Rhizoma ligustici, Herba leonuri, Radix achyranthis bidentatae, and Camellia sinensis) contain potent antioxidant moieties in addition to their phenolic constituents. Furthermore, these novel non-phenolic components are effective inhibitors of oxidative reactions mediated by the inflammatory oxidants, peroxynitrite,hypochlorous acid and hydroxyl radical as well as iron-dependent lipid peroxidation. In this review, we discuss the various antioxidant properties of CHM in the context of their biochemical mechanisms.
The degradation of high-molar-mass hyaluronan (HA) by copper(II) chloride and ascorbate was studied by means of rotational viscometry. It was found that even small amounts of CuCl(2) present in the oxidative system led to the pronounced degradation of HA, reflected in a rapid decrease of the dynamic viscosity of the biopolymer solution. Such degradation was induced by free radicals generated in elevated amounts in the presence of copper ions. Electron paramagnetic resonance investigations performed on a model oxidative system containing Cu(II) and ascorbic acid proved the formation of relatively stable ascorbate anion radicals resulting from the reaction of ascorbic acid with hydroxyl radicals. In this way, by scavenging the hydroxyl radicals, ascorbic acid protected HA from their degradative action. Matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry was applied to analyze the degraded HA. The results showed that only regular fragmentation of hyaluronan occurred using the mentioned oxidative system that led to the formation of HA oligomers with unaffected primary chemical structure.
Water-soluble polysaccharide(Glycyrrhiza polysaccharide, GP) was isolated from Glycyrrhiza uralensis Fisch, with glycosidic units were composed of alpha (1-4) linked D-glucana. We demonstrated that GP significantly induces nitric oxides (NO) production and inducible NO synthase (iNOS) transcription in peritoneal macrophages. Moreover, iNOS mRNA expression was strongly induced by GP. NO in the culture supernatant was measured by Griess reaction, the production of iNOS was determined by commercially available iNOS kit. GP (10-400 microg/ml) alone increased significantly NO and iNOS production in macrophages. Macrophages simultaneously treated with GP plus lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) increased NO and iNOS production as compared to that of GP treatments alone. The production of NO and iNOS in macrophages pretreated with LPS followed by GP was higher than that of treatment with GP and LPS simultaneously. Using RT-PCR reveals that GP may provide a second triggering signal for the expression of iNOS mRNA. Thus, the iNOS-mediated NO synthesis in response to GP may be one of the mechanisms whereby this herbal medicine elicits its therapeutic effects.