Methyl Gallate: A Potent Bioactive Compound Promoting Osteogenic Differentiation by Regulating Runx2 and Cbfa1 in Osteoblastic Cell Lines

Biotechnol Appl Biochem. 2025 Jun 26. doi: 10.1002/bab.2784. Online ahead of print.

Abstract

Osteoporosis is a widespread condition, particularly affecting women and high-aged groups, with limited allopathic treatment options leading to adverse effects. The interest in natural remedies for osteoporosis is growing, and plant-based compounds are being explored for their potential to promote bone regeneration. Vachellia nilotica, known for its various medicinal properties, has shown promise in traditional medicine but lacks scientific evidence for its role in osteoporosis treatment. This study focused on isolating from V. nilotica leaves and characterizing a compound, methyl 3,4,5-trihydroxybenzoate (methyl gallate), and its action upon osteoblastic cell lines to deal with osteoporotic disease. Methyl gallate is a phenolic compound. Methyl gallate is a substance that is used for many functions in the body; for example, it is used as an anti-inflammatory, an antioxidant, a neuroprotector, a hepato-protector, and an immunomodulator, as well as leading a range of research and development activities. The compound exhibited no cytotoxic effects at low concentrations on the MG 63 cell line, indicating its safety. It also demonstrated significant antioxidant activity, with the ability to scavenge radicals and reduce oxidative stress. Moreover, the isolated compound showed a stimulating effect on alkaline phosphatase activity, a marker of early differentiation of osteoblasts, thereby decreasing the activity of osteoclasts and thus leading to increased mineralization. The above results suggest the compound's potential to promote bone regeneration and healing. Overall, this study provides valuable insights into the compound's osteogenic differentiation properties from V. nilotica leaves and their potential as a natural remedy for osteoporosis.

Keywords: alkaline phosphatase (ALP) activity | methyl gallate | mineralization | osteoblasts | osteogenic differentiation | osteoporosis.