In Vitro Selective Antibacterial and Antiproliferative Effects of Ethanolic Extracts from Cambodian and Philippine Plants Used in Folk Medicine for Diarrhea Treatment.

Tomas Kudera,Edgardo E Tulin,Ladislav Kokoska,Barbora Fiserova,Marlito M Bande,Marie Korytakova,Samnang Nguon,Ivo Doskocil,Hana Salmonova

doi:10.3389/fphar.2021.746808

Abstract

Bacterial diarrhea remains a global health problem, especially in developing tropical countries. Moreover, dysbiosis caused by diarrheagenic bacteria and inappropriate antimicrobial treatment has been associated with intestinal carcinogenesis. Despite the rich tradition of the use of herbs for the treatment of gastrointestinal disorders in Cambodian and Philippine folk medicine, many of them have not yet been systematically studied for their in vitro selective inhibitory effects on intestinal bacteria and cells. In the present study, in vitro inhibitory activities of 35 ethanolic extracts derived from 32 Cambodian and Philippine medicinal plants were determined by broth microdilution method against 12 pathogenic bacteria. Furthermore, cytotoxicity against intestinal cancer cells (Caco-2 and HT-29) using thiazolyl blue tetrazolium bromide cytotoxicity assay and safety to six beneficial intestinal bacteria (bifidobacteria and lactobacilli) and intestinal normal cells (FHs 74 Int) were determined for the antimicrobially active extracts. Selectivity indices (SIs) were calculated among the averages of minimum inhibitory concentrations (MICs), half-maximal inhibitory concentrations (IC50), and 80% inhibitory concentrations of proliferation (IC80) for each type of the tested agents. The extracts of Artocarpus blancoi (Elmer) Merr. (Moraceae), Ancistrocladus tectorius (Lour.) Merr. (Ancistrocladaceae), and Pentacme siamensis (Miq.) Kurz (Dipterocarpaceae) produced significant growth-inhibitory effects (MICs = 32–512 μg/ml) against intestinal pathogenic bacteria at the concentrations nontoxic to normal intestinal cells (IC80 values >512 μg/ml; SIs = 0.11–0.2). Moreover, the extract of P. siamensis (Miq.) Kurz was relatively safe to beneficial bacteria (MICs ≥512 μg/ml; SI = 0.1), and together with A. blancoi (Elmer) Merr., they selectively inhibited intestinal cancer cells (IC50 values ≥51.98 ± 19.79 μg/ml; SIs = 0.3 and 0.6). Finally, a strong selective antiproliferative effect on cancer cells (IC50 values 37.89 ± 2.68 to 130.89 ± 13.99 μg/ml; SIs = 0.5) was exerted by Ehretia microphylla Lam. (Boraginaceae), Lagerstroemia cochinchinensis Pierre ex Gagnep. (Lythraceae), and Melastoma saigonense (Kuntze) Merr. (Melastomataceae) (leaves with flower buds). The results suggest that the above-mentioned species are promising materials for the development of new selective antibacterial and antiproliferative agents for the treatment of infectious diarrhea and associated intestinal cancer diseases. However, further research is needed regarding the isolation and identification of their active constituents.

Highlights

According to the latest data of the World Health Organization, infectious diarrhea is still the third leading cause of death among all communicable diseases worldwide, especially affecting underfive children in developing countries (World Health Organization, 2020a)
Diarrheagenic Bacterial Pathogens Considering the antibacterial activity against the pathogens, 16 of 35 tested extracts revealed a growth-inhibitory effect on at least one of these bacterial strains
While B. cereus, C. difficile, E. coli, and V. parahaemolyticus were the most susceptible bacteria inhibited by the highest number of extracts, none of the extracts exerted activity against E. coli O157:H7 and S. flexneri

Summary

Introduction

According to the latest data of the World Health Organization, infectious diarrhea is still the third leading cause of death among all communicable diseases worldwide, especially affecting underfive children in developing countries (World Health Organization, 2020a). The antimicrobial resistance rate among diarrheagenic bacteria recovered from human patients has significantly increased, especially in developing countries (Meng et al, 2011; World Health Organization, 2020b). The most common bacteria recognized to date as probiotics are Lactobacillus spp. and Bifidobacterium spp., belonging to the dominant bacterial phyla that can be found in human intestines (Behnsen et al, 2013). It is a simplified representation of beneficial gut microbiota, the counterscreen of in vitro inhibitory activities on gut commensals appears to be an effective way to avoid unnecessarily promiscuous agents (Gavrish et al, 2014)

Methods

Results

Conclusion