In vivo safety assessment of rhodomyrtone, a potent compound, from Rhodomyrtus tomentosa leaf extract

Thanyaluck Siriyong; Julalak Chorachoo Ontong; Sukanlaya Leejae; Sakol Suwalak; Peter John Coote; Supayang Piyawan Voravuthikunchai

doi:10.1016/j.toxrep.2020.07.013

In vivo safety assessment of rhodomyrtone, a potent compound, from Rhodomyrtus tomentosa leaf extract

Toxicol Rep. 2020 Jul 31:7:919-924. doi: 10.1016/j.toxrep.2020.07.013. eCollection 2020.

Authors

Thanyaluck Siriyong^{1

2}, Julalak Chorachoo Ontong^{2

3}, Sukanlaya Leejae⁴, Sakol Suwalak⁵, Peter John Coote⁶, Supayang Piyawan Voravuthikunchai⁴

Affiliations

¹ Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
² Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
³ Cosmetic Technology and Dietary Supplement Products Program, Faculty of Agro and Bio Industry, Thaksin University, Ban Pa Phayom, Phatthalung, 93210, Thailand.
⁴ Excellence Research Laboratory on Natural Products, Department of Microbiology, Faculty of Science, and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
⁵ Electron Microscopy Unit, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
⁶ Biomedical Sciences Research Complex, School of Biology, University of St Andrews, The North Haugh, St Andrews, Fife, United Kingdom.

Abstract

Background: Rhodomyrtus tomentosa (Aiton) Hassk. has been traditionally used to relieve various diseases. Rhodomyrtone, a bioactive acylphloroglucinol compound isolated from the leaves of Rhodomyrtus tomentosa, has been scientifically evidenced as a potential antibacterial agent. This study aimed to assess safety of rhodomyrtone in both invertebrate and vertebrate models.

Material and methods: Safety of rhodomyrtone was determined in an invertebrate model, Galleria mellonella as well as vertebrate models including zebrafish (Danio rerio) and murine. In addition, toxicity to human erythrocytes was also measured.

Results: Treatment of Galleria mellonella with rhodomyrtone at 100 mg/kg body weight up to four days showed no visible toxic effects (100 % survival). In zebrafish embryo model, at least 80 % survival of embryos was demonstrated when treated with rhodomyrtone at 0.5 μg/mL for three days. Prior to clinical trial, it is a prerequisite that rhodomyrtone has to be evaluated for its biocompatibility with human blood components. The results displayed that rhodomyrtone at 256 μg/mL did not cause any observable human erythrocyte haemolysis. Furthermore, preclinical assessment of rhodomyrtone formulation justified potential applications of rhodomyrtone in humans. Oral toxicity testing in a mouse model indicated the absence of systemic toxicity when the animals received up to 5000 mg/kg body weight of rhodomyrtone formulation for a period of fourteen days.

Conclusions: As the minimal inhibitory concentration of rhodomyrtone against most Gram-positive pathogens is 0.5-1 μg/mL, the results suggest that it should produce no toxic effects at concentrations used in human, thus support further development in pharmaceutical industries and public health applications.

Keywords: DMSO, dimethyl sulfoxide; Invertebrate; PBS, phosphate buffered saline; RBCs, red blood cells; Rhodomyrtone; Rhodomyrtus tomentosa; Toxicity; Vertebrate.