Pentagalloyl glucose (PGG) is a natural hydrolyzable gallotannin abundant in various plants and herbs. It has a broad range of biological activities, specifically anticancer activities, and numerous molecular targets. Despite multiple studies available on the pharmacological action of PGG, the molecular mechanisms underlying the anticancer effects of PGG are unclear. Here, we have critically reviewed the natural sources of PGG, its anticancer properties, and underlying mechanisms of action. We found that multiple natural sources of PGG are available, and the existing production technology is sufficient to produce large quantities of the required product. Three plants (or their parts) with maximum PGG content were Rhus chinensis Mill, Bouea macrophylla seed, and Mangifera indica kernel. PGG acts on multiple molecular targets and signaling pathways associated with the hallmarks of cancer to inhibit growth, angiogenesis, and metastasis of several cancers. Moreover, PGG can enhance the efficacy of chemotherapy and radiotherapy by modulating various cancer-associated pathways. Therefore, PGG can be used for treating different human cancers; nevertheless, the data on the pharmacokinetics and safety profile of PGG are limited, and further studies are essential to define the clinical use of PGG in cancer therapies.

Combining phytochemicals with chemotherapeutic drugs has demonstrated the potential to surmount drug resistance. In this paper, we explore the efficacy of pentagalloyl glucose (PGG) in modulating P-gp and reversing multidrug resistance (MDR) in drug-resistant leukemic cells (K562/ADR). The cytotoxicity of PGG was evaluated using a CCK-8 assay, and cell apoptosis was assessed using flow cytometry. Western blotting was used to analyze protein expression levels. P-glycoprotein (P-gp) activity was evaluated by monitoring the kinetics of P-gp-mediated efflux of pirarubicin (THP). Finally, molecular docking, molecular dynamics simulation, and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) calculation were conducted to investigate drug–protein interactions. We found that PGG selectively induced cytotoxicity in K562/ADR cells and enhanced sensitivity to doxorubicin (DOX), indicating its potential as a reversal agent. PGG reduced the expression of P-gp and its gene transcript levels. Additionally, PGG inhibited P-gp-mediated efflux and increased intracellular drug accumulation in drug-resistant cells. Molecular dynamics simulations and MM-GBSA calculation provided insights into the binding affinity of PGG to P-gp, suggesting that PGG binds tightly to both the substrate and the ATP binding sites of P-gp. These findings support the potential of PGG to target P-gp, reverse drug resistance, and enhance the efficacy of anticancer therapies.

Impaired wound healing, particularly in diabetic and chronic wounds, remains a significant global health challenge. While current therapies show promise, their effectiveness is often constrained by high costs, limited accessibility, and inconsistent outcomes across patient populations. This study investigates the potential of the Iron-Quercetin complex (IronQ) to enhance the regenerative secretory profile of peripheral blood mononuclear cells (PBMCs), with the aim of developing a cost-effective, cell-free therapeutic approach. PBMCs isolated from both healthy and diabetic donors were preconditioned with IronQ for 10 days. The resulting secretomes were analyzed for their protein and metabolic profiles, focusing on pro-angiogenic and immunomodulatory factors. In vitro assays were performed to assess the effects of IronQ-preconditioned secretomes on the proliferation, migration, and collagen production of endothelial cells, fibroblasts, and keratinocytes. IronQ preconditioning significantly enriched PBMC secretomes with cytokines such as TGF-α, TNF-α, IL-6, IL-10, HGF, G-CSF, M-CSF, GM-CSF, and GRO-α, along with enhanced glycolytic activity and the production of bioactive metabolites. Furthermore, these secretomes promoted the proliferation and migration of endothelial cells, fibroblasts, and keratinocytes, as well as collagen production by fibroblasts, with consistent effects observed across both healthy and diabetic donors. Collectively, these findings support the potential of IronQ-preconditioned PBMC secretomes as a scalable, autologous, and cost-effective alternative to current cell-based therapies for diabetic wound healing, warranting further in vivo and clinical evaluation.

Triple-negative breast cancer (TNBC) presents a major clinical challenge due to its aggressive behavior, limited targeted therapies, and frequent development of chemoresistance. Resistance to doxorubicin (DOX), a key chemotherapeutic agent, is often associated with epithelial-mesenchymal transition (EMT), overexpression of multidrug resistance (MDR) proteins, and dysregulation of microRNAs (miRNAs). This study investigates the potential of pentagalloyl glucose (PGG), a naturally occurring polyphenol, to overcome DOX resistance in TNBC cells by targeting EMT, miRNA expression, and MDR transporter activity. DOX-resistant MDA-MB-231/ADR cells were established and characterized. The cytotoxic and chemosensitizing effects of PGG were evaluated through MTT assays, apoptosis analysis, migration and invasion assays, Western blotting, miRNA sequencing, qRT-PCR, and drug accumulation studies. PGG significantly restored DOX sensitivity in resistant TNBC cells, as demonstrated by a reduction in the half-maximal inhibitory concentration (IC₅₀) and increased apoptosis. An EMT reversal effect was observed through upregulation of E-cadherin and downregulation of ZEB1 and vimentin, accompanied by reduced cell migration and invasion. miRNA profiling revealed the upregulation of miR-200c-3p and other tumor-suppressive miRNAs. Notably, overexpression of miR-200c-3p alone enhanced chemosensitizing and DOX-induced apoptosis in MDA-MB-231/ADR cells, highlighting its role in drug sensitivity. Additionally, PGG reduced the expression of P-glycoprotein (P-gp) and multidrug resistance protein-1(MRP-1), increased intracellular DOX accumulation, and inhibited efflux activity. In conclusion, PGG reverses DOX resistance in TNBC cells through multiple mechanisms involving EMT inhibition, MDR suppression, and restoration of miR-200c-3p expression. These findings suggest that PGG holds promise as an adjuvant therapeutic agent for managing multidrug-resistant TNBC.