Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter

Objective: To investigate the therapeutic effect of Yixin Ningshen Tablet(YXNS) on comorbidity of myocardial infarction(MI) and depression in rats and explore the underlying mechanism. Methods: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights,including control, model, fluoxetine(FLXT, 10 mg/kg), low-dose YXNS(LYXNS, 100 mg/kg), and high-dose YXNS(HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction(MI) area and myocardial apoptosis was also detected. Serum levels of interleukin(IL)-6, IL-1β, tumor necrosis factor-α(TNF-α), 5-hydroxytryptamine(5-HT), adrenocorticotrophic hormone(ACTH), corticosterone(CORT), and norepinephrine(NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5’-monophosphate-activated protein kinase(AMPK), p-AMPK,peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and nuclear respiratory factor 1(NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase(IDO1), kynurenine 3-monooxygenase(KMO), and kynureninase(KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. Results: Compared with the model group,the cardiac function of rats treated with YXNS significantly improved(P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats(P<0.01 or P<0.05), promoted AMPK phosphorylation,and increased PGC-1α protein expression(P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH,and CORT(all P<0.05). Moreover, HYXNS decreased the m RNA expressions of IDO1, KMO and KYNU(P<0.05).Conclusions: YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.

Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

Sodium nitrite(Na NO2) is an inorganic salt used broadly in chemical industry. Na NO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells(MSCs) are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against Na NO2 induced hypoxic brain injury. Rats were divided into control group(treated for 3 or 6 weeks), hypoxic(HP) group(subcutaneous injection of 35 mg/kg Na NO2 for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2 w R and N-3 w R(treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively), and MSCs treated groups N-2 w SC and N-3 w SC(treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of Na NO2 for 1 week in combination with 3 week self-recovery). The levels of neurotransmitters(norepinephrine, dopamine, serotonin), energy substances(adenosine monophosphate, adenosine diphosphate, adenosine triphosphate), and oxidative stress markers(malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, glutathione reduced form, and oxidized glutathione) in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neuroprotective effects against Na NO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain.

Inhibitory effect of baicalein on mice tremor induced by oxotremorine and mechanisms

OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.

Antipyretic Effect and Action Mechanism of Jinzhen Oral Liquid

[Objectives]To investigate the antipyretic effect and action mechanism of Jinzhen Oral Liquid.[Methods]The yeast-induced fever model was used to determine the rectal temperature of rats at 6,8,and 10 h after yeast injection.The contents of IL-6 and TNF-αin the rat serum and the contents of 5-HT and NE in the hypothalamus were detected by radioimmunoassay;the model of yeast-induced fever in rat was established by intraperitoneal injection of lipopolysaccharide(LPS),rectal temperature of the rats was determined,the contents of TNF-αand IL-1βin serum,cyclic adenosine monophosphate(cAMP)and prostaglandin E2(PGE2)in hypothalamus were detected by radioimmunoassay.[Results]After the intervention of Jinzhen Oral Liquid,the body temperature of rats in the yeast-induced fever model was significantly reduced,the IL-6 and TNF-αcontents in serum were significantly reduced,the 5-HT content in the hypothalamus was significantly reduced,while the NE content was significantly increased;after 2 h of intraperitoneal injection of LPS,the body temperature of the model rats increased significantly;after the intervention of Jinzhen Oral Liquid,the increase in rectal temperature of LPS-induced fever model rats decreased,and the TNF-αand IL-1βcontents in serum and cAMP and PGE2 contents in hypothalamus of model rats were significantly decreased.[Conclusions]Jinzhen Oral Liquid has a significant antipyretic effect,and its action mechanism may be related to reducing the inflammatory factors in the serum,thereby inhibiting the generation of pyrogenic media in the hypothalamus.

Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism

Objective:Anxiety is one of the most common symptoms associated with autistic spectrum disorder.The essential oil of Cananga odorata(Lam.)Hook.f.&Thomson,usually known as ylang-ylang oil(YYO),is often used in aromatherapy as a mood-regulating agent,sedative,or hypotensive agent.In the present study,the effects and mechanisms of YYO in alleviating anxiety,social and cognitive behaviors in autism-like rats were investigated.Methods:The prenatal valproic acid(VPA)model was used to induce autism-like behaviors in offspring rats.The effectiveness of prenatal sodium valproate treatment(600 mg/kg)on offspring was shown by postnatal growth observation,and negative geotaxis,olfactory discrimination and Morris water maze(MWM)tests.Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety,social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test,three-chamber social test,and MWM test.Finally,the monoamine neurotransmitters,including serotonin,dopamine and their metabolites,in the hippocampus and prefrontal cortex(PFC)of the rats were measured using a high-performance liquid chromatography.Results:Offspring of VPA exposure rats showed autism-like behaviors.In the VPA offspring,mediumdose YYO exposure significantly elevated the time and entries into the open arms in the elevated plusmaze test,while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test.VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test.YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring.Conclusion:YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats.The role of YYO was related to the regulation of the metabolism of serotonin and dopamine.