Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation

Hong, Zheng; Chen, Yuling; Zhang, Jingze; Wang, Lei; Jin, Zhaoxiang; Huang, Hanhan; Man, Shuli; Gao, Wenyuan

doi:10.1016/j.cbi.2016.03.003

Cited by 78 publications

(49 citation statements)

References 50 publications

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“…In vivo and in vitro studies report inhibition of necrosis by activation of TNF-α, interleukin B [75], and proinflammatory cytokines [76]. OME at 20 mg/kg presented antioxidant activity through mechanisms associated with increased superoxide dismutase (SOD) enzyme production [77,78], as well as glutathione peroxidase (GPx) and reduced glutathione (GSH) at 30 and 40 mg/kg [51,79]. In ethanol-induced gastritis rats, OME modulated mucosal lesions through its antioxidant and anti-inflammatory activity [80].…”

Section: Antioxidant and Anti-inflammatory Effects Several In Vivo Smentioning

confidence: 99%

“…To understand the mechanisms of drug toxicity, it is necessary to verify drug-drug interactions, the formation of reactive metabolites, and individual susceptibility by genetic polymorphisms in drug-metabolizing enzymes [153]. Gastric lesions are characterized by increased production of ⋅ OH and protein oxidation, especially in gastric ulcers [73], which are related to lesion severity [78], producing highly toxic lipid derivatives that may modify cell function and even cell death [79].…”

Section: Toxicity Of Omeprazolementioning

confidence: 99%

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Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Paz

Alencar

Lima

et al. 2020

Oxidative Medicine and Cellular Longevity

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Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

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Section: Antioxidant and Anti-inflammatory Effects Several In Vivo Smentioning

confidence: 99%

Section: Toxicity Of Omeprazolementioning

confidence: 99%

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Paz

Alencar

Lima

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…It has been demonstrated to have various pharmacological properties, including serving as an anti-lung injury, anti-hepatitis B virus and anti-liver injury agent. Cos has also been reported to inhibit ethanol-induced gastric ulcers in mice and to exert anti-cancer effects in vitro (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Costunolide isolated from Vladimiria�souliei inhibits the proliferation and induces the apoptosis of HepG2 cells

et al. 2018

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Costunolide (cos) is one of the major sesquiterpenes isolated from the ethyl acetate soluble fraction of the roots of Vladimiria souliei. In order to explore the effects and molecular mechanism of cos, the anti-proliferative and apoptotic effects of cos against the human hepatoblastoma HepG2 cell line was examined in vitro in the current study. Cell viability was measured using an MTT assay, and IC 50 values (indicating the concentration required to achieve half-maximal inhibition) were calculated to detect the inhibitory effect of cos on HepG2 cell growth. Cell morphology was subsequently observed under an inverted microscope, and cell cycle distribution and apoptosis were detected using flow cytometric analysis. In addition, changes in the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspases-3, -8 and -9 were detected by western blotting. The results of cell analyses indicated that cos treatment inhibited the proliferation and promoted the apoptosis of HepG2 cells in vitro. Cos markedly induced HepG2 cell apoptosis by arresting the cell cycle at the G 2 /M phase in a dose-dependent manner. In terms of the underlying mechanism, cos was revealed to inhibit the anti-apoptotic capacity of the cells, possibly via upregulating the expression levels of Bax protein and caspases-3, -8 and -9, and downregulating the expression of Bcl-2 protein. Taken together, the results of the present study indicate that cos may be a promising candidate for liver cancer therapy, and have provided an insight into the mechanism of action involved in its anti-cancer properties.

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“…If oxygen-glucose supply is not restored, or therapeutic windows exceed optimal levels, neurons become excited until these cells die (18). QIPENG ZHAO 1,2* , AILING cHEN 1,2* , XIAOBO WANG 1,3 , ZHUANZHUAN ZHANG 1,2 , YUNSHENG ZHAO 1,2 , YU HUANG 2 , SHUANGLAI REN 4 and YAFEI ZHU 1 dehydrocostuslactone (dHL) is a sesquiterpene lactone derived from the medicinal plant Aucklandia lappa dence, belonging to the family Asteraceae (19) and is a major active ingredient of Aucklandiae Radix. The metabolite of dHL can penetrate the blood-brain barrier and exhibit various pharmacological activities, including anti-inflammatory (20), anti-ulcer (19) and antimicrobial properties (21), anti-apoptotic and pro-apoptotic effects on different human cancer cell lines (22,23), and oxidative and endoplasmic reticulum stress responses (24).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of dehydrocostuslactone on rat hippocampal slice injury induced by oxygen‑glucose deprivation/reoxygenation

et al. 2018

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The present study aimed to investigate the protective effects of dehydrocostuslactone (DHL) against rat hippocampal slice injury caused by oxygen‑glucose deprivation/reoxygenation (OGD/R). Rat hippocampal slice injury was induced by OGD/R in vitro, and the degree of injury was evaluated through a lactate dehydrogenase (LDH) assay and 2,3,5‑triphenyltetrazolium chloride (TTC) staining. The protein expression levels of B‑cell lymphoma-2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), cytochrome c (cyt‑c), apoptotic protease activating factor 1 (apaf‑1), caspase‑9, caspase‑7, caspase‑3, sequestosome 1 (SQSTM1) and microtubule‑associated protein 1 light chain 3 (LC3) were analyzed through western blot analysis. The results showed that 1, 5 and 10 µM DHL decreased the levels of LDH (P<0.05) and increased the A490 value of TTC (P<0.05). Furthermore, the expression of Bcl‑2 was enhanced, and the protein expression levels of Bax, cyt‑c, apaf‑1, caspase‑9, caspase‑7, caspase‑3, SQSTM1 and LC3 were significantly inhibited (P<0.05), compared with those in the OGD/R group. These results suggested that DHL elicited protective effects against hippocampal OGD/R injury, and its underlying mechanism may be associated with inhibiting apoptosis.

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Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation

Cited by 78 publications

References 50 publications

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Costunolide isolated from Vladimiria�souliei inhibits the proliferation and induces the apoptosis of HepG2 cells

Protective effects of dehydrocostuslactone on rat hippocampal slice injury induced by oxygen‑glucose deprivation/reoxygenation

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