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Endometriosis (EMS) is a chronic, estrogen-dependent inflammatory disease affecting 5–10% of women of reproductive age, characterized by the growth of endometrial tissue on the outside of the uterus. The dysregulation of iron metabolism leads to the accumulation of iron ions at the lesion sites, resulting in oxidative stress and pro-inflammatory responses that promote the progression of EMS. The mechanisms underlying ferroptosis in EMS primarily involve iron accumulation, lipid peroxidation, and loss of glutathione peroxidase 4 activity. These mechanisms confer resistance to ferroptosis within the ectopic tissues and facilitate cell survival and proliferation. Traditional Chinese medicine (TCM) has demonstrated therapeutic potential for modulating ferroptosis. Studies have shown that TCM monomers may regulate ferroptosis by modulating iron transport proteins and anti-oxidant defense mechanisms. TCM formulas employ distinct treatment strategies depending on the stage of EMS: in the early stages, they promote ferroptosis to control lesion growth, whereas in the later stages, they inhibit ferroptosis to reduce oxidative stress and inflammation in order to improve reproductive health and slow disease progression. This study provides a new perspective on potential therapeutic strategies for the management of EMS by summarizing the role of ferroptosis in its pathological mechanisms and reviewing findings on the use of TCM in regulating ferroptosis.

Antiepileptic drug therapy in individuals with epilepsy can induce free radical generation and profound lipid peroxidation. Some Chinese herbs with antiepileptic potential show antioxidant effects. We performed an open add-on study of TW970, a modified formula of the Chinese medicine "Chaihu-Longu-Muli-Tang", on 20 patients with refractory epilepsy and a seizure frequency of at least four fits per month, and another 20 patients with benign epilepsy and a seizure frequency of less than four fits per month. The control group consisted of 20 age-matched healthy adults. Seizure frequency, serum malondialdehyde (MDA), glutathione (GSH) and copper-zinc superoxide dismutase (Cu,Zn-SOD) were investigated in patients with refractory and benign epilepsy before and after four months add-on treatment of TW970. There was a decrease in seizure frequency in refractory epileptics from 13.4 ± 3.4 to 10.7 ± 2.5/per month, although the p value was 0.084. Before TW970 add-on treatment, a significant enhancement of lipid peroxidation with increased MDA and Cu,Zn-SOD activities together with decreased GSH were seen in refractory epileptics compared with normal controls. After TW970 add-on treatment of refractory epileptics for four months, normalization of MDA and Cu,Zn-SOD levels was achieved. Before and after TW970 add-on treatment, there were no statistically significant changes of the above-mentioned parameters in the patients with benign epilepsy. These results suggest that TW970 can reduce the seizure frequency in patients with refractory epilepsy and this may be due to the antioxidant effects of the modified formula of Chaihu-Longu-Muli-Tang.

Acute p.o. administration of absolute ethanol (1.0 ml/kg) to fasted rats produced extensive necrosis of gastric mucosa. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could effectively and dose-dependently prevent such necrosis. This protective effect is called "cytoprotection." The maximal cytoprotective effect against absolute ethanol (AE)-induced gastric mucosal lesion was observed 1 hour after PEE administration. A gross examination of the gastric mucosa showed a marked improvement in groups receiving PEE. In order to further investigate the gastric protective mechanism of PEE, lipid peroxidation (LPO) levels in vivo and in vitro were estimated. PEE exhibited dose-dependent superoxide scavenging activity and antioxidant effects on AE-induced LPO in rat gastric mucosal homogenates. It was concluded that the gastric protective mechanism of PEE was due, at least in part, to its ability to inhibit LPO, and hence indirectly protect the gastric mucosa from oxidative stress.

Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the effect of tetramethylpyrazine (TMP) (10, 25 and 50 mg/kg), an active component of a Chinese medicinal plant Ligusticum wallich Franch (Chuanxiang), on streptozotocin (STZ)-induced diabetic male ICR mice. STZ was injected as a single daily dose (4 mg/kg i.p. in buffered citrate solution, pH 4.0) for one week. A single daily dose of TMP (10, 25 or 50 mg/kg i.p.) was administered for 2 weeks to the STZ-induced diabetic mice immediately following 1 week STZ induction. Plasma glucose and serum blood urea nitrogen (BUN) concentrations were estimated at the time of sacrifice. Malonialdehyde (MDA) formation was measured from the liver and kidney tissues. TMP dose dependently inhibited glucose concentration and BUN elevation. TMP also remarkably reduced the degree of lipoperoxidation. Our results indicate that TMP may be an effective agent for treatment of diabetes mellitus complications with oxidative stress.

The antioxidative activities of 12 medicinal plants and the compounds isolated from them were investigated using the thiocyanate method to evaluate inhibitory effects on lipid peroxidation in the linoleic acid system. The peroxide levels gradually increased during incubation in the presence of linoleic acid over 3 days, and most of the plants inhibited lipid peroxidation. In particular, of the plants tested, Cudrania tricuspidata, Zanthoxylum piperitum, Houttuynia cordata and Ulmus parvifolia reduced lipid peroxidation more effectively as lipid peroxidation progressed, resulting in inhibition of about 80% relative to the control value by the 3rd day of incubation. In addition, the polyphenols isolated from the plants also showed marked and dose-dependent inhibitory effects on lipid peroxidation. The compounds with the strongest activities were 3,4-dihydroxylbenzoic acid, quercetin, the quercetin glycosides quercetin-3-O-β-D-galactoside, quercetin-3-O-α-L-rhamnoside, quercetin-3-O-β-D-glucoside and quercetin-3-O-rutinose, catechin, gallic acid, methyl gallate and rosamultin isolated from Zanthoxylum piperitum, Houttuynia cordata, Rosa rugosa and Cedrela sinensis. Moreover, quercetin glycosides showed stronger activity than quercetin, suggesting that glycosylation increases the antioxidative activity of quercetin. Our results indicate that the medicinal plants and their polyphenols show promise as therapeutic agents for various disorders involving free radical reactions.

Acute p.o. administration of 99.5% ethanol (0.1 ml) to fasted mice produced heart toxicity. Pretreatment with p.o. administration of tetramethylpyrazine (TMP) could prevent such toxicity effectively and dose-dependently. The maximal antioxidative effect against 99.5% ethanol-induced heart toxicity could be observed at 1 hour after TMP administration. In order to further investigate the heart protective mechanism of TMP, both lipid peroxidation level in vivo and superoxide scavenging activity were conducted. TMP exhibited a dose-dependently anti-lipid peroxidation effect in mice heart homogenate, and results indicated that 99.5% ethanol-induced intoxicated mice hearts have higher malonic dialdehyde (MDA) levels compared with those in TMP administrated mice hearts. These results suggest that the potentially heart protective mechanism of TMP could be contributed, at least in part, to its prominent anti-lipid peroxidation and anti-free radical formation effects, hence it could protect the heart from lipid peroxidation-induced heart toxicity.

Wen-Pi-Tang is a Chinese prescription used traditionally as a medicine to treat moderate renal failure. In this study, we used rats subjected to subtotal nephrectomy and streptozotocin injection to examine the effects of Wen-Pi-Tang on diabetic nephropathy. Wen-Pi-Tang was administered at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. Diabetic nephropathy is one of the most serious chronic complications of diabetes mellitus, and renal dysfunction is reflected by proteinuria, decreased creatinine clearance (Ccr) and increased serum urea nitrogen and creatinine (Cr) levels. Wen-Pi-Tang treatment for 15 weeks resulted in significant reductions of blood glucose and serum urea nitrogen levels, while proteinuria, Ccr and serum Cr levels did not change significantly. Wen-Pi-Tang also lowered serum triglyceride and thiobarbituric acid-reactive substance levels in a dose-dependent manner. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were normalized by the administration of Wen-Pi-Tang through decreased formation of advanced glycation end-products in the kidney. Wen-Pi-Tang protected against the development of renal lesions, glomerular sclerosis and mesangial matrix expansion, assessed by histopathological evaluation and scoring. This study suggests that Wen-Pi-Tang treatment could be beneficial in reducing the risk of developing diabetic nephropathy.

The aim of this study is to investigate the antioxidant defense system induced by the methanol extract of Bauhinia racemosa L.(MEBR) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in Wister albino rats. The effects of MEBR on surface visible macroscopic (Morphometry) liver lesions (neoplastic nodules) and the levels of serum enzymes, lipid peroxidation and antioxidants were evaluated in NDEA-induced hepatocarcinogenesis in rats.In rats treated, with NDEA, significantly elevated levels of serum enzymes (SGOT, SGPT and ALP), bilirubin and decreased levels of protein and uric acid were observed. Significantly elevated amount of malondialdehyde (MDA), the end product of lipidperoxidation, indicated higher levels of lipid peroxidation, which was accompanied by significantly decreased levels of antioxidants like vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Administration of MEBR was able to suppress nodule development/hepatocellular lesion formation in rats. The extract treatment increases in antioxidant levels and dramatic decreases in lipid peroxidation levels. MEBR also produced a protective effect by decreasing the level of serum enzymes, bilirubin and increased the protein and uric acid levels. The results suggest that MEBR exert chemopreventive effects by suppressing nodule development and decreasing lipid peroxidation and enhancing the levels of antioxidants in NDEA carcinogenesis by reducing the formation of free radicals.

Oxidative stress plays a key role in the pathophysiologic process of acute and chronic renal diseases. Intracellular component such as lipids, proteins and nucleic acids are easily and rapidly oxidized by excessive reactive oxygen species (ROS), and such reactions lead to increased levels of lipid peroxide. The present study examined the antioxidant effects of Wen-Pi-Tang and its component crude drugs on 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)- or 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN)-induced ROS generation and lipid peroxidation of linoleic acid. As a result, Wen-Pi-Tang significantly decreased AAPH or AMVN-induced ROS in renal mitochondrial particles. For the components in Wen-Pi-Tang's prescription, Rhei Rhizoma and Glycyrrhizae Radix extracts strongly inhibited peroxide levels, but Ginseng Radix, Aconiti Tuber and Zingiberis Rhizoma extracts were comparably low. Rhei Rhizoma extract showed the strongest inhibitory activity on oxidative injury, and two of its tannin compounds, (-)-epicatechin 3-O-gallate and procyanidin B-2 3,3′-di-O-gallate, inhibited AAPH or AMVN-induced ROS significantly. Thus, the present data suggest that Wen-Pi-Tang and its component crude drugs effectively prevent biological toxicity on oxidative stress through potent antioxidant and anti-lipid peroxidation activities.

Ginkgo biloba extract (EGB) functions as a natural substantial antioxidant and hypolipidemic. Chronic alcohol abuse leads to sustained dyslipidemia characterized by hyperlipidemia and lipid peroxidation. Thus, the present study investigates the effect of EGB on lipid disorders induced by ethanol in rats. Male Sprague-Dawley rats were fed with ethanol (2.4 g/kg), and pretreated with a daily dose of low or high EGB (48 or 96 mg/kg, respectively). During the experiment, serum was collected on day 30, 60, and 90. Serum lipid profile, including lipid peroxidation, was determined by colorimetric methods. Our data showed that ethanol intake resulted in a time-dependent increase in serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA), and a decrease of the ratio of high-density lipoprotein cholesterol (HDL-C) against TC. EGB prophylactic medication (48 and 96 mg/kg), especially at the high dose, significantly increased HDL-C content, and normalized the abnormal lipid profile and peroxidation in comparison to ethanol-fed only rats. These results suggest that ethanol results in time-dependent hypercholesterolemia, hypertriglyceridemia and promotes serum lipid peroxidation. EGB pretreatment prevents hyperlipidemia and ameliorates lipid peroxidation induced by ethanol.

Nostoc sphaeroides Kuetzing has been used as a traditional medicine in China to treat a variety of ailments. This research identified the antioxidant activities of polysaccharide extract from Nostoc sphaeroides. The extract, which contains 46.2% carbohydrates, exhibited an effective scavenging capability on superoxide radical, hydroxyl radicals in non site-specific as well as site-specific assays, and also performed lipid peroxidation inhibition in a dose-dependent manner. Polysaccharide extract had no 1,1-diphenyl-2-picrylhydrazyl radical scavenging potential at all test concentrations. Activities of superoxide dismutase, catalase, and glutathione peroxidase in human embryo kidney 293 cells were increased effectively when Nostoc sphaeroides extract was applied. These results suggested that the use of N. sphaeroides in treating ailments may be based on the antioxidant capacities of polysaccharide composition.

This study was designed to investigate the antioxidant and free radical scavenging capacities of arjunic acid, an aglycone obtained from the fruit of medicine Terminalia Fruit. Liver microsomes, mitochondria, and red blood cells (RBCs) were prepared from Wistar rats. The antioxidant capacity was determined by the inhibitory effect on lipid peroxidation, hydrogen peroxide induced RBCs hemolysis, and RBCs autoxidative hemolysis. The free radical scavenging activity was tested by DPPH method and 2′,7′-dichlorodihydrofluoresc in diacetate (DCFH₂-DA) assay. Ascorbic acid was chosen as the positive controls. Results showed that arjunic acid was a strong antioxidant and a free radical scavenger, more potent than ascorbic acid, in microsomes lipid peroxidation, DPPH, hydrogen peroxide induced RBCs hemolysis, and (DCFH₂-DA) assay (p < 0.05). However, no significant difference was observed in the RBCs autoxidative hemolysis assay (p > 0.05).

This study was to investigate the protective effects and possible mechanisms of total flavones of rhododendra (TFR) against cerebral ischemia reperfusion injury in rats and mice. Cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). Infarct volume, neurological deficit, brain water content, levels of malondialdehyde (MDA), nitric oxide (NO) contents, lactate dehydrogenase (LDH) activity in plasma and brain, levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and mRNA expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in brain were evaluated 7 or 10 days after treatment. TFR significantly reduced infarct volume, ameliorated the neurological deficit and reduced the brain water content. The activities of SOD, LDH and GPX in brain were enhanced, while the activity of LDH in plasma and the contents of MDA and NO in plasma and brain were decreased. While, the expression of iNOS and nNOS mRNA in brain were down-regulated, the expression of eNOS mRNA in the brain was up-regulated. These results suggest that TFR has protective effects for cerebral injury in rats and mice, which might be associated with its antioxidant properties and ability to regulate the expression of NOS isoforms.

The hepatoprotective and antioxidant effect of an ethanolic extract of 'Rocket' Eruca sativa L. (EER), on liver injury induced by carbon tetrachloride (CCl₄) was investigated. Wistar albino rats were administered 250 and 500 mg/kg body weight extract orally for 10 consecutive days. Marker enzymes GOT, GPT, ALP, GGT and bilirubin were estimated in serum. Whereas, non-protein sulfhydryl (NP-SH), total protein (TP) and malondialdehyde (MDA) were estimated in liver tissue as markers for oxidative stress. Histopathological assessment was also done on liver tissue. CCl₄ induced liver poisoning in all treated animals was evident by elevated serum GOT, GPT, ALP, GGT and bilirubin levels. Induction of oxidative stress in the liver tissue by CCl₄ was evidenced by a fall in the levels of NP-SH and TP; and an increased level of MDA concentration. EER administration for 10 days prevented the CCl₄ induced hepatic injury and oxidative stress. Furthermore, the extract also reduced the pentobarbital-induced prolongation of sleeping time in mice. The ability of rocket extract to protect the liver toxicity in rats was further confirmed by histological findings in the liver tissue. In conclusion, it was observed that Eruca sativa L. extract protects the liver against CCl₄ induced hepatic injury through its potent antioxidant activity in rats.

The ethanolic extract of Amaranthus tricolor L. (ATE) leaves was tested for its efficacy against CCl₄-induced liver toxicity in rats. The hepatoprotective activity of ATE was evaluated via measuring various liver toxicity parameters, the lipid profile, and a histopathological evaluation. A sleeping time determination study and an acute toxicity test were performed in mice. The results clearly showed that oral administration of ATE for three weeks significantly reduced the elevated levels of serum GOT, GPT, GGT, ALP, bilirubin, cholesterol, LDL, VLDL, TG, and MDA induced by CCl₄. Moreover, ATE treatment was also found to significantly increase the activities of NP-SH and TP in liver tissue. These biochemical findings have been supported by the evaluation of the liver histopathology in rats. The prolongation of narcolepsy induced by pentobarbital was shortened significantly by the extract. The acute toxicity test showed that no morbidity or mortality was caused by the extract. The observed hepatoprotective effect appears to be due to the antioxidant properties of A. tricolor, which may pave the way to finding a new drug to be used for fighting liver diseases.

The present study was conducted to determine whether lyophilized aqueous extract of alfalfa, or Medicago sativa L. could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. The hepatoprotective activity of alfalfa extract was determined by assessing the levels of serum transaminases, ALP, bilirubin and lipid profile. Further, the effect of the test substance on malondialdehyde (MDA), an end product of lipid peroxidation; antioxidant liver enzyme non-protein sulfhydryl (NP-SH); and total protein (TP) were also studied. Serum transaminase, ALP, bilirubin level, lipid profile and liver MDA were significantly elevated and the antioxidant status in liver NP-SH and TP contents were declined in animals treated with CCl₄ alone. Pretreatment with alfalfa and silymarin for three weeks prior to the administration of CCl₄ significantly prevented the increase in the serum levels of hepatic marker, LDL, VLDL levels enzymes and reduced oxidative stress indicated by elevated NP-SH and TP concentration. The histopathological examination of the livers also showed that the alfalfa extract reduced the incidence of liver lesions induced by CCl₄. The in vitro antioxidant assessment of alfalfa extract on DPPH and carotene-linoleic assays demonstrated a moderate antioxidant potential. Results suggest that the alfalfa extract possesses hepatoprotective and antioxidative stress properties possibly through its antioxidant phytochemical constituents and substantiates its use in various liver disorders as a hepatoprotector.

Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones(yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2′-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.

Modern cosmetic products, with rich formulations of components, have become an ideal breeding ground for microorganisms. Implementing effective preservative systems is crucial to prevent microbial growth and contamination. Titanium dioxide nanoparticles, a familiar ingredient in cosmetics, can decompose the outer membrane of microbial cells by producing free radicals. Chitosan has shown antimicrobial activities by impairing cell wall integrity by binding to it aiding in the release of cytosolic contents. In line with this, this work was centered on evaluating the antimicrobial efficiency of chitosan-coated titanium dioxide (CS-TiO${}_2)$ nanoparticles against three bacterial species viz. Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and use them as a self-preservative agent in cosmetic formulations. The growth curve analysis exhibited a dose-dependent delay in bacterial growth. The minimum inhibitory concentration (MIC${}_{50})$ results revealed that the nanoparticles were effective at 31.25$\mu$g/ml and 62.5$\mu$g/ml concentrations in suppressing S. aureus, P. aeruginosa and E. coli, respectively. The redox imbalance, membrane lipid peroxidation, DNA damage and cell viability analyses showed that the CS-TiO₂ nanoparticles could disrupt the membrane leading to reactive oxygen species (ROS) formation and altering the genetic material. Therefore, the conclusions drawn from this research highlight the proficient microbial performance of CS-TiO₂, proposing its suitability for incorporation into consumer products, especially cosmetics. As far as the authors are aware, this study is believed to be the first to investigate the potential of CS-TiO₂ nanoparticles as a self-preservative.

The role of UV-induced oxidative stress (intracellular reactive oxygen species generation, DNA strand breakage and lipid peroxidation) in the inhibition of bacterial culturability and activity upon irradiation was assessed during experimental exposure of 9 different bacterial isolates to UV-B radiation. Intracellular ROS were quantified using the fluorimetric probe DCFH-DA. DNA strand breaks were determined using the fluorimetric analysis of DNA unwinding (FADU) method, while lipid peroxidation was assessed from the production of malonaldehyde (MDA). Bacterial culturability was assessed by enumeration of colony forming units (CFU) and bacterial activity was assessed by the incorporation of radiolabeled leucine. UV-B exposure resulted in a strong increase in intracellular ROS levels (12.4-42.3%), accompanied by enhanced formation of lipid peroxidation products (22.1-30.7%) in all strains. Bacterial culturability was inhibited by as much as 89.4% while bacterial activity was reduced by up to 99.6%. The results obtained reveal the contribution of oxidative stress in the impairment of bacterial culturability and activity and suggest the involvement of differences in the extent of oxidative damage in the variability of the responses of aquatic bacteria to UV-B radiation.

Isoproturon, an herbicide of pre- and pos-emergence of Autumn-Winter crops, persists occasionally in soil, groundwater and biological systems at levels above those established by European Directives. Saccharomyces cerevisiaeUE-ME₃ exposed in stationary phase to 50 and 100 μM isoproturon exhibit growth rates higher than control or exposed cells to 5 and 25 μM of this phenylurea. However, in S.cerevisiaeUE-ME₃ grown in the presence of 5 μM isoproturon, were observed a decrease of GSH/GSSG ratio, an increase of cytoplasmatic MDA level, GR and GPx activities, usual markers of cell damage and oxidative stress. Nevertheless, S.cerevisiae grown at 50 and 100 μM isoproturon, have developed adaptive responses to this phenylurea by stabilization of its reducing environment, lipid peroxidation decrease and GR, GPx activities increase, events regulated by isoproturon level in culture medium, facts which suggest that this yeast strain can be useful on bioremediation.