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：
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.
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：
Drug Discoveries & Therapeutics,2024年18(1):34-43 ISSN：1881-7831
作者机构：
[Chen, Shanshan; Wang, Shengfeng] Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Ouyang, Linqi] Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China;[Li, Lian] Department of Information, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Xiao, Yuyang] Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Wang, Shengfeng] Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
摘要：
To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.
期刊：
Ageing Research Reviews,2024年96:102286 ISSN：1568-1637
通讯作者：
Chen, Naihong;Yang, Yantao;Ai, Qidi
作者机构：
[Lin, Yuting; Yao, Jiao; Sun, Yang; Wang, Huiqin; Liang, Jinping; Liu, Xuan; Lin, Meiyu; Meng, Lei; Yang, Songwei; Yan, Qian; Chen, Naihong; Pei, Gang; Long, Junpeng] Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine,Changsha 410208,China;[Liu, Shasha] Department of Pharmacy, Changsha Hospital for Matemal&Child Health Care Affiliated to Hunan Normal University,Changsha 410007,China;[Chen, Chen] Department of Pharmacy, The First Hospital of Lanzhou University,Lanzhou 730000,China;[Yu, Jingbo] Technology Innovation Center/National Key Laboratory Breeding Base of Chinese Medicine Powders and Innovative Drugs, Hunan University of Chinese Medicine,Changsha 410208,China;[Yi, Fan] Key Laboratory of Cosmetic, China National Light Industry, Beijing Technology and Business University,Beijing 100048,China
通讯机构：
[Chen, Naihong] S;[Yang, Yantao; Ai, Qidi] H;State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China. Electronic address:;Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, College of Pharmacy, Hunan University of Chinese Medicine,Changsha 410208,China. Electronic address:
关键词：
CCR5;Disease;Inflammation;Treatment
摘要：
Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.
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.
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.
期刊：
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2024年169:106550 ISSN：1357-2725
通讯作者：
Wang, Wei;Yu, HH
作者机构：
[Wang, Wei; Shen, Xinyang; Li, Huanjie; Sheng, Wenbing; Li, Yunzhe; Deng, Yasi; Tian, Xing; Lin, Haokai; Yuan, Hanwen; Zheng, Hao; Li, Bin; Yu, Huanghe; Yang, Yong] 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; Yu, HH ] H;Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, TCM & Ethnomedicine Innovat & Dev Int Lab, Changsha 410208, Peoples R China.
摘要：
Tujia ethnomedicine Xuetong (the stems of Kadsura heteroclita) have been widely used in folk for rheumatoid arthritis (RA), which can alleviate rheumatic pain through liquor soaking in folk. In this study, we aimed to evaluate the pharmacological effects and underlying mechanism of Xuetongsu (a key chemical component of Xuetong) on bone destruction. In our previous study, it was found that Xuetong extract can reduce adjuvant arthritic rats paw swelling and inhibit inflammatory factors in serum. Furthermore, Xuetongsu has been demonstrated to inhibit the proliferation of fibroblast-like synoviocytes, but its potential to inhibit bone destruction has not been explored. To address this, we employed the STRING database to predict protein interactions and utilized Autodock software to simulate the binding of Xuetongsu to target proteins. In this study, administration of Xuetongsu significantly alleviated paw swelling and bone destruction in C57BL/6 mice with collagen-induced arthritis (CIA). Mechanistic studies have indicated that Xuetongsu promotes apoptosis of mature osteoclasts in joint tissues by activating Caspase-3 and Bax, while inhibiting Bcl-2. Additionally, Xuetongsu inhibits osteoclast differentiation by suppressing RANKL, RANK, P-NF-κB, and NFATc1, and reduces bone resorption activity by inhibiting MMP-9, CTSK, and TRAP. Importantly, Xuetongsu exhibits good biocompatibility in major organs of mice. In summary, Xuetongsu has the potential to treat bone destruction by promoting apoptosis of mature osteoclasts, inhibiting osteoclast differentiation, and reducing bone resorption. This study reveals the pharmacological effects of Xuetongsu and its mechanism of action, which may contribute to the development of novel approaches for treating RA.
作者机构：
[Lin, Limei; Lin, LM; Xiong, Suhui; Zhang, Zhimin; Sun, Miao; Yu, Jiahui; Xu, Chunfang; Xie, Jingchen; Li, Minjie] Human Univ Chinese Med, Sch Pharm, Key Lab Qual Evaluat Bulk Herbs Human Prov, Changsha 410208, Peoples R China.;[Li, Chun] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.
通讯机构：
[Lin, LM ] H;Human Univ Chinese Med, Sch Pharm, Key Lab Qual Evaluat Bulk Herbs Human Prov, Changsha 410208, Peoples R China.
摘要：
In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their (13)C-NMR and (1)H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.
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.
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.
作者：
Du, Lixin;Lu, Huiling;Xiao, Yifei;Guo, Zhihua;Li, Ya
期刊：
PLOS ONE,2024年19(4):e0301036 ISSN：1932-6203
作者机构：
[Lu, Huiling; Xiao, Yifei; Li, Ya; Du, Lixin] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China;[Guo, Zhihua] School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
PURPOSE: This study aims to investigate the protective mechanism of dihydromyricetin PLGA nanoparticles (DMY-PLGA NPs) against myocardial ischemia-reperfusion injury (MIRI) in vitro and the improvement of oral bioavailability in vivo. METHODS: DMY-PLGA NPs was prepared and characterized by emulsifying solvent volatilization, and the oxidative stress model of rat H9c2 cardiomyocyte induced by H2O2 was established. After administration, cell survival rate, lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected, and the expressions of PGC1α and PPARα were detected by western blot (WB). At the same time, the pharmacokinetics in rats were studied to explore the improvement of bioavailability. RESULTS: DMY-PLGA NPs can significantly increase cell survival rate, decrease LDH and MDA content, increase SOD content and PGC1α、PPARα protein expression. Compared with DMY, the peak time of DMY-PLGA NPs was extended (P<0.1), and the bioavailability was increased by 2.04 times. CONCLUSION: DMY-PLGA NPs has a significant protective effect on H9c2 cardiomyocytes, which promotes the absorption of DMY and effectively improves bioavailability.
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.
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.
