Corrigendum: Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats.

[This corrects the article DOI: 10.3389/fphar.2023.1305816.].

Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide.

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer's disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5-20 mg/kg/day, oral) for 3 weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1ß. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain.

Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase.

Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Zataria multiflora and its constituent, carvacrol, counteract sepsis-induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress.

BACKGROUND: Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury. METHODS: Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)- and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. RESULTS: Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. CONCLUSIONS: The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

Psidium guajava induces cytotoxicity in human malignant glioblastoma cell line: Role of reactive oxygen species.

One of the deadliest types of CNS primary brain cancers is glioblastoma multiforme (GBM), and the survival rate of patients is about 7.2%. The standard treatment for GBM is surgical interventions followed by temozolomide. We investigated for the first time, the cytotoxic impacts of Psidium guajava (P. guajava) on the U87 GBM cell line. We measured cell toxicity through the MTT test following 24 h, 48 h, and 72 h treatment with different concentrations of fruit and seed hydroalcoholic extracts of P. guajava (25-400 µg/ml). Lipid peroxidation assay, reactive oxygen species (ROS) production, and apoptosis rate were evaluated 24 h after treatment by extracts of P. guajava. Moreover, to determine the Bax/Bcl-2 and NF-κB genes expression, we performed a real-time polymerase chain reaction (RT-PCR). Our finding demonstrated that 50-400 µg/ml of P. guajava extracts dose-dependently decreased the viability of U87 cells. Also, treatment by extracts increased lipid peroxidation, ROS production, and apoptosis in a dose-dependent manner. Moreover, the RT-PCR demonstrated an up-regulation in Bax\Bcl-2 and NF-κB. Thus, P. guajava inhibited the proliferation of U87 GBM cells and increased apoptosis probably through Bax/Bcl-2 and NF-κB regulation.

The possible mechanism of Datura stramonium on pentobarbital-induced sleep in mice.

BACKGROUND: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. METHODS: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. RESULTS: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. CONCLUSION: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Protective effects of cinnamon on acetylcholinesterase activity and memory dysfunction in diabetic rats.

OBJECTIVES: Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes. METHODS: Forty-seven male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups. RESULTS: Vs. the control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group. CONCLUSIONS: These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury.

Boswellic acids as promising agents for the management of brain diseases.

Boswellic acid (BA)s are pentacyclic triterpenic acids present in gum resin of Boswellia species (such as B. serrata and B. carterii). They possess a variety of pharmacological effects such as anti-inflammatory, anti-oxidant, and anti-excitotoxic effects. These properties may have potential therapeutic implication in neurological disorders. Notably, the BAs-induced neuroprotection is proposed to be associated with the ability to reduce neurotoxic aggregates, decrease oxidative stress, and improve cognitive dysfunction. Recently, BAs have been suggested as potential agents for the treatment of brain tumors due to their potential to attenuate cell proliferation, migration, metastasis, angiogenesis, and promote apoptosis during both in vitro and in vivo studies. The present review aims to address these studies and highlights the possible underlying mechanisms of the observed effects. Besides, novel formulations and improving pharmacokinetic properties may enhance the therapeutic efficacy of BAs.

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats.

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI. Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted. Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract. Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress.

Anti-inflammatory effects of resveratrol in patients with cardiovascular disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic inflammation is one of the most important factors involved in the development and progression of cardiovascular disease (CVDs). Accumulating evidence has described the effect of resveratrol, a natural polyphenolic compound, on biomarkers of inflammation among patients with CVDs; however, findings are controversial. Here we performed a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of resveratrol supplements on TNF-α, IL-6, and CRP levels in CVDs patients. METHODS: Online research was conducted in the following database: MEDLINE, EMBASE, Cochrane Library, Web of Science databases, and Scopus. This systematic review and meta-analysis were conducted to investigate the effects of resveratrol supplements on inflammatory biomarkers among patients with CVDs. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. RESULTS: Six RCTs met the inclusion criteria and were selected for the current meta-analysis. Our results demonstrated that resveratrol significantly decreases serum levels of CRP (MD = -0.63, 95 % CI: -0.1.13, -0.12; p = 0.01), and TNF-α (MD = -0.55, 95 % CI: -1.04, -0.06; p = 0.02), however, resveratrol had not significant effect on serum concentration of IL-6 (MD = -0.12, 95 % CI: -0.52, 0.27; p = 0.53), in patients with CVDs. CONCLUSION: Our results suggest that resveratrol can be used as a potential treatment in patients with CVD by reducing inflammatory conditions.

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats.

Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum (R.turkestanicum) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity. Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed. Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes. Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.

Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review.

Potassium ion (K+) channels are pore-forming transmembrane proteins that control the transport of K+ ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K+ channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K+ channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 in vivo studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (KATP), and small (SKCa) and large (BKCa) conductance calcium-activated K+ channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K+ channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K+ channels can facilitate drug development for the treatment of various K+ channel-related disorders.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Effect of Sanguisorba minor on scopolamine-induced memory loss in rat: involvement of oxidative stress and acetylcholinesterase.

Sanguisorba minor (S. minor) has neuroprotective and antioxidant activities. However, its potential benefits in ameliorating learning and memory functions have been explored in no studies up to now. So, in the current study, rats were treated with S. minor hydro-ethanolic extract (50, 100, and 200 mg/kg, intraperitoneal (i.p.)) as well as rivastigmine (0.5 mg/kg, i.p.) for 21 consecutive days. Thereafter, their behavioral performance was assessed using Morris water maze (MWM) and passive avoidance (PA) tasks. Notably, 30 min before conducting the tasks, scopolamine was injected. Finally, the biochemical assessments were done using the brain tissue. The extract characterization was performed by liquid chromatography-mass spectrometry, which confirmed the presence of quercetin, myricetin, kaempferol, catechin, ellagic acid, and gallic acid derivatives. In the MWM test, the extract reduced both escape latency and the travelled distance, compared to the scopolamine group. Moreover, in the PA test, the latency to enter the dark chamber significantly increased by the extract, compared to the scopolamine group (p < 0.05-p < 0.001). Notably, the beneficial effects of S. minor on cognitive performance of the scopolamine-treated rats appeared to be similar or even better than rivastigmine in behavior performance. Similar to rivastigmine, it was observed that the extract attenuated both AChE activity and oxidative injury in the brain as evidenced by the increased antioxidant enzymes and total thiol content; however, it decreased malondialdehyde level (p < 0.05-p < 0.001). In conclusion, the results suggested the effectiveness of S. minor in preventing cognitive dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by the regulation of cholinergic activity and oxidative stress. S. minor could be considered as a potential alternative therapy in cognition disorders.

Acute and sub-acute toxicity assessment of the standardized extract of Sanguisorba minor in vivo.

Although Sanguisorba minor has been used as herbal medicine, no study has ever examined its potential toxicity. This study investigated acute and subacute toxicities of S. minor hydroalcoholic extract (SE). In the acute toxicity test, a single oral dose (300, 2,000, and 3,000 mg/kg) of SE was given to mice. The oral administration of SE (100, 200, and 400 mg/kg for 4 weeks) was performed to evaluate subacute toxicity. After the treatments, neurobehavioral, histopathology, hematological, and biochemical parameters were monitored. In vitro cytotoxicity was also assessed. Moreover, high-performance liquid chromatography fingerprint was done for the standardization of SE. The no-observed-adverse-effect level of SE was up to 2,000 mg/kg, and the LD50 of the prepared extract was over 3,000 mg/kg. The rats exposed to the extract did not show any marked change in their body weight. The extract at used doses did not affect neuromuscular coordination. According to the hematological, biochemical, and histological examinations, no significant treatment-related adverse effect of the extract was observed, even at 400 mg/kg. Only 48 h exposure to 400 µg/mL of SE reduced the viability of PC12 cells. The findings revealed that this plant could be well-tolerated, regarded safe, and used as herbal medicine.

Standardized extract of Sanguisorba minor attenuates injury in aging rat model via the Nrf2/HO­1 pathway.

Aging promotes damage to vulnerable organs like brain and liver. Sanguisorba minor has been traditionally used to cure various ailments. Few studies have reported pharmacological activities of this medicinal plant. This research aimed to investigate the effects of Sanguisorba minor extract (SME) on brain and liver injury in aging rats and identify the underlying mechanisms. The aging model was developed by subcutaneously injecting D­galactose and simultaneously treating them with SME. After biochemical and pathological assessments, mRNA expression levels of nuclear factor­erythroid factor 2­related factor 2 (Nrf2) and Nrf2­ regulated gene, heme oxygenase­1 (HO­1), in the brain and liver tissues were determined. As a result, malondialdehyde and acetylcholinesterase levels were elevated while total thiol content and superoxide dismutase were reduced in the aging rats. Treatment with the extract remarkably attenuated oxidative injury and pathological changes in liver and brain tissues. Concomitantly, the extract up­regulated Nrf2 and HO­1 genes. Our findings exhibited SME may improve the aging­related brain and liver damage through the Nrf2­HO­1 pathway.

The Effect of Hydro-alcoholic Extract of Rheum Turkestanicum Roots against Oxidative Stress in Endothelial Cells.

INTRODUCTION: Cardiovascular disorders (CVD) are a common cause of mortality worldwide. Oxidative stress is thought to be a major factor leading to CVD. Anti-oxidants such as medicinal plants may have a role in the mitigation of vascular problems through free radicals scavenging. In this study, we evaluated the protective effects of Rheum turkestanicum against hydrogen peroxide (H2O2)-induced toxicity in endothelial cells (BAE-1). METHODS: To evaluate the protective effect of R. turkestanicum against H2O2 toxicity, four groups comprised of control group (the cells without any treatment), H2O2 group (the cells incubated with H2O2 (200 µM)), and treatment groups (the cells treated with R. turkestanicum (12200 µg/ml) alone or 24h before exposure to H2O2). Quercetin (30.23 µg/ml) was used as a bioactive ingredient of the extract. Then the cell viability, reactive oxygen species, lipid peroxidation, and apoptosis were evaluated. RESULTS: H2O2 exposure reduced cell viability to 13.6 ± 1.6%, enhanced ROS generation to 1445 ± 80.7%, lipid peroxidation (LPO, 290 ± 13% of control), and apoptotic cells (P < 0.001). In contrast, compared with H2O2 group, R. turkestanicum and quercetin significantly restored the cell viability to 80.3 ± 1.6 and 87.2 ± 2.1%, ROS formation to 186 ± 10 and 129 ± 1%, as well as LPO to 130.7 ± 7.7 and 116 ± 2.5 of control, respectively (P < 0.001). Therefore, the extract reduced H2O2-induced toxicity in BAE-1 cells by scavenging of free radicals. CONCLUSION: Our findings demonstrated that the extract might reduce toxicity of endothelial cells by attenuation of oxidative stress, which can be related to the presence of active ingredients including quercetin.

The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases. AIM OF THE STUDY: There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS). MATERIALS AND METHODS: In vivo: 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemical analysis. In vitro: Primary microglia isolated from mouse was used in the present study. The cells were pretreated with C. spinosa extract (10-300 µg/ml) and then stimulated with LPS (1 µg/ml). The expression levels of inflammatory and anti-inflammatory cytokines were elucidated using Real-Time PCR and ELISA methods. RESULTS: The escape latency in the Morris water maze test in the LPS group was significantly greater than the control group (p < 0.001), while, in extract-treated groups, it was less than the LPS group (p < 0.001). Additionally, we found that the levels of IL-1ß, TNF-α, and iNOS/Arg-1 ratio was also significantly lower in extract-treated groups than the LPS group (p < 0.001). The results revealed that C. spinosa extract significantly reduced the levels of TNF-α, iNOS, COX-2, IL-1ß, IL-6, NO and PGE2, and the ratios of iNOS/Arg-1 and NO/urea, following the LPS-induced inflammation in microglia (p < 0.001). CONCLUSIONS: Our finding provides evidence that C. spinosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD.

Evaluation of Rheum Turkestanicum in Hexachlorobutadien-Induced Renal Toxicity.

Hexachlorobutadien is nephrotoxic agent in rodents. The mechanism of toxicity includes generation of free radicals, depletion of thiol groups and production of toxic metabolites. Antioxidant compounds may reduce HCBD-nephrotoxicity. In this research we investigated the effect of Rheum turkeatanicum extract against HCBD-toxicity. The animals were divided to 4 groups which were including control (saline, 1 mL/kg), HCBD (100 mg/kg) and treatment groups which received extract at doses 100 and 200 mg/kg. The extract were administered as intraperitoneally (i.p.) 1 h before HCBD injection (i.p.). The animals were anesthetized by ether, 24 h after HCBD administration. The results showed elevation of serum creatinine, serum urea, urinary protein, urinary glucose, malondialdehyde levels in kidney and reduction of thiol in kidney by HCBD. The histopathological studies showed that there was apoptosis and necrosis in HCBD treated groups. Administration of R.turkestanicum reduced HCBD toxicity. The extract reduced hitopathological changes in kidney. It may be concluded that the nephroprotective effect of extract may be due to different mechanisms such as antioxidant activity or by decreasing the toxic metabolites of HCBD or inhibition of enzymes which are involved in the bioactivation of HCBD such as glutathione-S-transferase (GST) or cysteine-S-conjugate ß-lyase.