Abstract

Methanol extract of Melastoma malabathricum (MEMM) has been traditionally used by the Malay to treat various ailments. In an attempt to develop the plant as an herbal product, MEMM was subjected to the subacute and subchronic toxicity and cytotoxicity studies. On the one hand, the subacute study was performed on three groups of male and three groups of female rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (500 and 1000 mg/kg) daily for 28 days, respectively. On the other hand, the subchronic study was performed on four groups of rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (50, 250, and 500 mg/kg) daily for 90 days, respectively. In the in vitro study, the cytotoxic effect of MEMM against the HT29 colon cancer cell line was assessed using the MTT assay. MEMM was also subjected to the UHPLC-ESI-HRMS analysis. The results demonstrated that MEMM administration did not cause any mortality, irregularity of behaviour, modification in body weight, as well as food and water intake following the subacute and subchronic oral treatment. There were no significant differences observed in haematological parameters between treatment and control groups in both studies, respectively. The in vitro study demonstrated that MEMM exerts a cytotoxic effect against the HT29 colon cancer cell line when observed under the inverted and phase-contrast microscope and confirmed by the acridine orange/propidium iodide (AOPI) staining. The UHPLC-ESI-HRMS analysis of MEMM demonstrated the occurrence of several compounds including quercetin, p-coumaric acid, procyanidin A, and epigallocatechin. In conclusion, M. malabathricum leaves are safe for oral consumption either at the subacute or subchronic levels and possess cytotoxic action against the HT29 colon cancer cells possibly due to the synergistic action of several flavonoid-based compounds.

Highlights

  • Melastoma malabathricum has been applied in various folklore medicines to heal diverse forms of maladies [1,2,3]

  • Taking into account that (i) MEMM was reported to be safe at 5000 mg/kg when assessed using the acute toxicity model MEMM and (ii) MEMM was cytotoxic only against 3LL, L1210, and U251 cancer cell lines with no report against HT29 colon cancer cell line, the present study was designed to determine the toxic effect of MEMM following its subacute and subchronic oral exposure for 28 or 90 days, respectively, and to evaluate the cytotoxic activity of MEMM against the HT29 cancer cell line

  • The dried leaves in powder form (200 g) were soaked in 4000 mL methanol for 72 h and this procedure was performed three times to obtain the supernatant. e supernatant was evaporated at 40°C under reduced pressure to acquire the crude methanol extract (MEMM). e extract was left in the oven at 40°C to allow the solvent residue to dry and occasionally weighed until a constant weight was obtained

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Summary

Introduction

Melastoma malabathricum (family Melastomaceae) has been applied in various folklore medicines to heal diverse forms of maladies [1,2,3]. With regard to the methanol extract of M. malabathricum leaves (MEMM) toxic effect, only the acute toxicity study has been carried out on MEMM using the OECD Guideline No 423 [5]. MEMM was reported to show no toxic effect at the dose of 5000 mg/kg when given orally [5]. Taking into account that (i) MEMM was reported to be safe at 5000 mg/kg when assessed using the acute toxicity model MEMM and (ii) MEMM was cytotoxic only against 3LL, L1210, and U251 cancer cell lines with no report against HT29 colon cancer cell line, the present study was designed to determine the toxic effect of MEMM following its subacute and subchronic oral exposure for 28 or 90 days, respectively, and to evaluate the cytotoxic activity of MEMM against the HT29 cancer cell line

Materials and Methods
In Vivo Study
In Vitro Study
Results
In Vitro Cytotoxic Study
Discussion
Conclusion
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