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JOURNAL OF NUTRITIONAL BIOCHEMISTRY · 2025 · IF 4.9

Isovaleric acid ameliorates chronic restraint stress and resists inflammation by inhibiting NF-κB activation in mice

Changtong Guo,Xiangda Shi,Bingbing Luo,Yuxuan Yang,Jian Huang,Jiale Xu,Rong Zheng,Siwen Jiang,Jin Chai

In actual production, the restraint stress caused by crowded and narrow spaces, as well as operations such as capture and transportation, can lead to intestinal inflammation and affect animal growth performance, damaging the economic benefits of livestock farms. Isovaleric acid, a type of short-chain fatty acid (SCFA), has been found to be useful in enhancing calf digestion and inhibiting the expression of inflammatory factors. In this study, we first constructed a mouse model of chronic restraint stress (CRS) and fed a diet supplemented with sodium isovalerate to mice with CRS to investigate the mitigating effect of exogenously added isovalerate on mice with chronic restraint stress. An inflammation model was then constructed using piglet jejunal epithelial cell line-J2 (IPEC-J2) to simulate intestinal inflammation after stress, and to investigate the mitigating effect of isovaleric acid on inflammation as well as the repairing effect on intestinal barrier. The results showed that feeding sodium isovalerate significantly increased the weight gain as well as the body weight growth rate of CRS mice from 1-28 days ( P < 0.05), and extremely significantly decreased the feed intake and feed to gain ratio of CRS mice ( P < 0.01). In addition, feeding sodium isovalerate ameliorated the decrease in organ index in mice caused by CRS and significantly increased leg muscle index in CRS mice ( P < 0.05). Meanwhile, feeding sodium isovalerate improved depressive behavior and promoted 5-HT secretion in the brain and hypothalamus of CRS mice. Besides, feeding sodium isovalerate ameliorated intestinal inflammation in CRS mice, as evidenced by extremely significantly decreased the expression of colonic inflammatory factors and increased the expression of tight junction proteins ( P < 0.01). It was found that the addition of isovaleric acid extremely significantly reduced the expression of inflammatory factors and the phosphorylation level of NF-κB p65 in inflammatory cells ( P < 0.01), extremely significantly increased the survival rate of inflammatory cells ( P < 0.01) and the expression of tight junction proteins ( P < 0.05), improved the morphology of inflammatory cells. After the addition of short-chain fatty acid receptor GPR41 and GPR43 antagonists, the resistance effect of isovaleric acid on inflammation was inhibited. The above results suggest that isovaleric acid has an ameliorating effect on CRS in mice and inhibits NF-κB activation thereby exerting its anti-inflammatory effect.

CAS / MDL: 150-83-4
研究领域: 生物化学 · 免疫学 · 动物营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY · 2025 · IF 2.7

Berberine Alleviates Chronic Restraint Stress-Induced Depression-Like Behavior by Modulating Gut Microbiota and SCFA Production in Mice

Ru Cheng,Aoqi Song,Jingjing Jiang,Xijier Qiaolongbatu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou

The exact mechanism by which berberine alleviates depression remains unclear. In this study, we explored the relationship between the antidepressant effect of berberine and the microbiota–brain–gut axis. The levels of IL-1β, TNF-α, IL-6, corticosterone, serotonin, and brain-derived neurotrophic factor (BDNF) were quantified using enzyme-linked immunosorbent assays (ELISA) and Western blotting. Variations in the composition of the gut microbiota were examined using 16S rRNA gene sequencing. Berberine significantly mitigated depressive behaviors in mice with CRS, as manifested by increased total distance traveled and central zone duration in the open-field examination, increased time and number of entries into the outstretched arms during the elevated and maze tests, and an increase in the exercise time during the tail suspension and forced swimming tests. Histopathological analysis indicated that berberine ameliorated CRS-induced hippocampal and colonic damage in mice. Additionally, berberine substantially restrained the generation of proinflammatory cytokines and corticosterone in mice with CRS, while increasing the levels of BDNF and serotonin. Importantly, berberine significantly ameliorated CRS-induced depression-like behaviors ( p < 0.01) and restored gut microbial diversity and short-chain fatty acid (SCFA) levels (fold-change: acetate 1.8-fold, butyrate 2.2-fold; p < 0.05). Furthermore, berberine restored the CRS-induced alterations in SCFA production. Our results indicate that berberine may exert antidepressant effects via a pleiotropic mechanism that modulates the microbiome–brain–gut axis.

CAS / MDL: 110429-35-1 633-65-8
研究领域: 神经生物学 · 精神病学 · 微生物组学 · 免疫学 · 分子药理学 · 转化医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Communications Biology · 2023 ·Vol. 6 ·期 1 ·1-10 · IF 5.9

Inhibition of c-Jun in AgRP neurons increases stress-induced anxiety and colitis susceptibility

Jiao Fuxin,Hu Xiaoming,Yin Hanrui,Yuan Feixiang,Zhou Ziheng,Wu Wei,Chen Shanghai,Liu Zhanju,Guo Feifan

Psychiatric disorders, such as anxiety, are associated with inflammatory bowel disease (IBD), however, the neural mechanisms regulating this comorbidity are unknown. Here, we show that hypothalamic agouti-related protein (AgRP) neuronal activity is suppressed under chronic restraint stress (CRS), a condition known to increase anxiety and colitis susceptibility. Consistently, chemogenic activation or inhibition of AgRP neurons reverses or mimics CRS-induced increase of anxiety-like behaviors and colitis susceptibility, respectively. Furthermore, CRS inhibits AgRP neuronal activity by suppressing the expression of c-Jun. Moreover, overexpression of c-Jun in these neurons protects against the CRS-induced effects, and knockdown of c-Jun in AgRP neurons ( c-Jun ∆AgRP ) promotes anxiety and colitis susceptibility. Finally, the levels of secreted protein thrombospondin 1 (THBS1) are negatively associated with increased anxiety and colitis, and supplementing recombinant THBS1 rescues colitis susceptibility in c-Jun ∆AgRP mice. Taken together, these results reveal critical roles of hypothalamic AgRP neuron-derived c-Jun in orchestrating stress-induced anxiety and colitis susceptibility.

CAS / MDL: 119-90-4
研究领域: 神经科学 · 免疫学 · 精神病学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2021 · IF 5.811

Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle

Lu Yulin,Huang Jingjing,Zhang Yao,Huang Zitong,Yan Weiming,Zhou Tianran,Wang Zhesheng,Liao Lu,Cao Hongying,Tan Bo

The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y1 receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.

研究领域: 药理学 · 胃肠病学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Neuro-stimulating effect of Citri Reticulata Pericarpium Viride essential oil through regulating Glu/NMDAR on olfactory bulb to improve anxiety-like behavior

Jingbin Chen,Yali Liu,Yonggui Song,Huihui Liang,Genhua Zhu,Bike Zhang,Liangliang Liao,Jian Luo,Ming Yang,Dan Su

Ethnopharmacological relevance Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. Aim of the study The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. Materials and methods This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. Results The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. Conclusions The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

CAS / MDL: 9005-65-6
研究领域: 药理学 · 神经科学 · 民族药理学 · 行为科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ALZHEIMERS DISEASE · 2015 ·Vol. 49 ·期 3 ·829-844 · IF 4.151

Aging as a Precipitating Factor in Chronic Restraint Stress-Induced Tau Aggregation Pathology, and the Protective Effects of Rosmarinic Acid

Shan Ye,Wang Dan-Dan,Xu Yu-Xia,Wang Chu,Cao Lan,Liu Yun-Sheng,Zhu Cui-Qing

Stress is an important risk factor of Alzheimer’s disease (AD). It has been evidenced that stress could induce tau phosphorylation and increase tau insolubility in brain; however, little is known about the interactional effect of stress with aging on tauopathy. Therefore, we explored the effects of aging on stress-induced tauopathy and the potential mechanism in mouse model of chronic restraint stress (CRS). Here we found that in general, the level of phosphorylated tau (P-tau) was higher in brain of middle-aged mice than that in adult mice under physiological conditions. CRS-induced tau phosphorylation and its insolubility were more prominent in middle-aged mice. The increase of AT8-labeled insoluble P-tau was dramatic in middle-aged mice, which was highly ubiquitinated but did not form PHF structures. The levels of chaperones were relatively lower in middle-aged mice brain; CRS further reduced the expression, especially for HDJ2/HSP40. CRS also suppressed the expression of Pin1, the peptidylprolyl cis/trans isomerase, in middle-aged mice but not in adult mice. Downregulation of HSP40 or Pin1 caused an increase of transfected extraneous tau in 293 cells. Rosmarinic acid (RA) could effectively suppress the elevation of P-tau and insoluble P-tau formation induced by CRS, and reversed the abnormal changes of chaperones and Pin1 particularly in middle-aged mice. Taken together, our findings provided evidence that aging could be a promoting factor in stress-induced tauopathy, which was relevant with malregulation of chaperones and Pin1, and RA might be a promising beneficial agent for stress-induced tauopathy.

CAS / MDL: 20283-92-5
研究领域: 神经科学 · 药理学 · 老年学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2024 · IF 6.7

Schisandrol B alleviates depression-like behavior in mice by regulating bile acid homeostasis in the brain-liver-gut axis via the pregnane X receptor

Peng Wang,Hui Ouyang,Guofang Bi,Fengting Liang,Shuang Hu,Chenhua Wu,Xiaowen Jiang,Wenhong Zhou,Dan Li,Shuaishuai Zhang,Xiao Yang,Mingliang Zhao,Jian-Hong Fang,Haitao Wang,Wei Jia,Zheng-jiang Zhu,Huichang Bi

Background Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from Schisandra chinensis(Turcz.)Baill. or Schisandra sphenanthera Rehd.etWils, is pivotal in regulating bile acid homeostasis via pregnane X receptor (PXR) in cholestasis. However, the potential of SolB in alleviating depression-like symptoms, its pharmacological effects, and the underlying mechanisms remain to be fully elucidated. Methods We confirmed the effect of SolB against depression induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) in mice. The role of SolB in bile acid homeostasis in depression was analyzed using the metabolomic. Gene analyses and 16S rRNA sequencing were employed to investigate the involvement of PXR. Experiments with Pxr −/− mice were conducted to confirm the essential role of the PXR pathway in SolB's antidepressant effects. Results SolB treatment significantly increased sucrose consumption in the SPT and the locomotor activity in the OFT, while decreasing immobility time in the FST and TST in mice exposed to CRS and CUMS. Additionally, SolB treatment significantly preserved the integrity of the dendritic spine, elevated synaptic protein PSD95 levels, and augmented CREB/BDNF expression. Metabolomic and gene analyses indicated that SolB treatment significantly facilitated bile acid metabolism, promoted intestinal bile acid efflux, decreased hippocampal levels of the secondary bile acids DCA and TLCA, and upregulated expression of the PXR target proteins CYP3A11, SULT2A1, MRP2, and OATP1B1 in the liver, and MRP2 and MDR1 in hippocampus, which are integral to bile acid homeostasis. 16S rRNA sequencing revealed that SolB reduced the abundance of the bile salt hydrolase (BSH)-producing bacteria Lactobacillus johnsonii and Bacteroides fragilis and subsequently decreased the production of TLCA and DCA. Moreover, SolB failed to protect against depression induced by CRS in Pxr -null mice, suggesting that the antidepressant effect of SolB was PXR-dependent. Conclusions These results provide direct evidence of the antidepressant effect of SolB via activation of PXR to regulate bile acid homeostasis in the brain-liver-gut axis, suggesting that SolB may serve as a novel potential target for preventing and treating depression.

CAS / MDL: 54910-89-3
研究领域: 神经科学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Translational Research · 2022 · IF 10.171

Adult hypertensive rats are more prone to gut microflora perturbation and fibrosis in response to moderate restraint stress

Tiantian Wang,Han Gao,Chengwei He,Lei Gao,Boya Wang,Rongxuan Hua,Yixuan Du,Chen Liang,Shuzi Xin,Hongwei Shang,Ying Wang,Wen Wang,Jingdong Xu

ABSTRACT Hypertension (HTN) is a common endpoint for numerous cardiovascular diseases, the prevalence of which has been quickly increasing due to a wide range of reasons. Previous research has found that following stress, ELISA and 16S rDNA sequencing indicated substantial changes in plasma cytokines or hormones, as well as alterations in gut microbiota in juvenile hypertensive rats. However, it remains still unclear how such interaction modifications affect microbial populations and organismal function. Stress-related hormones show a significant drop. Similar to earlier research, the stress group had dramatically increased release of pro-inflammatory cytokines such as IL-17. Importantly, a unified collection of tools that allows for deep and comprehensive colonic structural investigation has been developed. Stress may limit the transition of macrophages (Mφs) to M1Mφs while increasing the transfer to M2Mφs. Evidence highlighted that tight junction proteins were decreased along with enhancement in intestinal permeability . Morphological analysis revealed that the SHR-S group exhibited considerably higher levels of morphological alterations and fibrosis in colon, heart, and thoracic aorta tissues.Significant improvements in bacteria linked with short-chain fatty acid synthesis, such as Prevotella and Ruminococcus , were discovered by metagenomic analysis. Adult hypertensive rats are more susceptible to gut microbiota disruption and fibrosis as a result of mild restraint stress . This might contribute to some innovative ideas for HTN both treatment and prevention.

研究领域: 心血管疾病 · 微生物学 · 免疫学 · 病理生理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2025 · IF 5.4

Antidepressant effects of total phenols and total saponins of Kai-Xin-San mediated by synaptic plasticity induced by BDNF/TrkB/Akt pathway

Ya-Nan Tang,Yun-Feng Bai,Ai Dong,Qin-Ling Rao,Hong-Hua Wu,Chun-Guo Wang,Yan-Tong Xu

Ethnopharmacological relevance Kai-Xin-San (KXS) is a classic prescription for treating affective disorders in traditional Chinese medicine (TCM) over millennium. Although antidepressant effects of KXS have been demonstrated in both clinical and preclinical studies, antidepressant constituents and action mechanisms of KXS remain unclear. Aim of the study To reveal antidepressant constituents and action mechanisms of KXS using the method of “fraction-spectrum-effect-mechanism”. Materials and methods Homologous fractions of KXS were isolated through solvent extraction combined with macroporous resin chromatography methods. The quantification of the fractions was performed using chemical chromogenic methods. Antidepressant effects of the homologous fractions were assessed using tail suspension test (TST), forced swimming test (FST) and open field test (OFT) in mice. Two major fractions of total phenols (TP) and total saponins (TS) were chosen for further studies. The constituents of TP and TS were identified using UPLC-Q-Exactive Orbitrap-MS (UPLC-MS) method, and their antidepressant effects were verified on chronic restraint stress (CRS) model in mice by behavioral evaluations including sucrose preference test (SPT), TST, FST and OFT. Network pharmacology was used to predict antidepressant mechanisms of TP and TS based on the homologous constituents determined in UPLC-MS analysis. Proteomic analyses were undertaken with tissues of hippocampus (HP) and prefrontal cortex (PFC) in CRS mice treated by TP and TS. Western blot (WB) was employed to verify the findings in network pharmacology and proteomic analyses. Results Five homologous fractions of essential oils (EO), TP, TS, oligosaccharides (OL) and polysaccharides (PO) were isolated from KXS with homologous contents exceeding 50 %. Results of TST and FST indicated that all the five fractions significantly decreased the immobility time of mice, while OFT results exhibited that their locomotor activities remained unchanged. A total of 50 constituents and 114 constituents were identified in the TP and TS, respectively. CRS tests demonstrated that both TP and TS significantly increased the percent of sucrose consumption and decreased the immobility time in the TST and FST, without affecting their locomotor activities. Results of both network pharmacology and proteomic analyses primarily pointed to similar contents highly related to depression. GO analysis on TP and TS principally enriched in synaptic structures and functions, as well as neural metabolic and gene expression processes. KEGG analysis on TP and TS principally enriched in pathways of neurodegeneration-multiple diseases, as well as neurotrophin signaling pathway in HP and PFC. Results of WB verified that TP and TS significantly reversed the decrease in signature proteins of synaptic plasticity including presynaptic SYN1, postsynaptic PSD95 and GRIA1, as well as the underlying mechanism of BDNF/TrkB/Akt pathway in the HP and PFC induced by CRS. Conclusion This is the first study on antidepressant constituents and action mechanisms of KXS guided by the method of “fraction-spectrum-effect-mechanism”. Albeit the findings are still preliminary, it provides an example in methodology for unraveling the complicated chemical system and action mechanisms of TCM prescriptions.

CAS / MDL: 54910-89-3
研究领域: 药理学 · 神经科学 · 民族药理学 · 中医药学 · 精神药理学 · 蛋白质组学 · 网络药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Pharmaceutica Sinica B · 2024 · IF 14.7

GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection

Ruizhe Nie,Xinting Zhou,Jiaru Fu,Shanshan Hu,Qilu Zhang,Weikai Jiang,Yizi Yan,Xian Cao,Danhua Yuan,Yan Long,Hao Hong,Susu Tang

Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.

CAS / MDL: 163706-36-3
研究领域: 神经科学 · 药理学 · 分子生物学 · 行为科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Inflammation Research · 2021 · IF 6.922

Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis

Tiantian Wang,Lei Gao,Zejun Yang,Feifei Wang,Yuexin Guo,Boya Wang,Rongxuan Hua,Hongwei Shang,Jingdong Xu

Purpose Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels. Methods Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing. Results The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (Mφ) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio. Conclusion Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.

研究领域: 心血管疾病 · 药理学 · 免疫学 · 微生物学 · 病理生理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Lycopene Alleviates Chronic Stress-Induced Spleen Apoptosis and Immunosuppression via Inhibiting the Notch Signaling Pathway in Rats

Jiuyan Zhang,Yuan Zhao,Ning Sun,Manyu Song,Yongping Chen,Lin Li,Hailin Cui,Haotian Yang,Chuqiao Wang,Haiyang Zhang,Honggang Fan

Chronic stress induction in immunosuppression and splenocyte apoptosis is commonly associated with increased susceptibility to various diseases. Lycopene (LYC) is a member of the carotenoid family with immune restoration and anti-apoptotic function. However, little is known about the mechanisms underlying the protective roles of LYC against spleen injury induced by chronic stress. Herein, male Wistar rats were undergoing chronic restraint stress and/or administered LYC (10 mg/kg) for 21 days. The effective model establishment was validated by open-field tests and levels of corticosterone in serum. Histopathological staining observation displayed that LYC could reduce chronic stress-induced spleen structure damage. Furthermore, LYC treatment significantly reduced the number of apoptotic-positive splenocytes caused by chronic stress via the death receptor apoptotic pathway. We detected the interleukin 4 and interferon γ levels in serum and spleen to determine the ratio of Th1 and Th2 and found that LYC can alleviate the immunosuppression induced by chronic stress. Notably, western blot and real-time polymerase chain reaction indicated that LYC can reduce the expression of the Notch-pathway-related proteins and mRNA in rats exposed to chronic stress. Further study of the potential mechanisms by adding the Notch pathway inhibitor DAPT revealed that LYC alleviates the structure damage, apoptosis, and immunosuppression caused by chronic stress via the suppression of the Notch pathway. Overall, this study presents a strong rationale to target LYC as a treatment strategy to relieve chronic stress-induced spleen injury.

研究领域: 免疫学 · 药理学 · 分子生物学 · 应激生理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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