Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer

Tamaddonfard, Esmaeal; Erfanparast, Amir; Farshid, Amir Abbas; Imani, Mehdi; Mirzakhani, Navideh; Salighedar, Reza; Tamaddonfard, Sina

doi:10.1016/j.lfs.2019.03.054

Cited by 56 publications

(40 citation statements)

References 44 publications

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“…When duodenal ulcer is induced by IND or other NSAIDs, the generation of pro-and anti-inflammatory cytokines has been proposed to be a crucial aspect of the pathogenesis and etiology of DU. TNF-α is an important proinflammatory cytokine of the acute inflammation and is closely related to the apoptosis of duodenal mucosal cells that are damaged by various agents [35]. e administration of IND activated the innate immune response and promoted enhanced levels of TNF-α in the duodenal tissue, as evidenced by the TNF-α concentration in the negative control group.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: 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%

RETRACTED: 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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“…Similar to our results, Ghiasian et al found a significant increase in serum level of TAC in the Crocin group (30 mg) compared to the control group in MS patients (Ghiasian et al, 2019). An animal study reported that 0.063, 0.25, and 1 mg/kg Safranal significantly increased TAC activity and dose‐dependently reduced wound area (Tamaddonfard et al, 2019). A recent study conducted by Shahbazian et al indicated that there was no significant difference in the serum level of TAC after 12 weeks of treatment with 30 mg saffron in diabetic patients (Shahbazian et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: A randomized, double‐blind, placebo‐controlled study

Tahvilian

Masoodi

Kashani

et al. 2020

Phytotherapy Research

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Supplementation with saffron helps improve antioxidant status. Oxidative stress plays an important role in ulcerative colitis (UC). The present study aimed to investigate the effect of saffron supplementation on disease severity and Oxidative/Antioxidant factors in patients with UC. This randomized double‐blinded study was conducted on 80 mild to moderate UC patients. Participants were randomly divided into intervention (100 mg saffron/daily) and placebo (100 mg maltodextrin/daily) groups. Of all the participants, 75 completed the study. After 8 weeks, there were significantly increased in the mean score of simple clinical colitis activity index questionnaire (3.83 ± 1.78 to 3 ± 1.60, p = .004), the serum levels of total antioxidant capacity (2.68 ± 0.90 to 2.79 ± 0.87, p = .016), superoxide dismutase (60.69 ± 9.59 to 66.30 ± 10.79, p = .009) and glutathione peroxidase (22.05 ± 14.27 to 29.67 ± 17.97, p = .011) in patients received saffron compared to the placebo group. Whereas, there was no significant difference in serum levels of malondialdehyde between the two groups. Finally, dietary saffron as an alternative therapy may effective in improving antioxidant factors and reducing the severity of disease in UC patients.

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“…The area of lesions per stomach was quantified using Image J software (NIH, USA) and the gastric lesion (ulcer score) was classified on a scale of 0 to 4: 0, normal mucosa; 0.5, hyperemia; 1, one or two lesions; 2, severe lesions; 3, many severe lesions; and 4, mucosa full of lesions 55 . The percentage of ulcer protection was calculated based on the method described by Tamaddonfard et al: 2 Percentage of prevention = [(Ulcer area (indomethacin) –Ulcer area (treated) )/Ulcer area (indomethacin) ] × 100.…”

Section: Methodsmentioning

confidence: 99%

“…Nonsteroidal anti‐inflammatory drugs (NSAIDs) have a wide range of therapeutic properties, including analgesic, antithrombotic and antipyretic actions, and are among the most commonly prescribed classes of drugs worldwide 1,2 . However, long‐term use of NSAIDs is one of the leading causes of gastric ulcers 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Sildenafil attenuates nonsteroidal anti‐inflammatory‐induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms

Alves

Aires

Santos

et al. 2020

Clin Exp Pharma Physio

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Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID‐induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti‐inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30 mg/kg of lansoprazole), SIL 5 (5 mg/kg), SIL 25 (25 mg/kg) and SIL 50 (50 mg/kg). The animals were treated by gavage (a single dose) after 24 hours of fasting, and gastric lesions were performed after 30 minutes, with indomethacin (40 mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose‐dependent gastroprotective effect against NSAID‐induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin‐induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.

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Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer

Cited by 56 publications

References 44 publications

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

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

Effects of saffron supplementation on oxidative/antioxidant status and severity of disease in ulcerative colitis patients: A randomized, double‐blind, placebo‐controlled study

Sildenafil attenuates nonsteroidal anti‐inflammatory‐induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms

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