RESUMO
BACKGROUND: Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling. 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.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Ácido Mevalônico/metabolismo , Osteoporose/tratamento farmacológico , Animais , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Humanos , Terapia de Alvo Molecular , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Prenilação de Proteína/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Delayed wound healing (the diabetic ulcer) is one of the major complications of diabetes mellitus (DM), which has shown an increasing trend over previous decades to affect almost 15% of diabetic patients. Virgin coconut oil (VCO) is a natural oil rich in vitamins and antioxidants and possesses antimicrobial and antiviral activities. In the current study, we evaluated the effects of topical application of VCO on wound healing in diabetes-induced Sprague-Dawley rats. A total of 72 animals were divided into 4 groups: i.e. (I) non-diabetic nontreated (NN), (II) diabetic non-treated (DN), (III) diabetic treated with VCO (VCO), and (IV) diabetic treated with silver sulfadiazine cream (SS). Wounds were inflicted on all groups using punch biopsy needles, and the animals were treated for 14 days. Wound closure rate (WCR) was measured on day 5, 10, and 14. Histological analysis was performed on day 7 and 14. Total protein content and superoxide dismutase (SOD) activity were measured on day 1, 7, and 14. WCR in VCO group was higher on all days compared to DN. Histological analysis revealed that VCO promoted re-epithelialization and increased collagen content of wound tissue. Total protein content in VCO group was higher on day 7 and 14 compared to both DN and SS groups. VCO showed insignificant effects on SOD levels. In summary, VCO was found to be better than silver sulfadiazine cream in the healing of diabetic wounds via promoting reepithelialization and collagen synthesize as well as increasing WCR and total protein content
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