Paeonol is a naturally existing bioactive compound found in the root bark of Paeonia suffruticosa and it is traditionally used in Chinese medicine for the prevention and management of cardiovascular diseases. To date, a great deal of studies has been reported on the pharmacological effects of paeonol and its mechanisms of action in various diseases and conditions. In this review, the underlying mechanism of action of paeonol in cardiovascular disease has been elucidated. Recent studies have revealed that paeonol treatment improved endothelium injury, demoted inflammation, ameliorated oxidative stress, suppressed vascular smooth muscle cell proliferation, and repressed platelet activation. Paeonol has been reported to effectively protect the cardiovascular system either employed alone or in combination with other traditional medicines, thus, signifying it could be a hypothetically alternative or complementary atherosclerosis treatment. This review summarizes the biological and pharmacological activities of paeonol in the treatment of cardiovascular diseases and its associated underlying mechanisms for a better insight for future clinical practices.
Human liver fluke, Opisthorchis viverrini poses a significant risk for development of cholangiocarcinoma (CCA) in Thailand, primarily attributed to consumption of undercooked cyprinoid fishes. The current use of anthelmintic drug treatment such as praziquantel (PZQ), as the main therapeutic agent against O. viverrini. There is a need to explore the efficacy of alternative anthelmintic drugs for O. viverrini treatment. This study aimed to assess the efficacy of anthelmintic drugs, which are commonly use in endemic areas of Southeast Asian countries; PZQ, albendazole (AL), niclosamide (NI), and mebendazole (ME) at concentrations of 600, 400, 500, and 500 mg/ml. The study included a negative and positive control group treated with roswell park memorial institute (RPMI) and PZQ. Reactive oxygen species (ROS) levels, indicative of oxidative stress, were quantified using 2',7'-dichlorofluorescein diacetate staining. Morphological changes were observed using scanning electron microscopy. Furthermore, motility assessments were conducted at various time points (0, 5, 30 minutes, 1, 3, 6, 12, and 24 hours), calculating relative motility (RM) and survival index (SI). The results revealed a significant increase of ROS levels with the intensity and corrected total worm fluorescence (CTWF) mostly observed in order of PZQ, followed by NI, ME, and AL, respectively. Morphological damage was presented the tegumental swelling, papillae changes, and disruption of microvilli (Mv), particularly in the group treated with the most effective anthelmintics PZQ, NI, ME, and AL, while negative control group did not exhibit such alterations. Also, the most efficacy for suppressing the motility of adult worms were displayed in PZQ treatment group, followed by NI, ME, and AL, respectively. Overall, first novel findings suggest that apart from NI, ME, and AL demonstrate potential as alternative therapeutic options for O. viverrini infection. Furthermore, animal model is needed to investigate the efficacy of NI, ME, and AL compare with standard treatment.
The likelihood of survival for cancer patients has greatly improved due to chemotherapy medicines. However, these antitumor agents might also have unfavorable effects on the cardiovascular system, which could result in sudden or gradual cardiac failure. The production of free radicals that result in oxidative stress appears to be the key mechanism by which chemotherapy-induced cardiotoxicity (CIC) happens. Reports suggest that the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) signaling pathway has been considered an alternative path for counteracting cardiotoxicity by suppressing oxidative stress, inflammation, and apoptosis. This review concludes recent knowledge about CIC with a special focus on the anti-oxidative regulation properties of the Sirt1/Nrf2 pathway.
Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, β-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules.
Microplastics (MPs) are widely used and disposed of indiscriminately, posing a potential threat to aquatic life. Herein, Asian seabass (Lates calcarifer) fingerlings were exposed to various concentrations (1, 10 and 100 ppt or g/kg) of dietary polyethylene MPs for 16 days. The results indicated a significant increase in mortality among the fish fed with dietary MPs compared to the control. Furthermore, histological analysis of the liver revealed moderate-to-severe morphological alterations, hepatocyte necrosis and vacuolisation as the concentration gradient of MPs increased. The severity of the alterations was highest at a concentration of 100 ppt, indicating a direct correlation between MP and liver damage. In addition, RNA sequencing and Gene Ontology term enrichment analysis revealed that a total of 4137 genes were significantly differentially expressed, with 1958 upregulated and 2179 downregulated genes. The significantly enriched terms included 'oxidoreductase activity', 'endocytosis', 'mitochondrial', 'immune system process' and 'lipid catabolic process'. Moreover, the Kyoto Encyclopaedia of Genes and Genomes enrichment analysis demonstrated that dietary MPs triggered oxidative stress, immune response and adaptive mechanism pathways in fish. Thus, MPs can induce metabolic disorders in L. calcarifer, highlighting their potential threat to aquatic organisms.
Aging is characterized by progressive decline in physiological and body function due to increase in oxidative damage. Gelam honey has been accounted to have high phenolic and nonphenolic content to attenuate oxidative damage. This study was to determine the effect of local gelam honey on oxidative damage of aged rats. Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 mg/kg body weight of gelam honey for 8 months. DNA damage level was determined by comet assay and plasma malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The activity of blood and cardiac antioxidant enzymes was determined by spectrophotometer. The DNA damage and MDA level were reduced in both gelam honey supplemented groups. Gelam honey increases erythrocytes CAT and cardiac SOD activities in young and cardiac CAT activity in young and aged groups. The DNA damage was increased in the aged group compared to young group, but reduced at the end of the study. The decline of oxidative damage in rats supplemented with gelam honey might be through the modulation of antioxidant enzyme activities.
Recent advances in our understanding of the pathogenesis of alcohol-induced hepato-renal injury and the development of new approaches to its treatment have been reported in various works. This study involves alcohol-induced oxidative stress linked to the metabolism of ethanol involving both mitochondrial and peroxisomal fractions of liver and kidney. Alcohol treatment resulted in the depletion of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), Glutathione-S-Transferase (GST) activities, and reduced glutathione (GSH) content, higher level of malondialdehyde (MDA) and lower levels of protein carbonyls (PC) causing malfunction of hepatic and renal tissues, when compared to control rats. Thespesia populnea (TP) leaf extracts, administered to chronic alcohol ingested rats, were envisaged to possess significant antioxidant defence properties and help in the recovery of tissues from alcohol-induced oxidative damage. The results showed that degenerative changes in hepatic and renal cells of alcoholic groups were minimized by the administration of TP leaf extracts as also revealed by histopathological examination. The current findings indicate that treatment with TP extracts reduces alcohol-induced oxidative stress, thereby protecting the hepatic and renal tissue from alcohol-induced damage.
The incidence of diseases related to oxidative stress disorders have been increased dramatically. Alternatives medicine or the active compound extracted from the natural products received great attention among researches at the present era. Naringenin (NG), a common dietary flavanone, found in the citrus fruits such as oranges, bergamots, lemons and grapefruit. It is used in the several oxidative stress disorders as the nutraceutical value of the compound emerges. Functionally, the antioxidants effect of NG is primarily attributed by reducing the free radical like reactive oxygen species (ROS) and enhancing the antioxidants activity such as superoxide dismutase (SOD), catalase, glutathione (GSH) in chronic diseases such as cardiovascular, neurodegenerative, diabetes, pulmonary, cancer and nephropathy. The present review article summarised the antioxidant property of NG and its molecular mechanism towards such diseases. Pubmed, Science Direct, Scopus, Web of Science and Google scholar were searched using the terms 'naringenin', 'oxidative stress disorders', 'naringenin and cardiovascular diseases', 'naringenin and diabetes mellitus', 'naringenin and neurodegenerative diseases', 'naringenin and pulmonary diseases', 'naringenin and cancer' and 'naringenin and nephropathy'. There has been special attention on evaluating anti-oxidative effect of NG on neurodegenerative diseases. Although some mechanisms of action remain vague, the current review highlighted the potential use of NG as a oxidative stress reliever which can be used as next prophylaxis compound in the treatment of the various oxidative stress disorders.
The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.
BACKGROUND: Neuroinflammation and oxidative stress can aggravate the progression of Alzheimer's disease (AD). Centella asiatica has been traditionally consumed for memory and cognition. The triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid) have been standardized in the ethanolic extract of Centella asiatica (SECA). The bioactivity of the triterpenes in different solvent polarities of SECA is still unknown.
OBJECTIVE: In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells.
METHODS: HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting.
RESULTS: The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p stress events may be the result of the activation of antioxidant defense systems. The potential of SECA and its fractions in reducing neuroinflammation and oxidative stress can be further studied as a potential therapeutic strategy for AD.
Nano-plastics (NPs) have emerged as prevalent contaminants in aquatic ecosystems, gaining significant research interest. Nonetheless, limited research has addressed the toxicity mechanisms associated with PS-NPs (polystyrene nanoplastics) of varying particle sizes. In this investigation, genotoxicity, growth patterns, hepatopancreatic damage, and intestinal flora alterations in freshwater shrimp Neocaridina palmata (Shen 1948), subjected to 35 days PS-NPs exposure (two size PS-NPs: 75 nm and 200 nm were used for this experiment, and five concentrations were set: 0 mg/L, 0.5 mg/L, 2.5 mg/L, 5 mg/L, and 10 mg/L concentrations PS-NP concentrations were examined using RNA sequencing, histopathological analyses, enzyme activity assessments, and 16S rRNA sequencing. Noteworthy variations in differentially expressed genes (DEGs) were identified across groups exposed to different PS-NPs sizes. We observed that PS-NPs predominantly instigated cellular component-related processes and induced apoptosis and oxidative stress across tissues via the mitochondrial pathway. Although the 200 nm-PS-NPs are stronger than the 75 nm-PS-NPs in terms of fluorescence intensity, 75 nm-PS-NPs are more likely to promote apoptosis than 200 nm-PS-NPs. PS-NPs impeded standard energy provision in N. palmata, potentially contributing to decreased body length and weight. Moreover, PS-NPs inflicted damage on intestinal epithelial and hepatopancreatic tissues and significantly modified intestinal microbial community structures. Specifically, PS-NPs-induced intestinal damage was marked by a decline in some probiotics (notably Lactobacilli) and a surge in pathogenic bacteria. Moreover, supplementing N. palmata with Lactobacilli appeared ameliorate oxidative stress and strengthen energy metabolism. Our findings provided valuable insights into crustacean toxicity mechanisms when subjected to PS-NPs and the potential risks that different PS-NPs sizes posed to terrestrial ecosystems.
The global prevalence of chronic diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer and Alzheimer's disease is on the rise. These diseases, which constitute the major causes of death globally, are associated with oxidative stress. Oxidative stress is defined as an "imbalance between oxidants and antioxidants in favor of the oxidants, potentially leading to damage". Individuals with chronic diseases are more susceptible to oxidative stress and damage because they have elevated levels of oxidants and/or reduced antioxidants. This, therefore, necessitates supplementation with antioxidants so as to delay, prevent or remove oxidative damage. Honey is a natural substance with many medicinal effects such as antibacterial, hepatoprotective, hypoglycemic, reproductive, antihypertensive and antioxidant effects. This review presents findings that indicate honey may ameliorate oxidative stress in the gastrointestinal tract (GIT), liver, pancreas, kidney, reproductive organs and plasma/serum. Besides, the review highlights data that demonstrate the synergistic antioxidant effect of honey and antidiabetic drugs in the pancreas, kidney and serum of diabetic rats. These data suggest that honey, administered alone or in combination with conventional therapy, might be a novel antioxidant in the management of chronic diseases commonly associated with oxidative stress. In view of the fact that the majority of these data emanate from animal studies, there is an urgent need to investigate this antioxidant effect of honey in human subjects with chronic or degenerative diseases.
Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.
On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.
Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.
Poly(3-hydroxybutyrate) [P(3HB)], a polymer belonging to the polyhydroxyalkanoate (PHA) family, is accumulated by numerous bacteria as carbon and energy storage material. The mobilization of accumulated P(3HB) is associated with increased stress and starvation tolerance. However, the potential function of accumulated copolymer such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] remained unknown. In this study, Delftia acidovorans DS 17 was used to evaluate the contributions of P(3HB) and P(3HB-co-3HV) granules during simulated exogenous carbon deprivation on cell survival by transferring cells with PHAs to carbon-free mineral salt medium supplemented with 1% (w/v) nitrogen source. By mobilizing the intracellular P(3HB) and P(3HB-co-3HV) at 11 and 40 mol% 3HV compositions, the cells survived starvation. Surprisingly, D. acidovorans containing P(3HB-co-94 mol% 3HV) also survived although the mobilization was not as effective. Similarly, recombinant Escherichia coli pGEM-T::phbCAB(Cn) (harboring the PHA biosynthesis genes of Cupriavidus necator) containing P(3HB) granules had a higher viable cell counts compared to those without P(3HB) granules but without any P(3HB) mobilization when exposed to oxidative stress by photoactivated titanium dioxide. This study provided strong evidence that enhancement of stress tolerance in PHA producers can be achieved without mobilization of the previously accumulated granules. Instead, PHA biosynthesis may improve bacterial survival via multiple mechanisms.
Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H(2)O(2)-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H(2)O(2) insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H(2)O(2). Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H(2)O(2)-induced sub-G(1) population by LPAF. Moreover, apoptotic morphological analysis by DAPI nuclear staining demonstrated that NG108-15 cells treated with H(2)O(2) exhibited apoptotic features, while such changes were greatly reduced in cells pretreated with LPAF. Taken together, these findings confirmed that LPAF exerts marked neuroprotective activity, which raises the possibility of potential therapeutic application of LPAF for managing oxidative stress-related neurological disorders and supports the traditional use of L. parasiticus in treating brain-related diseases.
Oxidative stress is caused by imbalance between the productions of reactive oxygen species (ROS) and antioxidant defense mechanisms. Palm oil antioxidants such as tocotrienol rich fraction (TRF) is known to have neuroprotective effects on neurones by acting against free radical induced neuronal cell death. This study was undertaken to elucidate the effect of TRF on oxidative DNA damage and cognitive functions in experimental rats.
Vitamin E is an antioxidant that may protect bone against oxidative stress-induced osteoporosis. This in vitro study was conducted to determine the protective effects of a-tocopherol and γ-tocotrienol on osteoblasts, the bone forming cells, against oxidative stress.