通讯机构：
[Tan, Y; Pei, G ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410000, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410000, Peoples R China.
关键词：
H3K18la;LDHA;histone lactylation;liver injury;macrophages;salvianolic acid B
摘要：
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl(4)-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.
通讯机构：
[Wu, P; Lin, LM ] H;Hunan Univ Chinese Med, Coll Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
关键词：
AMPK;Diabetes mellitus;Medicinal and edible homologous;PI3K/Akt;Plant polysaccharides
摘要：
Medicinal and edible homologs (MEHs) can be used in medicine and food. The National Health Commission announced that a total of 103 kinds of medicinal and edible homologous plants (MEHPs) would be available by were available in 2023. Diabetes mellitus (DM) has become the third most common chronic metabolic disease that seriously threatens human health worldwide. Polysaccharides, the main component isolated from MEHPs, have significant antidiabetic effects with few side effects. Based on a literature search, this paper summarizes the preparation methods, structural characterization, and antidiabetic functions and mechanisms of MEHPs polysaccharides (MEHPPs). Specifically, MEHPPs mainly regulate PI3K/Akt, AMPK, cAMP/PKA, Nrf2/Keap1, NF-κB, MAPK and other signaling pathways to promote insulin secretion and release, improve glycolipid metabolism, inhibit the inflammatory response, decrease oxidative stress and regulate intestinal flora. Among them, 16 kinds of MEHPPs were found to have obvious anti-diabetic effects. This article reviews the prevention and treatment of diabetes and its complications by MEHPPs and provides a basis for the development of safe and effective MEHPP-derived health products and new drugs to prevent and treat diabetes.
摘要：
Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and alpha-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.
期刊：
European Journal of Pharmacology,2024年963:176264 ISSN：0014-2999
通讯作者：
Yang, Yantao;Chen, Naihong;Liu, F;Chen, NH
作者机构：
[Ai, Qidi; Peng, Caiwang; Sun, Yang; Zhao, Fengyan; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli; Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.;[Ai, Qidi; Peng, Caiwang; Sun, Yang; Yang, YT; Liu, Fang; Zhao, Fengyan; Chen, NH; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli] Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;[Peng, Caiwang; Zhao, Fengyan; Tang, Keyan; Li, Hengli; Liu, Fang] Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410208, Peoples R China.;[Chen, NH; Chen, Naihong] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;[Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
通讯机构：
[Yang, YT; Liu, F ; Chen, NH ; Chen, NH] C;Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
摘要：
AIMS: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including apoptosis, autophagy, pyroptosis and ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against ferroptosis in ischemic stroke. MATERIALS AND METHODS: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques. RESULTS: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22cells exposed to H(2)O(2) and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of ferroptosis. Both in vitro and in vivo, QRC was found to inhibit ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on ferroptosis can be reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: This study provides evidence that QRC has a neuroprotective effect by inhibiting ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.
摘要：
The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.
作者机构：
[Lu, Huiling; Xiao, Yifei; Li, Ya; Du, Lixin] Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Guo, Zhihua] Hunan Univ Chinese Med, Coll Chinese Med, Changsha, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
关键词：
Chuantieling gel patch;fingerprint;HPLC;network pharmacology;Q-markers
摘要：
The Chuantieling gel patch (CGP), a traditional Chinese medicine compound, is an external treatment for asthma. It has shown remarkable effectiveness in alleviating asthma-related airway hyperresponsiveness and inflammation. Nevertheless, there is currently no information available regarding the analysis of quality markers for CGP, and there is a need for further improvement in quality control research. In this study, we developed an HPLC fingerprinting method for CGP and conducted a comprehensive methodological investigation. We assessed the similarity among 10 batches of CGP, identified common peaks, and quantified the content of seven major quality markers. Furthermore, we built a network pharmacology-based 'active ingredients-targets-pathways-diseases' network to forecast the potential mechanisms of action for the primary active components in asthma treatment. Our findings demonstrated that the developed CGP fingerprinting and content determination methods were consistent and trustworthy. We verified the existence of 25 shared peaks and successfully identified 7 chromatographic peaks, including sinigrin thiocyanate, ephedrine hydrochloride, methyleugenol, imperatorin, cinnamaldehyde, emodin, and 6-gingerol, using reference standards. The network pharmacology analysis suggested that these seven active components may target proteins such as STAT3 (signal transducer and activator of transcription 3), MAPK3 (mitogen-activated protein kinase 3), and TP53 (tumor protein P53) and influence various diseases through pathways including cancer pathways, hepatitis B, and PI3K-Akt (phosphoinositide 3-kinase-protein kinase B) signaling. This study provides insight into the complex multicomponent composition of CGP, and the predictive analysis through network pharmacology sets the stage for uncovering the mechanisms responsible for the therapeutic effects of CGP.
期刊：
Journal of Ethnopharmacology,2024年323:117682 ISSN：0378-8741
通讯作者：
Liu, JJ;Wang, W
作者机构：
[Shi, Huan; Jiang, Lihong; Liu, Jianjun; Liao, Xiaolin; Zhao, Hongqing; Peng, Wangxia; Liu, JJ; Lu, Huaguan] Hunan Univ Tradit Chinese Med, Innovat Base Hunan State Key Lab Innovat Med & Tra, Sci & Technol Innovat Ctr, Changsha 410208, Peoples R China.;[Yang, Yupei; Wang, Wei] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
通讯机构：
[Wang, W ; Liu, JJ ] H;Hunan Univ Tradit Chinese Med, Innovat Base Hunan State Key Lab Innovat Med & Tra, Sci & Technol Innovat Ctr, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The Kadsura coccinea (Lem.) A. C. Smith is known as "Heilaohu" of the Tujia ethnomedicine in China. It has anti-tumor, anti-oxidation, anti-HIV, anti-inflammatory and liver protective effects, used to treat diseases such as rheumatoid arthritis, cancer, gastritis and hepatitis. In this research, we investigated the anti-fibrotic effect and possible mechanisms of acetylbinankadsurin A (ACBA) in vitro and in vivo, which is a natural compound derived from roots of K. coccinea. AIM OF THE STUDY: We try to evaluate the efficacy of ACBA in the treatment of liver fibrosis and to explore the underlying mechanisms of ACBA by network pharmacology, machine learning, molecular docking, molecular dynamics simulations, and experimental assessment. MATERIALS AND METHODS: ACBA was isolated from the CH(2)Cl(2) layer of the roots of K. coccinea through column chromatographic techniques. The structure of ACBA was determined by using 1D and 2D NMR. CCl(4)-induced C57BL/6 mouse liver fibrosis models were established to evaluate the anti-fibrosis effects of ACBA in vivo. The molecular targets of ACBA and liver fibrosis were obtained from various databases, then constructed a protein-protein interaction (PPI) networks through the STRING database. Gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were applied using the "clusterProfiler" R package. Furthermore, the key genes for ACBA treatment of liver fibrosis were identified by the least absolute shrinkage and selection operator (LASSO). Molecular docking and molecular dynamics simulations were also carried out. Finally, the target and pathway of ACBA were verified by immunofluorescence staining, RT-PCR and Western blot. RESULT: First, ACBA attenuated CCl(4)-induced liver injury and fibrosis in vivo. These findings were accompanied by decreased expression of α-SMA and collagen I. Second, ACBA significantly decreased serum levels of ALT, AST, TNF-α and IL-6. Then, we identified 133 potential targets of ACBA and 7987 targets of liver fibrosis. KEGG analysis showed that ACBA could regulate the drug metabolism - cytochrome P450, fructose and mannose metabolism, IL-17 and NF-κB signaling pathways. Next, six core targets was screened by LASSO analysis including AKR1B1, PFKFB3, EPHA3, CDK1, CCR1 and CYP3A4. Molecular docking showed that ACBA has a good binding affinity for CCR1. Furthermore, compared with CCR1 inhibitor BX-471, The results of molecular simulation dynamics showed that ACBA was stable in binding with CCR1. Consistently, ACBA remarkably downregulated the expression of CCR1, p-NF-κBp65, p-IκBα, p-STAT1 and TNF-α proteins, which were upregulated in CCl(4)-induced hepatic fibrosis and LPS-THP-1cells. CONCLUSION: Our results suggest that ACBA significantly attenuated CCl(4)-induced liver fibrosis in histopathological and in serum level. This effect may be mediated by CCR1, NF-κB and STAT1 signalling.
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.
作者机构：
[Fu, Fuhua; Mao, Yingchao; Zhu, Lingfeng] Hunan Acad Agr Sci, Hunan Agr Prod Proc Inst, Changsha 410125, Peoples R China.;[Chen, Jiajing; Huang, Dan; Liu, Jing; Lei, Chang; Zhu, Lijun] Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.
通讯机构：
[Huang, D; Lei, C ] H;Hunan Univ Chinese Med, Sci & Technol Innovat Ctr, State Key Lab Chinese Med Powder & Med Innovat Hun, Changsha 410208, Peoples R China.
摘要：
Puerariae Radix is one of the most widely used ancient traditional Chinese medicines and is also consumed as food, which has rich edible and medicinal value. Puerariae Radix can be divided into Puerariae Lobatae Radix (PL) and Puerariae Thomsonii Radix (PT). These two medicinal materials are very similar, and they are often mixed up or misused. In this study, gas chromatography-ion migration spectrometry (GC-IMS) was used to analyze the volatile organic compounds (VOCs) of PL and PT, and the differences in VOCs were analyzed using fingerprint, principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA). The results showed that a total of 173 VOCs were obtained from PL and PT, and 149 were qualitatively identified, including 38 aldehydes, 22 alcohols, 22 ketones, 19 esters, 13 esters, 10 acids, 10 pyrazines, 6 terpenes, 4 furans, and 2 pyridines. The characteristic VOCs of PL and PT were clarified by constructing GC-IMS fingerprints. PL and PT can be effectively distinguished, and five characteristic VOCs were screened using PCA and OPLS-DA analysis methods. This study identified and evaluated the types and differences in VOCs in PL and PT. The established method is simple, rapid, accurate, and sensitive, and it provides theoretical guidance for the identification, tracing, and quality evaluation of PL and PT.
摘要：
Background: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism.<&wdkj&>Methods: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.<&wdkj&>Results: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a- 5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis.<&wdkj&>Conclusions: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.
通讯机构：
[Li, L; Tan, Y ] H;Hunan Univ Chinese Med, Pharm Coll, Changsha 410208, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410208, Peoples R China.
摘要：
Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.
期刊：
Biochemical Systematics and Ecology,2023年109:104662 ISSN：0305-1978
通讯作者：
Wang, Wei;Jian, YQ
作者机构：
[Wang, Wei; Yang, Yupei; Li, Wenchu; Jiang, Sai; Jian, Yuqing; Guo, Tingsi; Wu, Juanjiang; Yang, Yong] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Wang, W; Jian, YQ ] H;Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Hunan, Peoples R China.
作者机构：
[Tang, Siqi; Huang, Hao; Li, Xiaojun; Wei, Kaixin; Suo, Zongwu; Xu, Yi] Gannan Med Univ, Natl Engn Res Ctr Modernizat Tradit Chinese Med, Sch Pharm, Hakka Med Resources Branch, Ganzhou 341000, Peoples R China.;[Liu, Dongxu; Li, Chunying; Zhao, Lei] Gannan Med Univ, Coll Basic Med, Ganzhou 341000, Peoples R China.;[Liu, Xiangqian] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Xiaojun Li] N;[Dongxu Liu] C;National Engineering Research Center for Modernization of Traditional Chinese Medicine—Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 341000, China<&wdkj&>College of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
摘要：
Abstract: The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. henryi. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways. Keywords: savinin; neuroinflammation; MAPK; NF-κB; NLRP3 inflammasome
摘要：
Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15mg/kg in mice or 1μM in cardiomyocyte) or Tra (15.75mg/kg in mice or 1μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS. Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction, myocardial hypertrophy, cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice. Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro. Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.
摘要：
BACKGROUND: Doxorubicin (Dox), a chemotherapeutic agent known for its efficacy, has been associated with the development of severe cardiotoxicity, commonly referred to as doxorubicin-induced cardiotoxicity (DIC). The role and mechanism of action of phloretin (Phl) in cardiovascular diseases are well-established; however, its specific function and underlying mechanism in the context of DIC have yet to be fully elucidated. OBJECTIVE: This research aimed to uncover the protective effect of Phl against DIC in vivo and in vitro, while also providing a comprehensive understanding of the underlying mechanisms involved. METHODS: DIC cell and murine models were established. The action targets and mechanism of Phl against DIC were comprehensively examined by systematic network pharmacology, molecular docking, transcriptomics technologies, transcription factor (TF) prediction, and experimental validation. RESULTS: Phl relieved Dox-induced cell apoptosis in vitro and in vivo. Through network pharmacology analysis, a total of 554 co-targeted genes of Phl and Dox were identified. Enrichment analysis revealed several key pathways including the PI3K-Akt signaling pathway, Apoptosis, and the IL-17 signaling pathway. Protein-protein interaction (PPI) analysis identified 24 core co-targeted genes, such as Fos, Jun, Hif1a, which were predicted to bind well to Phl based on molecular docking. Transcriptomics analysis was performed to identify the top 20 differentially expressed genes (DEGs), and 202 transcription factors (TFs) were predicted for these DEGs. Among these TFs, 10 TFs (Fos, Jun, Hif1a, etc.) are also the co-targeted genes, and 3 TFs (Fos, Jun, Hif1a) are also the core co-targeted genes. Further experiments validated the finding that Phl reduced the elevated levels of Hif3a (one of the top 20 DEGs) and Fos (one of Hif3a's predicted TFs) induced by Dox. Moreover, the interaction between Fos protein and the Hif3a promoter was confirmed through luciferase reporter assays. CONCLUSION: Phl actively targeted and down-regulated the Fos protein to inhibit its binding to the promoter region of Hif3a, thereby providing protection against DIC.
摘要：
BACKGROUND: Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity. METHODS: Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. RESULTS: A total of 66 patients were included, with a median age of 71.5 years (range 40-92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1-14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin <3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1-42) after intervention including antiepileptic administration, or hemodialysis. CONCLUSION: Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.
摘要：
Based on this communication we could recommend that this type of abandoned knowledge should be considered for the management and conservation of faunistic resources. However, the advantageous role of animals and their products was reported but more extensive research is required to explore the bioactive constituents in the raw material of these animals responsible for their beneficial effects. Abstract The use of traditional medicines has tremendously increased over the past few decades. Approximately 80% of the world's population relies on traditional medicines for their primary healthcare needs because of their cost effectiveness and efficiency with no or minimal side effects. Zootherapy refers to the use of medicines that are prepared or derived from animals or from their products. The current study documented the folk knowledge related to the practice of various animal‐derived products and ethnozoological based drugs used as medicines by the residents of the Cholistan desert of Bahawalpur (Pakistan). In this regard 46 knowledgeable and reliable elderly people, hakims and spiritual healers ranging from 35–60 years of age having knowledge related to zootherapy were included in the current study. A field survey from February 2006 to November 2007 was conducted by interviewing the selected respondents through a structured questionnaire. They provided knowledge regarding the use of animals and their derived products in traditional medicine. The zootherapeutic knowledge was based on both domestic animals as well as wild animals. A total of 20 animal species were included in the study, among which nine animals were domestic while 11 were wild animals. Among selected animals, nine were mammals, four birds, four reptiles and three insects. It was reported that camel was the most commonly used (n = 32 respondents) among mammals while Pigeon (n = 39 respondents), Spiny‐tailed lizard (n = 41 respondents) and Indian honey bee (n = 27 respondents) among birds, reptiles and insects, respectively, have significant use for the treatment of different diseases. Based on this communication we could recommend that this type of abandoned knowledge should be considered for the management and conservation of faunistic resources. However, the advantageous role of animals and their products was reported but more extensive research is required to explore the bioactive constituents in the raw material of these animals responsible for their beneficial effects.
作者机构：
[Xie, Qinling; Wang, Wei; Luo, Jiangyi; Liang, Ling; Jiang, Sai; Chen, Shenghuang; Fu, Yangfen; Yuan, Hanwen] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha, Peoples R China.
通讯机构：
[Luo, Jiangyi] T;TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Material Medical Research Institute, School of Pharmacy, Hunan University of Chinese Medicine Changsha China wangwei402@hotmail.com +86-731-8845-8227 +86-136-5743-8606
摘要：
Gentianae Macrophyllae Radix, the dried root of Gentiana macrophylla Pall., Gentiana crassicaulis Duthie ex Burk., Gentiana straminea Maxim., or Gentiana dahurica Fisch., is a traditional Chinese medicine with multi-origins and some adulterants. Liquid chromatography coupled to electrostatic orbitrap high-resolution mass spectrometry (LC-Orbitrap-MS) was used to search the different components of Gentianae Macrophyllae Radix of the four species. High-performance liquid chromatography (HPLC) combined with fingerprint analysis, principal components analysis (PCA), and partial least-squares discrimination analysis (PLS-DA) was also utilized to distinguish them and their adulterants based on the critical components identified by LC-MS. A single standard to determine the multi-components (SSDMC) method was established for the determination of the critical markers. A total of 93 compounds were identified from Gentianae Macrophyllae Radix, including 58 common ones. Their HPLC fingerprints show a significant difference with the adulterants. In addition, PCA and PLS-DA could make a distinction among the four species. Loganic acid, 6'-O-β-d-glucosylgentiopicroside, swertiamarine, gentiopicroside, and sweroside were identified as the critical markers and then quantified by the SSDMC method. The developed strategy is powerful for the quality control and authentication of Gentianae Macrophyllae Radix.
作者机构：
[Shi, Zhi Min; Wei, Jia-ming] Hunan Univ Chinese Med, Sch Chinese Med, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Yuan, Hui; Liu, Cheng-xin] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410208, Peoples R China.;[Wang, Zi-yan; Shi, Zhi Min; Yuan, Hui; Wei, Jia-ming; Liu, Cheng-xin] Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, Changsha 410208, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ; Shi, ZM ] H;Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent Tradit Chine, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.
关键词：
ApoE(-/-) mice;Atherosclerosis;NOX/ROS/NF-κB signal pathway;Vascular smooth muscle cell;Xin-tong-tai
摘要：
Background: Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. Purpose: This study aims to explore the potential mechanism of XTTG for treating AS. Methods: An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (oxLDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/ NF-.kappa B signaling pathway indicators were observed. Results: XTTG improved blood lipid levels and pathological aortic changes of ApoE / mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-alpha, IKK-ss, NF-.kappa B protein and mRNA expression and the phosphorylation of NF-.kappa B. Conclusion: XTTG can inhibit NOX/ROS/NF-.kappa B signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects.
