Levels Of Antioxidant Enzymes Research Articles

Ginger (Zingiber officinale Roscoe; Family: Zingiberaceae) in Non-Alcoholic Fatty Liver Disease: Review on the Existing Scientific Evidence and Way Forward

Abstract: Non-alcoholic fatty liver disease (NAFLD) is today the most prevalent hepatic disorder in the world. Although many pharmaceutical agents have been investigated for their potential to prevent or treat NAFLD, currently, there is no standard treatment to manage this ailment. Reports indicate that ginger and its phytochemicals gingerol and zingerone are effective in mitigating NAFLD in experimental study models. Furthermore, randomised control trials have demonstrated that ginger is also effective in preventing NAFLD in both adults and children. Mechanistic studies suggest that ginger mediates these beneficial effects by activating many pathways, such as reducing free radicals, dyslipidemia, and hepatic fat deposition. Concomitantly, ginger also increases antioxidant enzyme levels and insulin-sensitive effects, and all these pharmacological actions provide beneficial outcomes. In this review, the evidence from experimental and clinical trials has been emphasised. In addition, an attempt has been made to identify the gaps for future study to address for the benefit of the medical, pharmaceutical, nutraceutical, and agricultural businesses.

Modulatory effects of selenium nanoparticles against drought stress in some grapevine rootstock/scion combinations

BackgroundDrought is a significant abiotic stress that adversely affects plant growth, development, and metabolic processes, thereby reducing plant yield, quality, and production, and threatening global food security. In recent years, nanotechnology has emerged as a promising strategy to overcome the existing environmental challenges and has been tested on some plant species. But it is still awaiting investigation for grapevines. The aim of this study was to investigate the potential of selenium nanoparticles (Se-NPs) to modulate some morphological, physiological, and biochemical parameters in grapevine saplings (5 BB/Crimson Seedless, 41 B/Crimson Seedless, and 1103 P/Crimson Seedless) under drought stress conditions.ResultsIn the study, Se-NP solutions at different concentrations (0 (control), 1, 10, and 100 ppm) were applied by the spray method to wet the entire green surface of grapevine saplings grown under well-irrigated (90–100% field capacity) and drought stress (40–50% field capacity) conditions. Our results showed that 10 ppm Se-NP concentration had the most positive effect, 1 ppm concentration showed limited effects, and 100 ppm concentration led to toxic effects, especially when combined with drought conditions. Se-NP applications at 10 ppm concentration improved the growth parameters (leaf number, leaf area, root fresh and dry weight, shoot fresh and dry weight, etc.) and increased the SPAD index of grapevine saplings under both normal and drought conditions. Additionally, 10 ppm Se-NP applications improved the relative water content (RWC) and stomatal conductance values, proportional to the increases in protein content. On the other hand, under drought conditions, the drought index, leaf temperature, membrane damage index, hydrogen peroxide (H2O2) content, and malondialdehyde (MDA) levels significantly decreased as a result of 10 ppm Se-NP applications, showing an opposite trend. Furthermore, the levels of proline, total phenolics, and antioxidant enzymes (CAT, SOD, and APX) that rose significantly due to drought stress were reduced by 10 ppm Se-NP applications, which also helped to lessen the oxidative stress caused by the drought.ConclusionThe study concluded that foliar application of Se-NPs at 10 ppm significantly enhances drought tolerance in grapevine saplings by improving antioxidant defense, proline and protein accumulation, and overall growth, while lower concentrations are less effective and higher concentrations can cause phytotoxicity. These findings indicate that Se-NPs applications may hold promise not only for grapevines but also for mitigating drought stress effects and improving productivity in other economically important fruit species, warranting further exploration across diverse crop systems.Graphical

Overexpression of MtIPT gene enhanced drought tolerance and delayed leaf senescence of creeping bentgrass (Agrostis stolonifera L.)

BackgroundIsopentenyltransferases (IPT) serve as crucial rate-limiting enzyme in cytokinin synthesis, playing a vital role in plant growth, development, and resistance to abiotic stress.ResultsCompared to the wild type, transgenic creeping bentgrass exhibited a slower growth rate, heightened drought tolerance, and improved shade tolerance attributed to delayed leaf senescence. Additionally, transgenic plants showed significant increases in antioxidant enzyme levels, chlorophyll content, and soluble sugars. Importantly, this study uncovered that overexpression of the MtIPT gene not only significantly enhanced cytokinin and auxin content but also influenced brassinosteroid level. RNA-seq analysis revealed that differentially expressed genes (DEGs) between transgenic and wild type plants were closely associated with plant hormone signal transduction, steroid biosynthesis, photosynthesis, flavonoid biosynthesis, carotenoid biosynthesis, anthocyanin biosynthesis, oxidation-reduction process, cytokinin metabolism, and wax biosynthesis. And numerous DEGs related to growth, development, and stress tolerance were identified, including cytokinin signal transduction genes (CRE1, B-ARR), antioxidase-related genes (APX2, PEX11, PER1), Photosynthesis-related genes (ATPF1A, PSBQ, PETF), flavonoid synthesis genes (F3H, C12RT1, DFR), wax synthesis gene (MAH1), senescence-associated gene (SAG20), among others.ConclusionThese findings suggest that the MtIPT gene acts as a negative regulator of plant growth and development, while also playing a crucial role in the plant’s response to abiotic stress.

Co-delivery of a curcumin and asafoetida as a bioavailable complex using fenugreek galactomannan hydrogel scaffold alleviates inflammatory bowel disease on experimental animals

IntroductionInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder characterised by the disruption of the epithelial barrier and formation of mucosal ulceration. Though the current treatment mainly includes synthetic drugs, herein, we hypothesised that a co-delivery of bioavailable and water-soluble forms of turmeric extract (curcumin) along with asafoetida oleo-gum-resin (hereinafter referred to as ‘CUAS’) may have synergistic effects to alleviate IBD safely. MethodsThe study was conducted in two phases. In the first phase, bioavailability of the formulation was investigated and in the second phase, its effect on 2,4,6- trinitrobenzene sulfonic acid (TNBS)-induced IBD model of rats was investigated. In this model, Wistar rats (n = 30) were randomised into 5 groups, [Group I-control, Group II–TNBS treated IBD group (100mg/kg; intrarectal), Group III-Standard drug (Sulfasalazine; 50mg/kg b. wt. orally), Group IV – standard curcumin complex (UC; 200mg/kg b. wt.), Group V –Curcumin/asafoetida co-delivery form (CUAS; 200mg/kg b. wt.)]. IBD was induced to group II to V animals, and then treated with the respective drugs for 24 days. Then the animals were sacrificed and various biochemical parameters including ulcer index, antioxidant levels, oxidative stress markers, and histopathological analysis of the colon were carried out. ResultsThe results revealed a significant reduction (P < 0.05) of the clinical manifestations related to IBD, along with a significant reduction (P < 0.05) for the ulcer index and oxidative stress, and significant enhancement (P < 0.05) in endogenous antioxidant enzyme levels among CUAS treated animals. Histopathological observations also showed a significant reduction in TNBS-induced colon lesions. No necrosis, cellular infiltration, haemorrhage, or oedema was observed among the CUAS-treated animals, indicating better gastroprotective effect of CUAS compared to the standard curcumin treatment. ConclusionsThe enhanced effect of CUAS was attributed to the improved bioavailability (22.8-fold) of CUAS compared to standard curcumin treated group.

Effect of Bee Bread (Perga) on Histopathological Changes and Immunohistochemical Expression of Apoptosis Markers in the Kidney of Rats Exposed to Cadmium

Cadmium (Cd) is an environmental and industrial pollutant that causes toxicity in various organs in humans and animals. Bee bread (perga) is a natural flavonoid with a wide range of pharmacological properties. This study was conducted to examine the effects of perga on Cd-induced nephrotoxicity. Thirty-two male Wistar rats were randomly divided into 4 groups, as the Control group, Cd group (5 mg/kg/day, orally), Perga group (0.5 g/kg/day, orally), and Cd + Perga group. At the end of the 28-day experiment, kidney tissue samples were taken and histopathological, immunohistochemical, and biochemical analyses were performed. Histopathologically, severe tubular and glomerular damage occurred as a result of Cd exposure in the Cd group. Immunohistochemically, there was an increase in caspas-3 and Bax expression in the renal tissue in the Cd group. According to the biochemical results, while the catalase, superoxide dismutase, and glutathione peroxidase antioxidant enzyme levels decreased in the Cd group, and the malondialdehyde levels increased. However, most of the above-mentioned Cd-induced changes were attenuated by treatment with perga in the Perga + Cd group. In conclusion, perga supplementation may alleviate Cd-induced renal injury through inhibition of apoptosis in renal tissue.

Preliminary Investigation Into the Antidepressant Effects of a Novel Curcumin Analogue (CACN136) In Vitro and In Vivo.

The aim of this study was to develop a novel antidepressant with high activity. Based on the findings of molecular docking, eight novel curcumin analogues were evaluated in vitro to check for antidepressant efficacy. Among them, CACN136 had the strongest antidepressant effect. Firstly, CACN136 had a stronger 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) radical ion scavenging ability (IC50: 17.500 ± 0.267μg/mL) compared to ascorbic acid (IC50: 38.858 ± 0.263μg/mL) and curcumin (27.189 ± 0.192μg/mL). Secondly, only CACN136 demonstrated clear protective effects on cells damaged by glutamate and oxidative stress at all concentrations. Finally, only CACN136 showed ASP + inhibition and was more effective than fluoxetine hydrochloride (FLU) at low concentrations. To further confirm the antidepressant effect of CACN136 in vivo, the CUMS model was established. Following 28days of oral administration of CUMS mice, CACN136 increased the central area residence time in the open-field test, significantly increased the sucrose preference rate in the sucrose preference test (P < 0.001) and significantly reduced the immobility period in the tail suspension test (P < 0.0001), all of which were more effective than those of FLU. Subsequent research indicated that the antidepressant properties of CACN136 were linked to a decrease in the metabolism of5-HT and the modulation of oxidative stress levels in vivo. In particular, the activation of the Keap1-Nrf2/BDNF-TrkB signaling pathway by CACN136 resulted in elevated levels of antioxidant enzymes, enhancing the antioxidant capability in mice subjected to CUMS. In conclusion, CACN136 has the potential to treat depression and could be an effective antidepressant.

Reparative effects of Schizophyllum commune oat bran fermentation broth on UVB-induced skin inflammation via the JAK/STAT pathway

Human immortal keratinocyte cells (HaCaT) are induced with UVB to establish an injury model. This model is utilized to investigate whether oat bran fermentation broth (OBF) has a reparative effect on skin inflammation and damage to the skin barrier caused by UVB irradiation. The results show that compared with unfermented oat bran (OB), OBF exhibits higher structural homogeneity, increased molecular weight size, active substances content, and in vitro antioxidant activity. OBF has a scavenging effect on excess reactive oxygen species (ROS) and increases the intracellular levels of antioxidant enzymes. It was found that OBF has a stronger inhibitory effect on the release of inflammatory factors than OB. It increases the synthesis of AQP3 and FLG proteins while decreasing the secretion of KLK-7. OBF can inhibit the transcription level of inflammatory factors by suppressing the JAK/STAT signaling pathway. Safety experiments demonstrate that OBF has a high safety profile.Graphical

Exploring the protective role of Bacillus velezensis BV1704–Y in zebrafish health and disease resistance against Aeromonas hydrophila infection

Bacillus genus, particularly Bacillus velezensis, is increasingly considered as viable alternatives to antibiotics in aquaculture due to their safety and probiotic potential. However, the specific mechanisms through which probiotic B. velezensis confers protection against Aeromonas hydrophila infection in fish remain poorly understood. This study delved into the multifaceted impacts of B. velezensis BV1704–Y on diverse facets of zebrafish health, including gut barrier function, immune response, oxidative stress, gut environment, microbiome composition, and disease resistance. Our findings demonstrate that supplementation with B. velezensis BV1704–Y significantly alleviated symptoms and reduced mortality in zebrafish infected with A. hydrophila.Furthermore, a notable reduction in the expression of pivotal immune-related genes, such as IL-1β, IL6, and TNF-α, was evident in the gut and head kidney of zebrafish upon infection. Moreover, B. velezensis BV1704–Y supplementation resulted in elevated activity levels of essential antioxidant enzymes, including SOD, CAT, and GSH, in gut tissue. Notably, B. velezensis BV1704–Y positively modulated the structure and function of the intestinal microbiome, potentially enhancing immune response and resilience in zebrafish. Specifically, supplementation with B. velezensis BV1704–Y promoted the relative abundance of beneficial bacteria, such as Cetobacterium, which showed a noteworthy negative correlation with the expression of pro-inflammatory genes and a positive correlation with gut barrier-related genes. Altogether, our study suggests that B. velezensis BV1704–Y holds promise as an effective probiotic for protecting zebrafish against A. hydrophila infection, offering potential benefits for the aquaculture industry.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety

Ethnopharmacological relevanceThe safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. Aim of the studyThe current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. MethodologyCEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. ResultsBased on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. ConclusionThis study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Inhibition of JNK transcription via the Nrf2/Keap1a pathway to resist microcystin-induced oxidative stress and apoptosis in freshwater mussels Cristaria plicata

With global warming and increasing eutrophication of water bodies, a variety of algal toxins, including microcystin (MC), released into water by cyanobacterial blooms pose a serious threat to the survival of aquatic organisms. To investigate the mechanism of the Nrf2/Keap1a pathway on resisting MC-induced oxidative stress and apoptosis in Cristata plicata, we cloned the full-length cDNA of CpBcl-2. The cDNA full-length of CpBcl-2 was 760 bp, encoded a 177 amino acid peptide, and contained a highly conserved Bcl-2-like superfamily domain. MC stimulation increased the expression and activity levels of related antioxidant enzymes. After CpNrf2 knockdown, the transcription levels of NAD(P)H quinone redox Enzyme-1 (NQO1) and related antioxidant enzymes activity in the gills and kidney of C. plicata were significantly down-regulated upon MC stress, but that was significantly upregulated after knockdown of CpKeap1a. Additionally, Upon MC stress, the mRNA levels of CpBcl-2 were increased in the gills and kidney after knockdown of CpNrf2 at 24 h, and that of CpBcl-2 were decreased at 72 and 96 h in the CpKeap1a-siRNA+MC group. Moreover, MC stimulation significantly inhibited CpJNK expression in the gills and kidney, but which regulated the Nrf2/Keap1a pathway in C. plicata. However, the JNK inhibitor SP600125 promoted the expression of CpNrf2 and related enzymes with antioxidant response element (ARE-driven enzyme) in the gills and kidney. Then, we speculated that CpKeap1a was a negative regulator of CpNrf2, and C. plicata resisted MC-induced oxidative damage and apoptosis by inhibiting JNK transcription via the Nrf2/Keap1a pathway.

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-β-galactosidase (SA-β-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

Effect of kynurenic acid on enzymatic activity of the DNA base excision repair pathway in specific areas of the sheep brain

Relatively low levels of antioxidant enzymes coupled with high oxygen metabolism result in the formation of numerous oxidative DNA damages in the tissues of the central nervous system. Recently, kynurenic acid (KYNA), knowns for its neuroprotective properties, has gained increasing attention in this context. Therefore, our hypothesis assumed that increased KYNA levels in the brain would positively influence mRNA expression of selected enzymes of the base excision repair pathway as well as enhance their efficiency in excising damaged nucleobases in specific areas of the sheep brain. The study was conducted on adult anestrous sheep (n = 18), in which two different doses of KYNA (20 and 100 μg/day) were infused into the third brain ventricle for three days. Molecular and biochemical analysis included the hypothalamus (preoptic and mediol-basal areas), hippocampus (CA3 field) and amygdala (central amygdaloid nucleus), dissected from the brain of sheep euthanized immediately after the last infusion. The results revealed a significant increase P < 0.001) in the relative mRNA abundance of N-methylpurine DNA glycosylase (MPG) following administration of both dose of KYNA across all examined tissues. The transcription of thymine-DNA glycosylase (TDG) increased significantly (P < 0.001) in all tissues in response to the lower KYNA dose compared to the control group. Moreover, 8-oxoguanine (8-oxoG) DNA glycosylase (OGG1) mRNA levels were also higher in both animal groups (P < 0.001). In addition, in the hypothalamus, hippocampus and amygdala, AP endonuclease 1 (APE1) mRNA expression increased under both doses of KYNA. Moreover, the both dose of KYNA significantly stimulated the efficiency of 8-oxoG excision in hypothalamus and amygdala (P < 0.05–0.001). The lower and higher doses of KYNA significantly influenced the effectiveness of εA and εC in all structures (P < 0.01–0.001). In conclusion, the favorable effect of KYNA in the brain may include the protection of genetic material in nerve and glial cells by stimulating the expression and efficiency of BER pathway enzymes.

Germination and biological adaptation approaches as salt-stress tolerance process in selected paddy cultivars under salinity stress

Cultivating productive paddy crops on salty soil to maximise production is a challenging approach to meeting the world's growing food demand. Thus, determining salinity tolerance rates in specific paddy cultivars is urgently needed. In this study, the salt tolerance traits of selected paddy cultivars, ADT45 and ADT39, were investigated by analysing germination, metabolites (pigments and biomolecules), and enzymatic (Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) adaptation strategies as salt-stress tolerance mechanisms. This study found that salinity-induced reactive oxygen species (ROS) were efficiently detoxified by the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Peroxidase (POD) in ADT45 paddy varieties, followed by ADT39. Salinity stress had a significant impact on pigments and essential biomolecules in ADT45 and ADT39 paddy cultivars, including total chlorophyll, anthocyanin, carotenoids, ascorbic acid, hydrogen peroxide (H2O2), malondialdehyde, and proline. ADT45 demonstrated a significant relationship between H2O2 and antioxidant enzyme levels, followed by ADT39 paddy but not IR64. Morphological, physiological, and biochemical analyses revealed that ADT45, followed by ADT39, is a potential salt-tolerant rice cultivar.

Attenuation of adjuvant-induced arthritis with carnosic acid by inhibiting mPGES-1, COX-2, and bone loss in male SD rats

Objective Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by joint swelling, cartilage erosion, and bone destruction. This study investigated the therapeutic efficacy of Carnosic acid (CA), a natural compound with anti-inflammatory and antioxidant properties, in an adjuvant-induced arthritis model. Methods Paw swelling and arthritis index were measured. Oxidative stress markers, including lipid peroxidation and antioxidant enzyme levels, were assessed. Synovial tissue was analyzed for pro-inflammatory markers using real-time Q-PCR and Western blotting. The expression of mPGES-1 was determined by Western blotting. Peripheral neuropathic pain was assessed using cold and mechanical allodynia tests. Bone loss was quantitatively assessed through microcomputed tomography (μCT) scanning of femurs and X-ray radiography. Indomethacin-induced gastric ulcers were evaluated. Molecular docking studies were conducted to analyze the binding affinity of CA to mPGES-1. Results The CA treatment not only demonstrated a significant reduction in joint inflammation and paw swelling but also mitigated oxidative stress and improved the antioxidant defence system. CA inhibited microsomal prostaglandin E synthase-1 (mPGES-1) expression and the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS) and cyclooxygenases-2 (COX-2), thus attenuating the arthritis symptoms without severe gastrointestinal side effects. Additionally, it inhibited the expression of pro-inflammatory molecules such as iNOS and COX-2, contributing to the reduction of arthritis symptoms. Notably, CA treatment prevented the common side effects of traditional RA treatments like corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), including weight loss, bone degradation, and gastric ulcers. Conclusions These findings suggest that CA, through specific enzyme inhibition, offers a compelling alternative therapeutic approach for RA. Further research is warranted to explore the potential of CA in other arthritis models and its suitability for human RA treatment.

P-100 Prolonged exposure to polyethylene glycol (peg) 6000 severely affects the reproductive system of male Wistar rats

Abstract Study question Studies have shown that microplastics have adverse effects on aquatic reproductive health. Is there any potential effect of Polyethylene glycol (PEG)6000 on rodents reproductive system? Summary answer Despite its wide use in industry, medicine and cosmetic formulations, prolonged exposure to PEG 6000 may pose great risk, especially causing reproductive toxicity. What is known already The usage of Polyethylene glycol (PEG) 6000, a microplastic, is rising in industries, medicine, and cosmetic formulations. They serve as ointment bases, capsules, liquid prescription, suppositories and recently used to alleviate constipation. More so, it is one of the pivotal ingredients in soaps, detergents, and also used as chemical intermediates in textile, leather and plastic industries. Additionally, PEG 6000 is widely used in drug delivery systems and tissue engineering. Although approved for internal consumption by regulatory agencies like FDA, there are evidences of its developmental toxicity. Study design, size, duration Fifteen(15) rats weighing between 200-250g were used in this study. The rats were divided into three groups(A, B and C), of 5 rats in each group. Group A was designated as the control group while groups B and C were the test groups. Group A received distilled water, while groups B and C were administered 50 mg/kg and 200 mg/kg body weight of polyethylene glycol PEG6000 respectively via oral gavage daily for 6 weeks. Participants/materials, setting, methods After 6 weeks, the rats were sacrificed as reproductive organs and serum obtained. Enzyme immunosorbent assay (ELISA) was used for hormonal assays. Reproductive organs were weighed and tissue damage was determined using Haemoxylin /eosin staining. Antioxidant enzymes levels (Catalase, Superoxide dismutase), Glutathione peroxidise) and Lipid peroxidation (Malondialdehyde) were also evaluated. Computer-assisted sperm assay (CASA) was used to evaluate sperm parameters and sperm movement kinetics. Main results and the role of chance PEG 6000 caused a reduction in the weights of the rats in groups B and C when compared with control group. There was no significant change in the relative testicular and seminal vesicle organ/body weight ratio in groups B and C, however a pattern of reduction was seen in the organ/body weight ratio of epididymis and prostate, when compared to control group. Serum hormonal levels of Follicle stimulating hormone and Luteinizing hormone were reduced in the test groups when compared to control, but not significant. Testosterone was significantly reduced in groups B and C, while estradiol levels were significantly elevated in groups B and C when compared to control group. There was significant reduction in the levels of Superoxide dismutase, Catalase and Glutathione peroxidase, and a significant increase in Malondialdehyde levels in groups B and C when compared to the control group. Histopathological changes were also seen in the testes, epididymis, seminal vesicles and prostate glands of rats in the test groups. Semen analyses showed statistically significant reductions (p &amp;lt; 0.05) in sperm concentration, motility, vitality and sperm movement kinetics of rats in the test groups when compared to the control group. Limitations, reasons for caution Although this study was done in rats, it may not be easy to extrapolate the present findings to humans. However, this calls for caution as primates and rodents are both members of the superorder Euarchontoglires. Wider implications of the findings Prolonged ingestion of PEG 6000 affects male reproductive system, alters hormonal levels, reduces sperm parameters and induces oxidative stress. Interestingly, the disruptive effects of PEG 6000 are dose-dependent, and may lead to male infertility. Trial registration number not applicable

Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus).

Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties. KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL-1; superoxide dismutase: 0.589 μg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL-1). Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

Effects of gamma irradiation treatment on ROS accumulation and carotenoid metabolism in postharvest Cara Cara fruit (Citrus sinensis L. Osbeck) during storage

This study evaluated the effect of low-dose gamma irradiation (0.3–0.9 kGy) on carotenoid accumulation in Cara Cara fruit (Citrus sinensis L. Osbeck) during storage. Additionally, the irradiation-induced ROS (reactive oxygen species) response and transcriptional levels of carotenoid biosynthesis genes were investigated. Immediate irradiation caused a temporary decrease in most carotenoid levels; however, values recovered during storage and were even higher than those of the control, particularly at 0.6 kGy, especially for carotenoid precursors and carotenes. The upregulated expression of psy, zds and lcyb during majority of the storage period, coupled with the strengthened interaction among adjacent carotenoids, might contribute to the enhanced accumulation of carotenoids in irradiated fruit. A highly positive correlation was found among ROS content, total carotenoids, and upstream expression of zds and lcyb, suggesting that the enhanced carotenoid content in irradiated Cara Cara fruits might be regulated by zds and lcyb in response to ROS accumulation. Antioxidant enzymes of APX, SOD, and CAT levels were significantly correlated with ROS accumulation. In summary, gamma irradiation (0.6 kGy) elevated the levels of carotenoids and antioxidant enzymes, which were potentially modulated by ROS in response to irradiation stress.

Mitigating Effect of Matricin Against Benzo(a)pyrene-induced Lung Carcinogenesis in Experimental Mice Model.

Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kβ pathway.

The Use of Nanocarriers to Enhance the Anti-neuroinflammatory Potential of Dietary Flavonoids in Animal Models of Neurodegenerative Diseases: A Systematic Review.

Neurodegenerative diseases (NDs) have become a common and growing cause of mortality and morbidity worldwide, especially in older adults. The natural flavonoids found in fruits and vegetables have been shown to have therapeutic effects against many diseases, including NDs; however, in general, flavonoids have limited bioavailability to the target cells. One promising strategy to increase bioavailability is to entrap them in nanocarriers. This article aims to review the potential role of nanocarriers in enhancing the antineuroinflammatory efficacy of flavonoids in experimentally induced ND. A literature search was conducted in the scientific databases using the keywords "neurodegenerative", "anti-neuroinflammatory", "dietary flavonoids," "nanoparticles", and "therapeutic mechanisms". A total of 289 articles were initially identified, of which 45 articles reported on flavonoids. After completion of the selection process, five articles that met the criteria of the review were selected for analysis. Preclinical studies identified in this review showed that nanoencapsulated flavonoids attenuated cognitive impairment and seizure, improved behavioral patterns, and reduced levels of astrocytes. Importantly, they exhibited strong antioxidant properties, increasing the levels of antioxidant enzymes and reducing oxidative stress (OS) biomarkers. Moreover, nanocarrier-complexed flavonoids decreased the levels of the pro-inflammatory cytokines, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nod-like receptor protein 3 inflammasome activation (NLRP3). They also had remarkable effects on important ND-related neurotransmitters, improved cognitive function via cholinergic neurotransmission, and increased prefrontal cortical and hippocampal norepinephrine (NE) and 5-hydroxytryptamine (5-HT). Nanoencapsulated flavonoids should, therefore, be considered a novel therapeutic approach for the treatment of NDs.

Effect of Andrographis Paniculata Aqueous Extract on Hyperammonemia Induced Alteration of Oxidative and Nitrosative Stress Factors in the Liver, Spleen and Kidney of Rats

ABSTRACT Hyperammonemia (HA) can induce oxidative and nitrosative stress in peripheral organs, potentially exacerbating Hepatic Encephalopathy (HE). This study assessed the efficacy of Andrographis paniculata aqueous extract (APAE) in mitigating oxidative and nitrosative stress caused by non-cirrhotic HA in rat livers, spleens, and kidneys. HA was induced via intraperitoneal injection of ammonium acetate, while APAE was administered orally. The study measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione reductase (GR) to gauge oxidative stress, and nitric oxide (NO) levels as a marker of nitrosative stress. Both acute and chronic HA altered the levels of antioxidant enzymes, MDA, and NO in the organs studied. APAE treatment helped restore SOD, catalase, and GR levels, and decreased MDA and NO levels, demonstrating its potential in reducing oxidative stress linked to HA in the liver, spleen, and kidney.