BMC Oral Health
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2024
·Vol. 24
·期 1
·1-12
·
IF 2.6
Li Wei,Jiao Ruofeng,Luo Shiyi,Liu Zefei,Song Jukun,Chen Zhu
Objective Explore the therapeutic mechanism of Coptidis Rhizome (CR) in periodontitis using network pharmacology, and validate it through molecular docking and in vitro experiments. Methods Screened potential active components and target genes of CR from TCMSP and Swiss databases. Identified periodontitis-related target genes using GeneCards. Found common target genes using Venny. Conducted GO and KEGG pathway analysis. Performed molecular docking and in vitro experiments using Berberine, the main active component of CR, on lymphocytes from healthy and periodontitis patients. Assessed effects on inflammatory factors using CCK-8, flow cytometry, and ELISA. Results Fourteen active components and 291 targets of CR were identified. 30 intersecting target genes with periodontitis were found. GO and KEGG analysis revealed oxidative stress response and IL-17 signaling pathway as key mechanisms. Molecular docking showed strong binding of Berberine with ALOX5, AKT1, NOS2, and TNF. In vitro experiments have demonstrated the ability of berberine to inhibit the expression of Th17 + and other immune related cells in LPS stimulated lymphocytes, and reduce the secretion of IL-6, IL-8, and IL-17. Conclusion CR treats periodontitis through a multi-component, multi-target, and multi-pathway approach. Berberine, its key component, acts through the IL-17 signaling pathway to exert anti-inflammatory effects.
研究领域:
药理学
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牙医学
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分子生物学
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免疫学
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PubMed
高影响因子
Tissue Engineering and Regenerative Medicine
·
2021
·Vol. 18
·期 1
·113-125
·
IF 4.169
Mou Donggang,Yu Qunying,Zhang Jimei,Zhou Jianping,Li Xinmin,Zhuang Weiyi,Yang Xuming
Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.
研究领域:
骨科
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生物材料
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药理学
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风湿病学
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 7
·1043
·
IF 5.7
Xiaoxuan Mo,Fan Gao,Jiaye Tian,Fengyue Xu,Zeyang Xie,Hongyan Wei,Jinhu Yang,Jianming Jiang,Guoxing Deng,Qiuhong Guo
Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG.Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism.Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived fromCoptis chinensisFranch. andPogostemon cablin(Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism.Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG.
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高影响因子
Bioactive Materials
·
2024
·
IF 18
Hao Zhou,Jinpeng He,Renfeng Liu,Jun Cheng,Yuhao Yuan,Wanpu Mao,Jun Zhou,Honghui He,Qianqi Liu,Wei Tan,Cijun Shuai,Youwen Deng
Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.
研究领域:
生物医学工程
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组织工程
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骨科
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Minghui Wang,Xiaoxuan Xu,Mingxuan Sheng,Ming Zhang,Fang Wu,Zhi Zhao,Meng Guo,Bing Fang,Jianmin Wu
Tannic acid, a bioactive polyphenol found in various phytogenic foods and medicinal plants, has potential prevention effects on colitis, though more evidence and mechanistic studies are required to substantiate this. In this study, we investigated the effects of different doses from 0 to 3 mg/mL of tannic acid on mice, ultimately selecting a dose of 3 mg/mL for the anti-colitis trial based on growth and intestinal morphology assessments. Using the DSS-induced colitis model, we found that tannic acid may alleviate colitis by inhibiting the IL-17 - NF-κB p65 signaling pathway and modulating epigenetic pathways, particularly methylation modifications. Additionally, tannic acid altered the gut microbiota, increasing the abundances of Prevotella , Eubacterium_siraeum_group , and Enterorhabdus in the colon. Supplementation with Eubacterium siraeum via gavage also inhibited colitis, accompanied by increased folate and methylation regulators in the colon. These findings suggest that tannic acid may inhibit colitis through the suppression of the IL-17 - NF-κB pathway and the enhancement of microbiota-mediated methylation pathways.
研究领域:
免疫学
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胃肠病学
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微生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2024
·
IF 2.8
Tong Zhang,Zhuoqian Guo,Tao Ma,Shanlan Li,Ziqi Dai,Yujin Luo,Feng Gao,Qi Zeng,Jihui Lu,Junshuai Wang,Yongli Liu,Bing Xu,Haimin Lei
Qingfei Decoction (QFD) is recognized as one of the 100 classic prescriptions by the National Administration of Traditional Chinese Medicine of China and is widely used for the treatment of pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory condition primarily characterized by airway obstruction. It’s necessary to examine the therapeutic effect of QFD in the treatment of COPD and elucidate its potential effective components, targets, and pathways. This study utilized UHPLC coupled with HRMS to identify the chemical constituents of QFD, resulting in the qualitative analysis of 68 compounds. Network pharmacology predicted 30 gene targets, including IL6, AKT1, and EGFR, and revealed 45 compounds, including ruscogenin, schisandrin A, and esculetin that may contribute to its therapeutic effects on COPD. Subsequently, an elastase-induced COPD mouse model was employed to evaluate the efficacy of QFD. The effects of QFD were assessed through hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and real-time quantitative polymerase chain reaction (RT-qPCR) on lung tissues. Transcriptomic analysis indicating QFD treatment of COPD primarily acted on the IL-17 signaling pathway, which was consistent with the network pharmacology results. Furthermore, RT-qPCR, immunofluorescence, and western blot demonstrated reduced mRNA and protein expression levels of TRAF3IP2, TRAF6, IL17, and TNFα. These findings confirmed that QFD effectively reduced inflammation, likely by down-regulating the IL-17 signaling pathway, thereby treating COPD.
研究领域:
中医药学
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药理学
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呼吸系统疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
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IF 4.4
Zhang Jinju,Lin Danlin,Wu Yuting,Chen Lixia,Ma Zhiguo,Wu Menghua,Liu Xindan,Zhang Ying,Cao Hui
Background: Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao’s blood-supplementing effect and to explore the specific peptides contributing to its efficacy.Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms.Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao’s efficacy.Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.
研究领域:
药理学
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传统中药
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肽组学
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分子生物学
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DOI
PubMed
高影响因子
Advanced Science
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2024
·
IF 14.3
Zi Yi Wang,Ze Qiang Zhao,Yu Jun Sheng,Ke Jun Chen,Bo Zhi Chen,Xin Dong Guo,Yong Cui
Psoriasis is a chronic, immune-mediated disorder characterized by immune regulation disorders and abnormal keratinocyte proliferation. Deucravacitinib (Deu), a selective oral Tyrosine Kinase 2 (TYK2) inhibitor, shows promise in treating psoriasis but may cause systemic side effects and fail to address persistent localized thickened lesions. Herein, a self-locking microneedle (MN) patch with a polyvinyl alcohol (PVA) inner ring loaded with Deu is developed, designed to penetrate the transdermal barriers and dissolve rapidly, downregulating the IL-23/IL-17 pathway and serve as the first line of defense against the spread of skin-originated inflammation. Additionally, Calcipotriol (Cal), a vitamin D derivative, is incorporated into a methacrylated hyaluronic acid (HAMA) backing layer and outer ring that mimics occlusive administration, maintaining localized skin surface retention for prolonged anti-proliferative therapy. The Deu@Cal MN demonstrates satisfactory adhesiveness due to swelling-mediated mechanical interlocking via the outer ring, ensuring targeted drug release at lesion site. Besides its effectiveness in alleviating both skin inflammation and proliferation, it inhibits the differentiation of Th17 cells in the spleen, suggesting potential to reduce systemic inflammation. These findings offer a new therapeutic approach for treating psoriasis and other autoimmune and inflammatory conditions.
研究领域:
药学
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皮肤科
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免疫学
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2017
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IF 6.429
Ren Wenkai,Yin Jie,Xiao Hao,Chen Shuai,Liu Gang,Tan Bie,Li Nengzhang,Peng Yuanyi,Li Tiejun,Zeng Benhua,Li Wenxia,Wei Hong,Yin Zhinan,Wu Guoyao,Hardwidge Philip R.,Yin Yulong
Intestinal microbiota has critical importance in pathogenesis of intestinal infection; however, the role of intestinal microbiota in intestinal immunity during enterotoxigenic Escherichia coli (ETEC) infection is poorly understood. The present study tested the hypothesis that the intestinal microbiota is associated with intestinal interleukin-17 (IL-17) expression in response to ETEC infection. Here, we found ETEC infection induced expression of intestinal IL-17 and dysbiosis of intestinal microbiota, increasing abundance of γ-aminobutyric acid (GABA)-producing Lactococcus lactis subsp. lactis. Antibiotics treatment in mice lowered the expression of intestinal IL-17 during ETEC infection, while GABA or L. lactis subsp. lactis administration restored the expression of intestinal IL-17. L. lactis subsp. lactis administration also promoted expression of intestinal IL-17 in germ-free mice during ETEC infection. GABA enhanced intestinal IL-17 expression in the context of ETEC infection through activating mechanistic target of rapamycin complex 1 (mTORC1)-ribosomal protein S6 kinase 1 (S6K1) signaling. GABA–mTORC1 signaling also affected intestinal IL-17 expression in response to Citrobacter rodentium infection and in drug-induced model of intestinal inflammation. These findings highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases.
研究领域:
微生物学
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免疫学
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病理学
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分子生物学
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DOI
PubMed
高影响因子
HEREDITAS
·
2024
·Vol. 161
·期 1
·1-17
·
IF 2.1
Zheng Jianxiu,Wang Liyan,Liu Ahui,Shen Haofei,Wang Bin,Jiang Yanbiao,Jing Panpan,Guan Defeng,Yu Liulin,Zhang Xuehong
Background Indole-3-acetic acid (IAA), an indole analog produced by intestinal microorganisms metabolizing tryptophan, has anti-inflammatory and antioxidant properties and thus has potential applications in ovarian protection, although the exact mechanism is unknown. The present study preliminarily investigated the pharmacological mechanism of IAA in alleviating diminished ovarian reserve (DOR) by network pharmacology and molecular docking. Methods Relevant target proteins of IAA were searched in SwissTargetPrediction, PharmMapper, TargetNet, BATMAN-TCM, and SuperPred databases. The potential targets of DOR were obtained from GeneCards, DisGenet, OMIM, and Drugbank databases. Both common targets were then imported into the String website to construct a PPI network, and these targets were analyzed for GO and KEGG enrichment. Finally, we utilized molecular docking to validate the possible binding conformations between IAA and the candidate targets. We used in vitro experiments to preliminarily investigate the effects of IAA on DOR. Results We obtained 88 potential targets for IAA and DOR interaction. We received 16 pivotal targets by constructed protein interaction screening. KEGG enrichment analysis mainly included the AGE-RAGE signaling pathway, IL-17 signaling pathway, Chemical carcinogenesis—reactive oxygen species in diabetic complications, etc. GO functional analysis showed that IAA treatment of DOR may involve biological processes such as response to external stimuli, hypoxia, gene expression, and regulation of enzyme activity. Molecular docking and in vitro experiments further revealed the potential effects of IAA on MMP2, TNF-α, AKT1, HSP90AA1, and NF-κ B. Conclusion We preliminarily revealed the potential protective effects of IAA against DOR through multiple targets and pathways, which provides a new research strategy for the molecular mechanism of IAA to alleviate DOR in the future. However, further studies need to demonstrate whether IAA can be used as a compound to prevent and treat DOR.
研究领域:
药理学
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分子生物学
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生殖医学
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生物信息学
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DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2024
·
IF 9.1
Chuanhong Wu,Chaoyong Wu,Lixia Peng,Mingxuan Wu,Zhiqiang Li,Jianxin Chen
After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG’s effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene ( Ahr ), inflammatory cytokines genes ( IL-17a , IL-22 ), and an important coding gene for maintaining the mature Th17 ( rorc ) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.
研究领域:
中医药
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神经科学
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药理学
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微生物组研究
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分子生物学
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DOI
PubMed
高影响因子
npj Biofilms and Microbiomes
·
2025
·Vol. 11
·期 1
·1-17
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IF 9.2
Yang Ruili,Xu Yi,Xu Jinchun,Huang Chengqing,Zhu Feng,Wang Tian,Kong Rui,Xiao Jie,He Biao,Gu Xiaozhen,Wang Hui-Li
As a prevalent neurodevelopmental disease, whether ASD (autism spectrum disorder) can be ameliorated by the early use of a single microbe remains unknown. Here we used a lactobacillus strain, Lacticaseibacillus rhamnosus GR-1 (LGR-1), for prenatal intervention in autism-like mice with either environmental or idiopathic origins by exclusively administering to the pregnant dams at a dose of 10 9 /mouse/day, followed by offspring behavioral assessment with 3-chamber trial and marble burying test. The results revealed that LGR-1 prevented the occurrence of autism-like symptoms, as evidenced by the improved behaviors and restored E/I (excitatory-inhibitory) balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, probably mediated by the vertical transmission of maternal microbiome, with its roles further unraveled by fecal microbiota transplant and cross-fostering experiments. In addition to gut commensals, the LGR-1-shaping vaginal microbiota also contributed to the establishment of “beneficial” microbiome. Regarding key taxa in offspring, Akkermansia muciniphila was influenced by LGR-1 and exerted impact on behaviors via pathways related to IL-17-producing lymphocytes. Our findings demonstrate that prenatal microbial administration protects offspring against autism-like behavioral phenotypes through microbiome transmission, highlighting a potential microbe-based therapeutic avenue to mitigate ASD risk.
研究领域:
微生物学
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神经发育学
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围产期医学
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免疫学
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转化医学
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分子生物学
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菌群-宿主互作
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PubMed
高影响因子
危险品化学品经营许可证（带存储）