Punicalagin (PUN) is the predominant polyphenol in pomegranate peels, and it has antioxidant property. This study aimed to explore the potential of PUN binding in reducing the allergenicity of soybean protein 7S (a major soy allergen). Ultrasound pretreatment (U7S) was used to enhance the availability of PUN binding sites. After PUN binding, the U7S conformation became more disordered, and the surface hydrophobicity was reduced. The molecular docking results indicated that the formation of the U7S-PUN complexes mainly depended on hydrogen bonding interactions. The phenolic hydroxyl group from PUN endowed U7S with high antioxidant properties, which were retained after digestion in the gastrointestinal tract. At a molar ratio of 1:50, U7S-PUN complexes reduced the IgG binding capacity by approximately 58.05 % and increased the rate of degranulation inhibition to about 35.87 %. This research offers a theoretical foundation for the use of PUN in the production of hypoallergenic plant-based protein products.

18 Jun 2025·Journal of Toxicology and Environmental Health, Part A

Mutagenic assessment and toxicological impact of bergenin in a phenolic-enriched extract from Endopleura uchi (Huber) Cuatrec bark, a medicinal plant from the Amazon rainforest

Article

Author: da Cruz, Elkejer Ribeiro ; Farias, Ingrid Vicente ; Grivicich, Ivana ; da Silva, Juliana ; de Sousa, Jayne Torres ; de Barros Falcão Ferraz, Alexandre ; Bondan da Silva, Juliana ; Corrêa, Dione Silva ; Reginatto, Flávio Henrique ; Picada, Jaqueline Nascimento ; Miri, Jéssica Machado

Endopleura uchi bark traditionally used in folk medicine attributed to its anti-inflammatory properties is due to the presence of bergenin. This study aimed to determine the toxicological parameters associated with exposure to a phenolic-enriched extract of E. uchi bark and bergenin a bioactive byproduct of this compound. The total phenolic and flavonoid contents were determined through spectrometric analyses, while phenolic compounds were identified using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS). Antioxidant activity was assessed in vitro using the DPPH assay. Cytotoxicity and genotoxicity were assessed via the MTT assay and comet assay, respectively, whereas mutagenic activity was examined using Salmonella/microsome assay and micronucleus (MN) test. A high content of phenolic (732.22 ± 9.48 mg/g) GAE (gallic acid equivalence) and flavonoid 252.47 ± 5.7 mg/g QE (quercetin) compounds was found in bergenin the phenolic-enriched extract byproduct as well as isomers of gallic acid, epicatechin, isoquercitrin, castalagin, punicalin, and punicalagin. The DPPH value was 23.74 ± 0.45 μg/ml. In MTT assay, the extract exhibited an IC50 of 72.5 ± 2.6 µg/ml. Both extract and bergenin displayed genotoxic activity in L929 fibroblast cells at 50 µg/ml but not mutagenic effects in the Salmonella/microsome assay or MN test. Despite the genotoxic actions, E. uchi bark and bergenin extract did not induce gene or chromosomal mutations, suggesting a low risk of compromising genomic stability. The presence of bioactive compounds such as bergenin and punicalagin in E. uchi bark demonstrates a therapeutic potential of this native tree for treating inflammatory diseases.

09 Apr 2025·mBio

Natural compounds target the M23B zinc metallopeptidase Mpg to modulate Neisseria gonorrhoeae Type IV pilus expression

Article

Author: Nicholson, Kathleen R. ; Edwards, Jennifer L. ; Luan, Chi-Hao ; Yin, Shaohui ; Seifert, H Steven

ABSTRACTNeisseria gonorrhoeae uses the Type IV pilus (T4p) to colonize several sites within humans by adhering to host cells and tissues. Previously, we identified a periplasmic M23B zinc metallopeptidase, Mpg, that is necessary to protect from oxidative and nonoxidative killing and these phenotypes are mediated by Mpg activities on T4p expression. Here, we use a high-throughput, target-based screening approach to identify novel inhibitors of Mpg’s enzymatic activity. We identified two natural compounds, punicalagin and chebulinic acid, which inhibit the peptidoglycan-hydrolyzing activity of Mpg in a dose-dependent manner. Moreover, treatment of N. gonorrhoeae with these compounds leads to a concomitant decrease in the number of T4p, similar to an mpg mutant. However, these compounds are not toxic to N. gonorrhoeae . These compounds exhibit activity against Mpg orthologs from other bacterial species. Notably, these natural compounds inhibit N. gonorrhoeae colonization and survival in cell culture models of infection. This work provides the characterization of two natural compounds with activity against N. gonorrhoeae T4p through the Mpg M23B class zinc metallopeptidase. IMPORTANCENeisseria gonorrhoeae is a global health burden with high transmission rates and multidrug resistance. N. gonorrhoeae encodes a Type IV pilus (T4p), which is a major colonization and virulence factor. The importance of the T4p in multiple stages of infection makes it an attractive drug target. Previously, we identified an M23B zinc metallopeptidase, Mpg, important for T4p production and T4p-mediated resistance to neutrophil killing. In this study, we identified two natural compounds, punicalagin and chebulinic acid, as novel inhibitors of Mpg’s enzymatic activity that thus inhibit T4p expression. These findings identify two potential anti-colonization and anti-virulence compounds and provide a framework to target T4p components for future screens, poising the field to potentially discover additional compounds to combat N. gonorrhoeae infection.

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Indication	Highest Phase	Country/Location	Organization	Date
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	China	Changchun University of Chinese Medicine	02 Jun 2022

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