PHYTOMEDICINE
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2024
·
IF 6.7
Wang Yi,Jiang Yu,Li Mingxing,Xiao Yaqin,Zhao Qianyun,Zeng Jiuping,Wei Shulin,Chen Shuhan,Zhao Yueshui,Du Fukuan,Chen Yu,Deng Shuai,Shen Jing,Li Xiaobing,Li Wanping,Wang Fang,Sun Yuhong,Gu Li,Xiao Zhangang,Wang Shengpeng,Wu Xu
Background Rosavin (RSV) is a naturally occurring compound isolated from Rhodiola species. While RSV has been reported with pharmacological activities of anti-oxidation, anti-inflammation, anti-stress and immunomodulation, its effect on colitis and the underlying mechanisms remain unclear. Purpose This study aims to investigate whether and how RSV alleviated colitis in mice. Study design and methods The protective effect of RSV (50, 100, 200 mg/kg, p.o.) was investigated in dextran sulfate sodium (DSS) mediated mouse models of acute and chronic colitis. Alterations in fecal microbiota were evaluated by 16S rRNA sequencing. Pseudo germ-free mice achieved by antibiotics treatment were applied to assess the RSV-mediated functional role of gut microbiota in colitis. RNA sequencing was performed to determine RSV-induced colonic response. Primary T cell culture was conducted to examine the effect of RSV on Th17 and Treg differentiation. Whole blood assay, dual luciferase reporter assay, and molecular docking methods were applied to investigate the mechanisms and targets of RSV in Th17 regulation. Results Oral RSV significantly relieved DSS-mediated acute and chronic colitis in mice, which recovered body weight loss, reduced disease activity index, alleviated colon injury, inhibited inflammation, suppressed the apoptosis of intestinal epithelia, and maintained intestinal barrier function. Moreover, RSV specifically regulated intestinal microbiota by recovering DSS-mediated microbial changes and elevating beneficial microbes such as Lactobacillus and Akkermansia . Antibiotics treatment experiment showed that the protective role of RSV was at least partially dependent on gut microbiota; however, in vitro incubation showed that RSV did not directly promote the growth of Lactobacillus and Akkermansia strains. Further analysis showed that RSV-mediated genetic alterations in colon were enriched in pathways related to lymphocyte regulation. Additionally, RSV regulated the balance of Th17/Treg in colitis mice. Importantly, RSV inhibited the differentiation of Th17 cell in vitro , suppressed the production of IL-17 by Th17 cells, and downregulated Rorc encoding RORγt and its downstream Il17 . RSV significantly inhibited the RORγt transcription activity and bound to its ligand binding domain. Conclusion RSV alleviates murine colitis through regulating intestinal immunity. Notably, RSV is identified as a novel regulator of Th17 cells that inhibits RORγt-mediated Th17 differentiation. These findings potentiate the Rhodiola -derived natural chemicals as novel anti-colitis agents.
研究领域:
药理学
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免疫学
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微生物学
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分子生物学
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DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·
IF 7.3
Fangzhou Lou,Zhenyao Xu,Jing Bai,Xing’e Zhao,Linlin Cui,Qun Li,Honglin Wang
Background and Purpose Psoriasis vulgaris is a refractory skin inflammatory disorder with 80% of the cases belonging to the mild-to-moderate type, which can be controlled by topical treatment. Nevertheless, the drugs for external use have not been upgraded for decades. We modified acetyl-11-keto-beta-boswellic acid (ABKA), a natural compound shown to treat psoriasis animal models, to achieve improved efficacy and solubility for external use. Experimental approach Eleven compounds were synthesized using AKBA as a lead compound, and their effects on T helper 17 (Th17) cell differentiation were screened. 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid (CKBA) potently inhibited Th17 cell differentiation and we investigated its efficacy on treating a mouse model of psoriasis along with its pharmacology and safety profile when topically or systemically delivered to several species. Key Results CKBA inhibited mouse and human Th17 cell differentiation with an IC 50 of 3.28 μM and 3.61 μM respectively and directly targeted acetyl-CoA carboxylase 1 (ACC1). Safety evaluation and toxicity tests suggested that systemically delivered high-dose CKBA for 14 days had no dose-associated adverse effects on the central nervous, hematopoietic, cardiovascular, respiratory, and digestive systems of cynomolgus monkeys. CKBA ointment permeated the skin and did not irritate or sensitize intact skin. CKBA ointment mediated dose-dependent suppression of imiquimod-induced psoriasis-like skin inflammation with slow absorption and limited bioavailability (<10% in rats and <1% in minipigs). Conclusions and Implications CKBA is safe when topically or systemically delivered to animals. The positive effects of CKBA ointment in treating a mouse model of psoriasis indicate that this is a promising psoriasis drug candidate for further development.
研究领域:
药理学
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皮肤病学
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免疫学
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DOI
PubMed
高影响因子
Food & Function
·
2024
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IF 5.1
Xing Zhang,xiao chen,Fan Yang,Huming Shao,Tianliang Bai,Xuanyi Meng,Yong Wu,Anshu Yang,Hongbing Chen,Xin Li
The exposure of food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information of these changes may help in better understanding food allergy. In this research, we explored the relationship between food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proven to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergy, by building a unique animal model based on allergen-containing diet feeding. After 7-day consumption of an allergen-containing diet, the allergic mice showed severe enteritis with raised luminal ATP levels. The luminal dysregulated ATP deteriorated food-induced enteritis by boosting Th17 cell responses and promoting mucosal neutrophil accumulation. In vitro experiments indicated that the intervention of ATP promoted the differentiation of Th17 cells and the activation of neutrophils. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that the food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to food challenge by manipulating intestinal Th17 cells and neutrophils.
研究领域:
免疫学
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医学
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微生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2024
·Vol. 14
·期 49
·36804-36815
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IF 3.9
Yi Zheng,Haochen Liu,Bingkun Lu,Muchen Dong,Xinhai Wang
Dry eye syndrome (DES) is a prevalent condition linked to oxidative stress from Orthokeratology (OK) lens use, causing significant discomfort and impacting quality of life. Herein, this study investigates the role of Reactive Oxygen Species (ROS) in modulating T cell responses, particularly Th17 cells and IL-17A production, which are central to DES pathogenesis. We propose a novel therapeutic strategy using ceria nanoparticles (CeNPs) for ocular ROS clearance, hypothesized to attenuate Th17 activation and IL-1β and IL-17A production, thereby reducing DES symptoms. We developed a hybrid coating for OK lenses using Schiff base reactions to link tannic acid with CeNPs, aiming to neutralize ROS and mitigate inflammation. This approach could offer a transformative treatment for DES, especially among OK lens users. In comparison to existing therapies, our approach demonstrated a 70% reduction in corneal inflammation markers and a 2.5-fold increase in tear secretion, offering a transformative treatment for DES, especially among OK lens users.
研究领域:
免疫学
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眼科
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2019
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IF 3.414
Xiao Qiang Li,Yong Chen,Hong Mei Zhou,Hui Li Shi,Xiao Ning Yan,Li Ping Lin,Ren Xiang Tan
Ethnopharmacological relevance Rosin, an exudate of conifer trees such as Pinus masscnlana (Pinaceae), has been used to treat psoriasis for nearly two thousand years in China despite its so far undefined pharmacology. Unfortunately, the rosin intoxication is noted from time to time, but the water-boiled rosin (WBR) has been documented to be safer. This study was performed to evaluate the in vivo anti-psoriasis efficacy of WBR. Materials and methods The main phytochemicals in WBR were quantified by high performance liquid chromatography (HPLC). WBR was evaluated in the imiquimod-induced psoriasis-like inflammation mouse model for its anti-psoriasis effect at 130, 260, and 390 mg/kg, which were set according to the dose used for patients. Through a combination of q-PCR, flow cytometry, and histopathological and immunohistochemical (IHC) analysis, the in vivo efficacy was assessed in terms of the psoriasis area severity index (PASI), epidermal keratinocyte proliferation, Th1 and Th17 cell numbers in spleen, and mRNA expressions of inflammatory cytokines. Result Oral administration of WBR ameliorates the psoriasis-like dermatitis in the imiquimod-generated mouse model. In particular, WBR given at 260 or 390 mg/kg significantly restores the normal keratinization of dorsal lesion if compared with the untreated psoriatic mice. Such an effect was addressed to correlate to the Th1/Th17 cell reduction in spleen and the suppressed expression of IL-17A, IL-17F, IL-22, IL-23, TNF- α , K17, and proliferating cell nuclear antigen (PCNA) after the WBR administration. Conclusion WBR is effective in the imiquimod-induced psoriasis-like inflammation mouse model with the efficacy arising from its proliferation inhibition of Th1/Th17 cells and epidermal keratinocytes via the down-regulation of the relevant inflammatory cytokines such as IL-23, IL-17A, and IL-17F. Collectively, WBR harvested and processed in the traditional manner is an efficacious psoriasis-treating agent.
研究领域:
药理学
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免疫学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2025
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IF 3.9
Yijun Yang,Nengyi Wang,Yuankun Chen,Tianpeng Ma,Minhua Weng,Haifeng Wu,Qiuping Wu,Yiqiang Xie,Chuanwu Zhu,Wenting Li
Nonalcoholic fatty liver disease (NAFLD) has posed a huge threat to public health globally, but there are currently no approved drugs available. Growing evidence has proved the close association between increased Th17 cells and NAFLD progression. Interleukin-4 induced protein 1 (IL4I1), an amino acid oxidase secreted by immune cells, was reported to regulate the Th17 cells, but its exact role in NAFLD progression has not been fully explained yet. We found that IL4I1 was highly expressed in the liver of C57BL/6J mice with NAFLD induced by an 8-weeks western diet. To explore the IL4I1’s effect, mice were injected with AAV8 encoding IL4I1 1 week before western diet administration. The results showed that IL4I1 overexpression inhibited the NAFLD progression, demonstrated by relieved liver damage and lipid accumulation. The underlying mechanism in which IL4I1 acts on NAFLD might be attributed to the inactivated AKT/forkhead box protein O1 (FOXO1) signaling pathway–mediated decrease of Th17 cells in liver tissues. Subsequently, by culturing naive CD4 + T cells isolated from the spleen of mice in Th17 cell-polarizing conditions, we determined that IL4I1 overexpression inhibited Th17 cell differentiation by inactivating the AKT/FOXO1 pathway, whereas its knockdown exhibited opposite effects. Further, the AKT activator SC79 reversed the effect of IL4I1 overexpression on Th17 cell differentiation. Collectively, our study supports that compensatory upregulation of IL4I1 protects against liver damage and lipid accumulation in NAFLD progression, partially by inhibiting the activated AKT/FOXO1 signaling pathway-induced Th17 cell differentiation.
研究领域:
免疫学
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肝病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
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IF 5.714
Yilei Guo,Dandan Sun,Yajing Zhang,Xiaoxiao Yu,Yulai Fang,Changjun Lv,Qin Zhang,Yanrong Zhu,Simiao Qiao,Yufeng Xia,Zhifeng Wei,Yue Dai
The neuropeptide cortistatin (CST) has been reported to attenuate Th17 cell response in multiple disease models, but the mechanism of action remains obscure. Here, we show that either overexpression or exogenous addition of CST obviously restricts Th17 cell differentiation. As metabolic reprogramming plays an important role in Th17 cell development, we explore whether CST inhibits Th17 cell differentiation by regulating glycolysis. The results show that CST substantially attenuates the glycolysis during Th17 differentiation and down-regulates the mRNA expression of myelocytomatosis oncogene (Myc) and hexokinase 2 (HK2), the glycolysis rate-limiting enzyme. Following the overexpression of Myc and HK2, the inhibitory effect of CST on Th17 differentiation nearly disappears, suggesting that Myc-HK2 pathway is deeply involved. Furthermore, growth hormone secretagogue receptor 1 (GHSR1) is identified as the key receptor subtype for CST attenuating glycolysis and Th17 cell differentiation by the combined uses of CST with various receptor subtype blockers. The knockdown of GHSR1 abrogates the inhibition of CST on Th17 differentiation and glycolysis. Finally, in the colitis mice induced by dextran sulfate sodium, an intraperitoneal injection of CST markedly inhibits Th17 cell response and down-regulates the expression of HK2 in the Th17 cells, which is reversed by the combined use of GHSR1 antagonist. These findings suggest that inhibition of glycolysis is the key pathway for CST attenuating Th17 cell response, and GHSR1, Myc and HK2 are potential therapeutic targets of Th17 cell-related diseases.
研究领域:
免疫学
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细胞生物学
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神经内分泌学
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产品关联
DOI
PubMed
高影响因子
American Journal of Rhinology & Allergy
·
2021
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IF 2.467
Zhiqi Ma,Haijuan Lian,Xiaoyan Lin,Yong Li
BackgroundAllergic rhinitis (AR) is one of the most common noninfectious respiratory diseases caused by immunoglobulin E (IgE) response.ObjectiveThe study sought to explore the relationship between lncRNA MIAT and miR-10b-5p and their interaction in the regulation of allergic phenotypes in allergic rhinitis (AR) mice.MethodsA mice model of AR was constructed using ovalbumin (OVA) sensitization. AR mice were treated with miR-10b-5p agomiR and LNA mediated lncRNA MIAT. The targeting relationship between MIAT and miR-10b-5p was analyzed by the ENCORI website and dual-luciferase reporter assay. The numbers of rubbing and sneezing of mice were counted. Hematoxylin-eosin (HE) staining visualized the eosinophils infiltration in nasal mucosa tissues of mice. The percentage of Th17 cells was quantitated by flow cytometry analysis. ELISA was used to detect the levels of serum OVA-specific IgE, the Th12 cytokine IL-4, and inflammatory cytokines (IL-6, IL-17).ResultsMIAT was up-regulated in the nasal mucosa of AR mice, while miR-10b-5p was down-regulated. MIAT directly suppressed miR-10b-5p expression in AR mice. The numbers of rubbing and sneezing, the percentage of Th17 cells, and the levels of OVA-specific IgE, IL-4, IL-6, and IL-17 in AR mice were decreased by miR-10b-5p overexpression, which was reversed by MIAT overexpression. The eosinophils infiltration in AR mice was inhibited by miR-10b-5p overexpression, which was also reversed by MIAT overexpression.ConclusionThe present study demonstrates that MIAT overexpression Promotes allergic inflammation and symptoms by activating Th17 immune response via miR-10b-5p inhibition.
研究领域:
免疫学
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分子生物学
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过敏
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产品关联
DOI
PubMed
高影响因子
Journal of Traditional and Complementary Medicine
·
2024
·
IF 3.3
Jilang Li,Haixin Qiu,Siyuan Li,Shan Han,Yuming He,Jia He,Xiang Gao,Jingjing Li,Jianfang Feng,Shilin Yang,Renyikun Yuan,Hongwei Gao
Background and aim Pulsatilla saponin (Ps) was isolated from Pulsatilla chinensis (Bunge) Regel, a traditional Chinese medicine, that has anti-proliferation, anti-inflammation, anti-tumor and immunomodulation activities. However, the anti-psoriasis activity of Ps and its underlying mechanisms have not been fully elucidated. This study aims to investigate the effect and potential mechanisms of Ps on psoriasis. Experimental procedure Ps underwent quality control through HPLC and NMR analysis. Wound healing assay, MTT, clone assay, and EdU staining were used to detect HaCaT cells proliferation. Western blot and immunofluorescence were used to assess the expression of proteins. The th17 cells population was analyzed by flow cytometry. The levels of cytokines in the mice skin tissues were measured by RT-qPCR and ELISA. Results and conclusion In vitro, Ps has an inhibition effect on the proliferation of M5-induced HaCaT cells. Ps inhibited proliferation by regulating NF-κB and JAK1/STAT3 pathways. Additionally, Ps decreased TNF-α, IL-1β, and IL-6 mRNA levels in M5-induced HaCaT cells. In vivo, Ps improved the pathological damage of Imiquimod (IMQ)-induced psoriasis BALB/c mice skin and reduced the Ki67 level in mice skin tissue. Further results showed that Ps decreased Th17 cells differentiation and IL-22, IL-17A, IL-6, IFN-γ, TNF-α, and IL-1β secretion. Ps could ameliorate the psoriatic symptoms, decrease M5-induced HaCaT cell proliferation, and decrease the differentiation of Th17 cells in IMQ-induced psoriasis mice. Ps suppressed the release of inflammation cytokines by regulating NF-κB and JAK1/STAT3 pathways. Those results indicate that Ps has promising therapeutic potential for psoriasis treatment.
研究领域:
药理学
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免疫学
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皮肤病学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Nutrients
·
2024
·Vol. 16
·期 13
·2052
·
IF 4.8
Haidong Wang,Ji Qiu,Minyao Zhou,Yanqiu Luo,Xinyu Li,Minqi Wang
In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.
研究领域:
微生物学
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免疫学
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营养学
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动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zherui Fu,Yiwen Xu,Fangqi Xu,Haoyu Zhou,Na Lin,Ning Zhang,Feng Lin
The incidence of steroid-induced osteonecrosis of the femoral head (SONFH) is increasing annually; however, the underlying pathological mechanism remains unclear, which is an obstacle to its effective treatment. The negative effect of immune infiltration on the physiological activity of focal stem cells is one potential mechanism that has attracted attention. It is difficult to simulate the complex regulation of the interaction system between immune cells and stem cells using a single regulation method. In this study, we demonstrated that the immune infiltration of T helper 17 (Th17) cells plays an important role in the progression of SONFH. Based on this finding, we developed an injectable hydrogel system with both physical and chemical synergistic regulatory properties to enhance the activity of stem cells using electrical stimulation. This treatment was designed to prevent the infiltration of Th17 cells by regulating the physiological function of stem cells and blocking the negative effect of Th17 cells on stem cells pharmacologically. Thus, the dual synergistic regulation of immune infiltration at the lesion site of SONFH enhanced the physiological activity and function of the stem cells, thereby improving the therapeutic effect of SONFH. This hydrogel system provides insight for the future development of multifactorial regulatory systems and provides a strategy for the treatment of SONFH.
研究领域:
医学
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生物材料学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1395-1405
·
IF 2.693
Dan Wang,Zikun Zhang,Zekun Si,Yanlin Yang,Shuangshuang Li,Yaoming Xue
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
研究领域:
药理学
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免疫学
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糖尿病学
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肾病学
✓ 已验证
DOI
PubMed
高影响因子
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