Effects of asiatic acid on passive and active avoidance task in male Spraque–Dawley rats

Nasir, M.; Habsah, M.; Zamzuri, I; Rammes, Gerhard; Jaafar, Harlina Suzana; Abdullah, Jafri Malin

doi:10.1016/j.jep.2010.12.010

Cited by 37 publications

(28 citation statements)

References 38 publications

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“…Increasing evidence suggests that AA possesses biological effects, including anticancer, anti-inflammatory, hepatoprotective, and antioxidant properties [17, 18]. Some studies indicate that AA improves memory and enhances learning abilities in treated Sprague–Dawley rats [19]. AA was found to break down acetylcholinesterase more effectively than the acetylcho-linesterase inhibitor or physostigmine and galantamine in a thin-layer chromatography bio-autographic assay and then to block the excitatory transmission in the hippocampal Schaffer collateral-CA1 synapse in a dose-dependent manner for GABAA antagonists [20].…”

Section: Introductionmentioning

confidence: 99%

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Cheng¹,

Liao²,

Hu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP. Methods: Human lung adenocarcinoma A549/DDP cells were either exposed to different concentrations of AA or treated with DDP, and their viability was measured by the MTT assay. A Rhodamine 123 efflux assay, immunofluorescent staining, ATPase assay, reverse-transcription PCR (RT-PCR), and western blot analysis were conducted to elucidate the mechanisms of action of AA on MDR. Results: Our results showed that AA significantly enhanced the cytotoxicity of DDP toward A549/DDP cells but not its parental A549 cells. Furthermore, AA strongly inhibited P-gp expression by blocking MDR1 gene transcription and increased the intracellular accumulation of the P-gp substrate Rhodamine 123 in A549/DDP cells. Nuclear factor (NF)-kB (p65) activity, IkB degradation, and NF-kB/p65 nuclear translocation were markedly inhibited by pretreatment with AA. Additionally, AA inhibited the MAPK–ERK pathway, as indicated by decreased phosphorylation of ERK1 and -2, AKT, p38, and JNK, thus resulting in reduced activity of the Y-box binding protein 1 (YB1) via blockage of its nuclear translocation. Conclusions: AA reversed P-gp-mediated MDR by inhibition of P-gp expression. This effect was likely related to downregulation of YB1, and this effect was mediated by the NF-kB and MAPK–ERK pathways. AA may be useful as an MDR reversal agent for combination therapy in clinical trials.

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Section: Introductionmentioning

confidence: 99%

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Cheng¹,

Liao²,

Hu³

et al. 2018

Cell Physiol Biochem

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“…Several studies have demonstrated that AA enhances learning and memory, which are associated with hippocampal neurogenesis [21–23]. Acute administration of AA (30 mg/kg) has been shown to stimulate learning and memory as measured by a passive avoidance test [24]. In addition, subchronic and chronic administration of AA (30 mg/kg) has been shown to increase cell proliferation in the hippocampus and stimulate spatial working memory [25].…”

Section: Introductionmentioning

confidence: 99%

Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy

et al. 2017

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The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogenesis in the hippocampus and memory deficits induced by valproic acid (VPA). In the present study, we investigated the preventive effects of AA on the deficits in spatial working memory and cell proliferation and survival caused by 5-FU chemotherapy in a rat model. Male Sprague Dawley rats received 5-FU (5 i.v. injections, 25 mg/kg) on day 8, 11, 14, 17 and 20 of the study. This was co-administered with AA (30 mg/kg, oral gavage tube) either 20 days before receiving 5-FU (preventive), after receiving 5-FU (recovery), or for the entire period of the experiment (throughout). Spatial working memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival of dividing cells were quantified using immunohistochemistry. Rats in the 5-FU alone and recovery groups showed memory deficits in the NOL test and reductions in cell proliferation and cell survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Rats in the control, AA alone, and both preventive and throughout co-administration groups, however, did not exhibit these characteristics. The results showed that 5-FU chemotherapy impaired memory and reduced cell proliferation and cell survival in the SGZ of the hippocampal dentate gyrus. However, these impairments in the animals receiving 5-FU chemotherapy were restored to control levels when AA was co-administered before and during 5-FU treatment. These data demonstrate that AA can prevent the spatial working memory and hippocampal neurogenesis impairments caused by 5-FU chemotherapy.

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“…AA has been reported to have many biological effects such as acetylcholinesterase inhibitory effect, enhancement of cognitive functions, protective activities against UV‐induced photoaging, glutamate‐ or β‐amyloid‐induced neurotoxicity and hepatofibrosis . Preclinical findings suggest that AA shows apoptosis‐inducing activity in various cancer cells as well as a potentiation activity on the effect of anticancer drug irinotecan, suggesting promising perspective as a chemotherapeutic agent against cancer .…”

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confidence: 99%

A liquid chromatography/electrospray ionization tandem mass spectrometric method for quantification of asiatic acid from plasma: application to pharmacokinetic study in rats

Nair¹,

Menon

Shailajan³

2012

Rapid Comm Mass Spectrometry

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Effects of asiatic acid on passive and active avoidance task in male Spraque–Dawley rats

Cited by 37 publications

References 38 publications

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets

Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy

A liquid chromatography/electrospray ionization tandem mass spectrometric method for quantification of asiatic acid from plasma: application to pharmacokinetic study in rats

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