RESUMEN
ABSTRACT Curcuma zanthorrhiza Roxb., Zingiberaceae, a species from Indonesia with xanthorrhizol as the major metabolite, has been used as a folk medicine in several of pharmacological activities. This work aimed to evaluate the xanthorrhizol contents, α-glucosidase inhibition, and cytotoxic activities in ethyl acetate fraction from accessions of C. zanthorrhiza. High-performance liquid chromatography investigated xanthorrhizol content with the standard. Pharmacological activities were evaluated by inhibition of α-glucosidase, the brine shrimp lethality test, and anticancer activity. The ethyl acetate fraction yield varied from 8.24% (Karanganyar) to 13.13% (Sukabumi). The xanthorrhizol contents were found to be in the range 43.55% to 47.99% with Ngawi and Wonogiri promising accessions having the lowest and highest value, respectively. IC50 value for α-glucosidase inhibition ranged from 339.05 µg/ml (Karanganyar) to 455.01 µg/ml (Ngawi). LC50 value for cytotoxic activities ranged from 33.25 µg/ml (Ngawi) to 42.28 µg/ml (Karanganyar) in brine shrimp lethality test, 3.10 µg/ml (Karanganyar) to 9.85 µg/ml (cursina-III) in Vero cell, and 1.17 µg/ml (Ngawi) to 6.83 µg/ml (Sukabumi) in MCF-7 cell. In this study, C. zanthorrhiza accessions have a high in xanthorrhizol contents and cytotoxic activities that showed a high potential of studied accessions for breeding programs on a commercial scale.
RESUMEN
Xanthorrhizol (XNT) is one of major compounds from temulawak`s rhizome and its activity in several cancer cells is known. The aim of this study was to identify mechanism of xanthorrhizol from temulawak`s rhizome as an hERα inhibitor against breast cancer human cell lines. The cytotoxicity of XNT from temulawak`s rhizome on T47D human breast cancer cells lined by sulforhodamine B (SRB) method has been carried out, while molecular docking simulation and pharmacophore modelling methods were employed to predict mechanism of xanthorrhizol as hER inhibitor. Cytotoxicity studies showed that XNT of the isolated and standard had an IC50 100 and 55.50 μg/mL in T47D cells, respectively. Subsequently, molecular docking interaction showed that XNT might be able to compete with estradiol (E2) as a potential ERα inhibitor with the calculated binding free-energy of -8.2 kcal/mol, even the compound superimposed with tamoxifen (4-OHT). XNT formed hydrogen bonds with Arg394 and Glu353 as mention E2 and tamoxifen also formed same interaction with same residue and interacted hydrophobic bonds similar to 4-OHT with: Leu387, Leu384, Leu391, Phe404, L349, Leu346, Met388, and Leu525 of estrogen alpha Ligan Binding Domain (LBD), although 4-OHT indicated stronger hydrophobic when the tail of tamoxifen interacted with Tyr347, Asp351, Trp383 and Leu428. XNT missed two chemical features into HipHop models pharmacophore thus may result in reduced inhibitory activity against T47D compared than 4-OHT. The xanthorrhizol mechanism as a hER inhibitor is postulated as partial estrogen antagonist, is justifiable based on its competitive characteristic versus tamoxifen (OHT-200) which was located on the active side of HER-α.