scholarly journals Metabolomics of Aurantio-Obtusin-Induced Hepatotoxicity in Rats for Discovery of Potential Biomarkers

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3452 ◽  
Author(s):  
Longlong Xu ◽  
Jian Li ◽  
Xianglin Tang ◽  
Yuguang Wang ◽  
Zengchun Ma ◽  
...  
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Hematological Indices ◽  
Main Components ◽  
Kg Medium

Aurantio-obtusin is an anthraquinone derived from Cassia obtusifolia (cassiae semen). It is also used as a tool and a detection index for the identification of cassiae semen, as stipulated by the Chinese Pharmacopoeia. Anthraquinones, the main components in cassiae semen, have been reported to show hepatotoxicity. This study investigates the hepatotoxicity of aurantio-obtusin in male Sprague–Dawley rats. We randomly divided the animals into a blank control group and treated three test groups with different doses of aurantio-obtusin: Low dose (4 mg/kg), medium dose (40 mg/kg), and high dose (200 mg/kg). Each group was treated with aurantio-obtusin for 28 days, whereas the control group was administered an equal volume of 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution. Subsequently, we conducted biochemical, hematological, and pathological investigations and determined the weight of different organs. We used serum metabolomics to identify possible biomarkers related to hepatotoxicity. The low-dose group showed no significant liver injury, whereas the medium- and high-dose groups manifested obvious liver injury. Compared with the control group, the test groups showed an increase in alanine transaminase, aspartate transaminase, and alkaline phosphatase levels. The liver organ coefficient also significantly increased. Additionally, we found significant changes in the hematological indices. Metabolomics analysis showed that aurantio-obtusin induced 28 endogenous markers related to liver injury. Our data indicate that aurantio-obtusin induces hepatotoxicity in rat liver in a dose-dependent manner and is mediated by pathways involving bile acids, fatty acids, amino acids, and energy metabolism. In particular, changes in bile acid content during treatment with therapeutic agents containing aurantio-obtusin deserve increased attention.

scholarly journals Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

2019 ◽  
Vol 74 (2) ◽  
pp. 353-370 ◽  
Author(s):  
Li Tian ◽  
Weibin Qian ◽  
Qiuhai Qian ◽  
Wei Zhang ◽  
Xinrui Cai
Keyword(s):  
Low Dose ◽  
Area Postrema ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Delayed Emesis ◽  
Blank Control Group ◽  
Qrt Pcr ◽  
Underlying Mechanisms ◽  
Different Doses

Abstract Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

scholarly journals Blood Biochemical and Hematological Study after Subacute Intravenous Injection of Gold and Silver Nanoparticles and Coadministered Gold and Silver Nanoparticles of Similar Sizes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ji Hyun Lee ◽  
Mary Gulumian ◽  
Elaine M. Faustman ◽  
Tomomi Workman ◽  
KiSoo Jeon ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Low Dose ◽  
Systemic Toxicity ◽  
Blood Biochemistry ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Gold And Silver Nanoparticles ◽  
Blood Biochemical ◽  
Active Partial Thromboplastin Time

Background. To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods. AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results. There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion. The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.

scholarly journals The Effect Of Erythropoietin Administration In Experimental Burns Wound Healing: An Animal Study

2016 ◽  
Vol 3 (1) ◽  
pp. 1-8
Author(s):  
Afriyanti Sandhi ◽  
Aditya Wardhana
Keyword(s):  
Wound Healing ◽  
Animal Study ◽  
Low Dose ◽  
Healing Process ◽  
Control Group ◽  
Wound Healing Process ◽  
P Value ◽  
High Dose ◽  
Sprague Dawley ◽  
Surface Areas

Background: The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. The purpose of this study is to investigate the effect of EPO in experimental burn wounds healing. Methods: Fifteen healthy Sprague-Dawley, strain of Rattus Novergicus weighing 300-350 grams, were prepared to achieve deep dermal burns. Animals were randomized to receive either low-dose EPO injection (600 IU/mL), high-dose EPO injection (3000 IU/mL) or nothing (control group). After 14 days of observations, quantitative and qualitative assessments of wound healing was determined. Results: The size of the wound area and re-epithelialization rate percentage was determined on Day-0, Day-5, Day-10, and Day-14. The average of raw surface areas measurement (p value: 0.012 in day-5; 0.009 in day-10 and 0.000 in day-14) and healing percentage of the lesions (p value: 0.011 in day-5; 0.016 in day-10 and 0.010 in day-14) were significantly best in the low-dose EPO grup compared to the control group and high-dose EPO grup. The histopathology evaluation revealed that the highest score for for re-epithelialization, granulation tissue and neo-angiogenesis were achieved by the low-dose EPO injection group than in both control and high-dose EPO injection groups. Conclusion: In this animal study using Sprague-Dawley rats, Recombinant Human EPO (rHuEPO) injection administration prompted the evidences of improved re-epithelialization and wound healing process of the skin caused by deep dermal burns. These findings may lead to a new therapeutic approach to improve the clinical outcomes for the management of burns wound healing.

Effects of uranium depletion on 1α-hydroxylase in kidney of rats

2010 ◽  
Vol 30 (7) ◽  
pp. 786-790 ◽  
Author(s):  
Minfen Yan ◽  
Gaoren Zhong ◽  
Linfeng Gao ◽  
Xiqiao Xia ◽  
Lihua Wang ◽  
...  
Keyword(s):  
Active Form ◽  
Underlying Mechanism ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Sprague Dawley Rats ◽  
Dose Levels ◽  
Medium Dose

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity

2021 ◽  
pp. 096032712110267
Author(s):  
R Bademci ◽  
MA Erdoğan ◽  
E Eroğlu ◽  
A Meral ◽  
A Erdoğan ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Low Dose ◽  
Liver Toxicity ◽  
Histopathological Examination ◽  
Normal Liver ◽  
Chemotherapeutic Agents ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Group 2

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.

scholarly journals Androgenic Effects of Cinnamomum camphora in Male Sprague-dawley Rats

2019 ◽  
pp. 1-13
Author(s):  
O. H. Ayoade ◽  
G. G. Akunna ◽  
F. I. Duru
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Activity Level ◽  
Control Group ◽  
High Dose ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Medium Dose

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.

scholarly journals Efek pemberian metilprednisolon oral terhadap gambaran histopatologik hati tikus wistar (Rattus norvegicus)

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Muhammad Rifaldi ◽  
Poppy M. Lintong ◽  
Meilany F. Durry
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Clinical Manifestations ◽  
Control Group ◽  
High Dose ◽  
Drug Induced ◽  
Treatment Groups ◽  
Drug Induced Liver Injury ◽  
Histopathological Features ◽  
Group B

Abstract: Drug-induced liver injury (DILI) is an adverse drug reaction which vary in its clinical manifestations, ranging from an asymptomatic increase in liver enzymes to fulminant hepatic failure. Several drugs can cause DILI, one of which is corticosteroid. Methylprednisolone (MT) is a kind of corticosteroid drug which is considered to be a safe drug and it is not believed to cause DILI and often used for the treatment of severe hepatitis. However, there are some reports of DILI in patients treated with high-dose MT. The objectives of this study was to determine the effect of oral administration of MT on liver’s histological changes of witar rats. This study was using 15 rats which were divided into 3 groups; 1 negative control group (group A) and 2 treatment groups (group B and group C). Group B was given a low-dose oral MT, 2 mg/day, while group C was given oral high-dose MT, 4 mg/day for 14 consecutive days. The results showed steatohepatitis features in both low-dose and high-dose MT administration groups. Histopathological features of both treatment groups are similar. Qualitatively, high-dose MT group showed worse histopathological features than the low-dose MT group. Conclusion: Administration of MT by 2mg/day and 4mg/day may induced steatohepatitis in wistar rat’s liver.Keywords: methylprednisolone, liver histopathological features Abstrak: Drug-induced liver injury (DILI) atau cedera hati akibat obat merupakan reaksi efek samping obat dengan manifestasi klinis yang beragam, mulai dari peningkatan enzim-enzim hati yang bersifat asimptomatik sampai dengan timbulnya gagal hati fulminan. Banyak obat-obatan yang dapat menyebabkan DILI, salah satunya adalah golongan kortikosteroid. Metilprednisolon (MT) adalah obat golongan kortikosteroid yang dianggap sebagai obat yang aman dan tidak diyakini dapat menyebabkan DILI, bahkan sering digunakan untuk terapi pasien hepatitis berat. Akan tetapi, beberapa klinisi melaporkan kasus DILI pada pasien-pasien yang diterapi dengan MT dosis tinggi. Penelitian ini bertujuan untuk mengetahui efek pemberian MT oral terhadap perubahan histologik hati tikus wistar. Jenis penelitian yang dilakukan adalah eksperimental laboratorik menggunakan 15 ekor tikus yang dibagi dalam 3 kelompok; 1 kelompok kontrol negatif (kelompok A) dan 2 kelompok perlakuan (kelompok B dan kelompok C). Kelompok B diberikan MT oral dosis rendah sebanyak 2 mg/hari sedangkan kelompok C diberikan MT oral dosis tinggi sebanyak 4 mg/hari setiap hari selama 14 hari berturut-turut. Hasil penelitian menunjukkan gambaran yang sama secara mikroskopik pada kedua kelompok perlakuan yaitu terjadinya steatohepatitis. Tetapi secara kualitatif, kelompok tikus yang mendapatkan MT dosis tinggi memberikan gambaran histopatologik yang lebih jelek dibandingkan kelompok yang diberi dosis rendah. Simpulan: Pemberian metilprednisolon dosis 2mg/hari dan dosis 4 mg/hari dapat mencetuskan terjadinya steatohepatitis pada hati tikus wistar. Kata kunci: metilprednisolon, gambaran histopatologik hati

Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

1993 ◽  
Vol 70 (05) ◽  
pp. 817-821 ◽  
Author(s):  
Jean-P Carteaux ◽  
Beat Steiner ◽  
Sébastien Roux
Keyword(s):  
Platelet Count ◽  
Extracorporeal Circulation ◽  
Guinea Pigs ◽  
Low Dose ◽  
Treated Group ◽  
In Vivo Model ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Contact Activation

SummaryExtensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine secretion in vivo

1997 ◽  
Vol 272 (4) ◽  
pp. R1290-R1297 ◽  
Author(s):  
N. Yamaguchi
Keyword(s):  
High Performance ◽  
Low Dose ◽  
Dose Range ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Experimental Conditions ◽  
Chromatography Method ◽  
Liquid Chromatography Method

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164 microM), the CA response was further blocked by approximately 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151 microM), the CA response was only partially inhibited by approximately 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.

scholarly journals Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Lijing Yan ◽  
Xia Xu ◽  
Zhenyu He ◽  
Sheng Wang ◽  
Linlin Zhao ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Frontal Cortex ◽  
Signaling Pathway ◽  
Low Dose ◽  
Antidepressant Effect ◽  
Control Group ◽  
High Dose ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Bdnf Mrna

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

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