Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

Gui, Bo; Hua, Fuzhou; Chen, Jie; Xu, Zeping; Sun, Hongbin; Qian, Yanning

doi:10.1155/2014/451826

Cited by 29 publications

(20 citation statements)

References 33 publications

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“…Several studies reported that TDZD-8 as a GSK-3β inhibitor could reduce I/R injury of the intestines and brain due to its anti-inflammatory and anti-apoptosis activities. [19, 27, 28]. It was found in the present study that RI/RI resulted in renal tissue damage accompanied with elevation of serum BUN and Scr levels.…”

Section: Discussionsupporting

confidence: 53%

Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Shen

et al. 2017

Kidney Blood Press Res

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Background/Aims: Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI). The aim of the present study was to evaluate the protective effect of GSK-3β inhibition (TDZD-8) on I/R-induced renal injury through the Nrf2/HO-1 pathway in a streptozocin (STZ)-induced diabetic rat model. Methods: STZ-induced diabetic rats preconditioned with TDZD-8 and ZnPP were subjected to renal I/R. The extent of renal morphologic lesions. Renal function was assessed from blood urea nitrogen (BUN) and serum creatinine (Scr), as determined utlizing commercial kits. Oxidative stress and inflammatory activity in the kidney tissue was estimated from levels of malondialdehyde (MDA), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), as well as the activities of superoxide dismutase (SOD) and glutathione (GSH) using qRT-PCR and ELISA. The expressions of Nrf2, HO-1, Bcl-2 and NF-κB in the renal tissue were measured by qRT-PCR and western blotting. Results: I/R-induced renal inflammation was reduced significantly by TDZD-8 pretreatment. Preconditioning with TDZD-8 suppressed NF-κB expression and enhanced Bcl-2 expression in the renal tissue. The upregulated level of malondialdehyde (MDA), and reduced activities of superoxide dismutase (SOD) and glutathione (GSH) in I/R-shocked rats were markedly restored by TDZD-8 pretreatment. Furthermore, pretreatment with TDZD-8 enhanced activation of the Nrf2/HO-1 pathway in the renal tissue of diabetic RI/RI rats. Conclusion: These findings suggest that preconditioning with TDZD-8 may protect the kidney from I/R-induced damage via the activation of the Nrf2/HO-1 pathway in STZ-induced diabetic rats. Further detailed studies are needed to further clarify the underlying mechanisms.

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Section: Discussionsupporting

confidence: 53%

Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Shen

et al. 2017

Kidney Blood Press Res

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“…Pretreatment of rats with OA (100 mg/kg, ip for 6 days) protected against hepatic IR injury. OA increased p‐PI3K, p‐Akt and p‐GSK‐3β protein expression at preischaemia, ischaemia, 30 minutes after reperfusion and 60 minutes after reperfusion, suggesting that the protection of OA against IR injury during the acute phase is mediated partially through PI3K/Akt‐mediated GSK‐3β signalling . OA protection against IR injury was also observed in mice.…”

Section: Low Doses Of Oa Protect Against Hepatotoxicity Induced By a mentioning

confidence: 80%

“…Oral dose and time‐induced hepatoprotection and hepatotoxicity comparisons. The hepatoprotective studies are indicated by filled black circles, and the hepatotoxicity studies are indicated by open inverted triangles…”

Section: High Doses and Long‐term Use Of Oa And/or Oa Derivatives Promentioning

confidence: 99%

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

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Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.

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“…Oleanolic acid acetate is a derivative of oleanolic acid, a triterpenoid that is enriched in olive fruit and various legumes . OAA has been commonly used for the treatment of liver disorder, inflammatory diseases, and various types of cancer . The anticancer activity of OAA is mediated via cell cycle arrest, apoptosis induction, and DNA fragmentation .…”

Section: Introductionmentioning

confidence: 99%

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice

Adhikari

Neupane

Aryal

et al. 2019

J of Periodontal Research

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Objective We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis. Background Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss. Methods Maxillary left second molar was extracted from 8‐week‐old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)‐6, and osteocalcin, were observed. The volume of bone formation was examined by Micro‐CT. Osteoclasts were enumerated using tartrate‐resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging‐drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)‐β superfamily and Wnt signaling genes. Results Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA‐treated specimens showed the altered localization patterns of inflammatory and bone formation‐related signaling molecules including CD31, F4/80, IL‐6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)‐β superfamily and Wnt signaling. Conclusions Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF‐β and Wnt signaling.

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Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

Cited by 29 publications

References 33 publications

Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice

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