Anti‑osteoporotic activity of isoflavones from Iris germanica targeting NF‑kappaB

Background: Most of the available anti‑osteoporotic drugs are costly and possess great threat of severe side effects. Thus, an alternative approach is required to develop new therapeutic drugs. Materials and Methods: An attempt was made to isolate two novel compounds followed by its analog synthesis from Iris germanica. All the compounds were subjected for in vitro anti‑osteoporotic activities; % stimulation on osteoblast‑like cells, % inhibition on osteoclast‑like multinucleated cells (RAW264.7), cytotoxicity against RAW264.7 cell lines using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetra assay, % tartrate‑resistant acid phosphatase (TRAP) activity on RAW264.7 cell lines, and docking study into the active site of NF‑kappaB. Results: Out of six compounds, the compounds 1a, 1c, and 2a exhibited significant % stimulation (90%–98%) compared to standard drug diazedine (100%) while % inhibition was found in the range of 142–165, when compared with standard drug elcitonin. Cytotoxic assay results revealed that compound 1c and 1a have showed pronounced activity with IC50 values 4.2 and 5.2 against preosteoclastic RAW 264.7 cell lines. All the compounds showed significant inhibition of TRAP in NF‑kappaB ligand‑induced osteoclastic RAW 264.7 cells, with values ranging from 14.39% ± 2.62% to 66.67% ± 2.76%. Furthermore, all the compounds were docked into the active site of NF‑kappa B and 1a exhibited docking score (−7.98 kcal/mole). Conclusion: In vitro screening of all compound were carried out for anti‑osteoporotic activity using NF‑kappa B as a target. Isolated isoflavones showed excellent interactions with NF‑kappaB and established a noticeable correlation between in silico score and in vitro anti‑osteoporotic study.