METHODS: Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated.
RESULTS: Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy.
CONCLUSION: The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.
OBJECTIVE: This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.
DISCUSSION: Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.
CONCLUSION: Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.