Oleanolic acid and related derivatives as medicinally important compounds.
ABSTRACT Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.
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ABSTRACT: Oleanolic acid, a naturally occurring triterpenoid widely distributed in foods and medicinal plants, has anticancer, antioxidant, and antiaging properties. We hypothesized that oleanolic acid would suppress the production of the inflammatory adipokine resistin during adipogenic differentiation of 3T3-L1 adipocytes. 3T3-L1 adipocytes were cultured in adipogenic media with and without 1 to 25 μM oleanolic acid for up to 8 days to stimulate adipocyte differentiation. Adipocyte production of resistin was markedly enhanced during differentiation and was dose dependently attenuated by 1 to 25 μM oleanolic acid. This study further investigated whether Tyk2-Stat1/3 signaling was responsible for cellular production of resistin. Signal transducer and activator of transcription factor (STAT) 1 and STAT3 were activated during differentiation in a disparate temporal fashion; STAT1 was maximally phosphorylated on day 5 after initiating differentiation, whereas STAT3 was rapidly activated within 1 day of differentiation. When oleanolic acid was supplied to differentiating adipocytes, STAT1 and STAT3 phosphorylation was substantially suppressed. Upstream Tyk2 was rapidly activated in a manner similar to STAT3 and reactivated on days 3 to 5 after initiating differentiation, which was attenuated by incubating adipocytes with oleanolic acid. In addition, cellular expression of suppressor of cytokine signaling 3 (SOCS3), which inhibits Tyk2 activity, was markedly promoted from day 5 of adipocyte differentiation. Oleanolic acid attenuated SOCS3 expression, which was highly enhanced during the late phase of differentiation. Taken together, oleanolic acid suppressed adipocyte differentiation-associated resistin and adipogenesis production by disturbing the Tyk2-STAT1/3 signaling pathway and promoting SOCS3 expression. Therefore, oleanolic acid may be a possible bioactive agent that blunts adipogenesis and adipokine inflammation.Nutrition research (New York, N.Y.) 02/2013; 33(2):144-53. · 1.20 Impact Factor
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ABSTRACT: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.Journal of pharmacology & pharmacotherapeutics. 01/2013; 4(1):47-52.
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ABSTRACT: Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid contained in a variety of plant species, exhibits broad biological properties, including anticancer effects. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. APL has a unique and specific chromosomal aberration, t(15;17), which results in the formation of a fusion gene and protein PML/RARα, which is not only necessary for the diagnosis of APL, but is also critical for APL pathogenesis. In the present study, the cytotoxic effect of OA on NB4 cells was investigated. Cell viability was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of bax and bcl-2 mRNA were determined by quantitative PCR. Apoptosis was analyzed using DNA fragment analysis and cell cycle distributions were analyzed by flow cytometry. The activity of caspase-3 and caspase-9 was determined by colorimetric assays. The expression of the PML/RARα fusion protein was analyzed by western blotting. The MTT assay showed that OA inhibited the proliferation of the NB4 cells. The expression levels of pro-apoptotic bax mRNA were increased and the levels of anti-apoptotic bcl-2 mRNA were decreased following the treatment of the NB4 cells with OA at 80 μmol/l. Treatment of the NB4 cells with OA at 80 μmol/l induced apoptosis and G1 phase arrest, while caspase-9 and caspase-3 activity was significantly increased. Furthermore, the expression of the PML/RARα fusion protein was decreased. Together, these data suggest that OA exerts a cytotoxic effect that inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα, making it a potent therapeutic agent against leukemia.Oncology letters 10/2013; 6(4):885-890. · 0.24 Impact Factor