Osteogenic induction of asiatic acid derivatives in human periodontal ligament stem cells

• Published in: Scientific reports 2023-08, Vol.13 (1), p.14102-14102, Article 14102
• Main Authors: Thamnium, Sirikool, Laomeephol, Chavee, Pavasant, Prasit, Osathanon, Thanaphum, Tabata, Yasuhiko, Wang, Chao, Luckanagul, Jittima A.
• Format: Article
• Language: English
• Subjects: 631/154; 631/1647; 631/208; 631/337; 631/449; 631/45; 631/532; 631/535; 631/553; 631/80; 631/92; 639/301; 639/638; 639/925; 692/308; 692/4017; 692/53; 692/700; Biological effects; Bone growth; Bone morphogenetic proteins; Cell viability; Collagen (type I); Cytotoxicity; Gene expression; Humanities and Social Sciences; Ligaments; multidisciplinary; Osteogenesis; Periodontal ligament; Regeneration; Regenerative medicine; Science; Science (multidisciplinary); Signal transduction; Solubility; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-41388-8

Asiatic acid (AA) and asiaticoside, pentacyclic triterpenoid compounds derived from Centella asiatica, are known for their biological effects in promoting type I collagen synthesis and inducing osteogenesis of stem cells. However, their applications in regenerative medicine are limited due to their low potency and poor aqueous solubility. This work aimed to evaluate the osteogenic induction activity of AA derivatives in human periodontal ligament stem cells (hPDLSCs) in vitro. Four compounds were synthesised, namely 501, 502, 503, and 506. AA was used as the control. The 502 exhibited low water solubility, while the 506 compound showed the highest. The cytotoxicity analysis demonstrated that 503 caused significant deterioration in cell viability, while other derivatives showed no harmful effect on hPDLSCs. The dimethyl aminopropyl amine derivative of AA, compound 506, demonstrated a relatively high potency in inducing osteogenic differentiation. An elevated mRNA expression of osteogenic-related genes, BMP2 , WNT3A , ALP , OSX and IBSP was observed with 506. Additionally, the expression of BMP-2 protein was enhanced with increasing dose of 506, and the effect was pronounced when the Erk signalling molecule was inhibited. The 506 derivative was proposed for the promotion of osteogenic differentiation in hPDLSCs by upregulating BMP2 via the Erk signalling pathway. The 506 molecule showed promise in bone tissue regeneration.