Exploring the multifaceted neuroprotective actions of gallic acid: a review

Much attention has been recently given to the effect of diet compounds on physical and mental health. Gallic acid is a phenolic compound with antioxidant activity. This compound is widely presented in black tea leaves, green tea, apples, grapes, strawberries, and pineapples. During the past years, it has been reported that gallic acid is effective against nervous system's disorders including Alzheimer's disease, Parkinson's disease, ischemia, and reperfusion, depression and anxiety. These indicate that gallic acid can be considered as a valuable agent for nutraceutical interventions. In this study, several clinical studies suggested that gallic acid can improve human health by preventing or delaying the onset of neurological diseases. The present study indicated the neuroprotective features of gallic acid including the pre-clinical evidence for its effects in AD and PD and other diseases related to the nervous system. Significant efforts are required to confirm the neuroprotective effects of gallic acid in treating the diseases related to the nervous system. Keywords:Gallic acid; neurodegenerative diseases; Parkinson; psychiatric disorder

Medicinal plants: Past history and future perspective

Human societies have been in close contact with their environments since the beginning of their formation and used the ingredients of the environment to obtain food and medicine. Awareness and application of plants to prepare food and medicine have been realized through trial and error, and gradually human became able to meet his needs from his surroundings. Information about medicinal plants has long been transmitted gradually and from generation to generation, a human knowledge has gradually become complete with the formation of civilizations and the provision of more facilities. Medicinal plants are used as a medical resource in almost all cultures. Ensuring the safety, quality and effectiveness of medicinal plants and herbal drugs very recently became a key issue in industrialized and developing countries. By standardizing and evaluating the health of active plant-derived compounds, herbal drugs can help the emergence of a new era of the healthcare system to treat human diseases in the future. Awareness of traditional knowledge and medicinal plants can play a key role in the exploitation and discovery of natural plant resources. In order to maintain this knowledge, comprehensive approach and collaboration are needed to maintain historical records on medicinal plants and use these resources in favour of human beings, before they are destroyed forever. Therefore, this review was conducted to investigate and describe the process of using medicinal plants throughout history. This review focuses on the recent various important challenges in quality evaluation of medicinal plants in the authenticity, efficacy, toxicity and consistenc

Progesterone exerts antidepressant-like effect in a mouse model of maternal separation stress through mitigation of neuroinflammatory response and oxidative stress

Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1 beta, TNF-alpha, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects

Comparison effects of olive leaf extract and oleuropein compounds on male reproductive function in cyclophosphamide exposed mice

Spermatogenesis is a complicated process in which sperm is susceptible to various chemotherapy drugs such as cyclophosphamide (CP). As olive leaf extract (OLE) and its active ingredient, oleuropein, have variousantioxidant, anti-apoptotic, and anti-inflammatory properties the aim of the present study was to investigate the effects of OLE and oleuropein on male reproductive function focusing antioxidative effects and histological modifications in the testes of CP-exposed mice. In order to do this, 80 NMRI male mice were divided into eight groups including control group, group received CP, group received OLE, group received oleuropein, group received OLE following CP exposure, group received oleuropein following CP exposure, group received OLE plus oleuropein and group received OLE plus oleuropein following CP exposure. In all groups CP (single dose of 100 mg/kg (, OLE (100 mg/kg for consequence 28 days) and oleuropein (100 mg/kg for consequence 28 days) were injected intraperitoneally. Moreover, testis histology, sperm parameters and serum levels of LH, FSH, MDA and antioxidant capacity were investigated. Results showed that CP caused oxidative state and abnormal changes in sperms and testes. Besides, treatments with oleuropein and OLE led to mitigate the harmful effects of CP on the male reproductive system. In conclusion, our findings showed that olive's compounds can diminish the hazardous effects of CP on spermatogenesis in mice. Keywords: Spermatogenesis, Olive leaf extract, CyclophosphamideMice, Oleuropein, Cell biology, Plant biology, Pharmaceutical science, Pathophysiology, Laboratory medicin

Entinociceptive effects of Euphorbia helioscopia extract on Balb/c mice

Background and aims: Euphorbia helioscopia has multiple pharmacological activities, such as antibacterial, antiviral, antifungal,anticancer and/or antitumor, allelopathic, anti-allergic and anti-asthmatic, antioxidant, antinociceptive effect. The aim of the study was to evaluate the antinociceptive activities of Euphorbia helioscopia extract in Balb/c mice, as well as the total flavonoids, phenolic contents, and antioxidant activities of the extract. Methods: In this study, 90 Balb/c mice were randomly designated into 9 groups. Group 1 received normal saline, groups 2 to 7 received different doses of the E. helioscopia hydroethanolic extract (i.e., 0.05, 0.1, 0.2, 0.4, 2, & 8 mg/kg, i.p.).In addition, groups 8 and 9 received naloxone (1 mg/kg) and extract (8 mg/kg) plus naloxone (1 mg/kg), respectively (Naloxone was injected 15 minutes after extract administration). Then, pain response was evaluated for 30 minutes after the injection of 20 µL formalin (1.5%) in the plantar surface of the mice foot. Further, the beta-carotene-linoleate method was used for measuring antioxidant capacity. Finally, total phenolic and flavonoid content were measured based on Folin-Ciocalteu colorimetric and aluminum chloride colorimetric methods, respectively. Results: Total phenol and flavonoid content were 49.43 ± 1.8 mg GAE/g dried extract and 30.19 ± 1.96 mg rutin/g dried extract, respectively. Our results showed that during the first 5 minutes (the acute pain step), a significant difference (P<0.05) was observed between the control group and the group which received the E. helioscopia hydroethanolic extract (8 mg/kg). In the next 25 minutes (the chronic pain step), a significant difference (P<0.05) was found between the control group and the group which received 0.1 and 8 mg/kg doses of the extract. Based on the results, naloxone was unable to reverse the antinociceptive effects of the extract and the maximum antioxidant activity of the extract was 1.641 mg/g of rutin equivalent. Conclusion: In general, this study supports the use of the E. helioscopia extract in folk medicine as the analgesic agent and calls for further investigations regarding elucidating its mechanism of action. Eventually, our findings revealed that the extract of E. helioscopia possessed either antinociceptive or anti-oxidative activities. Keywords: Euphorbia helioscopia, Pain, Mice, Formalin test, Antioxidant activit

Phytotherapy in treatment of Parkinson's disease: a review.

Context: Parkinson's disease (PD) is a neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra (SN) in the midbrain. PD leads to certain motor disorders including resting tremor, muscle stiffness and slow movement. Medicinal plants have shown positive pharmacological effects in treating different models of PD. Objective: Tendency to use natural products, especially plants, for the treatment of PD has been growing. This article reviews the basic aspects of medicinal plants and their bioactive compounds that could be used to treat PD. Methods: Reliable articles indexed in databases ISI, SID, PubMed, PubMed Central, Scopus and Web of Science were used. A total of 12 plant-derived active ingredients and 18 herbal extracts were included. Different compounds have so far been isolated from plants that affect PD especially by targeting pathways associated with the pathogenesis of the disease. Results: Although some herbal extracts such as Hibiscus asper Hook. f. (Malvaceae), Ginkgo biloba L. (Ginkgoaceae), Carthamus tinctorius L (Asteraceae) and certain active ingredients, such as berberine and curcumin, have shown positive effects in animal models of PD, potential active ingredients and mechanisms of action should be investigated in additional studies. Discussion and conclusions: Despite the wide variety of plants in the world, a limited number of them have been studied for anti-Parkinsonian activity, and therefore, there are numerous perspectives in this field for future studies on plants and their bioactive compounds. KEYWORDS: ; Dopaminergic receptors; L-DOPA; curcumi

Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation

Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

Objectives: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI). Materials and Methods: In this study four groups (n = 6-8) of rats were used as follows: Sham, CCI, CCI + minocycline (MIN) 10 mg/Kg (IP) and CCI + MIN 30 mg/Kg (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV) assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx) were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress

Implication of NMDA-NO pathway in the antidepressant-like effect of ellagic acid in male mice

Depression is one the common psychiatric disorders through the world. Nitric oxide (NO) and N-methyl-d-aspartate receptor (NMDA-R) are involved in the pathophysiology of depression. Previous studies have been reported various pharmacological properties for ellagic acid (EA). We aimed to evaluate possible involvement of NMDA-NO pathway in the antidepressant-like effect of EA. To do this, we used relevant behavioral tests to evaluate depressive-like behavior. In order to find effective and sub-effective doses of agents, mice treated with EA (6.25, 12.5, 25, 50 and 100 mg/kg), L-NAME (5 and 10 mg/kg), L-arg (25 and 50 mg/kg), NMDA (75 and 150 mg/kg) and ketamine (0.25 and 0.5 mg/kg). Furthermore, mice were treated with combination of sub-effective dose of EA plus sub-effective doses of L-NAME and/or ketamine as well as treated with effective dose of EA in combination of effective doses of L-arg and/or NMDA. Level of NO and gene expression of NR2A and NR2B subunits of NMDA-R were assessed in the hippocampus. Results showed that EA dose dependently provoked antidepressant-like effects and also decreased the hippocampal NO level as well as expression of NMDA-Rs. Co-administration of sub-effective doses of L-NAME or ketamine with sub-effective dose of EA potentiated the effect of EA on behaviors, NO level as well as NMDA-Rs gene expression in the hippocampus. However, co-treatment of effective dose of EA with effective doses of L-arg or NMDA mitigated effects of EA. In conclusion, our data suggested that NMDA-NO, partially at least, are involved in the antidepressant-like effect of EA

Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test.

Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01 and 0.1µg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001µg/kg) with subeffective dose of l-NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron-treated mice compared with saline-injected mice. Also, co-administration of 7-nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO-cGMP pathway