Pentagalloyl Glucose: A Review of Anticancer Properties, Molecular Targets, Mechanisms of Action, Pharmacokinetics, and Safety Profile

Abstract

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.

Ethanolic Extract from Fruits of Pintoa chilensis, a Chilean Extremophile Plant. Assessment of Antioxidant Activity and In Vitro Cytotoxicity

“…Therefore, these compounds might also contribute to the observed activity of DF. Probably, in the case of β-D-allopyranose, its effect could be the consequence of a different mechanism, such as oxidative stress, arrested cell proliferation, enhanced autophagy, apoptosis, or angiogenesis inhibition [108]. Similar behavior has been observed for other sugars such as glucopyranose or sugar polymers such as pectin [109].…”

Pentagalloyl Glucose-Targeted Inhibition of P-Glycoprotein and Re-Sensitization of Multidrug-Resistant Leukemic Cells (K562/ADR) to Doxorubicin: In Silico and Functional Studies

“…The researcher should thus consider their negative consequences at a high dosage. Recent research results showed that high doses of PGG (100 or 200 mg/kg/day) administered orally to mice did not have any adverse effects or cause weight loss in mice after seven days of therapy and that 200 mg/kg/day was the highest dose that could be tolerated; these results suggest that high doses of PGG are safe for mice [ 32 ]. PGG exhibits a propensity for lipids, polysaccharides, and proteins as evidenced by its slow clearance rate at 0.023 ± 0.012 h −1 and extended apparent elimination half-life (t 1/2 ) around 38.66 ± 22.89 h after intraperitoneal administration to rats [ 33 ].…”

Phytochemical Profiling and Biological Activities of Quercus sp. Galls (Oak Galls): A Systematic Review of Studies Published in the Last 5 Years

“…Gallotannins, considered the simplest hydrolyzable tannins, are formed by gallic acid molecules bound to a central D-glucose with ester bonds (Figure 3) [82]. Tannic acid (penta-m-digalloyl glucose) is composed of a central glucose esterified to all five hydroxyl moieties with two molecules of gallic acid, totaling ten galloyl groups [83].…”