The Effects of Urolithin B and Auraptene on Quinolinic Acid-induced Toxicity in the SH-SY5Y Neuroblastoma Cell Line.

The pathological accumulation of quinolinic acid (QA) is often associated with neuritis and neuronal cell death in several neurodegenerative diseases, through the overproduction of free radicals. Urolithin B and auraptene have been reported to exert potent antioxidant effects - however, little is known about the protective effects of these compounds against QA-induced neurotoxicity. Therefore, this study aimed to explore the in vitro protective effects of urolithin B and auraptene against QA-induced neurotoxicity in the SH-SY5Y neuroblastoma cell line. The MTT assay was used to evaluate cell viability, and flow cytometry was carried out to evaluate effects on the cell cycle and apoptosis. The intracellular levels of reactive oxygen species (ROS) were also determined. Our findings showed that auraptene at non-toxic concentrations had no protective effect on QA-induced toxicity. However, urolithin B at concentrations of 0.6 µM and 2.5 µM enhanced the viability of cells treated with QA. Moreover, while the percentage of apoptotic cells (i.e. in the sub-G1 phase) was shown to significantly increase after QA treatment, pre-treatment with urolithin B reduced the number of these apoptotic cells. Furthermore, urolithin B, as an antioxidant, also significantly reduced QA-induced ROS production. Our findings suggest that urolithin B may possess potent antioxidant and neuroprotective effects against QA-induced neurotoxicity that merit further investigation.

The possible role of pedunculopontine tegmental nucleus (PPT) opioid receptors in the cardiovascular responses in normotensive and hemorrhagic hypotensive rats.

BACKGROUND: The pedunculopontine tegmental nucleus (PPT) is involved in cardiovascular regulation. The presence of mu (µ) opioid receptors in the PPT nucleus has been determined. In the present study, the role of this nucleus in normotensive conditions and then the role of these receptors on cardiovascular function in hypotension induced by hemorrhage (HEM) were investigated. METHOD: Animals were divided into the following groups: Group 1: control, Group 2: HEM, Group 3: morphine at dose 100 nmol (a general opioid receptor agonist), Group 4: naloxone at dose 100 nmol (a general opioid receptor antagonist), Group 5: morphine + HEM, and Group 6: naloxone + HEM. After anesthesia, two femoral arteries were cannulated to record the cardiovascular parameters and blood withdrawal. Two minutes after induction of HEM, drugs were injected into the nucleus, and cardiovascular parameters were measured. Changes (Δ) in cardiovascular responses due to drug injection and HEM were calculated and compared to control and HEM groups. RESULTS: HEM significantly reduced changes in systolic and mean arterial pressures and increased heart rate changes compared to control. Morphine microinjection in normotensive and HEM rats significantly decreased systolic blood pressure, mean arterial pressure, and heart rate, and naloxone significantly increased all these parameters. CONCLUSION: This study showed that the PPT nucleus plays a role in modulating the cardiovascular responses induced by HEM. The µ opioid receptor of the PPT nucleus in the normotensive and HEM rats have inhibitory effects on blood pressure and heart rate mainly, and these effects are eliminated by naloxone microinjection.

Cardiovascular responses induced by the activation of muscarinic receptors of the pedunculopontine tegmental nucleus in anesthetized rats.

BACKGROUND: The cardiovascular effects of nicotinic receptors of cholinergic system in the pedunculopontine tegmental nucleus (PPT) were shown. OBJECTIVE: In the following, the cardiovascular effects of the muscarinic receptor, another receptor in this system, were examined. METHODS: Rats were divided into eight groups: 1) control; 2 and 3) Ach (acetylcholine, an agonist) 90 and 150 nmol; 4 and 5) Atr (atropine; a muscarinic antagonist) 3 and 9 nmol; 6) Atr 3 + Ach 150; 7) Atr 9 + Ach 150; and 8) Atr 3 + hexamethonium (Hexa; 300 nmol) + Ach 150. After anesthesia, cannulation of the femoral artery was performed, and then the mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were recorded using a power lab apparatus. RESULTS: Following drug microinjection, the maximum change (Δ) in MAP, SBP, and HR was calculated and analyzed. Both doses of Ach (90 and 150) significantly decreased ΔMAP and ΔSBP but could not change ΔHR. Neither of the doses of Atr significantly affected ΔMAP, ΔSBP, and ΔHR. Co-injection of Atr 3 + Ach 150 only increased ΔHR, but Atr 9 + Ach 150 decreased ΔMAP and ΔSBP than Ach 150 alone. The effect of the co-injection of Atr 9 + Hexa 300 + Ach 150 was also the same as the Atr 9 + Ach 150 group. CONCLUSION: The present results revealed that cholinergic muscarinic receptors in the PPT have an inhibitory effect on MAP and SBP with no important effect on HR.

The testicular protective effects of standardised hydroalcoholic extract of Ziziphus jujuba Mill against adriamycin-induced toxicity.

In this study, because of the anti-inflammatory and antioxidant effect of the Ziziphus jujuba (ZJ), we assessed the protective properties of the ZJ extract against testis toxicity caused by Adriamycin in the rat. Twenty rats were grouped into (a) control, (b) Adriamycin, (c) ZJ group and (d) treatment group in which Adriamycin was administrated and the ZJ hydroalcoholic extract was used for three weeks. On the 21st day, two testes were removed to determine the oxidation markers and pathological evaluation. The levels of sex hormones were determined. Epididymis also was crushed, and its spermatozoa were evaluated as concentration, motility and normality. Adriamycin increased oxidative stress markers as well as Luteinising hormone, and follicle-stimulating hormone and decreased testosterone levels compared to control. In the treated group, the levels of the above markers improved. The decreased number and motility of spermatozoa in treatment group increased, and the increased rate of abnormal spermatozoa in this group decreased. Pathological evaluations also show the healing process of damaged testicular tissue in the group receiving the ZJ extract. The ZJ extract relatively improves oxidative stress, sperm characteristics, hormonal alternation and pathological changes. These findings reveal the probable role of ZJ effective compounds in repairing tissue damage.

Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of Rhus coriaria L. (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.

Effect of Aqueous and Ethyl Acetate Fractions of Ziziphus jujuba Mill Extract on Cardiovascular Responses in Hypertensive Rats.

BACKGROUND: Ziziphus jujuba Mill (ZJ) is a plant with anti-hypertensive property. In this regard, the present study investigated the effect of aqueous and ethyl acetate fractions of ZJ extract on acute hypertension (HTN) induced by nitro-L-arginine methyl ester (L-NAME). METHODS: The current study was carried on 49 hypertensive rats divided into seven groups, including i) control; ii) L-NAME (10 mg/kg); iii) sodium nitroprusside (SNP) (50 µg/kg) plus L-NAME; iv and v) aqueous fraction of ZJ (150 mg/kg and 300 mg/kg) plus L-NAME; vi) and vii) ethyl acetate fractions of ZJ (150 mg/kg and 300 mg/kg) plus L-NAME. The rats were orally treated with both fractions for four weeks and received intravenous L-NAME on the 28th day. The mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (HR) of the rats were recorded then maximal changes (Δ) of MAP, SBP and HR were calculated and compared with changes of control and L-NAME. RESULTS: According to the obtained results of the present study, it was shown that the administration of L-NAME significantly increased ΔMAP, ΔSBP and ΔHR, and these effects were significantly attenuated by administration of SNP. The pre-treatment with both doses (150 mg/kg and 300 mg/kg) of aqueous and ethyl acetate fractions could significantly reduce cardiovascular responses induced by L-NAME that comparable with SNP. However, a lower dose of aqueous fractions and higher dose of ethyl acetate fractions were reported with stronger effects. CONCLUSION: The results of the current study showed that both the aqueous and ethyl acetate fractions of ZJ through the effect on nitric oxide system can prevent the development of HTN induced by L-NAME.

Anti-Hypolipidemic and Anti-Oxidative Effects of Hydroalcoholic Extract of Origanum majorana on the Hepatosteatosis Induced with High-Fat Diet in Rats.

INTRODUCTION: The aim of the current study is to evaluate the antihyperlipidemic and anti-oxidative effects of hydro-alcoholic extract of marjoram (HAEM) in rats fed with a high-fat diet (HFD). METHODS: In the experimental study, the rats were randomly divided into four groups of five rats in each and fed with high-fat diet for 12 weeks as follows: One group (normal diet group) was fed with a standard diet, one group was fed with HFD, and two groups were fed with HFD and orally fed with 150 and 450 mg/kg/day HAEM. The serum samples and liver tissues were used for measuring the biochemical and oxidative parameters and histopathological studies. HFD induced hepatosteatosis in rats as evidenced by the altered liver enzymes activity, serum lipid profile and oxidative status. RESULTS: Serum lipid profile (triglyceride, cholesterol and low-density lipoprotein) in rats fed with HFD + HAEM (150 and 450 mg/kg/day) was significantly decreased. Furthermore, the evaluation of oxidative stress showed a reduction of the malondialdehyde (MDA) level and an increase in ferric-reducing anti-oxidant power. Meanwhile, liver enzyme activities declined in response to HAEM. CONCLUSION: Using the HAEM could be a future therapeutic agent in treating hepatosteatosis and reducing oxidative damages of HFD in the liver.

Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root.

Traditionally, people use harvested Ferula gummosa for medicinal purposes. However, no information about its safety and toxicity is available. In the present study, the toxicological profile of sub-chronic oral administration of hydroalcoholic extract of F. gummosa radix is evaluated in rats. The extract was orally administrated at 100 and 600 mg/kg to male rats for 28 days. After 28 days, clinical signs, mortality, body weights, food and water consumption, organ weights, hematology, serum biochemistry, as well as histopathological and neurobehavioral changes were examined. Also, the sedative effect of this extract was evaluated in mice at the doses of 100, 600, and 800 mg/kg. Its cytotoxicity against human stroma-vascular cells and human renal epithelial cells were also evaluated. No lethality or adverse toxic signs were seen during the experimental period. There were no significant changes in body and organ weights, hematology, serum biochemistry, and histopathological examination. The extract decreased the rotarod performance, but did not increase pentobarbital-induced hypnosis. Also, F. gummosa extract significantly decreased cell viability at the concentrations of higher than 400 µg/mL. In conclusion, the sub-chronic toxicity study of F. gummosa hydroalcoholic extract demonstrated the extract to be safe for the tested dosage and route of administration.

Evaluating the strengths and weaknesses of large language models in answering neurophysiology questions.

Large language models (LLMs), like ChatGPT, Google's Bard, and Anthropic's Claude, showcase remarkable natural language processing capabilities. Evaluating their proficiency in specialized domains such as neurophysiology is crucial in understanding their utility in research, education, and clinical applications. This study aims to assess and compare the effectiveness of Large Language Models (LLMs) in answering neurophysiology questions in both English and Persian (Farsi) covering a range of topics and cognitive levels. Twenty questions covering four topics (general, sensory system, motor system, and integrative) and two cognitive levels (lower-order and higher-order) were posed to the LLMs. Physiologists scored the essay-style answers on a scale of 0-5 points. Statistical analysis compared the scores across different levels such as model, language, topic, and cognitive levels. Performing qualitative analysis identified reasoning gaps. In general, the models demonstrated good performance (mean score = 3.87/5), with no significant difference between language or cognitive levels. The performance was the strongest in the motor system (mean = 4.41) while the weakest was observed in integrative topics (mean = 3.35). Detailed qualitative analysis uncovered deficiencies in reasoning, discerning priorities, and knowledge integrating. This study offers valuable insights into LLMs' capabilities and limitations in the field of neurophysiology. The models demonstrate proficiency in general questions but face challenges in advanced reasoning and knowledge integration. Targeted training could address gaps in knowledge and causal reasoning. As LLMs evolve, rigorous domain-specific assessments will be crucial for evaluating advancements in their performance.

Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats.

Gold nanoparticles (AuNPs) have unique features that might lead to the development of a new class of diabetic medicines. AuNPs were biosynthesized utilizing sodium-alginate. UV-Vis-spectroscopy, Fourier transforms infrared, field emission scanning electron microscopy (FESEM), and energy dispersive X-ray were used to examine the particles. The potential of AuNPs for improving the diabetes condition was examined along with swimming in rats. FESEM image revealed the spherical morphology with an average particle size of 106.6 ± 20.8 nm. In the diabetic group, serum glucose, blood urea nitrogen (BUN), creatinine, cholesterol, and triglyceride (TG) levels were significantly higher than the control group. Low-density lipoprotein (LDL) was significantly higher and high-density lipoprotein (HDL) was significantly lower in the diabetic group compared to the control group. Malondialdehyde (MDA) levels were also significantly higher in the D group. However, in the groups treated with swimming and gold, these parameters were significantly improved. Specifically, serum-glucose, BUN, creatinine, cholesterol, and TG levels were significantly reduced, while LDL was significantly decreased in the diabetic + swimming + AuNPs group and HDL was significantly increased in the diabetic + AuNPs group. MDA levels were significantly decreased in the treated groups, and other antioxidants were significantly improved in the diabetic + swimming + AuNPs group. Catalase levels were also significantly improved in the D + gold group. It can be concluded that both AuNPs and swimming can decrease diabetic complications.

Propolis and its therapeutic effects on renal diseases: A review.

Propolis is produced by bees using a mixture of bees wax and saliva. It contains several bioactive compounds that mainly induce anti-oxidant and anti-inflammatory effects. In this review, we aimed to investigate the effects of propolis on kidney diseases. We used "Kidney", "Disease", "Propolis", "Renal", "Constituent", "Mechanism", "Infection", and other related keywords as the main keywords to search for works published before July 2023 in Google scholar, Scopus, and Pubmed databases. The search terms were selected according to Medical Subject Headings (MeSH). This review showed that propolis affects renal disorders with inflammatory and oxidative etiology due to its bioactive compounds, mainly flavonoids and polyphenols. There have been few studies on the effects of propolis on kidney diseases; nevertheless, the available studies are integrated in this review. Overall, propolis appears to be effective against several renal diseases through influencing mechanisms such as apoptosis, oxidative balance, and inflammation.

Antihypertensive and Antioxidant Effects of an Aqueous Extract of Asafetida in Renovascular Hypertensive Rats.

Recently, the effect of an aqueous extract of asafetida on acute angiotensin II hypertensive rats was evaluated. The present study evaluated the antihypertensive and antioxidant effects of asafetida on a rat model of renovascular hypertension (RVH) using four groups. RVH was induced by clipping the renal artery; the sham group underwent surgery but without clipping. The RVH rats received losartan (Los, an AT1 receptor antagonist) or asafetida by gavage for 4 weeks. On the 28th day, the femoral artery was cannulated, and the systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Finally, the levels of superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol content in the kidney and heart tissues were measured. In RVH rats, SBP and MAP significantly increased compared with the control. Los and the extract significantly reduced the changes in SBP, MAP, and HR that were induced in the RVH rats (P <0.05-0.001). In RVH rats, levels of MDA significantly increased and the content of total thiol and SOD decreased in both the heart and kidney tissues. Los plus the extract significantly decreased MDA and increased total thiol and SOD in the heart and kidney tissues. We concluded that an aqueous extract of asafetida gum has antihypertensive and antioxidant effects in the RVH rat model. The effect of the extract is similar to that of Los, which suggests that this effect of asafetida is mediated via an effect on the angiotensin Type I receptor.

Effect of the cholinergic system of the lateral periaqueductal gray (lPAG) on blood pressure and heart rate in normal and hydralazine hypotensive rats.

Objectives: Due to the presence of the cholinergic system in the lateral periaqueductal gray (lPAG) column, the cardiovascular effects of acetylcholine (ACH) and its receptors in normotensive and hydralazine (HYD) hypotensive rats in this area were evaluated. Materials and Methods: After anesthesia, the femoral artery was cannulated and systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and also electrocardiogram for evaluation of low frequency (LF) and high frequency (HF) bands, important components of heart rate variability (HRV), were recorded. ACH, atropine (Atr, a muscarinic antagonist), and hexamethonium (Hex, an antagonist nicotinic) alone and together microinjected into lPAG, changes (Δ) of cardiovascular responses and normalized (n) LF, HF, and LF/HF ratio were analyzed. Results: In normotensive rats, ACH decreased SBP and MAP, and enhanced HR while Atr and Hex did had no effects. In co-injection of Atr and Hex with ACH, only ACH+Atr significantly attenuated parameters. In HYD hypotension, ACH had no affect but Atr and Hex significantly improved the hypotensive effect. Co-injection of Atr and Hex with ACH decreased the hypotensive effect but the effect of Atr+ACH was higher. In normotensive rats, ACH decreased nLF, nHF, and nLF/nHF ratio. These parameters in the Atr +ACH group were significantly higher than in ACH group. In HYD hypotension nLF and nLF/nHF ratio increased which was attenuated by ACH. Also, Atr+ACH decreased nLF and nLF/nHF ratio and increased nHF. Conclusion: The cholinergic system of lPAG mainly via muscarinic receptors has an inhibitory effect on the cardiovascular system. Based on HRV assessment, peripheral cardiovascular effects are mostly mediated by the parasympathetic system.

Anti-inflammatory, immunomodulatory and anti-oxidant effects of Ocimum basilicum L. and its main constituents: A review.

Ocimum basilicum L. (O. basilicum) is an ornamental and therapeutic plant with various pharmacological effects and medical applications. In this article, detailed information on the anti-oxidant, immunomodulatory, and anti-inflammatory properties of O. basilicum and its main constituents was provided. The literature survey of the different databases until the end of November 2021 was explored on the immunomodulatory, anti-inflammatory and anti-oxidant effects of the herb and its constituents. The plant and its constituents showed diverse pharmacological effects including immunomodulatory, anti-inflammatory and anti-oxidant properties by improving of the inflammatory mediators including interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), nitric oxide (NO), serum levels of IFN-γ, IL10 and IL-4, Ig. G, Ig. M and phospholipase A2 (PLA2), immunoglobulin E (Ig. E), total protein (TP), oxidant and anti-oxidant markers. O. basilicum and its main constituents therefore, could be effective on the treatment of diseases associated with inflammation, immune dysregulation and oxidative stress. The present review article provides readers with organized information about the anti-oxidant, immunomodulatory, and anti-inflammatory properties of O. basilicum.

The Role of microRNAs in Alcoholism: A Meta-analytic Review.

INTRODUCTION: A growing body of evidence indicates that repeated alcohol exposure or withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular adaptation that occurs is the regulation of gene expression, which is believed to lead to functional alterations that characterize addiction. MicroRNAs (miRs) have been recently identified as master regulators of gene expression through posttranscriptional regulation. The aim of this meta-analytic review was to evaluate the regulatory forms of miRs during alcoholism. METHODS: We used several databases such as PubMed, Scopus, and Web of Science without limitations on publication time. All studies were analyzed by Comprehensive Meta-Analysis software. RESULTS AND DISCUSSION: Six clinical papers with 243 alcoholic patients and 162 controls were included. In this study, 1680 articles were initially reviewed and eventually, six clinical studies were included in the metaanalysis. The results of the meta-analysis showed that according to the random model, the difference between the upregulation and downregulation of central addiction targets was statistically significant, indicating that most dopamine- or gamma-aminobutyric acid receptor subunit (GABA)-related miRs are upregulated in alcoholics (P: 0.00, CI: 0.149-0.439). CONCLUSION: This study strongly suggests that dopamine- or GABA-related miRs were mostly upregulated in alcoholism. Our findings revealed that about 9% of miRs were downregulated in alcoholism, including miR- 567, miR-126, miR-1, miR-432, and miR-153. To identify other or specific miRs as potential biomarkers in alcoholics, large-scale studies and more clinical work are required.

A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals.

Therapeutic experiments are commonly performed on laboratory animals to investigate the possible mechanism(s) of action of toxic agents as well as drugs or substances under consideration. The use of toxins in laboratory animal models, including rats, is intended to cause toxicity. This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals. The current narrative review used databases such as Medline, Web of Science, Scopus, and Embase and appropriate keywords until June 2021. Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin, acetaminophen, doxorubicin, some anticancer drugs, and other materials through various signaling pathways are investigated. To understand the models of renal or hepatotoxicity in laboratory animals, we have provided a list of toxic agents and their toxicity procedures in this review.

Cardiovascular Effect of Dorsal Periaqueductal Gray During Lipopolysaccharide-induced Hypotension.

Introduction: The central mechanism related to the cardiovascular response to lipopolysaccharide (LPS)-induced hypotension is not entirely known, but it is suggested that numerous brain areas such as dorsal periaqueductal gray (dPAG) are involved in this process. In the current work, the cardiovascular effect of the dPAG during LPS-induced hypotension is investigated. Methods: The study animals (rats) were divided into four groups: control (saline microinjected into dPAG), lidocaine 2%, LPS (intravenously injected), and lidocaine + LPS. Catheterization of the femoral artery and vein was performed to record blood pressure and LPS injection, respectively. Saline and lidocaine were microinjected into the dPAG nucleus then the LPS injection was performed. The changes (Δ) in systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were measured and compared with those of the control and LPS groups. Results: LPS significantly declined ΔMAP and ΔSBP (P<0.05) but did not change the ΔHR compared to the control. Lidocaine did not significantly affect basic ΔSBP, ΔMAP, and ΔHR compared to the control. Injection of lidocaine before LPS significantly attenuated the reduction of ΔSBP and ΔMAP evoked by LPS (P<0.05). Conclusion: Our data showed that blockade of the dPAG by lidocaine significantly ameliorates the hypotension induced by LPS. this finding confirms the involvement of the dPAG in cardiovascular regulation during LPS-induced hypotension. Highlights: Inactivation of the dPAG by lidocaine significantly ameliorates cardiovascular responses in hypotensive rats.LPS significantly lowers blood pressure and does not affect the heart rate. Plain Language Summary: The mechanism of hypotension induced by endotoxin is not yet clear. However, it is often attributed to the direct effect of lipopolysaccharide (LPS) as a component of the outer wall of Gram-negative bacteria and other vascular mediators, including tumor necrosis factor (TNF) and nitric oxide (NO). One possibility is that the initial drop in LPS-induced arterial hypertension is mediated by a central mechanism. The ventral region of the transcranial gray matter is involved in lowering blood pressure, and the dorsal region is involved in increasing blood pressure. The dorsolateral region of the transcranial gray matter (dlPAG) also causes tachycardia, vasodilation in muscles, and tachypnea. dlPAG contains cells that produce NO and serotonin (5HT) and 5HT1 and 5HT2 receptors, which may play a role in hypotension due to stimulation of this region. LPS (1 mg/kg or higher IV) typically elicits a biphasic hypotensive response in rats. The first stage of this response begins immediately after LPS injection. The second phase begins about 1 hour after LPS injection. Thus, endotoxic hypertension begins through a central mechanism and further suggests that hypotension may play a critical role in developing fatal hypotension, representing the second stage of septic shock. Although dlPAG is an important site for regulating cardiovascular responses, its role in hypotension induced by LPS has not been investigated. We investigated the role of this nucleus in cardiovascular changes after LPS injection.

Effects of some anti-diabetic herbal extracts on the insulin-degrading enzyme in human colon cancer Caco-2 cell line.

Objective: Type 2 diabetes mellitus (T2DM) is a condition characterized by insufficient insulin production or insulin resistance. The insulin-degrading enzyme (IDE) is responsible for degrading insulin and is a potential drug target for T2DM treatment. Numerous activities have been proposed for plant extracts, but research on the effects of plant extracts on IDE expression and activity is riddled with drawbacks. Materials and Methods: We investigated the effect of Phaseolus vulgaris, Allium cepa, Portulaca oleracea, Cinnamomum verum, and Citrullus colocynthis extracts on the expression and activity of IDE in the Caco-2 cell line. Results: Findings of RT-PCR showed that IDE gene expression was reduced following treatment with P. vulgaris, C. colocynthis, and C. verum extracts. The results of IDE activity with fluorogenic peptide substrate V also indicated that P. vulgaris, C. colocynthis, and P. oleracea extracts reduced IDE activity in a significant and dose-dependent manner. Conclusion: The hydroalcoholic extracts studied, except for A. cepa, can prevent insulin degradation by reducing the expression and activity of the IDE enzyme. This new insight into the effects of herbal medicines on IDE activity can help future studies.

The role of nitric oxide in the dorsomedial periaqueductal gray (dmPAG) column in cardiovascular responses in urethane-anesthetized male rats.

BACKGROUND: The dorsomedial periaqueductal gray (dmPAG) is a mesencephalic area and has numerous functions including cardiovascular regulation. Because nitric oxide (NO) is present in the dmPAG, here we investigate, the probable cardiovascular effect of NO in the dmPAG. METHODS: Five groups (n = 6 for each group) were used as follows: (1) control; (2) L-NAME (NG -nitro-L-arginine methyl ester, a NO synthase inhibitor, 90 nmol); (3) L-arginine (L-Arg, a precursor for NO, 60 nmol); (4) Sodium nitroprusside (SNP, a NO donor, 27 nmol); and (5) L-Arg + L-NAME. The cardiovascular parameters were recorded by a Power Lab device after cannulation of the femoral artery. Drugs were injected using a stereotaxic instrument. The changes (∆) in systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated at different times and compared to the control group. RESULTS: Microinjection of L-NAME significantly increased ∆SBP, ∆MAP, and ∆HR more than saline (from p < 0.05 to p < 0.001). L-Arg only significantly increased ∆HR (p < 0.05). In the L-Arg + L-NAME group, the above parameters also significantly increased (from p < 0.01 to p < 0.05) but not as significantly as with L-NAME alone. Microinjection of SNP significantly decreased ∆SBP and ∆MAP more than in the control and L-NAME groups (from p < 0.01 to p < 0.001), but ∆HR did not change significantly. CONCLUSION: The results indicated that NO in dmPAG has an inhibitory effect on cardiovascular responses in anesthetized rats.