摘要:
Seco-triterpenoids are a unique class of triterpenoids possessing distinct structural features. Based on the differences in their parent nucleus, they can be divided into two categories: tetracyclic triterpenes and pentacyclic triterpenes, which are widely distributed across various plant species. Previous studies indicate that natural seco-triterpenoids have diverse chemical structures and exhibit extensive biological activities, including anti-tumor, anti-inflammatory, hypoglycemic, and neuroprotective effects. This review comprehensively summarizes recent research (2020–2023) on seco-triterpenoids and derived saponins, encompassing their chemical structures, plant distributions, pharmacological activities, structure–activity relationships, and future development trends. Furthermore, we utilized the latest bibliometric tool, VOSviewer, to conduct a keyword cluster analysis, enabling us to identify current research hotspots and patterns. Besides, we have cataloged and analyzed 351 compounds, inclusive of 298 tetracyclic triterpenoids and 53 pentacyclic triterpenoids, in order to provide valuable references for activity mining and structural modification of seco-triterpenoids, facilitating further clinical applications and developments. Collectively, seco-triterpenoids represent an important class of natural products with significant potential for pharmacological use. By summarizing recent research achievements, this review provides a beneficial resource for scientists in the field, promoting the exploration and development of seco-triterpenoid-based drugs.
通讯机构:
[Peng, QH ; Yao, XL] H;Hunan Univ Tradit Chinese Med, Changsha, Hunan, Peoples R China.;Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
关键词:
nonspecific orbital inflammation (NSOI);purine metabolism genes (PMGs);LASSO regression;SVM-RFE;bioinformatics
摘要:
Background Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA. Despite its significance, the contribution of Purine Metabolism Genes (PMGs) to the pathophysiological landscape of NSOI remains a mystery, highlighting a critical gap in our understanding of the disease's molecular underpinnings.Methods To bridge this knowledge gap, our study embarked on an exploratory journey to identify and validate PMGs implicated in NSOI, employing a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 92 known PMGs, we aimed to pinpoint those with potential roles in NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), facilitated a deep dive into the biological functions and pathways associated with these PMGs. Further refinement through Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled the identification of key hub genes and the evaluation of their diagnostic prowess for NSOI. Additionally, the relationship between these hub PMGs and relevant clinical parameters was thoroughly investigated. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the seven PMGs identified as potentially crucial to NSOI pathology.Results Our investigation unveiled seven PMGs (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, and ALLC) as intimately connected to NSOI. Functional analyses shed light on their involvement in processes such as peroxisome targeting sequence binding, seminiferous tubule development, and ciliary transition zone organization. Importantly, the diagnostic capabilities of these PMGs demonstrated promising efficacy in distinguishing NSOI from non-affected states.Conclusions Through rigorous bioinformatics analyses, this study unveils seven PMGs as novel biomarker candidates for NSOI, elucidating their potential roles in the disease's pathogenesis. These discoveries not only enhance our understanding of NSOI at the molecular level but also pave the way for innovative approaches to monitor and study its progression, offering a beacon of hope for individuals afflicted by this enigmatic condition.
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.
摘要:
The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.
期刊:
Journal of Drug Targeting,2024年32(1):1-20 ISSN:1061-186X
通讯作者:
Zhang, Liang;Ai, K
作者机构:
[Qu, Qirui; Zhang, Liang; Zhao, Lingyun; Wu, Qingze; Ai, Kun; Qi, Fang; Ai, K; Zhang, L] Hunan Univ Chinese Med, Coll Acupuncture & Tuina & Rehabil, Changsha 410208, Peoples R China.;[Long, Yiying] Hunan Tradit Chinese Med Coll, Zhuzhou, Peoples R China.;[Liu, Li] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Peoples R China.
通讯机构:
[Ai, K ; Zhang, L] H;Hunan Univ Chinese Med, Coll Acupuncture & Tuina & Rehabil, Changsha 410208, Peoples R China.
关键词:
Rheumatoid arthritis;angiogenesis;miR based therapeutics;microRNAs;therapeutic target
摘要:
Vascular neogenesis, an early event in the development of rheumatoid arthritis (RA) inflammation, is critical for the formation of synovial vascular networks and plays a key role in the progression and persistence of chronic RA inflammation. microRNAs (miRNAs), a class of single-stranded, non-coding RNAs with approximately 21-23 nucleotides in length, regulate gene expression by binding to the 3' untranslated region (3'-UTR) of specific mRNAs. Increasing evidence suggests that miRNAs are differently expressed in diseases associated with vascular neogenesis and play a crucial role in disease-related vascular neogenesis. However, current studies are not sufficient and further experimental studies are needed to validate and establish the relationship between miRNAs and diseases associated with vascular neogenesis, and to determine the specific role of miRNAs in vascular development pathways. To better treat vascular neogenesis in diseases such as RA, we need additional studies on the role of miRNAs and their target genes in vascular development, and to provide more strategic references. In addition, future studies can use modern biotechnological methods such as proteomics and transcriptomics to investigate the expression and regulatory mechanisms of miRNAs, providing a more comprehensive and in-depth research basis for the treatment of related diseases such as RA.
摘要:
A549 cells were treated with different concentrations of anlotinib to create anlotinib‐resistant A549 cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β‐sitosterol at different concentrations. Cell Counting Kit‐8 (CCK‐8) was used to measure cell proliferation. The apoptosis level was detected by flow cytometry. Real‐time fluorescence quantitative PCR was used to detect the expression of miR‐181a‐3p. miR‐181a‐3p interaction with H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted by miRDB and TargetScan Human databases and verified by luciferase reporter assay. The expressions of SHQ1, activating transcription factor 6 (ATF6) and glucose regulated protein 78 (GRP78) were detected by western blot. Our results show that β‐Sitosterol markedly promoted anlotinib‐resistant A549 cells apoptosis and inhibited the cell proliferation via activating SHQ1/UPR signaling via inhibiting miR‐181a‐3p. Abstract Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.
期刊:
FRONTIERS IN ENDOCRINOLOGY,2024年14:1290731 ISSN:1664-2392
通讯作者:
Yu, R
作者机构:
[Yu, Yunfeng; Yu, Rong; Yu, R] Hunan Univ Chinese Med, Hosp 1, Dept Endocrinol, Changsha, Hunan, Peoples R China.;[Hu, Gang; Yang, Xinyu; Yin, Yuman] Hunan Univ Chinese Med, Coll Chinese Med, Changsha, Hunan, Peoples R China.;[Tong, Keke] Hosp Hunan Univ Tradit Chinese Med, The Hospital, Changde, Hunan, Peoples R China.
通讯机构:
[Yu, R ] H;Hunan Univ Chinese Med, Hosp 1, Dept Endocrinol, Changsha, Hunan, Peoples R China.
关键词:
tea intake;Caffeine;Gout;gout due to impairment of renal function;Uric Acid;Mendelian randomization
摘要:
Objective: The effect of tea on gout and uric acid is still controversial. This study aims to analyze the effect of tea intake on genetic predisposition to gout, idiopathic gout, gout due to impairment of renal function as well as uric acid by Mendelian randomization (MR). Methods: Forty independent single nucleotide polymorphisms (SNPs) associated with tea intake were selected from UK Biobank. SNPs for uric acid were obtained from BioBank Japan, SNPs for gout were obtained from UK Biobank, and SNPs for gout due to impairment of renal function and idiopathic gout were derived from FinnGen. The causal relationship of exposure-outcome was tested using inverse variance weighted, MR-Egger and weighted median. MR-Egger intercept was employed to assess horizontal pleiotropy, Cochran's Q test was used to assess heterogeneity, and leave-one-out sensitivity analysis was utilized to analyze the stability of the results. Results: The results of MR analysis showed that tea intake was negatively associated with gout due to impairment of renal function (OR 0.997, 95% CI 0.994 to 0.999, P = 0.017), whereas there was no causal association with gout, idiopathic gout, and uric acid (P > 0.05), for which sensitivity analysis suggested that these results were robust. Conclusions: There was a genetic predisposition effect of increased tea intake on the reduced risk of gout due to impairment of renal function, whereas there was no such effect on gout, idiopathic gout, and uric acid. Tea intake may become an important option in the dietary treatment of gout due to impairment of renal function.
摘要:
BACKGROUND: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. METHODS: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). RESULTS: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. CONCLUSION: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.
摘要:
AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1β, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.
通讯机构:
[Liu, BY ] H;Hunan Acad Chinese Med, 58 Lushan Rd, Changsha 410007, Hunan, Peoples R China.
关键词:
Angiogenesis;Buyang huanwu decoction;Cerebral infarction;Glycolysis;Traditional Chinese medicine
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation. AIM OF THE STUDY: This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI. MATERIALS AND METHODS: According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA-mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA-mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways. RESULTS: PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis. CONCLUSION: BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important.
摘要:
The aim of this study was to investigate the alleviating effect of wogonin on intracerebral hemorrhage (ICH) and its mechanism. The hemin-treated PC-12 cells were constructed to mimic ICH in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis was used for cell viability measurement and flow cytometry was for pyroptosis detection. Enzyme-linked immunosorbent assay (ELISA) assay and western blot were used to detect the protein levels of pyroptosis-related proteins. The modification level of N6-methyladenosine (m(6)A) methylation was detected by quantitative real-time polymerase chain reaction (qRT-PCR) combined with m(6)A dot blot assays. Molecular docking experiments analyzed the binding of wogonin and METTL14 protein. The correlation between METTL14 and NLRP3 was confirmed by bioinformatics analysis and dual luciferase reporter gene detection. ICH was induced in mice injected with collagenase into the basal ganglia, and the neurobehavioral damage was evaluated. Triphenyltetrazolium chloride monohydrate (TTC) staining and neurological scores were used to assess brain damage in mice. The results demonstrated that wogonin alleviated neuronal cell pyroptosis, and was molecularly docked with METTL14. Overexpression of METTL14 partly reversed the protecting effects of wogonin on brain in vitro and in vivo. Furthermore, NLRP3 was methylated by METTL14. Taken together, wogonin inhibits neuronal pyroptosis and thus treats IHC by inhibiting METTL14 and its methylated NLRP3.
摘要:
OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group. MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs. RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001). CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs. CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.
关键词:
Nonspecific orbital inflammation (NSOI);Gln-Metabolism genes (GlnMgs);Lasso regression;SVM-RFE;Bioinformatics
摘要:
Nonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis and progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect in cancer. Metabolic reprogramming is known to influence clinical outcomes in various malignancies. However, comprehensive research on glutamine metabolism's significance in NSOI is lacking. This study conducted a bioinformatics analysis to identify and validate potential glutamine-related molecules (GlnMgs) associated with NSOI. The discovery of GlnMgs involved the intersection of differential expression analysis with a set of 42 candidate GlnMgs. The biological functions and pathways of the identified GlnMgs were analyzed using GSEA and GSVA. Lasso regression and SVM-RFE methods identified hub genes and assessed the diagnostic efficacy of fourteen GlnMgs in NSOI. The correlation between hub GlnMgs and clinical characteristics was also examined. The expression levels of the fourteen GlnMgs were validated using datasets GSE58331 and GSE105149. Fourteen GlnMgs related to NSOI were identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, and GFPT2. Biological function analysis indicated their involvement in responses to extracellular stimulus, mitochondrial matrix, and lipid transport. The diagnostic performance of these GlnMgs in distinguishing NSOI showed promising results. This study successfully identified fourteen GlnMgs associated with NSOI, providing insights into potential novel biomarkers for NSOI and avenues for monitoring disease progression.
摘要:
Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.
期刊:
International Journal of Cardiology,2024年400:131705 ISSN:0167-5273
通讯作者:
Lin, Yan;Wang, XD
作者机构:
[Gao, Xin; Wang, Xindong; Lin, Yan; Mao, Chenhan; Xu, Xiaojin; Lin, Y] Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Wester, Nanjing, Jiangsu, Peoples R China.;[Gao, Xin; Wang, Xindong; Lin, Yan; Mao, Chenhan; Xu, Xiaojin] Jiangsu Prov Acad Tradit Chinese Med, Nanjing, Jiangsu, Peoples R China.;[Sun, Xuemei] Changzhou Hosp Tradit Chinese Med, Changzhou, Jiangsu, Peoples R China.;[Long, Dan] Hunan Univ Chinese Med, Hosp 1, Changsha, Hunan, Peoples R China.;[Zhang, Meng] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Shanghai, Peoples R China.
通讯机构:
[Wang, XD ; Lin, Y] N;Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Wester, Nanjing, Jiangsu, Peoples R China.
关键词:
Children;Epidemiology;GBD;Global burden of disease;Joinpoint regression analysis;Rheumatic heart disease
摘要:
BACKGROUND: Rheumatic heart disease (RHD) is the most common acquired heart disease among children in developing countries. However, there is a lack of systematic studies on the epidemiology of pediatric RHD. This study aimed to report the burden of pediatric RHD at global, regional, and national levels between 1990 and 2019, which may provide some reference for policymakers. METHODS: The numbers and age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for childhood RHD from 1990 to 2019 were analyzed based on data obtained from the Global Burden of Disease Study 2019 (GBD 2019). In addition, Joinpoint regression analysis was used to assess temporal trends in the burden of childhood RHD. RESULTS: Globally, the number of incidence and prevalence cases of RHD in children increased by 41.89% and 40.88%, respectively, from 1990 to 2019. Age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased with an average annual percentage change (AAPC) of 0.75% and 0.66%, respectively. In contrast, the age-standardized DALY rate and age-standardized mortality rate (ASMR) decreased significantly since 1990 by an AAPC of -3.47% and-2.65%, respectively. Girls had a significantly higher burden of RHD than boys during the study period. At the age level, the RHD burden was significantly highest in the age group of 10-14years. Moreover, the ASRs of incidence, prevalence, mortality, and DALYs were negatively associated with sociodemographic index (SDI). Nationally, Fiji had the most significant increase in incidence and prevalence, and Philippines had the most remarkable rise in DALYs and mortality rates. CONCLUSION: From 1990 to 2019, although the incidence and prevalence of childhood RHD increased globally, DALYs and mortality rates markedly reduced. Countries with lower levels of sociodemographic development shoulder a higher burden of childhood RHD. Children aged 10-14years are critical populations for whom targeted measures are needed to reduce the RHD burden, while attention to girls cannot be neglected.
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: Huzhang-Guizhi herb pair (HGHP), composed of Polygonum cuspidatum (Huzhang [HZ] in Chinese, the root of Polygonum cuspidatum Sieb. & Zucc.) and Ramulus Cinnamomi (Guizhi [GZ] in Chinese, the dried twig of Cinnamomum cassia Presl.), is a popular herb pair commonly used to treat arthritis and involved in many Chinese prescriptions. In order to reveal the influence of GZ on HZ on bioavailability, the pharmacokinetic behaviors and tissue distribution variations of the three analytes from HZ were detected between oral administration of HZ and HGHP extracts to rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to two groups for pharmacokinetics study and eight groups for tissues distribution research with the equivalent dose of 18g crude HZ/kg. Assays for analytes from HZ (polydatin, resveratrol, emodin) were developed and validated using high performance liquid chromatography with ultraviolet detection (HPLC-UV). RESULTS: Part pharmacokinetic parameters including area under the concentration-time curve (AUC), the maximum plasma concentration (C(max)), biological half-life (t(1/2)), mean residence time (MRT), time to peak concentration (T(max)), clearance rate/bioavailability (CL/F) and volume of distribution/bioavailability (Vd/F) showed significant difference (P<0.05) after oral administration of HGHP, as compared to those of HZ. The three analytes could be detected in heart, liver, spleen, lung, kidney and brain. Compared with the HZ group, AUC(0-t) of polydatin in heart, liver and kidney increased significantly (p<0.05) while that in spleen decreased significantly (p<0.05); AUC(0-t) of resveratrol in all detected tissues increased conspicuously (p<0.05) in the HGHP group; AUC(0-t) of emodin in heart, liver, spleen, lung, and kidney increased conspicuously (p<0.05), and decreased obviously (p<0.05) in brain in the HGHP group. CONCLUSIONS: GZ could strongly influence the pharmacokinetic parameters and tissue distribution characteristics of polydatin, resveratrol and emodin in rats when administrated with HZ or HGHP extracts. It might provide a reference for further explanation of the compatibility mechanism and the clinical application of HGHP.
期刊:
Journal of Ethnopharmacology,2024年319(Pt 3):117343 ISSN:0378-8741
通讯作者:
Wang, Xianwen;He, YC
作者机构:
[Wang, Xianwen; He, Yingchun; Liu, Liu; Zhou, Fangliang; Tang, Le; Wang, Wen; Xu, Runshi; Lin, Ting] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.;[Zhou, Fangliang; Tang, Le; Wang, Wen; He, Yingchun; He, Lan] Hunan Univ Chinese Med, Hunan Prov Engn & Technol Res Ctr Prevent & Treatm, Changsha 410208, Peoples R China.;[Lin, Ting] Hunan Univ Chinese Med, Hunan Prov Key Lab Prevent & Treatment Ophthalmol, Changsha 410208, Peoples R China.;[Wang, Wen; He, Lan] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China.
通讯机构:
[Wang, XW; He, YC ] H;Hunan Univ Chinese Med, Changsha 410208, Peoples R China.
关键词:
Nasopharyngeal carcinoma;Network pharmacology;Non-targeted-metabolomics;Traditional Chinese medicine;Yiqi Jiedu formula
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Jiedu formula (YQJDF), rooted in the traditional Chinese medicinal principle of "tonifying qi and detoxifying", is remarkably efficacious in the clinical treatment of nasopharyngeal carcinoma (NPC). Previous studies have shed light on some of its anti-NPC effects and mechanisms, but the responsible pharmacological substances and their precise mechanisms of action remain unclear. AIM OF THE STUDY: The purpose of this study was to identify components of YQJDF that entered the bloodstream and to investigate their mechanisms of action against NPC through network pharmacology and serum metabolomics. MATERIAL AND METHODS: Components of YQJDF in serum were identified using liquid chromatography-tandem mass spectrometry. With these serum species as the focus of our research, network pharmacology analysis was used to identify active compounds and target genes that might mediate the efficacy of YQJDF in the treatment of NPC. Following establishment of an NPC xenograft model in nude mice, a non-targeted metabolomics approach was adopted to identify significant serum metabolites and metabolic pathways influenced by YQJDF. RESULTS: Thirty-six components of YQJDF were identified, primarily consisting of alkaloids, phenylpropanoids, and flavonoids. Notably, pathways such as PI3K/AKT, factors associated with Epstein-Barr virus infection, IL-17 signaling, and lipid metabolism, were highlighted as potential therapeutic targets of YQJDF during NPC treatment. Additionally, our findings suggested that YQJDF modified the metabolism of arginine and proline in the serum of mice bearing nasopharyngeal tumor grafts. CONCLUSIONS: This study identified the primary active components of YQJDF, highlighting its holistic role in the treatment of NPC through multiple targets and pathways. Furthermore, our findings provided a roadmap for future research into the mechanism of YQJDF in the therapy of NPC, setting the stage for its clinical application.
摘要:
Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking. Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted. Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C(17)H(18)N(2)O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk. Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.
摘要:
Objective: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods: Tumor necrosis factor (TNF)- alpha -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 mu mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg<middle dot>day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-alpha, interleukin-6 (IL-6), and IL-1 beta, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-alpha, IL-6, and IL-1 beta in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-alpha, IL-6, and IL-1 beta (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-alpha, IL-6, and IL-1 beta, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). Conclusion: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.