Antiproliferative and antimicrobial efficacy of the compounds isolated from the roots of Oenothera biennis L.
Authors: Singh Shilpi , Dubey Vijaya , Singh Dhananjay Kumar , Fatima Kaneez , Ahmad Ateeque , Luqman Suaib 
Published: May 2017

Abstract

Background
Oenothera biennis L., commonly known as evening primrose, harbours the flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of biological activity, such as antitumour, anti-arthritic and anti-inflammatory effects. In addition to the previous reports from aerial parts of this plant, studies related to antiproliferative or antimicrobial activity from the roots are warranted.

Objective
To investigate antiproliferative and antimicrobial activity of compounds/mixture (1–8) isolated and characterized from the roots of O. biennis L. A possible mechanism of antiproliferative activity was also studied by targeting ornithine decarboxylase (ODC) and cathepsin D (CATD).

Study design
Antiproliferative efficacy of the compounds/mixture was examined in selected cancer cell lines along with their probable mechanism of action. The antimicrobial activity was also studied against selected microbes (bacteria and fungi).

Methods
Antiproliferative potential was evaluated by MTT assay against selected cell lines. The mechanism of action was studied spectrophotometrically by targeting ODC and CATD using both an in-vitro and an in-silico approach. The antimicrobial efficiency was analysed using the disc diffusion and broth dilution methods.

Key findings
Oenotheralanosterol B (3) and the mixture of oenotheralanosterol A and oenotheralanosterol B (4) exhibited antiproliferative activity against breast, hepatic, prostate and leukaemia cancer cell lines as well as in mouse macrophages (IC50 8.35–49.69 μg/ml). Oenotheralanosterol B (3) and the mixture of oenotheralanosterol A and oenotheralanosterol B (4) displayed a strong molecular interaction with succinate dehydrogenase (binding energy −6.23 and −6.84 kcal/mol and Ki 27.03 and 9.6 μm, respectively). Oenotheralanosterol A (1), oenotheralanosterol B (3) and mixture of oenotheralanosterol A and oenotheralanosterol B (4) potently inhibited the ODC activity with IC50 ranging from 4.65 ± 0.35 to 19.06 ± 4.16 μg/ml and also showed a strong interaction with ODC (BE −4.17 to −4.46 kcal/mol). Oenotheralanosterol A (1), cetoleilyl diglucoside (2), oenotheralanosterol B (3), dihydroxyprenylxanthone acetylated (6) and dihydroxyprenylxanthone (7) inhibited CATD activity (IC50 3.95 ± 0.49 to 24.35 ± 2.89 μg/ml). The in-silico molecular interaction analysis of compounds with CATD revealed the non-specific interaction. A moderate antimicrobial activity was observed against selected microbes with a growth inhibition ranging from 6 to 14 mm and minimum inhibitory concentration between 125 and 500 μg/ml. Oenotheralanosterol B (3) and dihydroxyprenylxanthone acetylated (6) exhibited better antimicrobial activity with an MIC range from 62.50 to 500 μg/ml.

Conclusion
Oenotheralanosterol B (3) exhibited stronger antiproliferative and antimicrobial potential with respect to the other compounds tested, whereas oenotheralanosterol A (1) was a potent inhibitor of ODC and CATD. Hence, it is suggested that these in-vitro findings could be studied further in vivo for biological activity, safety evaluation and derivatization to enhance potency and efficacy.