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1.
Front Pharmacol ; 12: 746808, 2021.
Article in English | MEDLINE | ID: mdl-34899301

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.

2.
Mol Med Rep ; 16(6): 8463-8470, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28983588

ABSTRACT

Dipterocarpus obtusifolius has been traditionally used as a herbal medicine and is considered to have anticancer properties. The biological activity of D. obtusifolius in inflammation and the underlying mechanisms of its activity remain to be elucidated. The present study investigated the effects of D. obtusifolius methanolic extract (DOME) on lipopolysaccharide (LPS)­stimulated inflammation in RAW264.7 cells. The effects of DOME on the production of nitric oxide, prostaglandin E2 and pro­inflammatory cytokines were assessed by ELISA, western blot analysis and reverse transcription­quantitative polymerase chain reaction. It was demonstrated that expression of inducible nitric oxide synthase, cyclooxygenase­2, interleukin­1ß and tumor necrosis factor­α was suppressed by DOME in LPS­stimulated cells. Furthermore, treatment with DOME suppressed phosphorylation of mitogen activated protein kinase (MAPK) molecules, including extracellular signal­regulated kinase, c­Jun N­terminal kinase and p38 MAPK. Translocation of the nuclear factor­κB p65 subunit into the nucleus was additionally inhibited by DOME. Phosphorylation of MAPK promoter activity was inhibited by treatment with DOME, PD98059, SB202190 and SP600125. These results demonstrated that DOME inhibits LPS­induced inflammatory responses. Therefore, DOME may be a potential therapeutic approach for the treatment of inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/etiology , Inflammation/metabolism , Lipopolysaccharides/adverse effects , Macrophages/immunology , Macrophages/metabolism , Plant Extracts/pharmacology , Animals , Cell Survival/drug effects , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Dinoprostone/metabolism , Inflammation/drug therapy , Inflammation Mediators/metabolism , Macrophages/drug effects , Mice , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , RAW 264.7 Cells
3.
Chemotherapy ; 59(6): 447-52, 2013.
Article in English | MEDLINE | ID: mdl-25138175

ABSTRACT

BACKGROUND: The anti-inflammatory drug diacetyl rhein has been found to possess promising antistaphylococcal effects against various drug-resistant strains in our previous study. In the present work, we explored the in vitro combinatory interactions of diacetyl rhein with oxacillin and tetracycline against 13 standard strains and clinical isolates of Staphylococcus aureus, including those resistant to erythromycin, methicillin and tetracycline. METHODS: Minimum inhibitory concentrations were determined by broth microdilution assay, and the effects of combinations were evaluated according to the sum of fractional inhibitory concentrations (ΣFICs). RESULTS: Synergistic or additive effects were observed against all S. aureus strains (ΣFIC 0.258-1), whereas diacetyl rhein-oxacillin appeared to be the most effective combination, synergistically inhibiting the growth of 4 strains tested. CONCLUSION: To our best knowledge, this is the first report on a synergistic antibacterial effect of diacetyl rhein. Our results suggest this promising compound for further evaluation of its synergistic anti-infective potential as an agent with a combined anti-inflammatory and synergistic antibacterial action.


Subject(s)
Anthraquinones/pharmacology , Anti-Bacterial Agents/pharmacology , Oxacillin/pharmacology , Staphylococcus aureus/drug effects , Tetracycline/pharmacology , Diacetyl/chemistry , Drug Synergism , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification
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