NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls the transcription of DNA, cytokine production and cell survival. Moreover, NF-κB is present in virtually all animal cell types. Incorrect regulation of NF-κB links to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.

Bone is a volatile equilibrium organ that constantly regenerates and resorbs. Osteoclasts are special monocyte macrophages that possess a bone resorption function. In particular, when osteoclasts exert an excessive effect on bone resorption, osteoporosis is prone to occur and is distinguished by bone loss, destruction of the bone structure, and fragile fractures. Besides, the NF-κB pathway acts as a downstream pathway of MAPK and a classical pathway of osteoclasts, which are affected by the MAPK pathways that inhibit osteoclast production.

Dehydromiltirone (also known as 1,2-Didehydromiltirone) is a natural diterpenoid quinone with anti-inflammatory effects.

From: Deng W, et al. Front Pharmacol. 2022 Sep 21;13:1015693.

Dehydromiltirone prevents liver injury by modifying the MAPK and NF-κB signaling pathways, reducing neuroinflammatory responses, and inhibiting platelet aggregation. Thus, it has the potential for osteoporosis research. Moreover, Dehydromiltirone inhibits the expression of osteoclast-associated genes, including NFATc1, CTSK, c-Fos, Acp5, and MMP9; as well as the phosphorylation of P38, ERK, and JNK of the MAPK signaling pathway; and the degradation of IκB-α of NF-κB signaling pathway. Furthermore, Dehydromiltirone (50-200 mg/kg, p.o.) protects the liver from CCl4-induced injury in rats. This compound reduces the increase in the pro-inflammatory cytokines TNF-α, IL-1 and IL-6, indicating an effect on alleviating liver inflammation.

To sum up, Dehydromiltirone is a natural diterpenoid quinone with anti-inflammatory and antioxidant effects and has the potential for osteoporosis research.

[1]. Shuqiang Yue, et al. Pharm Biol. 2014 Oct;52(10):1278-85.

[2]. Wei Deng, et al. Front Pharmacol. 2022 Sep 21;13:1015693.