scholarly journals Mechanism of Mongolian Medicine Eerdun Wurile in Improving Postoperative Cognitive Dysfunction Through Activation of the PI3K Signaling Pathway

2022 ◽  
Vol 15 ◽  
Author(s):  
Zhixin Lv ◽  
Limuge Che ◽  
Yiri Du ◽  
Jianshe Yu ◽  
Enboer Su ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cognitive Dysfunction ◽  
Water Maze ◽  
Low Dose ◽  
Escape Latency ◽  
Postoperative Cognitive Dysfunction ◽  
Treated Group ◽  
Control Group ◽  
Model Group ◽  
Group D

ObjectiveTo study the effect of Eerdun Wurile (EW), a traditional Mongolian medicine, on the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway in an animal model of postoperative cognitive dysfunction (POCD).MethodsFifty clean-grade adults Sprague Dawley (SD) male rats were assigned to one of five groups: (1) a control group with no anesthesia (Group C), (2) a POCD model group with anesthesia only (Group P), (3) POCD group with low-dose EW treated (Group L), (4) a POCD group with high-dose EW treated (Group H), and (5) a POCD model group with dexmedetomidine treated (Group D) for positive control. The study started 7 days after all rats had acclimated to housing. Rats were trained in the Morris Water Maze navigation 5 days before surgery. All rats underwent the same maze for navigation and spatial exploration experiments on the preoperative day 1 and postoperative days 1, 3, 5, and their learning and memory abilities were assessed. At the end of the water maze experiment, rats were sacrificed to obtain hippocampal tissue. The mRNA levels of IRS-2, PI3K, AKT, and GLUT4 were measured in the hippocampus by real-time PCR, and the expression of IRS-2, PI3K, AKT, and GLUT4 protein in the hippocampus was determined by Western blotting to investigate the potential mechanisms at the molecular level.ResultsCompared to control Group C, Group P, L, H, and D showed prolonged escape latency (P < 0.05) and decreased number of times to cross the platform (P < 0.05) at 1, 3 and 5 days after surgery. Compared to Group P, Group L, H, and D showed a decrease in escape latency with an increased number of crossing the platform at all-time points after surgery (P < 0.05). Within individual P, L, H, and D groups, escape latencies decreased (P < 0.05) and the number of times that the platform was crossed increased (P < 0.05) between postoperative days 3 and 5 compared to postoperative 1 day. Compared to Group C, the mRNA expression of IRS-2, PI3K, AKT and GLUT4 in the hippocampus of P, L, H, and D groups were decreased (P < 0.05). Compared to Group P, IRS-2, PI3K, AKT, and GLUT4 in the hippocampus of L, H, and D groups were increased (P < 0.05). Compared with Group D, the expression levels of IRS-2 and AKT in both L and H groups were higher. The expression level of PI3K in Group L was also higher (P < 0.05) vs Group D. The expression of AKT mRNA in Group H was higher than in Group L (P < 0.05). Compared to Group C, the p-IRS-2/IRS-2 ratio in the hippocampus of Group P was higher than that of Group C (P < 0.05). Compared to Group P, the ratios of p-IRS-2/IRS-2 in Group L, Group H, and Group D were lower, and the ratios of the p-PI3K/PI3K, p-AKT/AKT, and p-GLUT4/GLUT4 were higher (P < 0.05).ConclusionAdministration of EW showed the effect on the signaling pathway in rats with POCD. The therapeutic effect was better in the low-dose group. This could be related to the insulin downstream signal molecule PI3K and the IRS-PI3K-AKT-GLUT4 signaling pathway.

scholarly journals Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Klaske Oberman ◽  
Iris Hovens ◽  
Jacco de Haan ◽  
Joana Falcao-Salles ◽  
Barbara van Leeuwen ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Morris Water Maze ◽  
Rat Model ◽  
Gut Microbiome ◽  
Water Maze ◽  
Single Injection ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Short Term ◽  
Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

scholarly journals Effects of L-655,708 on expression changes of GABA, glutamate, and beta-endorphin induced by propofol anesthesia in rats

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Dysfunction ◽  
Sham Group ◽  
Postoperative Cognitive Dysfunction ◽  
Expression Level ◽  
Control Group ◽  
Beta Endorphin ◽  
Anesthetized Rats ◽  
Significant Difference ◽  
Dentate Gyrus Region

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.

scholarly journals Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang
Keyword(s):  
Ovarian Reserve ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Menopausal Syndrome ◽  
Primordial Follicles ◽  
Akt Phosphorylation ◽  
Vinylcyclohexene Diepoxide ◽  
Sd Rats

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

scholarly journals PHARMACOLOGICAL EVALUATION OF TRIPHALA CHURNA INSTREPTOZOTOCIN (I. C. V.) INDUCED DEMENTIA IN RATS

2018 ◽  
Vol 10 (3) ◽  
pp. 97
Author(s):  
Purabi Deka ◽  
Arun Kumar
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Memory Impairment ◽  
Treated Group ◽  
Control Group ◽  
Standard Group ◽  
Glutathione Level

Objective: The objective of the study was to investigate the memory improving activity of Triphala Churna hydro-methanolic fruit extract on learning and memory functions in Streptozotocin (I. C. V) induced dementia in rats by using morris water maze and elevated plus maze.Methods: A total of 42 albino wistar rats weighing 80-100 g were randomized into 7 equal groups as follows: Normal control group received normal saline (1 ml/kg p. o.) for 24 d, STZ treated group (3 mg/kg, i. c. v) were administered in two dosage regimen i.e. on first day and third day.), Standard group: Streptozotocin (3 mg/kg i. c. v)+Vitamin E (100 mg/kg/day p. o.) were administered for 21 d, Standard group: Streptozotocin (3 mg/kg i. c. v)+Rivastigmine (2 mg/kg/day p. o.) were administered for 21 d. The learning and memory-impaired rats were treated with Triphala Churna Formulation 1, Triphala Churna Formulation 2 and Triphala Churna Formulation 3 for 21 d (100 mg/kg p. o.). AchE activity, lipid peroxidation, superoxide dismutase, glutathione level of brain homogenate was estimated in Control/STZ (I. C. V)/Standard/Triphala Churna fruits extract treated rats.Results: Administration of Triphala Churna fruits extract significantly restored learning and memory impairment induced by STZ (I. C. V) in the elevated plus maze and morris water maze. Furthermore, in the TPLC F2 and TPLC F3 treated group brain AchE level was decreased (P≤0.01) as well as brain lipid peroxidation was also decreased (P≤0.001). Brain antioxidant enzymes such as glutathione level were increased (P≤0.001) in the TPLC1 and TPLC2 treated group when compared to the STZ treated group, TPLC F2 and TPLC F3 treated group showed significant (P≤0.001, P≤0.01) increase in superoxide dismutase level. Conclusion: Triphala Churna fruits extract has an improving effect on learning and memory impairment rats produced by Streptozotocin (I. C. V) and may have a useful effect in the treatment of dementia and Alzheimer's disease.

scholarly journals Effect of Malus halliana Koehne Polysaccharides on Functional Constipation

2018 ◽  
Vol 16 (1) ◽  
pp. 956-962 ◽  
Author(s):  
Yingying Niu ◽  
Junya Wang ◽  
Pengyu Wang ◽  
Xiuchun Guo ◽  
Jinmei Wang ◽  
...  
Keyword(s):  
Substance P ◽  
Moisture Content ◽  
Dose Group ◽  
Low Dose ◽  
Functional Constipation ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Group Model ◽  
Model Group

AbstractThe effects of Malus halliana Koehne polysaccharides on functional constipation was investigated in this study. The rats were divided into six groups: normal group, model group, positive control group, M. halliana polysaccharides high dose groups 1200 mg/ kg, medium dose groups 1000 mg/ kg and low dose groups 800 mg/kg. The model of constipation was established by loperamide hydrochloride. Feces weight at 6 and 24 hours after treatment, Colon moisture content, in addition the levels of motilin (MTL), gastrin (Gas), somatostatin (SS), substance P (SP) in serum were used to evaluate the preventive effects of M. halliana polysaccharides on constipation. Compared with the model group, the positive control group, M. halliana polysaccharide high, medium and low dose group 6 h weight of feces, colon moisture content, the levels of motilin (MTL), gastrin (GAS) and substance P(SP) significantly (p <0.01) increased, the levels of somatostatin (SS) significantly decreased. The results indicated that the high, middle and low dosage of M. halliana polysaccharide could effectively improve functional constipation. Amongst these doses, the low dose group was better than others.

scholarly journals Neuroprotective Effect of Modified Xijiao Dihuang Decoction against Oxygen-Glucose Deprivation and Reoxygenation-Induced Injury in PC12 Cells: Involvement of TLR4-MyD88/NF-κB Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xu Zhang ◽  
Xiaojun Fei ◽  
Weiwei Tao ◽  
Jingbo Li ◽  
Hao Shen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Glucose Deprivation ◽  
Treated Group ◽  
Chinese Herbs ◽  
Oxygen Glucose Deprivation ◽  
Control Group ◽  
Stroke Treatment

Modified Xijiao Dihuang (XJDH) decoction has been shown to exert powerful neuroprotective properties in clinical ischemic stroke treatment. It consists of 4 Chinese herbs: Buffalo Horn, Paeonia suffruticosa Andrews, Rehmannia glutinosa (Gaertn.) DC, and Paeonia lactiflora Pall. In the present study, the neuroprotective effect and specific mechanisms of XJDH in protecting PC12 cells from oxygen-glucose deprivation-induced injury were investigated. It was found that OGD/R significantly decreased the cell viability and lactate dehydrogenase (LDH) activity and increased the release of IL-1β, IL-6, and TNF-α in PC12 cells, and these effects were suppressed by XJDH and one of its major active constituents, paeoniflorin. Additionally, XJDH inhibited caspase-3 activity and reduced cleaved caspase-3 level. Mechanistic studies showed that the expressions of TLR4, MyD88, TRAF6, and NF-κB p65 and phosphorylation of IκBα and p65 were significantly lower in the XJDH-treated group than in the OGD/R control group. Additionally, XJDH reversed the OGD/R-induced increases in p-JNK and p-ERK1/2 expression. These results suggest that XJDH protects PC12 cells from oxygen-glucose deprivation-induced injury, which may be associated with the inhibition of the TLR4-MyD88/NF-κB signaling pathway. As an anti-inflammation factor, XJDH might be used as a neuronal protection strategy for the ischemia injury and related diseases.

The Effects of Moxibustion on Serum Interleukins and T Cell Subset in H.polyri Infected Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 38-45
Author(s):  
Jing Shen ◽  
Yan Peng ◽  
Dong-Mei Shi ◽  
Yin-Shuai Feng ◽  
Yan-Ling Hou ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Control Group ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Model Group ◽  
Tnf Α ◽  
Group A ◽  
Histomorphological Changes ◽  
Group B ◽  
Group D

Abstract Objective: to observe the effects of moxibustion on histomorphological changes of gastric mucosa, as well as on serum IL-6、IL-8、TNF-α，Hp IgG、CD3+、CD4+、CD8+ in helicobacter pylori (Hp) infected rats, so that to better understand how the moxibustion repairs the Hp- induced gastric mucosal injury. Methods: 40 SD rats were randomly assigned to four groups: group A (blank control), group B (Hp infection model), group C (moxibustion plus model), group D (electro-acupuncture plus model), 10 for each group. The “NaHCO3 plus Indometacin and Hp intragastric administration” method was employed to make gastritis model. Acupoints selected for “repair” purpose were Zu San Li (ST36), Zhong Wan (CV12), Guan Yuan (RN4), Pi Shu (BL20), Wei Shu(BL21). The histomorphological changes of gastric mucosa in rats were observed under light microscope after HE stain; IL-6, IL-8, TNF-α, Hp IgG values were evaluated by ELISA method; values of CD3+、CD4+、CD8+、CD4+/CD8+ were measured by flow cytometry method. Results: compared with group A, the values of IL-6, IL-8, TNF-α, Hp IgG and CD8+ in group B were increased（P＜0.01）, whereas the values of CD3+、CD4+、CD4+/CD8+ were decreased（P＜0.01）. Compared with group B, the values of IL-8（P＜0.05）,TNF-α（P＜0.05）, IL-6（P＜0.01）, Hp IgG（P＜0.01） and CD8+ （P＜0.05） in group C were decreased, whereas the values of CD3+（P＜0.05）,CD4+（P＜0.05）,CD4+/CD8+ （P＜0.05） were increased, meanwhile such values in group D had no significant changes. Compared with group D, the values of IL-6（P＜0.05）,IL-8 （P＜0.05）and Hp IgG （P＜0.01）in group C were decreased, whereas CD4+/CD8+（P＜0.05）were increased, all those changes had statistical significance. Conclusion: the preventive and therapeutic effects of moxibustion on Hp related gastritis might be realized by two ways- to inhibit the secretion of proinflammatory cytokines such as IL-6, IL-8 and TNF-α, or to regulate the production of immune factors (such as up-regulation of CD3+, CD4+ and down-regulation of CD8+).

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