Aromatase inhibitors identified from Saraca asoca to treat infertility in women with polycystic ovary syndrome via in silico and in vivo studies.

Polycystic ovary syndrome (PCOS) is a widely occurring metabolic disorder causing infertility in 70%-80% of the affected women. Saraca asoca, an ancient medicinal herb, has been shown to have therapeutic effects against infertility and hormonal imbalance in women. This study was aimed to identify new aromatase inhibitors from S. asoca as an alternative to the commercially available ones via in silico and in vivo approaches. For this, 10 previously reported flavonoids from S. asoca were chosen and the pharmacodynamic and pharmacokinetic properties were predicted using tools like Autodock Vina, GROMACS, Gaussian and ADMETLab. Of the 10, procyanidin B2 and luteolin showed better interaction with higher binding energy when docked against aromatase (3S79) as compared to the commercial inhibitor letrozole. These two compounds showed higher stability in molecular dynamic simulations performed for 100 ns. Molecular mechanics Poisson-Boltzmann surface analysis indicated that these compounds have binding free energy similar to the commercial inhibitor, highlighting their great affinity for aromatase. Density functional theory analysis revealed that both compounds have a good energy gap, and ADMET prediction exhibited the drug-likeness of the two compounds. A dose-dependent administration of these two compounds on zebrafish revealed that both the compounds, at a lower concentration of 50 µg/ml, significantly reduced the aromatase concentration in the ovarian tissues as compared to the untreated control. Collectively, the in silico and in vivo findings recommend that procyanidin B2 and luteolin could be used as potential aromatase inhibitors for overcoming infertility in PCOS patients with estrogen dominance.Communicated by Ramaswamy H. Sarma.

De novo assembly and annotation of Caesalpinia bonducella L. seed transcriptome identifies key genes in the biosynthesis of bonducellin, a homoisoflavonoid.

Caesalpinia bonducella L. is a traditional medicinal plant containing a potential homoisoflavonoid, bonducellin, with therapeutic values against polycystic ovary syndrome, oxidative damage, pathogenic bacteria, irregular menstrual cycle, ovarian cancer and diabetes. Owing to the multi-therapeutic properties of bonducellin, knowledge of its biosynthetic pathway genes will help understand its regulatory mechanism and thus improve the yield. This study sequenced C. bonducella seed mRNA transcriptome to identify the genes in bonducellin biosynthesis. Before this, the presence of bonducellin in the seed samples was analysed by HPLC using the chemically synthesised bonducellin as the standard. Seven key genes encoding enzymes involved in the synthesis of bonducellin via the phenylpropanoid pathway were identified. The expression of selective genes from the bonducellin biosynthetic pathway was validated using qRT-PCR and comparable with RNA-Seq data. Here, we put forth the sequences of 67,560 genes from C. bonducella and highlight the bonducellin biosynthetic pathway genes.