JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jiahui Wang,Wei Liu,Jia Lu,Mengyue Zhu,Yanni Wu,Wenhui Pan,Boyi Fan,Yan Song,Wenli Wang,Guangtong Chen
The prevalence of neurodegenerative diseases has increased in recent decades. Its exact pathogenesis is not yet fully understood, and only a few drugs can be used clinically to alleviate disease symptoms. Increasing evidence highlights plant-derived compounds are becoming a promising resource for mitigating the onset and progression of neurodegenerative diseases. Uvaol (1) is an ursane-type triterpenoid commonly found in olive leaves, fruits, and virgin olive oil. It is one of the rare compounds in olive oil that can penetrate the blood–brain barrier. Despite its potential neuroprotective activity, research on its structural variations and antineuroinflammatory properties remains sparse. This study explored the biotransformation of uvaol using three fungal species: Actinomucor elegans, Aspergillus flavus, and Circinella muscae. This process yielded 15 new compounds along with seven known ones. Their structures were determined through comprehensive spectroscopic analysis. Furthermore, the antineuroinflammatory activities of compounds were evaluated by using MTT and Griess assays. Notably, compound 9 was found to markedly suppress the transcriptional levels of inflammation-associated elements such as TNF-α, IL-1β, IL-6, iNOS, and COX-2 in BV-2 cells stimulated by lipopolysaccharides (LPS). Moreover, compound 9 also facilitated autophagy by upregulating ULK1 mRNA expression and downregulating the p62 protein. These results suggested that biotransformation was an effective approach for rapidly diversifying uvaol and providing a basal material for the discovery of candidates in treating neurodegenerative diseases.
研究领域:
药理学
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神经科学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2024
·
IF 2.5
Min Li,Wenjia Tong,Chao Dai,Guoping Lu,Danqun Jin,Fang Deng
Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.
研究领域:
免疫学
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肾病学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
Food Science & Nutrition
·
2019
·Vol. 7
·期 3
·949-958
·
IF 1.747
Yaqiong Zhang,Ming Li,Hang Gao,Bo Wang,Xu Tongcheng,Boyan Gao,Liangli (Lucy) Yu
In this study, a new red sorghum variety (Ji Liang No. 1) was investigated for its triacylglycerol (TAG) and fatty acid profiles, carotenoid and tocopherol compositions, total phenolic, total flavonoid and phenolic acid contents, and antioxidant and anti-inflammatory properties. A total of 17 TAGs were identified in the red sorghum oil. Linoleic and oleic acids were the primary fatty acids, contributing more than 80% of the total fatty acids. β-Carotene was the primary carotenoid at a level of 26.14 μg/g. α-, γ-, and δ-tocopherols were at levels of 0.19, 4.08, and 0.10 μg/g, respectively. Moreover, acetone–water (60:40, v/v) extract of the red sorghum exhibited the greatest total phenolic content of 2.77 mg GAE/g and total flavonoid content of 5.44 mg RE/g. The extract had scavenging capacities against DPPH, ABTS + , and peroxyl radicals and suppressed LPS stimulated IL-1β, IL-6, and COX-2 mRNA expressions in a dose-dependent manner. Ferulic, p -coumaric, isoferulic, and p -hydroxybenzoic acids were found in the red sorghum, with ferulic acid as the predominant phenolic acid and mostly in an insoluble bound form. These data indicated a potential utilization of the red sorghum in health-promoting functional food or supplemental products.
研究领域:
农业
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食品科学
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营养学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Wenze Zhang,Zhuoxia Shen,Chaoran Li,Yumeng Yang,Tiange Zhang,Bo-Yang Yu,Xianchuang Zheng,Jiangwei Tian
Hepatic ischemia reperfusion injury (HIRI) following transplantation or resection can lead to irreversible liver dysfunction and even failure, yet current therapeutic interventions are limited. Herein, we introduce a “defend–attack and capture flag” nanotheranostic strategy for the cascade management of HIRI. Firstly, the NIR-II photothermal pretreatment with the developed nanosystem provides preprotection for the liver, acting as “defend”. Subsequently, the pharmacotherapy furnishes direct cure for HIRI via the delivery and controlled release of wedelolactone from the nanosystem, serving as “attack”. Meanwhile, the photoacoustic (PA) imaging ability of the nanosystem enables the real-time monitoring of the inflammatory hypoxia, which is the “flag” to be captured in HIRI treatment. The photothermal preprotection can activate heat shock factor 1 (HSF-1), while the pharmaceutical therapy directly attacks NF-κB, both of which eventually inhibits NLRP3 inflammasome, thus reducing the activity of proinflammatory cytokine IL-1β, ending up with the alleviation of necrosis and apoptosis in HIRI. Such treatment effect can be reported by the real-time PA imaging. By the organic combination of the above three-step mechanism, significantly enhanced therapeutic efficacy was achieved in the animal model of HIRI, providing an effective solution for overcoming the challenge of HIRI.
研究领域:
纳米技术
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药学
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医学影像
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移植医学
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炎症生物学
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产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2017
·
IF 4.581
Xiaoguang Gao,Ting Fu,Changyuan Wang,Chenqing Ning,Yulong Kong,Zhihao Liu,Huijun Sun,Xiaodong Ma,Kexin Liu,Qiang Meng
Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a novel therapeutic strategy against cholestasis . Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene (AUR), a natural product, can activate FXR to exert hepatoprotective effect against cholestatic liver injury in vivo and in vitro . Importantly, AUR was found to significantly decrease the mortality of cholestatic mice. Dynamic change analysis of bile acids and gene analysis revealed that AUR promoted bile acid efflux from liver into intestine via an induction in FXR-target genes Bsep and Mrp2 expression, and reduced hepatic uptake through an inhibition in Ntcp . Furthermore, AUR reduced bile acid synthesis through repressing FXR-target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in Sult2a1 . In addition, AUR promoted liver repair through an induction in liver regeneration-related gene, and suppressed liver inflammation through repressing inflammation-related gene NF-κB, TNF-α, IL-1β and IL-6. However, the changes in these genes and protein, as well as ameliorative liver histology induced by AUR were abrogated by FXR antagonist guggulsterone in vivo and FXR siRNA in vitro . These findings suggest that AUR may be an effective approach for the prevention against cholestatic liver diseases.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2022
·Vol. 22
·期 1
·1-13
·
IF 2.838
Gong Linna,Miao Zhishuo,Zhang Li,Shi Birui,Xiao Zuoqi,Qiu Panzi,Liu Menghua,Zou Wei
Background Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.Methods The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC–MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).Results The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9—-0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.Conclusion The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.
研究领域:
药理学
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传统中药
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炎症研究
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Mengting Li,Lingyu Ma,Jiahao Lv,Zhe Zheng,Wenyu Lu,Xunkai Yin,Weijiang Lin,Ping Wang,Jian Cui,Lihong Hu,Jian Liu
Acute lung injury (ALI) is a severe respiratory disorder closely associated with the excessive activation of the NLRP3 inflammasome. Oridonin ( Ori ), a natural diterpenoid compound, had been confirmed as a specific covalent NLRP3 inflammasome inhibitor, which was completely different from that of MCC950 . However, the further clinical application of Ori was limited by its weak inhibitory activity against NLRP3 inflammasome (IC 50 = 1240.67 nM). Fortunately, through systematic structure-optimization of Ori , D6 demonstrated the enhancement of IL-1β inhibitory activity (IC 50 = 41.79 nM), which was better than the parent compound Ori . Then, by using SPR, molecular docking and MD simulation, D6 was verified to directly interact with NLRP3 via covalent and non-covalent interaction. The further anti-inflammatory mechanism studies were revealed that D6 could inhibit the activation of NLRP3 inflammasome without affecting the initiation phase of NLRP3 inflammasome activation, and D6 was a broad-spectrum and selective NLRP3 inflammasome inhibitor. Finally, D6 demonstrated a favorable therapeutic effect on LPS-induced ALI in mice model, and the potent pharmacodynamic effect of D6 was correlated with the specific inhibition of NLRP3 inflammasome activation in vivo . Thus, D6 is proved as a potent NLRP3 inhibitor, and has the potential to develop as a novel anti-ALI agent.
研究领域:
药理学
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炎症
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呼吸系统疾病
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药物设计
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 11
·5963
·
IF 4.9
Qi Zhang,Sen Shang,Xu Li,Xiaoyun Lu
The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz) technology, the biological effects of this emerging nonionizing radiation, particularly its influence on immune function, remain insufficiently explored but are progressively attracting attention. Here, we demonstrated that 0.1 sub-THz radiation can modulate the immune system and alleviate symptoms of arthritis in collagen-induced arthritis (CIA) mice through a nonthermal manner. The application of 0.1 sub-THz irradiation led to a decrease in proinflammatory factors within the joints and serum, reducing the levels of blood immune cells and the quantity of splenic CD4+T cells. Notably, 0.1 sub-THz irradiation restored depleted Treg cells in CIA mice and re-established the Th17/Treg equilibrium. These findings suggested that sub-THz irradiation plays a crucial role in systemic immunoregulation. Further exploration of its immune modulation mechanisms revealed the anti-inflammatory properties of 0.1 sub-THz on LPS-stimulated skin keratinocytes. Through the reduction in NF-κB signaling and NLRP3 inflammasome activation, 0.1 sub-THz irradiation effectively decreased the production of inflammatory factors and immune-active substances, including IL-1β and PGE2, in HaCaT cells. Consequently, 0.1 sub-THz irradiation mitigated the inflammatory response and contributed to the maintenance of immune tolerance in CIA mice. This research provided significant new evidence supporting the systemic impacts of 0.1 sub-THz radiation, particularly on the immune system. It also enhanced the field of photoimmunology and offered valuable insights into the potential biomedical applications of 0.1 sub-THz radiation for treating autoimmune diseases.
研究领域:
光免疫学
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免疫学
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风湿病学
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生物医学工程
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辐射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·
IF 4.259
Wanyan Deng,Quanxin Long,Jie Zeng,Ping Li,Wenmin Yang,Xinchun Chen,Jianping Xie
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity. Macrophages infected by M. smegmatis harboring PE_PGRS41 decreased the production of TNF-α, IL-1β and IL-6. In addition, PE_PGRS41 boosted the survival of M. smegmatis within macrophage accompanied with enhanced cytotoxic cell death through inhibiting the cell apoptosis and autophagy. Taken together, these results implicate that PE_PGRS41 is a virulence factor of M. tuberculosis and sufficient to confer pathogenic properties to M. smegmatis.
研究领域:
微生物学
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免疫学
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致病机制
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Dongyi Cao,Ruiying Xi,Hongye Li,Zhonghui Zhang,Xiaoke Shi,Shanshan Li,Yujie Jin,Wanli Liu,Guolin Zhang,Xiaohua Liu,Shunxi Dong,Xiaoming Feng,Fei Wang
Caspase-1 plays a central role in innate immunity, as its activation by inflammasomes induces the production of proinflammatory cytokines and pyroptosis. However, specific inhibition of the enzymatic activity of this protease is not effective in suppressing inflammation, owing to its enzyme-independent function. Herein, we identified a cyclohexenyl isothiocyanate compound (CIB-1476) that potently inhibited caspase-1 activity and suppressed the assembly and activation of the NLRP3 inflammasome and gasdermin-D-mediated pyroptosis. Mechanistically, CIB-1476 directly targeted pro-caspase-1 as an irreversible covalent inhibitor by binding to Cys285 and Cys397, resulting in more durable anti-inflammatory effects in the suppression of enzyme-dependent IL-1β production and enzyme-independent nuclear factor κB activation. Chemoproteomic profiling demonstrated the engagement of CIB-1476 with caspase-1. CIB-1476 showed potent therapeutic effects by suppressing inflammasome activation in mice, which was abolished in Casp1–/– mice. These results warrant further development of CIB-1476 along with its analogues as a novel strategy for caspase-1 inhibitors.
研究领域:
免疫学
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药理学
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生物化学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
·
2024
·
IF 1.9
Guo Z,Qin Y,Li Y,Tang P
Objective Given the crucial role of the PI3K/Akt signaling pathway in chondrocyte survival and inflammation in osteoarthritis (OA), this study aimed to investigate the effects of Gu Bi Tang on chondrocyte proliferation, apoptosis, and inflammatory factor expression in a rat model of OA, with a focus on the PI3K/Akt signaling pathway. Methods Forty-five specific pathogen-free (SPF) C57 mice were randomly divided into three groups: the model group (Group A), the Gu Bi Tang group (Group B), and the Amfenac group (Group C), with 15 rats in each group. All 45 rats underwent anterior cruciate ligament transection (ACLT) surgery to establish an OA model. The ACLT procedure is a well-established method for inducing OA in rodents, as it leads to the destabilization of the knee joint and the development of degenerative changes characteristic of human OA. After 8 weeks of modeling, Group A rats received an equivalent volume of normal saline by gastric lavage, Group B rats were administered 13 mL/kg of Gu Bi Tang, and Group C rats received 19.5 mg/kg of Amfenac solution by gastric lavage. The dosages of Gu Bi Tang and Amfenac were selected based on previous studies examining the therapeutic effects of these interventions in rodent OA models. The gastric lavage frequency for all three groups was maintained at twice daily. The researchers analyzed cartilage morphological changes using toluidine blue staining, chondrocyte proliferation and apoptosis using the TUNEL method, and the expression of PI3K/AKT/mTOR proteins in chondrocytes using Western blotting. Additionally, the expression of inflammatory factors (TNF-α and IL-1β) in serum was measured using ELISA. Results Staining: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed significant improvement in cartilage tissue, with deeper toluidine blue staining. Toluidine blue staining is a marker of cartilage integrity and glycosaminoglycan content, indicating improved cartilage structure and composition in the treatment groups. Chondrocyte proliferation and apoptosis: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly reduced chondrocyte apoptosis (P < .05). This reduction in chondrocyte death contributes to a healthier cartilage environment and helps prevent further cartilage degradation. Protein expression: In comparison to the model group (Group A), the expression of PI3K, AKT, and mTOR proteins in the joint cartilage of the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly decreased, with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). The inhibition of this detrimental PI3K/AKT/mTOR signaling pathway promotes chondrocyte survival and a more favorable cartilage homeostasis. Inflammatory factor expression: Prior to treatment, there was no significant difference in the expression levels of the inflammatory factors TNF-α and IL-1β in serum among the three groups (P > .05). However, after treatment, both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed a significant reduction in the serum expression of TNF-α and IL-1β compared to the model group (Group A), with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). This is important, as TNF-α and IL-1β are key pro-inflammatory cytokines that drive the destructive processes in osteoarthritis. Conclusion In summary, this study demonstrates that Gu Bi Tang exerts protective effects on chondrocytes in a rat model of osteoarthritis. Specifically, Gu Bi Tang was shown to inhibit chondrocyte apoptosis, reduce the expression of key proteins in the PI3K/AKT/mTOR signaling pathway, and decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1β. These findings suggest that Gu Bi Tang could offer a novel therapeutic approach for osteoarthritis by modulating key signaling pathways and inflammatory responses. The ability of Gu Bi Tang to preserve chondrocyte viability and maintain a more favorable cartilage homeostasis makes it a promising candidate for further investigation as a potential treatment for osteoarthritis. Future studies should explore the precise mechanisms by which Gu Bi Tang exerts its beneficial effects and evaluate its efficacy in additional animal models and clinical settings.
研究领域:
药理学
·
风湿病学
·
骨科
·
分子生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
JOR Spine
·
2024
·Vol. 7
·期 4
·e70020
·
IF 3.4
Xiaoqiang Wang,Chao Song,Daqian Zhou,Yongliang Mei,Weiye Cai,Rui Chen,Jiale Lv,Houyin Shi,Zongchao Liu
Intervertebral disc degeneration (IVDD) stands as a prevalent chronic orthopedic ailment, profoundly impacting patients' well‐being due to incapacitating low back pain. Studies have highlighted a close correlation between IVDD and the programmed cell death of nucleus pulposus (NP) cells orchestrated by interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), and caspase‐3 (CASP3). Puerarin, renowned for its anti‐inflammatory attributes and its influence on IL‐1β and TNF‐α, emerges as a promising candidate for IVDD treatment. However, the precise mechanism by which it regulates apoptosis via these pathways remains ambiguous. This investigation utilizes bioinformatics to unveil the molecular intricacies of puerarin‐mediated apoptosis regulation in IVDD, substantiated by preliminary in vitro experiments. Analysis exposes aberrant expression of pivotal apoptosis‐associated proteins (IL‐1β, TNF‐α, CASP3, CASP8, and BCL2) in IVDD patients, with network pharmacology indicating puerarin's potential efficacy in IVDD treatment by modulating apoptosis and cellular senescence pathways. Further experiments elucidate puerarin's capacity to stimulate NP cell proliferation while inhibiting apoptosis, potentially contributing to IVDD mitigation. Western blot and PCR outcomes reveal escalated expression of apoptosis‐related proteins (IL‐1β, TNF‐α, and CASP3) in lipopolysaccharide‐treated NPCs, ameliorated by puerarin intervention. Molecular docking simulations demonstrate favorable binding properties of puerarin with apoptotic proteins, while flow cytometry analysis indicates its ability to diminish NPC apoptosis. These discoveries imply that puerarin might alleviate NPC apoptosis by modulating key targets, thereby potentially ameliorating IVDD. In summary, this study unveils the intrinsic mechanism of puerarin in regulating NPC apoptosis to alleviate IVDD, underscoring its therapeutic promise. Network pharmacology and bioinformatics analyses suggest that puerarin may mitigate intervertebral disc degeneration (IVDD) by inhibiting nucleus pulposus (NP) cell apoptosis. This hypothesis was validated through in vitro experiments, which demonstrated that puerarin significantly reduces apoptosis in NPCs.
研究领域:
骨科
·
药理学
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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