ReviewPost screenPharmacological effects of vitamin D and its analogs: recent developments
Introduction
Vitamin D includes several forms (vitamers) that are important from a physiological standpoint. Animals synthesize 7-dehydrocholesterol, the immediate precursor of cholesterol. Absorption of ultraviolet B radiation (290–315 nm) leads to a rearrangement of the 5–7-diene in the B ring of 7-dehydrocholesterol, causing ring breakage to form pre-vitamin D3 (9,10-secosterol), which is thermodynamically unstable and rearranges to cholecalciferol – the more stable vitamin D3 structure. Two more steps of oxidation lead to the vitamin D hormonally active form – calcitriol [1].
Calcitriol (1,25-dihydroxyvitamin D3) regulates various physiological processes directly, through vitamin D receptors (VDRs), or indirectly through crosstalk between proteins of signaling cascades. It is an essential factor for homeostasis of calcium and phosphorus and it has numerous biological functions, including modulation of cell proliferation, differentiation and apoptosis, neuromuscular, hormone and immune function, as well as other physiological processes 1, 2, 3. The diverse functionalities offer a wide variety of clinical applications for vitamin D and its analogs in various diseases such as dermatological diseases, cancer, osteoporosis, inflammation and autoimmune diseases. Vitamin D deficiency in the body is of great importance for health in children as well as adults and elderly people 1, 2. It can lead to various malignancies of the large bowel, prostate and breasts and to diabetes mellitus type 2. The purpose of this review is to provide an overview on various physiological and pharmacological activities of calcitriol and its newly discovered synthetic analogs, and to discuss the mechanisms of their actions and possible methods for delivery and targeting.
Section snippets
Calcium and bone metabolism by vitamin D
Calcitriol acts on various tissues and cells that are related or unrelated to homeostasis of calcium and phosphate. One of the most important roles of calcitriol is to maintain skeletal calcium balance 3, 4, 5. Therefore, maintenance of normal serum calcium levels by vitamin D is essential to warrant the skeletal calcium balance and the optimal functioning of multiple vital processes. This constant maintenance activity occurs in several systems including the intestine (site of absorption), the
Skin diseases and vitamin D analogs
Vitamin D has several important roles in the skin (Table 1). Many in vitro and in vivo studies demonstrate dose-dependent effects of vitamin D on cell proliferation and differentiation 15, 16, 17. Although the mechanisms that mediate the antiproliferative and pro-differentiating effects of vitamin D analogs on keratinocytes are not completely understood, it is well known that these effects are at least in part genomic and mediated by VDRs (1,25-dihydroxyvitamin D3) [15]. Vitamin D can reduce
Vitamin D and its analogs in cancer treatment and prevention
The role of vitamin D and its analogs in cancer treatment and prevention was investigated in different research tracks including clinical and epidemiological studies. According to extensive epidemiological research reports 39, 40, it was found that there is a clear association between various factors responsible for vitamin D levels in the body (e.g. geography and latitude, history of sun exposure, lifestyle) and increased morbidity from cancer. It was also found that vitamin D and its analogs
Antidiabetic activity of vitamin D and its analogs
Type 1 diabetes is an autoimmune disease characterized by the immune-mediated destruction of insulin-producing β cells from islets of Langerhans in the pancreas. As mentioned above, vitamin D plays a vital part in the normal functioning of the immune system and its deficiency could lead to impaired functioning of the immune system. Epidemiological studies have shown a direct correlation between the increase in the prevalence of the disease and deficiency of vitamin D. It was shown that vitamin
Vitamin D and its analogs in multiple sclerosis
Various genetic and environmental risk factors appear to interact and contribute to multiple sclerosis (MS), an autoimmune disease initiated by autoreactive T cells that recognize central nervous system antigens. In genetics, several human leukocyte antigen alleles (more particularly HLA-DRB1*1501) could favor the disease whereas others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also have a significant role in MS [75]. Based on epidemiological
Delivery and targeting of vitamin D
Most orally administered drugs gain access to the blood by direct absorption through the portal vein. However, lipophilic compounds can reach the systemic circulation via the intestinal lymphatic system, an alternative absorption pathway that involves association of the lipophilic drug with the lipoprotein chylomicron inside the enterocyte. The overall bioavailability of these molecules is the sum of the portion transported via the lymphatic system and the portion absorbed through the portal
Concluding remarks and future perspectives
The current collected data could suggest that vitamin D and its analogs have a promising therapeutic potential, especially for prevention and treatment of various skin diseases, cancer development, diabetes and MS. Additional information on vitamin D research is needed from an interdisciplinary perspective. There is a need for long-term clinical studies with relevant outcomes, including bone health, immune function, autoimmune disorders and chronic disease prevention. In addition, there is a
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2019, Epilepsy ResearchCitation Excerpt :This finding may also indicate the importance of vitamin D as a therapeutic agent. It has been thought that vitamin D and its analogs have promising therapeutic potential particularly in various skin diseases, cancer development, diabetes and multiple sclerosis (Sintov et al., 2014). In conclusion, this study demonstrates that vitamin D has a protective effect against hippocampal apoptosis related with KA and PTZ induced seizures in rats.
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