JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Yongping He,Qianxue Yu,Xiaoyu Ma,Diya Lv,Hui Wang,Weian Qiu,Xiao fei Chen,Yang Jiao,Yue Liu
Ethnopharmacological relevance Tanacetum parthenium (L.) Schultz-Bip, commonly known as feverfew, has been traditionally used to treat fever, migraines, rheumatoid arthritis, and cancer. Parthenolide (PTL), the main bioactive ingredient isolated from the shoots of feverfew, is a sesquiterpene lactone with anti-inflammatory and antitumor properties. Previous studies showed that PTL exerts anticancer activity in various cancers, including hepatoma, cholangiocarcinoma, acute myeloid leukemia, breast, prostate, and colorectal cancer. However, the metabolic mechanism underlying the anticancer effect of PTL remains poorly understood. Aim of the study To explore the anticancer activity and underlying mechanism of PTL in human cholangiocarcinoma cells. Material and methods In this investigation, the effects and mechanisms of PTL on human cholangiocarcinoma cells were investigated via a liquid chromatography/mass spectrometry (LC/MS)-based metabolomics approach. First, cell proliferation and apoptosis were evaluated using cell counting kit-8 (CCK-8), flow cytometry analysis, and western blotting. Then, LC/MS-based metabolic profiling along with orthogonal partial least-squares discriminant analysis (OPLS-DA) has been constructed to distinguish the metabolic changes between the negative control group and the PTL-treated group in TFK1 cells. Next, enzyme-linked immunosorbent assay (ELISA) was applied to investigate the changes of metabolic enzymes associated with significantly alerted metabolites. Finally, the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established using MetaboAnalyst 5.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. Results PTL treatment could induce the proliferation inhibition and apoptosis of TFK1 in a concentration-dependent manner. Forty-three potential biomarkers associated with the antitumor effect of PTL were identified, which primarily related to glutamine and glutamate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, fatty acid metabolism, phospholipid catabolism, and sphingolipid metabolism. Pathway analysis of upstream and downstream metabolites, we found three key metabolic enzymes, including glutaminase (GLS), γ-glutamyl transpeptidase (GGT), and carnitine palmitoyltransferase 1 (CPT1), which mainly involved in glutamine and glutamate metabolism, glutathione metabolism, and fatty acid metabolism. The changes of metabolic enzymes associated with significantly alerted metabolites were consistent with the levels of metabolites, and the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established. PTL may exert its antitumor effect against cholangiocarcinoma by disturbing metabolic pathways. Furthermore, we selected two positive control agents that are considered as first-line chemotherapy standards in cholangiocarcinoma therapy to verify the reliability and accuracy of our metabolomic study on PTL. Conclusion This research enhanced our comprehension of the metabolic profiling and mechanism of PTL treatment on cholangiocarcinoma cells, which provided some references for further research into the anti-cancer mechanisms of other drugs.
研究领域:
药理学
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肿瘤学
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代谢组学
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PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 6
·694
·
IF 6.9
José Márcio Fernandes da Silva,Dominique Mesquita e Silva,Danilo de Souza Costa,Monique C. Amaro,Rayssa A. Cajas,Josué de Moraes,Guilherme Diniz Tavares,Ademar Alves Da Silva Filho
Background:Schistosomiasis remains a major neglected tropical disease, with praziquantel (PZQ) as the only widely used treatment, despite its limitations. Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy.Objective:This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL.Methods:PTL was isolated fromTanacetum partheniumand incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model ofSchistosoma mansoniinfection.Results:NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p< 0.001). Blank NLC had no antiparasitic effect.Conclusions:Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis.
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 8.3
Xueling He,Chen Wang,Ruihao Zhang,Yuanyuan Wang,Ying Zhang,Tong Yang,Junzhe Zhang,Shuan Rao,Huan Tang,Xin Peng,Jigang Wang
Background Sepsis, a life-threatening condition, arises from an aberrant or uncontrolled immune response of the host to severe infection. Timely and precise control of this inflammatory response is of paramount importance in sepsis prevention and constitutes the core of sepsis prevention efforts. Parthenolide (PA), recognized as an NF-κB inhibitor, has previously demonstrated its capacity to mitigate the inflammatory response. This study aimed to investigate whether and how PA can inhibit inflammation, thereby alleviating sepsis, and to profile functional target proteins using chemoproteomics strategy. Methods The cecal ligation and puncture (CLP) procedure was performed to induce a mouse model of sepsis, and lipopolysaccharide (LPS) was employed to establish a model of cellular inflammation in mouse mononuclear macrophage cells (RAW264.7) in vitro . Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (H&E) staining were utilized to evaluate the therapeutic effects of PA on septic mice. In the in vitro experiments, streamlined cysteine activity-based protein profiling (SLC-ABPP) and proteomics techniques were employed to identify potential protein targets and molecular pathways responsible for the anti-inflammatory properties of PA. Results We demonstrated that PA could enhance the survival rate, reduce inflammatory cytokines release, ameliorate histopathological changes, and balance macrophage polarization in a sepsis model. Similarly, PA could effectively alleviate the inflammatory response in LPS-stimulated RAW264.7 cells. Chemoproteomics profiling revealed that Trim33 protein was a potential covalent target of PA via cysteine engagement, and the expression changes of global proteins indicated by proteomics analysis suggested that PA mitigated inflammation by inhibiting the NF-κB pathway. Finally, through a series of molecular biology experiments, we confirmed that PA suppresses the NF-κB pathway by functionally binding to Trim33 and subsequently reducing the ubiquitin dependent degradation of Smad4, thereby exhibiting anti-inflammatory activity. Conclusion Our findings demonstrated that PA significantly mitigated inflammation in sepsis by targeting the Trim33 protein and consequently suppressing ubiquitination on Smad4 as well inhibiting the NF-κB pathway, thus providing new insights into the clinical use of PA in treatment of inflammation related diseases.
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PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Ning-Ke Guo,Han She,Lei Tan,Yuan-Qun Zhou,Chun-Qiong Tang,Xiao-Yong Peng,Chun-Hua Ma,Tao Li,Liang-Ming Liu
Background Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results The encapsulation rate of Nano PTL was 95±1.5%, the drug loading rate was 11±0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.
研究领域:
药理学
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免疫学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Nanomedicine
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2019
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IF 4.717
Xin Jin,Qing Yang,Ning Cai,Zhenhai Zhang
Aim: Lung cancer has a very high incidence rate, and thus, there is an urgent need for novel and effective therapies. Materials & methods: In this study, we proposed a potential treatment option by combining four natural products in liposome systems. Results:In vitro studies indicated that the combination of betulinic acid, parthenolide, honokiol and ginsenoside Rh2 exhibited a synergistic action. When these four natural products were loaded into liposome systems, we observed an increased effect. The relative action was also observed in vivo. The cisplatin group presented obvious kidney damage, whereas both cocktail therapy and cocktail liposome therapy were safer. Conclusion: Therefore, we propose cocktail liposome systems may provide a more efficient and safer treatment for lung cancer.
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DOI
高影响因子
MOLECULAR NEUROBIOLOGY
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2025
·Vol. 63
·期 1
·210
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IF 4.3
Mao Niping,Zheng Yihui,Yuan Junhui,Feng Xiaoli,Ren Yi,Wang Xun,Tao Xiaoyue,Wang Xingyun,Fang Mingchu,Lin Zhenlang
Perinatal hypoxia causes hypoxic-ischemic brain damage (HIBD), which can result in neurological sequelae of varying severity. This syndrome is a major cause of neonatal mortality and pediatric impairment. Although research is ongoing to better understand its origins and develop targeted treatments, endoplasmic reticulum stress (ERS)–mediated apoptosis via the unfolded protein response (UPR) is crucial for the progression of cerebral ischemia injury. Parthenolide (PN), a sesquiterpene lactone derived from the Asteraceae family, exhibits anti-inflammatory, anti-apoptotic, and antioxidant properties that are beneficial in treating central nervous system disorders. To investigate the role of PN in HIBD and its underlying mechanism. In vivo and in vitro experiments were conducted to observe apoptosis and endoplasmic reticulum (ER) hyperactivation in HIBD, followed by a comparison of the neuroprotective effects of PN through modulation of the protein kinase Ribonucleic Acid-like ER kinase (Perk) pathway of ER stress. An in vivo model of HIBD was established using postnatal day 7 rat pups exposed to hypoxia for 2 h after left common carotid artery ligation. The in vitro model involved rat brain astrocyte cells that were depleted of glucose and oxygen for 7 h. Perfusion imaging and 2,3,5-triphenyltetrazolium chloride staining were used to visualize cerebral edema and infarction in HIBD brain tissue. Nissl staining and other histological techniques were used to detect nerve cell loss and destruction in damaged areas. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and CCAAT/enhancer binding protein-homologous protein (CHOP) staining were used to localize sites with high expression of apoptosis-positive cells in the liver. Real-time quantitative polymerase chain reaction and Western blotting were used to observe apoptosis and pathway markers at the transcriptional and translational levels, respectively. Behavioral tests were conducted to evaluate the motor and memory abilities of rats over time. In this study, we observed that phosphorylated Perk/Perk (P-Perk/Perk), glucose-regulated protein-78, activating transcription factor 4 (ATF4), phosphorylated eukaryotic translation initiation factor 2α/eukaryotic translation initiation factor 2α (P-eIf2α/eIf2α), CHOP, and various apoptotic factors were significantly elevated in the cortex of rats with HIBD compared to normal rats. PN acts through the Perk pathway, regulating ERS and reducing apoptosis after HIBD in neonatal rat models. Our findings demonstrate that elevated P-Perk expression activates the UPR-mediated pathway and triggers apoptosis, thereby counteracting the protective effects of PN both in vivo and in vitro. Conversely, PN inhibits Perk and the Perk/eIf2α/ATF4/CHOP pathway, leading to reduced apoptosis and astrocyte activation in neonatal rats. This study highlights the preventive role of PN in HIBD by downregulating apoptotic expression, potentially through the modulation of the Perk/eIf2α/ATF4/CHOP pathway within the disease framework.
研究领域:
神经科学
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分子生物学
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药理学
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新生儿医学
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细胞凋亡
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脑缺血
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转化医学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Jingwen Guo,Yuanzhi He,Jiaqi Li,Min Lin,Yihan Wu,Jiayi Yang,Zehui He,Long Meng,Zhi Wang,Qing Xia,Chunyun Zhu,Yongtai Zhang,Nianping Feng
Ulcerative colitis (UC), a chronic disease characterized by continuous damage to the intestinal mucosa and inflammation in the colon, comprises a series of gastrointestinal reactions and is difficult to cure. Here, we have designed a nanotherapeutic strategy combining pharmacotherapy with physical protection, which is achieved by constructing a green nanocarrier named cyclodextrin-based nanosponges (CDNSs) and encapsulating the insoluble drug parthenolide (PTL). CDNSs were transformed into a hydrogel driven by water, releasing the anti-inflammatory agent PTL and forming a sticky barrier in the position of the ulcer lesion to confront pathogenic bacteria at the same time. Notably, the resulting PTL-loaded CDNS (PTL@CDNS) had improved the solubility and intestinal cellular uptake of PTL. The orally delivered transformable PTL@CDNS via a colon-specific capsule significantly relieved UC in rats by enhancing the regulation of c-kit and STAT6 pathways as well as normalizing inflammatory cytokines, including IL-4, IL-6, IL-10, IL-13, nitric oxide, malondialdehyde, and TNF-α, with excellent biocompatibility. To sum up, transformable PTL@CDNSs were demonstrated as a promising strategy for in situ treatment of mucosal ulcers including UC.
研究领域:
药学
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生物医学工程
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消化系统疾病
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
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2018
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IF 3.026
Xin Jin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Background Combinations of natural products with low toxicities using tumor-targeting carriers may improve cancer treatment. The combined parthenolide and ginsenoside compound K (CK) within tLyp-1 liposomes, with the aim of improving the efficacy of lung cancer treatment.Results In vitro studies in A549 human pulmonary adenocarcinoma cells demonstrated that parthenolide/CK tLyp-1 liposomes increased reactive oxygen species levels and induced mitochondrial apoptosis. It enters into cells via receptor-mediated uptake and micropinocytosis, followed by endosomal/lysosomal escape. In vivo studies illustrated that it produced a greater antitumor effect than combined administration of these compounds, with minimal toxicity.Conclusion The findings of this study indicated that combined application of natural products in nanocarriers could offer attractive therapeutic options.
研究领域:
药理学
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肿瘤学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 4
·640
·
IF 5.7
Zeting Tan,Rongshun Liang,Adam Junka,Haoxuan Sun,Jie Jiang,Haojia Ma,Shisong Fang,Yanfang Sun
Background: Respiratory syncytial virus (RSV) is a leading global pathogen of acute lower respiratory tract infection, posing significant risks to infants, the elderly, and immunocompromised patients.Artemisia argyiLevl.et Vant Extract (AALE) and its active components have a variety of pharmacological effects, but their anti-RSV potential remains unclear. The aim of this study is to investigate the anti-RSV activity of AALE and parthenolide and its underlying mechanisms.Methods: Cell counting kit-8 (CCK-8) assay was used to determine the anti-RSV activities of AALE and parthenolide. Time-of-addition assay and phase of action analysis were used to explore the effect of drugs on the viral replication cycle. Quantitative polymerase chain reaction (qRCR), immunofluorescence (IF) and Western blot (WB) were used to investigate the effects of AALE and parthenolide on RSV-F gene and protein and on RIG-I/TLR-3 pathway related molecules in vitro. In vivo antiviral efficacy was verified by hematoxylin–eosin (HE) staining for lung histopathology, quantitative real-time PCR (qPCR) quantification of RSV-F, RIG-I, TLR-3, IRF3, IL-6, and IFN-β gene expression in lung tissues, and enzyme-linked immunosorbent assay (ELISA) for serum IL-6 and IFN-β levels.Results: AALE exhibited the strongest anti-RSV activity among the extracts (SI = 27.6), while parthenolide was the most potent monomeric compound (SI = 8.19). In vitro, both AALE and parthenolide were effective in the co-treatment and post-treatment models, reducing RSV-F gene and F protein levels in infected cells. Furthermore, they alleviated RSV infection by regulating RIG-I and TLR-3 pathway-related genes and proteins. In vivo, AALE and parthenolide suppressed lung index and RSV proliferation, attenuated lung injury, and down-regulated RIG-I, TLR-3, IRF3, IL-6, and IFN-β expression in the lungs of RSV-infected mice.Conclusions: AALE and its component parthenolide can inhibit the invasion and replication of RSV, making it a potential candidate for the treatment of RSV-related diseases.
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PubMed
高影响因子
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