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Depression is a mental disorder characterized by persistent low mood and belongs to the category of "stagnation syndrome" in traditional Chinese medicine （TCM）， with the characteristics of high prevalence， high disability rate， high suicide rate， and high recurrence rate. The pathogenesis of depression is extremely complex and involves factors such as genetics， psychology， and social environment. Currently， clinical antidepressant drugs such as tricyclic and tetracyclic antidepressants， and selective serotonin reuptake inhibitors， have slow onset of action and significant adverse effects with long-term application. Furthermore， clinical statistics show that about one-third of patients do not respond to these types of medications. Enhancing the effectiveness of depression treatment has become a major challenge in the medical field. TCM， based on the holistic view and treatment based on syndrome differentiation， has unique advantages in the prevention and treatment of depression， including stable therapeutic effects， low recurrence rate， minimal side effects， and good patient compliance. As one of the heat-clearing drugs， Gardeniae Fructus has the effects of clearing heat， purging fire， cooling blood， and relieving restlessness， which makes it effective in treating patients with "stagnation syndrome". Literature studies have found that active components of Gardeniae Fructus， such as geniposide， genipin， and crocin， as well as drug pairs such as Gardeniae Fructus-Chuanxiong Rhizoma， Gardeniae Fructus-Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis， and Gardeniae Fructus-Lycii Fructus， and prescriptions such as Zhizichi Tang， Yuejuwan， Zhizi Houpotang， Danzhi Xiaoyaosan， and Jieyu Anshen Granules， have shown significant antidepressant effects. The mechanism of action may be related to regulating the hypothalamic-pituitary-adrenal （HPA） axis， modulating neurotransmitters such as serotonin （5-HT） and dopamine （DA）， increasing brain-derived neurotrophic factor （BDNF） in the hippocampus， enhancing neurogenesis in the hippocampus， and regulating the nuclear factor-kappa B （NF-κB） signaling pathway to inhibit neuroinflammation. This article summarized the research progress on the active components of Gardeniae Fructus， drug pairs， and Chinse medicinal prescriptions containing Gardeniae Fructus， providing references for further promoting the clinical application of Gardeniae Fructus and its prescriptions in the treatment of depression.
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AIM:To observe the effect of rapamycin (Rapa) on human neuroblastoma SH-SY5Y cell injury induced by oxygen-glucose deprivation (OGD), and to explore the role of autophagy in this process .METHODS: The SH-SY5Y cells were randomly divided into 4 groups:normal control group:the cells were cultured without OGD treatment;Rapa group:the cells were pretreated with Rapa for 1 h;OGD group:the culture medium was replaced by glucose-free me-dium and the cells were transferred to a humidified incubation chamber flushed by a gas mixture of 1%O2 , 94%N2 and 5% CO2 for 12 h; Rapa+OGD group: the cultured cells were treated with Rapa for 1 h, and then were given the same treatments as those in OGD group .The cell viability was assessed by MTT assay .The degree of the cell damage was evalu-ated by determining the leakage of lactate dehydrogenase ( LDH) .The enzyme activity of caspase-3 was detected .TUNEL staining were used to detect the variation of cell apoptosis .The protein levels of apoptosis-related proteins Bax and Bcl-2, autophagy-related protein beclin-1 and autophagy marker protein LC 3B were determined by Western blot .RESULTS:Compared with OGD group, the viability of the SH-SY5Y cells was significantly increased, and the activity of caspase-3 was significantly reduced in Rapa +OGD group (P<0.05).The SH-SY5Y cell injury was apparent after OGD with a great in-crease in the apoptotic rate (P<0.05).Compared with OGD group, the apoptotic rate significantly decreased in Rapa +OGD group (P<0.05).Compared with control group, the protein level of Bcl-2 was significantly decreased (P<0.05) and the protein level of Bax was significantly increased in OGD group .Compared with OGD group , the levels of Bcl-2, be-clin-1 and LC3B-Ⅱwere significantly increased and the protein level of Bax was significantly increased in Rapa +OGD group (P<0.05).CONCLUSION: Rapamycin has a protective effect on in vitro cultured SH-SY5Y cells injured by OGD.The mechanism may be related to the promotion of autophagy .
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Objective To investigate the therapeutic effects of mesenchymal stem cells (MSCs) on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in C57BL mice.Methods Different doses of MNU (30 mg · kg-1,45 mg · kg-1,60 mg · kg-1,75 mg · kg-1 and 90 mg · kg-1) were injected to C57BL mice for 7 days.Then electroretinogram (ERG) detection and HE staining were performed to examine retinal electrophysiological function and morphological changes on day 1,day 3 and day 7 after MNU treatment,respectively.Then we could explore the optimum condition to establish stable animal model of retinitis pigmentosa.MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection.Then ERG detection and HE staining were performed to evaluate the effect of MSCs on retinitis pigmentosa induced by MNU.Results When compared with control group,30 mg · kg-1 and 45 mg · kg-1 MNU could cause mild retinal damage in morphology and function in mice;while 60 mg · kg-1 and above dose of MNU induced serious retinal damage,leading to decreased ERG amplitude of the retina (all P ＜ 0.001) and outer nuclear layer (ONL) thickness (all P ＜ 0.001).On day 1 and day 3 after single dose of 60 mg · kg-1 MNU injection,ERG amplitude of the retina was decreased,and outer nuclear layer thickness became thin;while the retinal damage was serious badly in morphological structure on day 7,with the ERG amplitude extinguished (all P ＜ 0.001),ONL thickness thin (all P ＜ 0.001) and internal and external nuclear layer fusion.When compared with MNU alone treatment group,following injection of 60 mg · kg-1 MNU for 1 day MSCs were transplanted to C57BL mice by intravitreal or tail intravenous injection,and the amplitude of ERG and retinal ONL thickness were increased on day 7 after MSCs transplantation (all P ＜ 0.001).Conclusion MSCs transplantation has a certain therapeutic effect on MNU-induced retinitis pigmentosa in C57BL mice.
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ABSTRACT:Objective To explore the protective effect of the antioxidant N‐acetylcysteine (NAC) on the retinal nerve tissue of early diabetic rats .Methods We randomly divided 60 healthy adult Sprague‐Dawley (SD) rats weighing between 180 g and 220 g into 2 groups:normal control (CON , n=20) and diabetic (DM , n=40) .By intraperitoneal injection of streptozotocin (60 mg/kg) ,the model of diabetic rats was established .The rats were considered diabetic only when they had hyperglycemia (set at ≥16 .7 mmol/L) (32) .The CON group was injected with the same amount of citric acid and sodium citrate buffer solution .After successful model establishment ,the diabetic rats were randomly divided into 1‐month diabetes group and 2‐month diabetes group ,with 16 rats in each group .The left eye of each experimental diabetic rat was set for diabetes control group (D) while the right eye was set as NAC treatment group (NAC) .At 2 weeks of diabetes ,4μL (1 .6μg/μL) of NAC was injected into the vitreous chamber of NAC group and 4μL (0 .01 mmol/L) of PBS was injected into the vitreous chamber of the other diabetic rats .The thickness changes of outer nuclear layer retina was observed by HE ,ultrastructural changes of retinal ganglion cells were observed under the transmission electron microscope ,and the number of retinal ganglion cells was detected by immunofluorescence method .Results At different time points ,retina outer nuclear layer in NAC group was thicker than in D group (P0 .05) .Under the transmission electron microscope ,NAC group had more retinal ganglion cell organelles ,higher electron density of the cytoplasm ,and milder mitochondria swelling than D group .The NAC group did not differ from CON group in the ultrastructure of retinal ganglion cells . NAC group had an increased number of retinal ganglion cells at different time points compared with the D group (P 0 .05) .Conclusion The antioxidant N‐acetylcysteine has a protective effect on the retinal nerve tissue of early diabetic rats .
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AIM: To examined the effects of hypoxic preconditioning ( HPC) on oxygen-glucose deprivation ( OGD)-induced PC12 cells, and to investigate its possible mechanisms of autophagy .METHODS: Cultured PC12 cells were randomly divided into control group , HPC group, 3-methyladenine (3-MA) group, HPC+OGD group, 3-MA+HPC+OGD group and OGD group .CCK-8 assay was used to detect the cell viability .The caspase-3 activity was also tested . TUNEL staining and flow cytometry were used to detect the cell apoptosis .The protein levels of apoptosis-related protein caspase-3 and autophagy-marked protein LC3-2 and beclin-1 were determined by Western blot .RESULTS:Compared with control group, the viability of PC12 cells was significantly reduced , and the activity of caspase-3 was significantly increased in OGD group.Compared with 3-MA+HPC+OGD group and OGD group , the viability of PC12 cells was significantly in-creased, and the activity of caspase-3 was significantly reduced in HPC +OGD group (P<0.05).The PC12 cell injury was apparent after OGD with a great increase in the apoptotic rate (P<0.05).Compared with OGD group, the apoptotic rate significantly decreased in HPC +OGD group ( P<0.05 ) .Compared with control group , the protein level of cleaved caspase-3 was significantly increased in OGD group ( P<0.05) .Compared with OGD group , the protein level of cleaved caspase-3 was significantly decreased , and the levels of LC3-2 and beclin-1 were significantly increased in HPC +OGD group (P<0.05).CONCLUSION:OGD decreases cell survival and induces apoptosis .Activation of cell autophagy may be the mechanism by which hypoxic preconditioning protects the PC 12 cells from OGD induced injury .