Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats

Koç, Kübra; Çeriğ, Salim; S, Ucar; Çolak, Suat; Bakır, Murat; Erol, Hüseyin Serkan; Yıldırım, Serkan; Hosseinigouzdagani, Mirkhalil; Özek, Nihal Şimşek; Aysin, Ferhunde; Koçpınar, Enver Fehim; Budak, Harun; Geyikoğlu, Fatime

doi:10.1080/01480545.2018.1530261

Cited by 29 publications

(27 citation statements)

References 58 publications

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“…To investigate the protective effect of LZD on gastrointestinal tract, a IND-induced duodenal ulcer model in rats was established, which is commonly and classically used in the search for gastroprotective natural medicines [27,28]. IND causes the duodenal damage by suppressing the prostaglandin biosynthesis, decreasing the mucus production, and reducing the blood circulation within the mucosa [29,30]. Acute exposure of the duodenal mucosa of rats to IND results in severe lesions similar to those emerging in patients with duodenal ulcers.…”

Section: Discussionmentioning

confidence: 99%

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway

Song

Zeng

Chen

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) often causes small intestinal ulcers in patients, but few effective drugs are currently available to manage such serious adverse events of NSAIDs. Li-Zhong decoction (LZD), a well-known traditional Chinese medicine (TCM) formula, is commonly prescribed for treatment of gastrointestinal diseases. The present study aimed to investigate the anti-ulcerogenic activity of LZD on indomethacin- (IND-) induced duodenal ulcer in rats. Mechanistic studies of action of LZD were focused on involvement of TLR-2/MyD88 signaling pathway. Methods. Fifty male Sprague-Dawley (SD) rats were randomly and evenly divided into five groups: normal control, ulcer control (IND, 25 mg/kg), IND + esomeprazole (ESO, 4.17 mg/kg), and IND + low and high doses of LZD (3.75 and 7.50 g/kg). Macroscopic and histopathological examinations were performed for evaluation of ulcer index (UI), curative index (CI), and microscopic score (MS). Levels of duodenal inflammatory biomarkers and cytoprotective mediators including interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA. Expression levels of TLR-2 and MyD88 mRNA were assessed by qRT-PCR. The expression and distribution of TLR-2 and MyD88 proteins were analyzed by western blot and immunohistochemistry, respectively. Results. Gross and microscopic examinations of the IND-treated rats revealed severe duodenal hemorrhagic necrosis, inflammatory infiltration, villus destruction, and crypt abscess, while LZD-treated rats manifested these pathological events to a markedly lesser degree. LZD significantly decreased UI and MS, increased CI, preserved the integrity of the villus and crypt, and normalized the tissue architecture of the duodenum of rats. The elevated TNF-α levels in the IND-treated rats were markedly diminished in the LZD-treated rats, while lower levels of IL-4, IL-10, and PGE2 observed in IND-treated rats were significantly increased in LZD-treated rats. Interestingly, improvement of immune function in duodenal mucosa by reduction of mRNA and protein expression levels of TLR-2 and MyD88 was also observed in rats treated with LZD. Consistently, immunohistochemical analyses revealed a lower co-localization of TLR-2 and MyD88 proteins in the duodenal mucosa of LZD-treated rats as compared to the IND-induced rats. Conclusions. Our data demonstrate that LZD protects the duodenal mucosa from IND-caused lesions, which is at least partially attributable to the interaction of its potential cytoprotective and anti-inflammatory mechanisms together with enhancement of the mucosal immunity through TLR-2/MyD88 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway

Song

Zeng

Chen

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Rats were randomly classified into four groups (eight rats per group) and were injected as follows: (1) control group—nonirradiated rats injected with 0.5% DMSO in normal saline (0.5 ml/100 g BW IP) for 5 days; (2) irradiated saline-injected rats—rats injected with 0.5% DMSO in normal saline (0.5 ml/100 g BW IP) on day 1 and exposed to 3.2 Gy whole-body gamma radiations on day 3; (3) irradiated carvacrol-injected rats—rats injected with CAR in 0.5% DMSO in normal saline (80 mg/kg BW IP) for 5 days, 3 days before exposure to whole-body irradiation (3.2 Gy) and 2 days after; and (4) irradiated thymol-injected rats—rats injected with a single dose of thymol in 0.5% DMSO in normal saline (50 mg/kg BW IP) for 5 days, 3 days before exposure to whole-body irradiation (3.2 Gy) and 2 days after. Carvacrol-thymol doses were chosen according to previous studies, respectively [32–34]. Rats were weighed daily until the day of sacrifice.…”

Section: Methodsmentioning

confidence: 99%

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Mahran

Badr

Aldosari

et al. 2019

Oxidative Medicine and Cellular Longevity

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Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD20) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.

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“…For this reason, the study of neuroprotective effects from other secondary metabolites that can be obtained from lowcost natural sources such as food by-products, and in our case olive leaves is an interesting topic of research. In this regard, phenolic derivatives from olive leaves have been deeply investigated [35][36][37][38][39][40], and in a less extent other compounds such as terpenoids [40][41][42]. These compounds have been shown to provide a wide range of health properties [14,43], such as anti-inflammatory [44,45], antioxidant [15,16,46], and anticancer [11,17,47,48].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Terpenoids Recovered from Olive Oil By-Products

Montenegro

Álvarez‐Rivera

Sánchez-Martínez

et al. 2021

Foods

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The neuroprotective potential of 32 natural extracts obtained from olive oil by-products was investigated. The online coupling of supercritical fluid extraction (SFE) and dynamic adsorption/desorption allowed the selective enrichment of olive leaves extracts in different terpenoids’ families. Seven commercial adsorbents based on silica gel, zeolite, aluminum oxide, and sea sand were used with SFE at three different extraction times to evaluate their selectivity towards different terpene families. Collected fractions were analyzed by gas chromatography coupled to quadrupole-time-of-flight mass spectrometry (GC-QTOF-MS) to quantify the recoveries of monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenes (C30). A systematic analysis of the neuroprotective activity of the natural extracts was then carried out. Thus, a set of in vitro bioactivity assays including enzymatic (acetylcholinesterase (AChE), butyrylcholinesterase (BChE)), and anti-inflammatory (lipoxidase (LOX)), as well as antioxidant (ABTS), and reactive oxygen and nitrogen species (ROS and RNS, respectively) activity tests were applied to screen for the neuroprotective potential of these extracts. Statistical analysis showed that olive leaves adsorbates from SS exhibited the highest biological activity potential in terms of neuroprotective effect. Blood–brain barrier permeation and cytotoxicity in HK-2 cells and human THP-1 monocytes were studied for the selected olive leaves fraction corroborating its potential.

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Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats

Cited by 29 publications

References 58 publications

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway

Antiulcerogenic Activity of Li-Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR-2/MyD88 Signaling Pathway

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Neuroprotective Effect of Terpenoids Recovered from Olive Oil By-Products

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