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Assessment of antimycobacterial activities of pure compounds extracted from Thai medicinal plants against clarithromycin-resistant Mycobacterium abscessus

ABSTRACT:

Background

Infection with Mycobacterium abscessus is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against M. abscessus.

Methods

Twenty-three compounds were evaluated for antimycobacterial activity against thirty M. abscessus clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity.

Results

Five out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against M. abscessus, with MIC values ranging from <1 to >128 μg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%).

Conclusions

This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant M. abscessus. This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.

SUBMITTER: Sirichoat A

PROVIDER: S-EPMC8555507 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTraditional folk medicinal plants have recently become popular and are widely used for primary health care. Since Thailand has a great diversity of indigenous (medicinal) plant species, this research investigated 52 traditionally used species of Thai medicinal plants for their in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities.MethodsThe 55 dried samples, derived from the medicinally used parts of the 52 plant species were sequentially extracted by hexane, dichloromethane, ethanol and water. These 220 extracts were then screened for in vitro (i) cytotoxicity against four cell lines, derived from human lung (A549), breast (MDA-MB-231), cervical (KB3-1) and colon (SW480) cancers, using the MTT cytotoxicity assay; (ii) antioxidant activity, analyzed by measuring the scavenging activity of DPPH radicals; (iii) lipase inhibitory activity, determined from the hydrolytic reaction of p-nitrophenyllaurate with pancreatic lipase; and (iv) antimicrobial activity against three Gram-positive and two Gram-negative bacteria species plus one strain of yeast using the disc-diffusion method and determination of the minimum inhibitory concentration by the broth micro-dilution assay.ResultsThe crude dichloromethane and/or ethanol extracts from four plant species showed an effective in vitro cytotoxic activity against the human cancer cell lines that was broadly similar to that of the specific chemotherapy drugs (etoposide, doxorubicin, vinblastine and oxaliplatin). In particular, this is the first report of the strong in vitro cytotoxic activity of Bauhinia strychnifolia vines. The tested tissue parts of only six plant species (Allium sativum, Cocoloba uvifera, Dolichandrone spathacea, Lumnitzera littorea, Sonneratia alba and Sonneratia caseolaris) showed promising potential antioxidant activity, whereas lipase inhibitory activity was only found in the ethanol extract from Coscinum fenestratum and this was weak at 17-fold lower than Orlistat, a known lipase inhibitor. The highest antimicrobial activity was observed in the extracts from S. alba and S. caseolaris against Pseudomonas aeruginosa and Candida albicans, respectively.ConclusionThe Thai medicinal plant B. strychnifolia is first reported to exert strong in vitro cytotoxic activities against human cancer cell lines and warrants further enrichment and characterization. The broad spectrum of the biological activities from the studied plant extracts can be applied as the guideline for the selection of Thai medicinal plant species for further pharmacological and phytochemical investigations.

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