Sorafenib and Piperine co-loaded PLGA nanoparticles: Development, characterization, and anti-cancer activity against hepatocellular carcinoma cell line

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(5), P. 102064 - 102064

Published: April 7, 2024

Hepatocellular carcinoma (HCC) exhibits high mortality rates in the advanced stage (>90 %). Sorafenib (SORA) is a targeted therapy approved for treatment of HCC; however, reported response rate to such therapeutic suboptimal (<3%). Piperine (PIP) an alkaloid demonstrated exert direct tumoricidal activity HCC and improve pharmacokinetic profiles anticancer drugs including SORA. In this study, we developed strategy efficacy outcomes using PIP as add-on support first-line SORA biodegradable Poly (D, L-Lactide-co-glycolide, PLGA) nanoparticles (NPs). (both exhibit low aqueous solubility) were co-loaded into PLGA NPs (PNPs) stabilized with various concentrations polyvinyl alcohol (PVA). The PIP-loaded PNPs (SP-PNPs) characterized Fourier Transform Infrared (FTIR) Spectroscopy, X-ray Powder Diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Release these from SP-PNPs was investigated vitro at both physiological acidic pH, kinetic models employed assess mechanism drug release. against cells (HepG2) also evaluated. FTIR XRD analyses revealed that encapsulated amorphous state, no observed chemical interactions among or excipients. Assessment release pH 5 7.4 showed loaded 0.5 % PVA released sustained manner, unlike pure drugs, which exhibited relatively fast spherical, had average size 224 nm, encapsulation efficiency (SORA ∼ 82 %, 79 %), well superior cytotoxicity compared monotherapy vitro. These results suggest combining may be effective set comprehensive vivo study evaluate safety novel formulation murine model.

Language: Английский

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Piperine: an emerging biofactor with anticancer efficacy and therapeutic potential

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract Anticancer drug discovery needs serious attention to overcome the high mortality rate caused by cancer. There are still many obstacles treating this disease, such as cost of chemotherapeutic drugs, resulting side effects from drug, and occurrence multidrug resistance. Herbaceous plants a reservoir natural compounds that can be anticancer drugs with novel mechanisms action. Piperine, bioactive compound derived Piper species, is gaining due its unique dual role in directly inhibiting tumor growth enhancing bioavailability drugs. Unlike conventional treatments, Piperine exhibits mechanism action modulating multiple signaling pathways, including apoptosis autophagy, low toxicity. Additionally, acts bioenhancer improving absorption effectiveness other agents, reducing required dosage, minimizing effects. Therefore, review aims visualize summary sources, phytochemistry, chemical structure–anticancer activity relationship, activities semi‐synthetic derivatives, pharmacokinetic bioavailability, vitro vivo preclinical studies, antitumor action, human clinical trials, toxicity, effects, safety Piperine. References were collected Pubmed/MedLine database ( https://pubmed.ncbi.nlm.nih.gov/ ) following keywords: “Piperine anticancer,” derivatives,” mechanism” bioavailability,” after filter process inclusion exclusion criteria, 101 selected 444 articles. From 2013 2023, there numerous studies regarding various cell lines, breast cancer, prostate lung melanoma, cervical gastric osteosarcoma, colon hepatocellular carcinoma, ovarian leukemia, colorectal hypopharyngeal carcinoma. In vivo, study has also been conducted on some animal models, Ehrlich carcinoma‐bearing mice, ascites carcinoma cells‐bearing Balbc Wistar rat, A375SM A375P SNU‐16 BalbC HGC‐27‐bearing baby mice. Treatment leads proliferation inhibition induction apoptosis. used for trials diseases, but no cancer patient report exists. Various derivatives show efficacy an across lines. shows promise use either standalone treatment or bioenhancer. Its properties may enhance existing providing valuable foundation developing new therapies.

Language: Английский

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Piperine enhances doxorubicin sensitivity in triple-negative breast cancer by targeting the PI3K/Akt/mTOR pathway and cancer stem cells

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 6, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype of that lacks actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure often encountered due to inherent or acquired resistance Previous studies implicated PI3K/Akt/mTOR signaling pathway in stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect piperine (PIP), amide alkaloid isolated from Piper nigrum, on enhancing sensitivity TNBC doxorubicin (DOX) vitro MDA-MB-231 cell line vivo animal model Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX PIP cells. In addition, combination elicited enhanced suppression paralleled upregulation this pathway's negative regulator, PTEN, along curtailment levels CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, investigations demonstrated regimen enhance necrosis while downregulating PTEN curbing PI3K as well p-Akt, mTOR, ALDH-1 immunoreactivities. Notably, failed change cleaved poly-ADP ribose polymerase suggesting pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest role decreasing vivo, likely by interfering CSCs.

Language: Английский

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Impact of pH and ZnO NPs on the fabricated PVA-PVP/ZnO nanofibers: Morphology, absorption behavior, anticancer, and antibacterial activity

Ceramics International, Journal Year: 2024, Volume and Issue: 50(20), P. 40161 - 40170

Published: July 26, 2024

Language: Английский

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Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Medicine, Journal Year: 2024, Volume and Issue: 103(5), P. e36458 - e36458

Published: Feb. 2, 2024

This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association (GWAS) data, we conducted analysis. Instrumental variable selection for markers – namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, fatty acid-binding protein 4 was informed by SNP data from IEU database. Strongly associated SNPs served as instrumental variables. We applied suite of statistical methods, including Inverse Variance Weighted (IVW), Median Estimator (WME), MR-Egger, mode-based estimates, compute odds ratios (ORs) that articulate impact these on susceptibility. The IVW method revealed receptor inversely correlated with progression (OR = 0.86, 95% CI 0.74–0.99, P .03), whereas found elevate 1.21, 1.05–1.39, .03). variables comprised 5, 4, 7, 2, 3 respectively. Convergent findings WME, analyses corroborated associations. Sensitivity checks, heterogeneity, horizontal pleiotropy assessments, leave-one-out diagnostics, affirmed robustness reliability our instruments across diverse malignancy tissues without substantial bias. Our research suggests potentially mitigates, while may contribute pathogenesis (GC). Unraveling intricate biological interplay inflammation oncogenesis offers valuable insights preemptive strategies therapeutic interventions in management.

Language: Английский

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Synergistic enhancement: Exploring the potential of piperine in cancer therapeutics through chemosensitization and combination therapies

Life Sciences, Journal Year: 2024, Volume and Issue: 354, P. 122943 - 122943

Published: Aug. 6, 2024

Language: Английский

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Black pepper extract reduces tumour incidence via suppressing tumour - promoted cytokines / chemokines and modulating T cell subtype

Food and Agricultural Immunology, Journal Year: 2024, Volume and Issue: 35(1)

Published: Oct. 22, 2024

Our study aimed to evaluate tumour retardation effects of low-piperine fractional Piper nigrum extract (PFPE or LP-PE) related enhancement immune response. Results showed that PFPE at doses 50 (low), 100 (intermediated) and 150 (high) mg/kg BW had a incidence 20, 20 0%, respectively. low dose inhibited cytokines/chemokines in the early stages cancer however it could not suppress longer than 3 months. Intermediated including sICAM-1, CX3CL1, CXCL7, VEGF, TIMP-1, CCL5, CCL20, CXCL1, CXCL5, CXCL9 IL-1β. Interestingly, stimulated IFN- γ months after treatment all doses. high increased Th1 reduced Th2. Moreover, only Treg. Additionally, ER-α NF-κB IL-6R STAT3 proteins tissues. findings indicate suppressed breast via modulation.

Language: Английский

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Network pharmacology and molecular docking technology for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba herb-pair on anti-hepatitis: A review

Medicine, Journal Year: 2023, Volume and Issue: 102(48), P. e35443 - e35443

Published: Dec. 1, 2023

The Radix Bupleuri and Paeoniae Alba herb-pair (RRH) are the most classic compatible drug pair for treatment of hepatitis. However, underlying mechanism remains unclear. Therefore, network pharmacology molecular docking were conducted to investigate prospective therapeutic constituents, targets, pharmacological mechanisms RRH in active components from TCMSP database disease-related targets OMIM, PharmGkb, GeneCards, TTD, DrugBank databases identified. "drug-target-disease" diagram protein-protein interaction (PPI) constructed using Cytoscape (v3.8.0) Online STRING 11.0. GO KEGG pathway enrichment analyses performed R version 4.1.2, was verify results. We placed 176 overlapping cross genes into 11.0 obtained 14 core targets. A "Component-Target-GO-KEGG" constructed, which composed 7 components, 10 biological processes, signal pathways. total 2413 processes 174 pathways explored hepatitis treatment. Quercetin, kaempferol, isorhamnetin, beta-sitosterol, main bioactive employed bind disease's hub ensuring fulfillment spatial energy matching. anti-hepatitis may be associated with several including RELA, AKT1, JUN, MAPK1, TP53, CCND1, MYC, NFKBIA, CDKN1A, their respective signaling RRH, quercetin, used disease, provide insights development

Language: Английский

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Molecular Aspects of Piperine in Signaling Pathways Associated with Inflammation in Head and Neck Cancer

Published: March 4, 2024

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim this study was to investigate the molecular mechanisms action piperine in relation its potential anticancer effect on head neck cells. Parameters related neoplastic potential, analysis cyto-kine, protein gene expression were investigated cell lines (HEp-2 SCC-25) treated piperine. results tests indicated that modified mor-phology, inhibited viability formation colonies. Piperine promoted genotoxicity by triggering apoptosis cycle arrest G2/M S. A decrease migration also observed, decreased MMP2/9 genes. reduced inflammatory molecules (PTGS2 PTGER4), regulated secretion cytokines (IF-y IL-8) modulated ERK p38. These suggest exerts anti-cancer effects tumor cells, could be a promising natural treatment regulating signaling pathways cancer.

Language: Английский

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Molecular Aspects of Piperine in Signaling Pathways Associated with Inflammation in Head and Neck Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5762 - 5762

Published: May 25, 2024

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory which involve inhibiting molecular events associated with various stages of cancer development. The aim this study was to investigate the mechanisms action piperine in relation its potential anticancer effect on head neck cells. Parameters related neoplastic cytokine, protein gene expression were investigated cell lines (HEp-2 SCC-25) treated piperine. results tests indicated that modified morphology inhibited viability formation colonies. Piperine promoted genotoxicity by triggering apoptosis cycle arrest G2/M S phases. A decrease migration also observed, there decreased MMP2/9 genes. reduced inflammatory molecules (PTGS2 PTGER4), regulated secretion cytokines (IFN-γ IL-8) modulated ERK p38. These suggest exerts effects tumor cells regulating signaling pathways cancer.

Language: Английский

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