Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

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Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Language: Английский

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Celastrol ameliorates fibrosis in Western diet/tetrachloromethane-induced nonalcoholic steatohepatitis by suppressing Notch/osteopontin signaling

Phytomedicine, Journal Year: 2025, Volume and Issue: 137, P. 156369 - 156369

Published: Jan. 6, 2025

Language: Английский

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From natural herbal wisdom to nano innovation: Revolutionizing tumor treatment through metabolic reprogramming

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189263 - 189263

Published: Jan. 1, 2025

Language: Английский

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Genetic susceptibility and potential therapeutic targets of unruptured intracranial aneurysms: a genome-wide study based on Mendelian randomization

Clinical Neurology and Neurosurgery, Journal Year: 2025, Volume and Issue: 249, P. 108749 - 108749

Published: Jan. 21, 2025

Language: Английский

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Development of Chinese Medicinal Ointment with Antibacterial Properties from Tripterygium wilfordii

Pharmacognosy Magazine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Background Chinese medicinal ointment was first recorded in the Shan Hai Jing ( The Classic of Mountains and Seas). Different formulations ointments have been made based on traditional medicine (TCM) theory. Many TCMs possessed antibacterial properties that were used as microecological regulators to inhibit growth gram-negative bacteria, “ Escherichia coli.” Purpose To develop make an by Tripterygium wilfordii (TW) evaluate its function. Materials Methods methodologies included physical (cream selection), chemical [ultraviolet–visible (UV–Vis) high-performance liquid chromatography-diode array detector (HPLC-DAD)], biological (agar assay) experiments for making TW ointment. Results An active ingredient, “celastrol,” extracted from TW. Aqueous Cream BP chosen base since it did not any smell contained only natural substances. UV–Vis HPLC-DAD identified ingredient “celastrol” with absorption peak at 230 nm a symmetrical retention time 19.855 min. 1%, 2%, 5% inhibitory effects colony formation units E. coli 109.33 ± 14.32, 85.67 10.22, 44.00 6.66, respectively. Conclusion successfully developed using plant “TW.” “TW,” determined studies. evaluated effectiveness properties. These starting milestone further studying mechanisms or applications human skin.

Language: Английский

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Celastrol-loaded ginsenoside Rg3 liposomes boost immunotherapy by remodeling obesity-related immunosuppressive tumor microenvironment in melanoma

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Exploring the interplay between adipokine-mediated celastrol target genes and T cells in diabetic nephropathy: a mendelian randomization-based causal inference

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 18, 2025

Diabetic nephropathy (DN) is influenced by dysregulated adipokines, which play a key role in inflammation, immune responses, and lipid metabolism. However, the precise molecular mechanisms linking adipokine dysregulation, cell infiltration, metabolic reprogramming DN remain poorly understood. Celastrol, bioactive regulator, has been shown to mitigate renal immune-inflammatory damage inhibiting PI3K/Akt/NF-κB signaling pathway. Yet, its specific impact on adipokine-mediated responses metabolism unclear. This study aims elucidate interplay between target genes investigate how celastrol modulates these interactions. Gene expression profiles of patients were obtained from GEO datasets (GSE30122 GSE30528) analyzed for differentially expressed (DEGs) using limma package. set variation analysis (GSVA) was conducted assess pathways, while Mendelian randomization (MR) Pearson correlation evaluated association DEGs adipokines. Immune infiltration IOBR R package (MCP-counter xCell methods), followed MR DN-related responses. Celastrol identified SEA database. A total 70 intersecting identified. GSVA revealed that brown beige adipocyte differentiation pathways downregulated, adipocyte-related upregulated (p < 0.05). demonstrated adiponectin negatively associated with (OR = 0.77, P 0.005), whereas leptin 1.92, 0.016) resistin 1.43, 0.001) positively associated. Three genes, MAGI2, FGF9, THBS2 linked risk T infiltration. correlated 0.51, 6.7e-06), FGF9 -0.8, 2.2e-16) MAGI2 0.75, 1.3e-13) correlated. 22 including THBS2, Our findings reveal progression through adipokine-immune crosstalk, emerging as regulatory genes. These insights provide new avenues biomarker discovery therapeutic implications development DN.

Language: Английский

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Recombinant high-density lipoprotein targeted delivery of celastrol to promote foam cells lipophagy against early atherosclerosis

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 22, 2025

Atherosclerosis serving as the main underlying factor of cardiovascular disease (CVD) remains primary cause mortality and morbidity globally, while deposition massive cholesterol in macrophage-derived foam cells exerts pivotal roles occurrence progression atherosclerosis. Celastrol (CEL) is a bioactive ingredient owning potent capability to modulate lipid metabolism, whereas poor bioavailability potential toxicity limit its clinical application. This study aims design CEL-loaded recombinant high-density lipoprotein (rHDL) delivery platform for active targeting, which may effectively promote degradation reversely transport excessive liver metabolism time. The rHDL loaded with CEL (CEL-rHDL) was prepared by thin film dispersion method. Then anti-atherosclerotic efficacy targeted atherosclerotic lesions were verified both vitro vivo. RNA-sequence applied reveal mechanism against early atherosclerosis, further validated through several molecular biology experiments. CEL-rHDL increased targeting efficiency lesions, mitigated off-target toxicity, improved efficacy. Importantly, decreased storage triggering lipophagy via activation Ca2+/CaMKKβ/AMPK/mTOR signaling pathway reverse (RCT). A combination hypolipidemic chemo-intervention participated specific offer promising strategy biocompatible treatment

Language: Английский

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Effects of Celastrol-Enriched Peanuts on Metabolic Health and the Development of Atherosclerosis

Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1418 - 1418

Published: April 23, 2025

Background: Celastrol, a pentacyclic triterpenoid active component isolated from the root bark of traditional medicinal plant Tripterygium wilfordii, displays significant anti-inflammatory, antioxidant, and immunomodulatory properties. However, its clinical application remains limited due to inadequate bioavailability. Methods: Regarding these issues, we innovatively developed novel peanut cultivar (cel-peanut) enriched with celastrol through distant hybridization combined metabolomics screening. Guided by research concept “natural anti-inflammatory diets for metabolic disease management”, established high-fat diet-induced ApoE−/− atherosclerotic mouse model systematically evaluate anti-atherosclerosis effects mechanisms cel-peanut. Results: Our results revealed that cel-peanut significantly reduced serum levels triglycerides (TGs) increased high-density lipoprotein cholesterol (HDL-C). Concurrently, markedly decreased lesion area enhanced collagen content within plaques. Mechanistic investigations demonstrated malondialdehyde (MDA) suppressed concentration pro-inflammatory cytokine IL-6 in lesions. Furthermore, promoted intestinal health modulating composition functionality gut microbiota, thereby attenuating atherosclerosis progression. Conclusions: Overall, findings indicate exerts therapeutic against microbiota-modulating This study proposes nutritional intervention strategy provides promising adjuvant treatment.

Language: Английский

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