Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance.

The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.

Multilayer PVA/gelatin nanofibrous scaffolds incorporated with Tanacetum polycephalum essential oil and amoxicillin for skin tissue engineering application.

Wound infection is still an important challenge in healing of different types of skin injuries. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action. In this study, by electrospinning process Tanacetum polycephalum essential oil (EO), as a natural antibacterial and anti-inflammatory agent, along with Amoxicillin (AMX) as an antibiotic are incorporated into PVA/gelatin-based nanofiber mats individually and in combination to fabricate a novel wound dressing. Briefly, we fabricated PVA/gelatin loaded by Amoxicillin as first layer for direct contact with wound surface to protects the wound from exogenous bacteria, and then built a PVA/gelatin/Tanacetum polycephalum essential oil layer on the first layer to help cleanses the wound from infection and accelerates wound closure. Finally, PVA/gelatin layer as third layer fabricated on middle layer to guarantee desirable mechanical properties. For each layer, the electrospinning parameters were adjusted to form bead-free fibers. The morphology of fabricated nanofiber scaffolds was characterized by Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM). Microscopic images demonstrated the smooth bead-free microstructures fabrication of every layer of nanofiber with a uniform fiber size of 126.888 to 136.833 nm. While, EO and AMX increased the diameter of nanofibers but there was no change in physical structure of nanofiber. The water contact angle test demonstrated hydrophilicity of nanofibers with 47.35°. Although EO and AMX had little effect on reducing hydrophilicity but nanofibers with contact angle between 51.4° until 65.4° are still hydrophilic. Multilayer nanofibers loaded by EO and AMX killed 99.99 % of both gram-negative and gram-positive bacteria in comparison with control and PVA/gelatin nanofiber. Also, in addition to confirming the non-toxicity of nanofibers, MTT results also showed the acceleration of cell proliferation. In vivo wound evaluation in mouse models showed that designed nanofibrous scaffolds could be an appropriate option for wound treatment due to their positive effect on angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound closure.

Inhibition of TLR4, NF-κB, and INOS pathways mediates ameliorative effect of syringic acid in experimental ulcerative colitis in rats.

OBJECTIVE: Numerous therapeutics and pharmacological properties have been reported in syringic acid (SA). In this study, we aimed to evaluate effect of SA in ulcerative colitis (UC) in rats considering effect on TLR4, NF-κB, and INOS pathways. MATERIALS AND METHODS: 48 Wistar rats were randomly designated into six groups (n = 8). UC was induced via intra-rectal administration of 7% acetic acid (0.8 ml). SA at doses of 10, 25, 50 mg/kg was administrated through gavage, and dexamethasone (2 mg/kg) administrated intra-peritoneally for 5 consecutive days. The macroscopic and histopathological damages as well as expression of inflammatory and apoptotic genes along with superoxide dismutase (SOD) and catalase (CAT) activities, total antioxidant capacity (TAC), nitric oxide (NO), and malondialdehyde (MDA) levels in the colon tissue were assessed. RESULTS: UC led to an increase in the apoptotic and inflammatory genes, NO and MDA levels as well as decrease in TAC level, and SOD and CAT activities (p < 0.05). UC also caused severe damage, edema, inflammation, and necrosis in the colon. SA significantly reduced gene expressions of INOS, TLR4, IL-6, IL-1ß, NF-κB, Caspase-3, Caspase-8, and Bax. SA ameliorated negative macroscopic and histopathologic effects of UC. SA significantly reduced MDA and NO levels, and increased TAC level and CAT activity in the colon tissue in comparison to the UC rats without treatment (p < 0.05). CONCLUSION: SA via attenuation of the TLR4-NF-κB, NF-κB-INOS-NO pathways, oxidative stress, inflammation, and apoptosis of UC in rats.

Maternal separation stress through triggering of the neuro-immune response in the hippocampus induces autistic-like behaviors in male mice.

Autism spectrum disorder (ASD) is the fastest-growing neurodevelopmental disease throughout the world. Neuro-immune responses from prenatal to adulthood stages of life induce developmental defects in synaptic signaling, neurotransmitter imbalance, and even structural changes in the brain. In this study, we aimed to focus on the possible role of neuroinflammatory response in the hippocampus in development of the autistic-like behaviors following maternal separation (MS) stress in mice. To do this, mice neonates daily separated from their mothers from postnatal day (PND) 2 to PND 14 for 3 h. During PND45-60, behavioral tests related to autistic-like behaviors including three-chamber sociability, Morris water maze (MWM), shuttle box, resident-intruder, and marble burying tests were performed. Then, hippocampi were dissected out, and the gene expression of inflammatory mediators including TNF-α, IL-1ß, TLR4, HMGB1, and NLRP3 was assessed in the hippocampus using RT-PCR. Results showed that MS mice exerted impaired sociability preference, repetitive behaviors, impaired passive avoidance, and spatial memories. The gene expression of inflammatory mediators significantly increased in the hippocampi of MS mice. We concluded that MS stress probably via activating of the HMGB1/TLR4 signaling cascade in the hippocampus induced autistic-like behaviors in mice.

Anethole via increase in the gene expression of PI3K/AKT/mTOR mitigates the autistic-like behaviors induced by maternal separation stress in mice.

Autism spectrum disorder (ASD) is a neurodegenerative disease with increasing incidence in the world. The maternal separation (MS) stress at early life with its own neuroendocrine and neurostructural changes can provide the basis for development of ASD. Previously it has been reported neuroprotective characteristics for anethole. The PI3K/AKT/mTOR signaling pathway has pivotal role in the function of central nervous system (CNS). This study aimed to evaluate the possible effects of anethole on the autistic-like behaviors in the maternally separated (MS) mice focusing on the potential role of the PI3K/AKT/mTOR pathway. Forty male Naval Medical Research Institute (NMRI) mice were assigned to five groups (n = 8) comprising a control group (treated with normal saline) and four groups subjected to MS and treated with normal saline and or anethole at doses of 31.25, 62.5 and 125 mg/kg, respectively. All gents were administrated via intraperitoneal (i.p.) route for 14 constant days. Behavioral tests were conducted, including the three-chamber test, shuttle box and resident-intruder test. The gene expression of the PI3K, AKT and mTOR assessed in the hippocampus by qRT-PCR. Findings indicated that MS is associated with autistic-like behaviors. Anethole increased the sociability and social preference indexes in the three-chamber test, increased duration of secondary latency in the shuttle box test and decreased aggressive behaviors in the resident-intruder test. Also, anethole increased the gene expression of PI3K, AKT and mTOR in the hippocampus of MS mice. We concluded that anethole through increase in the gene expression of PI3K/ AKT/mTOR mitigated autistic-like behaviors induced by MS in mice.

The nephrotoxicity of Aristolochia rotunda L. in rats: Mitochondrion as a target for renal toxicity of Aristolochic acids-containing plants.

In recent years, there has been a growing trend in the usage of traditional medicine and herbal treatments. However, the misconception that they are completely safe resulted in irreversible complications and damages. The present study was conducted to investigate the potential renal toxicity of a commonly used drug in Iran's traditional medicine and pharmacy, known as Zaravand Gerd or Nokhod Alvand (Aristolochia rotunda L.). In Iranian traditional medicine, Zaravand Gerd is used as a remedy for respiratory system ailments, back pain, anxiety, headache and septic wounds. Fifty-six male rats were divided into seven groups (n = 8). The first group served as the control and received normal saline, while the second to seventh groups were administered varying doses of the aqueous extract of Zaravand Gerd (0.1, 0.5, 1.25, 2.5, and 5 g/kg) for a period of three weeks. Various parameters were measured to evaluate the potential kidney damage caused by the extract, including serum creatinine and BUN levels, as well as urine protein and glucose levels, which were analyzed using an autoanalyzer. Additionally, kidney tissue samples were examined pathologically, and mitochondria from the kidney tissue were isolated to assess mitochondrial parameters. The results of this study revealed that high doses of Zaravand Gerd extract led to a significant increase in urinary glucose and protein excretion compared to the control group. Pathological examination of the isolated kidney tissues indicated that the concentrations of 2.5 and 5 g/kg of Zaravand Gerd extract resulted in kidney damage and dilation of proximal convoluted tubules. Furthermore, the study demonstrated that high doses of the extract (2.5 and 5 g/kg) caused damage to the mitochondria. Based on the findings of this study, it can be concluded that the administration of high doses of Zaravand Gerd extract, which are not commonly used in traditional medicine, can have toxic effects on the kidneys in rats as an animal model. These results highlight the importance of considering the potential risks associated with herbal medicines and the necessity of usage based on scientific evidence.

Quinic acid ameliorates ulcerative colitis in rats, through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.

OBJECTIVE: In this study, the therapeutic effect of quinic acid (QA), which has anti-inflammatory activity, was investigated on acetic acid-induced colitis in male Wistar rats. METHODS: Ulcerative colitis (UC) was induced in rats by acetic acid intrarectally, and the protective effects of QA in 10, 30, 60, and 100 mg/kg doses were investigated. Rats were treated for 5 days and their colon tissues were dissected out at the end. Macroscopic and histopathological examinations were performed in colon tissues. Also, the expression of inflammatory and apoptotic genes, including TLR4, IL-1ß, INOS, IL-6, TNF-α, NF-κB, Caspase-3, Caspase-8, Bax, and Bcl-2, was measured. Biochemistry indices, such as malondialdehyde (MDA) and nitrite oxide (NO) content, in addition to, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and enzymes activities were also assessed. RESULTS: Colitis increased the levels of MDA and NO, and enhanced the inflammatory and apoptotic gene expressions, while reducing the SOD and CAT enzymes activity, and TAC levels in the colitis rats. Also, results showed that colitis was associated with the infiltration of inflammatory cells, epithelium damage, and edema in colon tissue. QA significantly ameliorated histopathological indices, oxidative stress, inflammation, and apoptosis in colitis rats. CONCLUSION: QA ameliorated UC through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways, which results in the reduction of colitis complications, including oxidative stress, inflammation, apoptosis and histopathological injuries in rats. Therefore it can be concluded, that QA exerts its therapeutic effects through antiapoptotic, antioxidant, and anti-inflammatory properties.

Ferulic acid ameliorates ulcerative colitis in a rat model via the inhibition of two LPS-TLR4-NF-κB and NF-κB-INOS-NO signaling pathways and thus alleviating the inflammatory, oxidative and apoptotic conditions in the colon tissue.

INTRODUCTION: Ulcerative colitis is a chronic inflammation of the colon. However, the common treatment for it is accompanied by many complications. Therefore, the present study was aimed to determine the ameliorative effects of ferulic acid on acetic acid-induced colitis in rat. MATERIALS AND METHODS: To induce ulcerative colitis, animals received 0.8 ml of 7% acetic acid intra-rectally. Ferulic acid in 20, 40, and 60 mg/kg doses was administered orally one hour after the ulcerative colitis induction. Animals received treatments for five consecutive days and then were euthanized on the sixth day. The colon was dissected out and macroscopic lesions were examined. Colon samples were evaluated for histopathological examination, biochemical analysis, determination of the expression of inflammatory, and apoptotic genes as well as total antioxidant capacity. RESULTS: Ferulic acid significantly inhibited inflammatory and apoptotic genes mRNA expression, also production of MDA and NO. Ferulic acid significantly increased the activity of antioxidant factors (TAC content, and SOD and CAT activity), thereby preventing inflammation and histopathological damage in the colon tissue of colitis rats. CONCLUSION: The results of the present study confirmed the antioxidant, anti-inflammatory, and anti-apoptotic properties of ferulic acid. About the mechanism of action of this compound, it can be concluded that the ability of ferulic acid in the amelioration of ulcerative colitis is related to the inhibition of two LPS-TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.

Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG.

In spite of the broad biological and also anticarcinogenic effects which have been reported for galbanic acid in various studies, its toxic effects are not still well characterized. The study was accomplished to evaluate the acute oral toxicity of galbanic acid pursuant to Organisation for Economic Co-operation and Development (OECD) TG No. 425. Female rats were received asafoetida extract and galbanic acid in distilled water by oral gavage. According to the existing information, limit test was done for aqueous extract of asafoetida and main test was done for galbanic acid. The animals were monitored for 2 weeks. Then under general anesthesia, the blood samples were obtained from the heart for biochemical and hematological assessment and the vital organs of rats were isolated for pathological evaluation. The results showed that although the Median lethal dose (LD50) of asafoetida extract was above the 2000 mg/kg body weight, the galbanic acid estimated LD50 was 310.2 mg/kg. There was no considerable change in body weight of vehicle and extract treated animals but in galbanic acid treated animals, the body weights were not normally increased. A significant rise was observed in high-density lipoprotein (HDL), (aspartate aminotransferase) AST and (alanine aminotransferase) ALT levels as well as in white blood cells (WBC), platelet and lymphocytes counts in galbanic acid group compared to vehicle and extract groups. Based on the obtained results, we suggest that although the asafoetida aqueous extract could be categorized as group 5 (LD50 > 2000 mg/kg), but galbanic acid estimated LD50 is about 310.2 mg/kg and toxicity signs also appeared in lung, liver enzymes and complete blood count (CBC) of galbanic acid treated animals.

The effect of infusion time on Echium amoenum extract -induced hepatotoxicity in vitro.

Echium amoenum is an annual herb native to the northern mountains of Iran which has medicinal application. Petals of Echium amoenum (Gole-Gavzaban) is one of the most valuable medicinal plants in Iranian folk medicine. The dry petals of E. amoenum have long been used as a sedative, tonic, anxiolytic and as a treatment for sore throat, cough and inflammation. Previous studies have shown that petals of E. amoenum contain four toxic pyrrolizidine alkaloids but conflicting results have been acquired in experimental studies investigating the hepatotoxicy of E. amoenum. However, the direct effect of E. amoenum on liver cells and the complete mechanisms of its possible cytotoxic effects toward these cells remain to be defined. The main aim of this study was to assay the mechanisms underlying the toxic effects of E. amoenum toward hepG2 cells. E. amoenum extract was obtained by infusion of dried petals in hot water (90 centigrade) for 15 or 30 min. Cell viability and mechanistic parameters were determined following 12 h incubation of hepG2 with E. amoenum extract that was obtained after 15 or 30 min infusion. The results indicated that E. amoenum extract exerts cytotoxic effects on hepG2 cells, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress.

Ellagic acid through attenuation of neuro-inflammatory response exerted antidepressant-like effects in socially isolated mice.

Recent studies have been demonstrated that neuroinflammation plays a crucial role in the pathophysiology of depression. Therefore, anti-inflammatory medications could be regarded as a potentially effective treatments for depression. Ellagic acid (EA) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study aimed to evaluate the antidepressant-like effect of EA in a mouse model of social isolation stress (SIS), considering its potential anti-neuroinflammatory properties. In this study, 48 male mice were divided into six groups (n = 8), including saline-treated control (socially conditioned (SC)) group and SIS (isolation conditioned (IC)) groups treated with saline or EA at doses of 12.5, 25, 50, and 100 mg/kg, respectively. Saline and EA were administrated intraperitoneally for 14 constant days. Immobility time in the forced swimming test (FST) and grooming activity time in the splash test were measured. The gene expression of inflammatory cytokines relevant to neuroinflammation was assessed in the hippocampus by real-time PCR. Results showed that SIS significantly increased immobility time in the FST and reduced grooming activity time in the splash test. In addition, the expression of inflammatory genes, including TNF-α, IL-1ß, and TLR4 increased in IC mice's hippocampi. Findings showed that EA decreased immobility time in the FST and increased grooming activity time in the splash test. Moreover, EA attenuated neuroimmune-response in the hippocampus. In conclusion, finding determined that EA, through attenuation of neuroinflammation in the hippocampus, partially at least, exerted an antidepressant-like effect in the mouse model of SIS.

The coumaric acid and syringic acid ameliorate acetic acid-induced ulcerative colitis in rats via modulator of Nrf2/HO-1 and pro-inflammatory cytokines.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes uncontrolled inflammation and ulcers in your digestive tract. The coumaric acid and syringic acid are phenolic derivative found in many fruits and vegetables and is widely recognized for the ability of anti-parasitic, anti-microbial, anti-viral, anti-inflammatory, and antioxidant. The purpose of this study was to investigate the anti-inflammatory and antioxidant properties of coumaric acid and syringic acid on acetic acid-induced colitis in rats. METHODS: A total of 64 male Wistar rats were divided into eight equal groups (n = 8). Colitis was induced by intrarectal administration of acetic acid, and rats orally received coumaric acid (100 and 150 mg/kg), syringic acid (10, 25, and 50 mg/kg), and dexamethasone (2 mg/kg) once per day for four days after colitis induction. Then, HO-1, Nrf2, and NQO1 mRNA expression were quantified by real time-PCR. Finally, the tissue levels of TNF-α and IL-1ß protein were measured by ELISA. RESULTS: Colitis led to a decrease in HO-1, Nrf2, and NQO1 mRNA expression and an increase in the tissue levels of TNF-α and IL-1ß protein in the colon tissue. Treatment with dexamethasone significantly increased HO-1, Nrf2, and NQO1 mRNA expression and decreased the tissue levels of TNF-α and IL-1ß protein compared to the UC group. Treatment with 150 mg/kg of coumaric acid and 50 mg/kg of syringic acid significantly increased HO-1, Nrf2, and NQO1 mRNA expression compared to the UC group. Also, treatment with 100 and 150 mg/kg of coumaric acid and 10, 25, and 50 mg/kg of syringic acid significantly decreased the tissue levels of TNF-α and IL-1ß protein compared to the UC group. CONCLUSION: The coumaric acid and syringic acid, especially at high doses, may be an alternative strategy for the treatment of UC by the reduction of TNF-α and IL-1ß levels and upregulation of the Nrf2/HO-1 pathway.

Anticonvulsant effect of quercetin in pentylenetetrazole (PTZ)-induced seizures in male mice: The role of anti-neuroinflammatory and anti-oxidative stress.

BACKGROUND: Epilepsy is one of the major neurological disorders. The inflammatory process and oxidative stress are closely related to seizure progression. Quercetin is a flavonoid with anti-inflammatory and antioxidant properties as well as neuroprotective effects. We aimed to evaluate the effect of quercetin on pentylenetetrazole- (PTZ-) induced seizures in male mice focusing on its possible anti-neuroinflammatory and anti-oxidative stress. METHODS: In this study, 50 male NMRI mice were divided into five groups (n = 10) and given the following treatments: normal saline, quercetin at doses of 10, 20, and 40 mg/kg, and diazepam at a dose of 10 mg/kg. In order to induce seizures, PTZ was administered intravenously. Drugs were administered intravenously 60 min before the seizure induction. The seizure threshold was measured, and finally, malondialdehyde (MDA), total antioxidant capacity (TAC), and the gene expression of IL-1ß, TNF-α, NLRP3, and iNOS were determined in the prefrontal cortex. RESULTS: It was confirmed that quercetin increased the seizure threshold. And quercetin increased TAC, and decreased levels of MDA as well as gene expression of TNF- α, NLRP3, IL-1ß, and iNOS in the prefrontal cortex at the time of seizure induction. CONCLUSION: It was suggested that the anticonvulsant effect of quercetin in PTZ-induced seizures in mice may be due to the reduction of inflammatory responses and oxidative stress in the prefrontal cortex.

Efficacy of Calcium Hydroxide/Saline versus Calcium Hydroxide/Artemisia persica Essential Oil as Intracanal Medicament to Improve Radiographic Visualization of Periapical Lesions in Necrotic Teeth: A Randomized Clinical Trial.

Objectives: This study aimed to compare the efficacy of calcium hydroxide (CH)/saline and CH/Artemisia persica (A. persica) essential oil as an intracanal medicament for radiographic resolution of periapical (PA) lesions in necrotic teeth. Materials and Methods: This randomized clinical trial was conducted on 22 patients with necrotic teeth and PA lesions presenting to two private endodontic offices. The patients were randomly divided into two groups (n = 11) to receive CH/saline (control group) and CH/A. persica essential oil (10%) (intervention group) as intracanal medicaments between treatment sessions. The size of PA radiolucency was measured on parallel PA radiographs taken before treatment and also at 1 and 3 months after completion of treatment. The mean time of healing of PA lesions was also compared between the two groups. Data were analyzed by the independent t-test, chi-square test, and Fisher's exact test (alpha = 0.05). Results: No significant difference was found between the two groups regarding the changes in the size of PA lesions, relative healing percentage, and speed of healing, neither at 1 nor at 3 months postoperatively (P > 0.05). Regarding the presence/absence of clinical symptoms in the second treatment session, the intervention group showed greater resolution of symptoms, although the difference did not reach statistical significance (P > 0.05). Conclusion: According to the present results, it appears that the addition of A. persica essential oil to CH for application as intracanal medicament does not add any particular advantage.

Implication of nitrergic system in the anticonvulsant effects of ferulic acid in pentylenetetrazole-induced seizures in male mice.

OBJECTIVES: Seizures are abnormal discharge of neurons in the brain. Ferulic acid (FA) is a phenolic compound with antioxidant and neuroprotective effects. The present study aimed to investigate the role of the nitrergic system in the anticonvulsant effect of FA in pentylenetetrazol (PTZ)-induced seizures in male mice. METHODS: 64 male Naval Medical Research Institute (NMRI) mice weighing 25-29 g were randomly divided into eight experimental groups (n=8). FA at doses 5, 10, and 40 mg/kg alone and in combination with L-nitro-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) or L-arginine (L-arg) (nitric oxide [NO] precursor) was administrated (intraperitoneal). PTZ was injected (i.v. route) 30 min after drugs administration (1 mL/min). Seizure onset time was recorded and the nitrite levels of prefrontal cortex and serum were determined by the Griess method. RESULTS: FA at doses of 10 and 40 mg/kg significantly increased the seizure threshold as well as reduced the serum and brain NO levels in comparison to the saline-received group. Co-administration of the effective dose of FA (10 mg/kg) plus L-arg significantly decreased the seizure threshold in comparison to the effective dose of FA alone. Co-injection of the sub-effective dose of FA (5 mg/kg) with L-NAME significantly increased the seizure threshold as well as significantly decreased the brain NO level in comparison to the sub-effective dose of FA alone. CONCLUSIONS: We showed that the nitrergic system, partially at least, mediated the anticonvulsant effect of FA in PTZ-induced seizures in mice. We concluded that L-NAME potentiated while L-arg attenuated the anticonvulsant effect of FA.

Umbelliprenin via increase in the MECP2 and attenuation of oxidative stress mitigates the autistic-like behaviors in mouse model of maternal separation stress.

Introduction: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition. Maternal separation (MS) stress is an early-life stress factor associated with behaviors resembling Autism. Both MECP2 and oxidative stress are implicated in the pathophysiology of Autism. Umbelliprenin (UMB) is a coumarin compound with various pharmacological properties. Our study aimed to investigate the potential effects of UMB in mitigating autistic-like behaviors in a mouse model subjected to MS stress, focusing on probable alterations in MECP2 gene expression in the hippocampus. Methods: MS paradigm was performed, and mice were treated with saline or UMB. Behavioral tests consisting of the three-chamber test (evaluating social interaction), shuttle box (assessing passive avoidance memory), elevated plus-maze (measuring anxiety-like behaviors), and marble-burying test (evaluating repetitive behaviors) were conducted. Gene expression of MECP2 and measurements of total antioxidant capacity (TAC), nitrite level, and malondialdehyde (MDA) level were assessed in the hippocampus. Results: The findings demonstrated that MS-induced behaviors resembling Autism, accompanied by decreased MECP2 gene expression, elevated nitrite, MDA levels, and reduced TAC in the hippocampus. UMB mitigated these autistic-like behaviors induced by MS and attenuated the adverse effects of MS on oxidative stress and MECP2 gene expression in the hippocampus. Conclusion: In conclusion, UMB likely attenuated autistic-like behaviors caused by MS stress, probably, through the reduction of oxidative stress and an increase in MECP2 gene expression.

Oral microbiota in cancer: could the bad guy turn good with application of polyphenols?

The human oral cavity is comprised of dynamic and polynomial microbes which uniquely reside in the microenvironments of oral cavities. The cumulative functions of the symbiotic microbial communities maintain normal homeostasis; however, a shifted microbiota yields a dysbiosis state, which produces local and systemic diseases including dental caries, periodontitis, cancer, obesity and diabetes. Recent research reports claim that an association occurs between oral dysbiosis and the progression of different types of cancers including oral, gastric and pancreatic ones. Different mechanisms are proposed for the development of cancer, such as induction of inflammatory reactions, production of carcinogenic materials and alteration of the immune system. Medications are available to treat these associated diseases; however, the current strategies may further worsen the disease by unwanted side effects. Natural-derived polyphenol molecules significantly inhibit a wide range of systemic diseases with fewer side effects. In this review, we have displayed the functions of the oral microbes and we have extended the report regarding the role of polyphenols in oral microbiota to maintain healthy conditions and prevention of diseases with emphasis on the treatment of oral microbiota-associated cancer.

Plant based food bioactives: A boon or bane for neurological disorders.

Neurological disorders are the foremost occurring diseases across the globe resulting in progressive dysfunction, loss of neuronal structure ultimately cell death. Therefore, attention has been drawn toward the natural resources for the search of neuroprotective agents. Plant-based food bioactives have emerged as potential neuroprotective agents for the treatment of neurodegenerative disorders. This comprehensive review primarily focuses on various plant food bioactive, mechanisms, therapeutic targets, in vitro and in vivo studies in the treatment of neurological disorders to explore whether they are boon or bane for neurological disorders. In addition, the clinical perspective of plant food bioactives in neurological disorders are also highlighted. Scientific evidences point toward the enormous therapeutic efficacy of plant food bioactives in the prevention or treatment of neurological disorders. Nevertheless, identification of food bioactive components accountable for the neuroprotective effects, mechanism, clinical trials, and consolidation of information flow are warranted. Plant food bioactives primarily act by mediating through various pathways including oxidative stress, neuroinflammation, apoptosis, excitotoxicity, specific proteins, mitochondrial dysfunction, and reversing neurodegeneration and can be used for the prevention and therapy of neurodegenerative disorders. In conclusion, the plant based food bioactives are boon for neurological disorders.

Effects of Hyssopus Officinalis Hydroalcoholic Extract on Pentylenetetrazol-Induced Convulsive Seizures in Rat.

Hyssopus officinalis L. is one of the most important medicinal plants in traditional medicine used to treat seizures. In this study, we assessed the effects of H. officinalis hydroalcoholic extract against pentylenetetrazol (PTZ)-induced seizures in rat. The anti-seizure activity of the extract was assessed in three doses of 25, 50, and 100 mg/kg. Kindling was induced by intraperitoneal injection of PTZ (35 mg/kg) every 48 h, and H. officinalis extract was administered daily and behavioral tests performed. The possible involvement of GABA receptors in the extract activity was investigated using flumazenil. Tonic seizure threshold and mortality rate were measured following intraperitoneal injection of 60 mg/kg PTZ on the 14th day, following 14 days administration of H. officinalis hydroalcoholic extract. Blood and hippocampus samples were prepared to measure brain and serum antioxidant capacity, malondialdehyde (MDA), and nitric oxide (NO). Finally, the expression of GABA receptor gene in brain tissue was investigated. H. officinalis extract increased tonic seizure threshold and decreased mortality due to PTZ. Flumazenil, as a GABA receptor antagonist, reduced the tonic seizure threshold. Extract treatment significantly improved memory and learning, increased brain antioxidant capacity, decreased brain MDA and NO in kindled rats. It also increased GABA receptor gene expression in pre-treated groups compared to the negative control group. H. officinalis extract probably exerts potential antiepileptic effects through the GABAergic system. Also, H. officinalis extract has a supportive effect against hippocampal neuronal damage and improves memory and learning in kindled rats.

Coumaric acid ameliorates experimental colitis in rats through attenuation of oxidative stress, inflammatory response and apoptosis.

OBJECTIVE: Due to the high side effects of commonly used drugs and according to the pharmacological properties reported for coumaric acid (CA), this study was designed to determine the impact of CA on acetic acid-induced colitis in rats, considering its possible anti-inflammatory, antioxidant, and anti-apoptotic properties. MATERIALS AND METHODS: Forty-eight male Wistar rats were divided into 6 equal groups (n = 8). Colitis was induced by acetic acid intrarectally. CA in three different doses (50, 100, and 150 mg/kg) was administrated for 5 days. Finally, the macroscopic and histopathological changes in the colon tissue were examined. The expression of inflammatory and apoptotic genes, including NF-κB, TNF-α, INOS, IL-1ß, IL-6, TLR4, Caspase-3, Caspase-8, Bax, Bcl-2 was assessed. In addition, changes in the levels of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrite, and total antioxidant capacity (TAC) were measured in the colon tissue. RESULTS: Colitis led to a decrease in TAC and the activity levels of CAT and SOD and an increase in the expression of inflammatory and apoptotic genes, MDA, and nitrite levels in the colon. Colitis was also associated with edema and severe damage to the epithelium, infiltration of inflammatory cells, and the presence of ulcers and necrosis in the colon tissue. CA significantly improved the inflammation, oxidative stress, apoptosis, and histopathological indices caused by acetic acid-induced colitis on the colon. CONCLUSION: It is concluded that CA probably exerts its positive effects in the management of colitis, through its anti-inflammatory, antioxidant, and anti-apoptotic properties.