Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities

Zhang, Yinan; Zhang, Wei; Hong, Deshun; Shi, Lei; Shen, Qiang; Li, Jingya; Li, Jia; Hu, Lihong

doi:10.1016/j.bmc.2008.07.080

Cited by 141 publications

(71 citation statements)

References 36 publications

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“…It has been demonstrated that administration of oleanolic acid has been found to reverse recognition memory impairments in mice (Park et al , 2014). Furthermore, synthetically modifying side chains on oleanolic acid to a derivative form, such as BM, significantly increases its potency (Zhang et al , 2008). Therefore, this suggests that BM has the potential to significantly prevent recognition memory decline, which was examined in our study.…”

Section: Introductionmentioning

confidence: 83%

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Camer

Szabo

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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X. (2015). Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 59 68-75. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory AbstractHigh fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF dietinduced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus. AbstractHigh-fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), HF (40% of energy as fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM a...

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Section: Introductionmentioning

confidence: 83%

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Camer

Szabo

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Accordingly, inhibition of PTP1B is predicted to be an excellent and novel target to treat type 2 diabetes and obesity (3). In addition, only several of the recent inhibitors have been derived from natural products, which had been considered as a great diverse library for potential drugs (8). Rheum undulatum L. (Polygonaceae, RU), a well known Chinese medicine, is a perennial herb that is distributed and cultivated mainly in South Korea (9).…”

Section: Introductionmentioning

confidence: 99%

Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

Lee¹,

Yoon²,

Hwang³

et al. 2012

BMB Reports

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Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPARα and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis. [BMB reports 2012; 45(3): 141-146]

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“…Oleanolic acid improves glucose tolerance through a multi-factorial mechanism including increasing insulin biosynthesis and secretion, as well as the promotion of beta-cell proliferation and survival [23]. Oleanolic acid also improves the sensitivity of insulin in peripheral tissues via multi-targeted mechanisms including: stimulation of insulin receptor autophosphorylation [24], inhibition of protein-tyrosine phosphatases PTP1B and TCPTP [25], activation of PI3K/Akt [26], activation of LKB1/AMPK [27], inhibition of glycogen synthase kinase-3β by phosphorylation [28], transactivation of peroxisome proliferator-activated receptors [29]. The mechanism of the anti-hyperglycemic activity of oleanonic acid is unknown and could include any of the above-mentioned.…”

Section: Discussionmentioning

confidence: 99%

The Hypoglycaemic Effect of Oleanonic Acid Isolated From Pilea Elizabethae in a Rat Model

Lindo

Salmon

McGrowder

2017

Int J Curr Pharm Sci

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Objective: The objective of this study is to isolate and identify the chief hypoglycaemic component of Pilea elizabethae Methods:The chief hypoglycaemic component of Pilea elizabethae was isolated and identified. The bio-directed purification of the chief hypoglycaemic agents contained in Pilea elizabethae followed a sequence of steps alternating oral glucose tolerance test (OGTT) bioassay and chromatographic methods. The ethyl acetate crude extract which was most hypoglycaemic in activity was flash chromatographed on silica gel using a gradient hexane-ethyl acetate solvent system of increasing polarity. Elucidation of the chemical structures of R-E2Gii was determined using NMR and FT-IR spectroscopy, melting point determination and comparison with the literature. The Pilea elizabethae extracts were tested for hypoglycaemic activity in Sprague-Dawley albino rats using the oral glucose tolerance test (OGTT) method. Isolated hypoglycaemic compounds obtained after bio-directed purification were identified through nuclear magnetic resonance (NMR) spectroscopy and infra-red (IR) spectroscopy.Results: Bio-directed purification of Pilea elizabethae extracts yielded a hypoglycemic principle that were coded R-E2Gii. By comparison of its NMR chemical shift values and physical properties with literature values, R-E2Gii found to be the triterpenoid oleanonic acid [C30H40O3; M. W=124]. Conclusion:Bio-directed purification of the hexane-ethyl acetate extracts and using nuclear magnetic resonance (NMR) spectroscopy and infra-red (IR) spectroscopy revealed oleanonic acid, that may be responsible for the anti-hyperglycemic properties of this extract.The isolate R-E2Gii demonstrated significant hypoglycaemic activity. When administered intravenously, values were as low as 4.87±0.09 mmol/l thirty minutes post-load compared with 5.63±0.19 mmol/l for the control (p<0.006). An increase in dosage up to 10 mg/kg body weight amplified the post-prandial hypoglycaemic effect of R-E2Gii. Comparison of the hypoglycaemic effect of R-E2Gii with glibenclamide showed that the isolate was only mildly effective in reducing post-prandial hyperglycaemia. Hexane-ethyl acetate extracts from Pilea elizabethae was found to possess antihyperglycaemic activity on OGTT.

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Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities

Cited by 141 publications

References 36 publications

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

The Hypoglycaemic Effect of Oleanonic Acid Isolated From Pilea Elizabethae in a Rat Model

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