The efficacy of Linum usitatissimum seeds to inhibit estrogen receptor as a natural therapy for PCOS: An in silico and in vitro analysis.

Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen and estrogen hormones, thus leading to the formation of multiple cysts, imposing life‐threatening conditions. This manuscript aimed to introduce a natural estrogen receptor (ESR) inhibitors that can provide protection against PCOS. The computational analysis of Linum usitatissimum seeds compounds against ESR alpha receptor was performed, and the binding affinities of the ligand compounds and receptor proteins were scrutinized. Nine lignin compounds were docked, and the results were compared with that of reference estrogen receptor inhibitors, clomiphene, and tamoxifen. The binding affinity scores for pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol were −10.67, −10.66, −10.91, and −10.60 kcal mol−1, respectively. These were comparable to the binding affinity score of reference compounds −11.406 kcal mol−1 for clomiphene and −10.666 kcal mol−1 for tamoxifen. Prime MM‐GBSA studies showcased that Linum usitatissimum seeds compounds exhibit significant efficacy and efficiency towards receptor protein. Moreover, MD‐simulation studies were performed and the results depict that the lignin compounds form stable complexes at 300 K throughout the simulation time. For further clarity, in‐vitro experiments were carried out. The results exhibit the decline in cell proliferation in a concentration‐dependent manner by extract 1 (ethyl acetate) EX1 and extract 2 (petroleum ether) EX2. Hence, providing evidence regarding the anti‐estrogenic activity of the sample extracts. Collectively, these results showed that flax seed can reduce the levels of estrogen, which can induce ovulation and prevent cyst formation, and ultimately can provide protection against PCOS. Significance statement: The Linum usitatissimum (flax seeds) plant has been traditionally used in the past for treating different diseases. In this study, natural estrogen receptor inhibitors were analyzed, and they were proven to show the desired results for the management of polycystic ovarian syndrome (PCOS). Herein the affinity of naturally occurring compounds, lignin from flax seeds as natural estrogen inhibitors for estrogen receptor (ESR) alpha, was determined using the in silico and in vitro approaches. In this regard, four lignin compounds from flax seeds, pinoresinol (1), lariciresinol (2), secoisolariciresinol (3), and matairesinol (4), were considered and studied against ESR alpha protein by molecular docking, prime MM‐GBSA calculations and Molecular‐dynamic simulations. The in silico and in vitro study of lignans in flax seeds provided evidence that besides their antioxidant effect on the body, they can also inhibit ESRs. The results of both these studies opened a gateway and provided a convenient approach for the management of PCOS and better ovulation. Thus, this manuscript focuses on outlining the affinity, stability, efficacy, toxicity, and potential of the flax seed compounds, under analysis, to assess how well they could emerge as a viable natural therapy for PCOS in the future. These natural inhibitors have the benefit of being less hazardous, and have comparable inhibitory action against ESR than synthetic medicines available commercially. Moreover, they not only protect against PCOS but also help to alleviate the harmful effects resulting from PCOS. Additionally, plant‐based medicines are more affordable and readily available than commercial medications in countries with less developed healthcare systems. [ABSTRACT FROM AUTHOR]