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.
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 MICROBIOLOGY AND BIOTECHNOLOGY,2024年34(2):467-475 ISSN：1017-7825
作者机构：
[Gao, Xin; Yuan, Xiwei; Tan, Chaoyang; Xu, Dehong; Wu, Wenmei] Biological Engineering Laboratory, College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China;[Xu, Dehong; Li, Shunxiang] Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, P.R. China;[Xu, Dehong; Li, Shunxiang] Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, P.R. China
摘要：
ρ-Hydroxyacetophenone is an important and versatile compound that has been widely used in medicine, cosmetics, new materials, and other fields. At present, there are two ways to obtain ρ-hydroxyacetophenone. One is to extract it from plants, such as Artemisia capillaris Thunb and Cynanchum otophyllum Schneid, and the other is to synthesize it by using chemical methods. Of these two methods, the second is the main one, although it has problems, such as flammable and explosive reagents, difficult separation of by-products, and harsh reaction conditions. To solve these issues, we adopted genetic engineering in this study to construct engineered Escherichia coli containing Hped gene or EbA309 gene. Whole-cell biotransformation was conducted under the same conditions to select the engineered E. coli with the higher activity. Orthogonal tests were conducted to determine the optimal biotransformation condition of the engineered E. coli. The results showed that the optimal condition was as follows: substrate concentration of 40 mmol/l, IPTG concentration of 0.1 mmol/l, an induction temperature of 25°C, and a transformation temperature of 35°C. Under this condition, the effects of transformation time on the ρ-hydroxyacetophenone concentration and cell growth were further studied. We found that as the transformation time extended, the ρ-hydroxyacetophenone concentration showed a gradually increasing trend. However, when the ρ-hydroxyacetophenone concentration increased to 1583.19 ± 44.34 mg/l in 24 h, cell growth was inhibited and then entered a plateau. In this research, we realized the synthesis of ρ-hydroxyacetophenone by biotransformation, and our findings lay a preliminary foundation for further improving and developing this method.
期刊：
INTERNATIONAL JOURNAL OF NANOMEDICINE,2024年19:2091-2112 ISSN：1178-2013
通讯作者：
Xin Li
作者机构：
[Yang, Yuan; Yuan, Fang; Yang, Rui; Xiang, Debiao; Li, Xin; Qiao, Yong] Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan Province, People's Republic of China;[Yuan, Fang; Xiang, Debiao; Li, Xin; Qiao, Yong] Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Changsha, Hunan Province, People's Republic of China;[Yuan, Fang; Xiang, Debiao; Li, Xin; Qiao, Yong] The Clinical Application Research Institute of Antibiotics in Changsha, Changsha, Hunan Province, People's Republic of China;[Zhou, Lili; Xu, Yilin; Yang, Yuan; Yang, Rui] College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan Province, People's Republic of China
通讯机构：
[Xin Li] D;Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan Province, People’s Republic of China<&wdkj&>Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Changsha, Hunan Province, People’s Republic of China<&wdkj&>The Clinical Application Research Institute of Antibiotics in Changsha, Changsha, Hunan Province, People’s Republic of China
摘要：
Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc(-). Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.
期刊：
Journal of Nanobiotechnology,2023年21(1):1-21 ISSN：1477-3155
通讯作者：
Xinhua Xia
作者机构：
[Qiuyan Guo; Shengmei Wang; Peng Lin; Rubing Xu] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China;[Guoyan Deng] The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China;[Xinhua Xia] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. xiaxinhua001@hnucm.edu.cn
通讯机构：
[Xinhua Xia] S;School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
摘要：
Immunotherapy has good potential to eradicate tumors in the long term. However, due to the low immunogenicity of tumor cells, current cancer immunotherapies are not effective. To address this limitation, we constructed a BSA-FA functionalized iron-containing metal-organic framework (TPL@TFBF) that triggers a potent systemic anti-tumor immune response by inducing ferroptosis and pyroptosis in tumor cells and releasing large quantities of damage-associated molecular patterns (DAMPs) to induce immunogenicity, and showing excellent efficacy against melanoma lung metastases in vivo. This nanoplatform forms a metal-organic framework through the coordination between tannic acid (TA) and Fe3+ and is then loaded with triptolide (TPL), which is coated with FA-modified BSA. The nanoparticles target melanoma cells by FA modification, releasing TPL, Fe3+ and TA. Fe3+ is reduced to Fe2+ by TA, triggering the Fenton reaction and resulting in ROS production. Moreover, TPL increases the production of intracellular ROS by inhibiting the expression of nuclear factor erythroid-2 related factor (Nrf2). Such simultaneous amplification of intracellular ROS induces the cells to undergo ferroptosis and pyroptosis, releasing large amounts of DAMPs, which stimulate antigen presentation of dendritic cells (DCs) and the proliferation of cytotoxic T lymphocytes (CD4+/CD8 + T cells) to inhibit tumor and lung metastasis. In addition, combining nanoparticle treatment with immune checkpoint blockade (ICB) further inhibits melanoma growth. This work provides a new strategy for tumor immunotherapy based on various combinations of cell death mechanisms.
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.
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.
作者机构：
[Liu, Xiu; Zou, Junju; Tan, Danni; Yu, Rong; Xiang, Qin; Wu, Yongjun; Shi, Liuyang] Hunan Univ Tradit Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Liu, Xiu; Zou, Junju; Tan, Danni; Yu, Rong; Xiang, Qin; Shi, Liuyang] Hunan Univ Chinese Med, Hunan Key Lab Tradit Chinese Med Prescript & Syndr, Changsha 410208, Hunan, Peoples R China.;[Wu, Yongjun] Hunan Univ Tradit Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Zou, Junju] Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Yongjun Wu; Rong Yu] S;School of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Hunan University of Traditional Chinese Medicine School of Pharmacy, Changsha, Hunan 410208, China<&wdkj&>School of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要：
Non-alcoholic fatty liver disease (NAFLD) pathogenesis is affected by dysbiosis of the gut microbiome and the metabolites it generates. Therefore, restoring the equilibrium between the gut microbiome and the generated metabolites may have therapeutic potential for the syndrome. Zuogui Jiangtang Qinggan Fang (ZGJTQGF) is a Chinese herbal formulation used clinically to treat type 2 diabetic mellitus (T2DM) and fatty liver disease. However, its pharmacological mechanisms have not been well characterized. This work aimed to evaluate the hepatoprotective mechanism of ZGJTQGF in T2DM with NAFLD mice by incorporating gut microbiota, short-chain fatty acids（SCFAs）, and metabolomic analysis, and then to provide strong support for clinical treatment of T2DM with NAFLD. The sequencing of 16S rRNA revealed that ZGJTQGF therapy modified the composition and abundance of the gut microbiome, raised the level of SCFAs, and restored the intestinal mucosal barrier. The non-targeted metabolomic analysis of liver tissues identified 212 compounds, of which108 were differentially expressed between the HFD and ZGJTQGF groups. Moreover, L-glutamic acid, L-Phenylalanine, Glycine, Taurine, Deoxycholic acid, and citric acid levels were also considerably altered by ZGJTQGF. Our findings suggest that ZGJTQGF ameliorates HFD-induced hepatic steatosis by modulating the gut microbiota composition and its metabolites and boosting the levels of SCFAs. More notably, ZGJTQGF may be a promising medication for preventing and treating NAFLD.
摘要：
(1) Background: Ginsenoside Rb1-PLGA nanoparticles (GRb1@PLGA@NPs) represent a novel nanotherapeutic system, yet their therapeutic efficacy and underlying mechanisms for treating heart failure (HF) remain unexplored. This study aims to investigate the potential mechanisms underlying the therapeutic effects of GRb1@PLGA@NPs in HF treatment; (2) Methods: The left anterior descending coronary artery ligation was employed to establish a HF model in Sprague-Dawley rats, along with an in vitro oxidative stress model using H9c2 myocardial cells. Following treatment with GRb1@PLGA@NPs, cardiac tissue pathological changes and cell proliferation were observed. Additionally, the serum levels of biomarkers such as NT-proBNP, TNF-alpha, and IL-1 beta were measured, along with the expression of the ROS/PPAR alpha/PGC1 alpha pathway; (3) Results: GRb1@PLGA@NPs effectively ameliorated the pathological status of cardiac tissues in HF rats, mitigated oxidative stress-induced myocardial cell damage, elevated SOD and MMP levels, and reduced LDH, MDA, ROS, NT-proBNP, TNF-alpha, and IL-1 beta levels. Furthermore, the expression of PPAR alpha and PGC1 alpha proteins was upregulated; (4) Conclusions: GRb1@PLGA@NPs may attenuate myocardial cell injury and treat HF through the ROS/PPAR alpha/PGC1 alpha pathway.
摘要：
Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.
关键词：
atherosclerosis;endothelial cell;endothelial cell senescence;endothelial cell death
摘要：
Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.
摘要：
Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.
摘要：
Brain disorders such as neurodegenerative diseases and neuropsychiatric diseases have become serious threatens to human health and quality of life. Oleanolic acid (OA) and ursolic acid (UA) are pentacyclic triterpenoid isomers widely distributed in various plant foods and Chinese herbal medicines. Accumulating evidence indicates that OA and UA exhibit neuroprotective effects on multiple brain disorders. Therefore, this paper reviews researches of OA and UA on neurodegenerative diseases, neuropsychiatric diseases and other brain disorders including ischemic stroke, epilepsy, etc, as well as the potential underlying molecular mechanisms. [GRAPHICS]
作者机构：
[Li, Li; Yuan, Zhiying; Huang, Shiyi; Huang, Chencun; Xu, Guangming; Zhao, Yuan] Hunan Univ Chinese Med, Coll Pharm, Changsha, Hunan, Peoples R China.;[Xu, Guangming] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Guangming Xu] C;College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
关键词：
affinity ultrafiltration mass spectrometry (AUF-MS);Ligusticum chuanxiong;molecular docking;screening of active compounds;thrombin
摘要：
INTRODUCTION: Ligusticum chuanxiong ('chuanxiong') is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, which is often used to treat thrombotic diseases. However, its potential anticoagulant active ingredients have been unexplored. OBJECTIVES: The study aims to establish an affinity ultrafiltration mass spectrometry (AUF-MS) method for rapid screening of anti-thrombin active components of chuanxiong and to verify it in vitro. METHOD: In this study, the chemical constituents of different parts of chuanxiong were determined. A method for rapid screening of anticoagulant active ingredients by AUF-MS was established using thrombin as an affinity receptor target. Subsequently, the anticoagulant effect of such ligands was verified by in vitro anticoagulation experiments such as chromogenic substrate method and in vitro coagulation assay. Then the possible interaction mechanism between these ligands and thrombin was further studied by molecular docking. RESULTS: Twenty-one components were detected from different parts of chuanxiong. And three potential anti-thrombin active components were screened: ferulic acid, chlorogenic acid, isochlorogenic acid A by AUF coupled with high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (HPLC-Q-Orbitrap-MS(n) ). The in vitro activity experiments and molecular docking revealed that these potential ligands exhibited strong binding ability and inhibitory activities on thrombin. CONCLUSION: The present study revealed that chuanxiong is a traditional Chinese medicine with excellent anticoagulation effects. Meanwhile, the integrated strategy based on AUF-MS, in vitro experiments and molecular docking also provided a powerful tool for further exploration of active ingredients responsible for the anticoagulant activity in chuanxiong.
期刊：
Journal of Biochemical and Molecular Toxicology,2023年37(6):e23344 ISSN：1095-6670
作者机构：
[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Dept Pharm, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Yuan; Yuan, Fang; Deng, Yang; Xiang, Debiao; Li, Xin] Third Hosp Changsha, Inst Clin Applicat Antibiot, Changsha, Hunan, Peoples R China.;[Xiao, Guiying; Xiong, Liguang; Li, Xin] Hunan Univ Chinese Med, Hosp Changsha 3, Dept Pharm, Changsha, Hunan, Peoples R China.;[Li, Yuan; Li, Xin] Third Hosp Changsha, Dept Pharm, 176 Western Laodong Rd, Changsha 410015, Hunan, Peoples R China.
关键词：
Nrf2/NQO1 pathway;apoptosis;nephrotoxicity;oxidative stress;polymyxin B
摘要：
Polymyxin B (PMB) is a polypeptide antibiotic widely used in treating multidrug-resistant Gram-negative bacteria. However, nephrotoxicity is a serious adverse effect that limits its clinical use. Therefore, clarification of the molecular mechanism of PMB-induced renal injury is essential. Our study aimed to explore possible mechanisms of PMB-induced nephrotoxicity in vivo and in vitro. Mice were treated with PMB to construct the kidney injury model. The antioxidant capacity was assessed by measuring the superoxide dismutase (SOD) and catalase (CAT) activities and the glutathione (GSH)and malondialdehyde (MDA) contents. The pathway of the nuclear factor erythroid 2-related factor 2/NADH quinone oxidoreductase 1 (Nrf2/NQO1) was examined after PMB treatment in NRK-52E cells and mice. Finally, the expressions of genes and proteins (Bax, Bcl-2, Caspase-3, Caspase-9) related to apoptosis were evaluated through quantitative polymerasechain reaction and western blot assay. The study verified PMB-induced nephrotoxicity in mice and NRK-52E cells in a dose- and time-dependent manner. PMB treatment significantly decreased the expression of Nrf2 and its downstream target gene NQO1 and increased the apoptosis-related proteins expression. In summary, our results suggested that PMB-induced oxidative stress damage by inhibiting the Nrf2/NQO1 pathway and promoting apoptosis in kidney tissues.
