Sains Malaysiana 47(10)(2018): 2429–2435

http://dx.doi.org/10.17576/jsm-2018-4710-19

 

Graveoline from Ruta angustifolia (L.) Pers. and Its Antimicrobial Synergistic Potential in Erythromycin or Vancomycin Combinations

(Graveolin daripada Ruta angustifolia (L.) Pers. dan Potensi Sinergistik Antimikrobnya dalam Gabungan Erithromicin atau Vancomicin)

 

LAINA ZARISA MOHD KAMAL¹, NORAZIAN MOHD HASSAN^1*, NURHAYA MD TAIB¹ & MAY KHIN SOE²

 

¹Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

 

²Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

 

Diserahkan: 9 April 2017/Diterima: 7 Jun 2018

 

ABSTRACT

Ruta angustifolia (L.) Pers. is a Rutaceous species which contains various anthranilic acid derived alkaloids including the bioactive quinolones. This study is aimed at identifying the antimicrobial active alkaloids of R. angustifolia and evaluating their potential as synergistic enhancers in alkaloid-antibiotic combinations. Antimicrobial bioautography-guided isolation of alkaloidal fractions of R. angustifolia leaves has led to the identification of 2,3-dimethoxy-1-hydroxy-10-methylacridone [arborinine]; and 4,7,8-trimethoxyfuro[2,3-b]quinoline [skimmianine]; together with the major active alkaloid, 1-methyl-2-[3’,4’-methylenedioxyphenyl]-4-quinolone [graveoline]. Graveoline showed Minimum Inhibitory Concentration (MIC) values ranging from 500 to 1000 μg/mL against Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212 and Escherichia coli ATCC 25922. Checkerboard assay for antimicrobial combination effects between graveoline with either erythromycin or vancomycin showed enhancement of the antimicrobial activity of both antibiotics with Fractional Inhibitory Concentration Indices (FICI) ranged from 0.37 to 1.50. Synergistic effect with FICI of 0.37 was observed for graveoline-erythromycin combination against S. aureus compared to FICI of 1.00 for ciprofloxacin-erythromycin additive effect. Graveoline was a potential candidate for antimicrobial combination agent especially against S. aureus. The result supports the idea of using plant metabolites as antimicrobial synergistic agents.

 

Keywords: Antimicrobial; graveoline; Ruta angustifolia; synergistic enhancer

 

ABSTRAK

Ruta angustifolia (L.) Pers. adalah spesies Rutaceae yang mengandungi pelbagai alkaloid yang hasilkan daripada asid anthranilik seperti alkaloid quinolon. Kajian ini bertujuan untuk mengenal pasti alkaloid aktif daripada R. angustifolia dan potensinya sebagai penggalak kesan sinergi bersama antibiotik terpilih. Pemencilan alkaloid aktif berpandukan bioautografi antimikrob daripada pecahan ekstrak daun R. angustifolia berjaya mengenal pasti 2,3-dimetoksi-1-hidroksi-10-metilakridon [arborinin]; dan 4,7,8-trimetoksifuro[2,3-b]quinolin [skimmianin]; dan akaloid aktif utama 1-metil-2-[3’,4’-metilenedioksifenil]-4-quinolon [graveolin]. Graveolin menunjukkan Kepekatan Perencatan Minima (MIC) pada julat antara 500 dan 1000 μg/mL terhadap Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212 dan Escherichia coli ATCC 25922. Gabungan antara graveolin dan erithromicin atau vankomicin yang dinilai melalui Assay Checkerboard menunjukkan bahawa graveolin meningkatkan aktiviti kedua-dua antibiotik dengan Indeks Pecahan Kepekatan Perencatan (FICI) antara 0.37 dan 1.50. Kesan sinergi dengan nilai FICI 0.37 ditunjukkan oleh gabungan graveolin-erithromicin terhadap S. aureus berbanding kesan tambahan dengan nilai FICI 1.00 oleh gabungan ciprofloxacin-erithromicin. Graveolin mempunyai potensi sebagai agen gabungan antimikrob terutama terhadap S. aureus. Keputusan kajian ini menyokong penggunaan metabolit daripada tumbuhan sebagai agen sinergi antimikrob.

 

Kata kunci: Antimikrob; graveolin; penggalak sinergistik; Ruta angustifolia

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*Pengarang untuk surat-menyurat; email: norazianmh@iium.edu.my