Silibinin effects on cognitive disorders: Hope or treatment?

Objective: Almost all diseases of the nervous system are related to neuroinflammation, oxidative stress, neuronal death, glia activation, and increased pro-inflammatory cytokines. Cognitive disorders are one of the common complications of nervous system diseases. The role of some plant compounds in reducing or preventing cognitive disorders has been determined. Silibinin is a plant bioflavonoid and exhibits various effects on cognitive functions. This article discusses the different mechanisms of the effect of silibinin on cognitive disorders in experimental studies. Materials and Methods: Databases, including ISI, , Google Scholar, Scopus, Medline and PubMed, were investigated from 2000 to 2021, using related keywords to find required articles. Results: Silibinin can improve cognitive disorders by different pathways such as reducing neuroinflammation and oxidative stress, activation of reactive oxygen species- Brain-derived neurotrophic factor- Tropomyosin receptor kinase B (ROS-BDNF-TrkB) pathway in the hippocampus, an increase of dendritic spines in the brain, inhibition of hyperphosphorylation of tau protein and increasing the expression of insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R), inhibiting inflammatory responses and oxidative stress in the hippocampus and amygdala, and decrease of Homovanillic acid/Dopamine (HVA/DA) ratio and 3,4-Dihydroxyphenylacetic acid + Homovanillic acid/Dopamine (DOPAC+ HVA/DA) ratio in the prefrontal cortex and 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratio in the hippocampus. Conclusion: These results suggest that silibinin can be considered a therapeutic agent for the symptom reduction of cognitive disorders, and it acts by affecting various mechanisms such as inflammation, programmed cell death, and oxidative stress.

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.

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.

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.