Development of GI-safe NSAID; progression from the bark of willow tree to modern pharmacology

Kangwan, Napapan; Park, Jong Min; Hahm, Ki Baik

doi:10.1016/j.coph.2014.06.003

Cited by 19 publications

(13 citation statements)

References 46 publications

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“…The results of evaluation of gastric lesions after exposition to high dose of PMFA are in agreement with clinical studies where non-selective NSAI was compared with COX-2 inhibitors and the ulcer index was observed, suggesting that PMFA might act by a mechanism independent of COX-1 inhibition (Kangwan et al, 2014). Emphasizing this, in a previous study we demonstrated that PMFA has no effect on platelet aggregation in vitro (Verdam et al, 2009), which is dependent on action of this enzyme (Dovizio et al, 2014).…”

Section: Resultssupporting

confidence: 77%

Anti-inflammatory action of Justicia acuminatissima leaves

Verdam

Guilhon-Simplicio

Barbosa

et al. 2015

Revista Brasileira de Farmacognosia

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BJP 122 1-5 Revista Brasileira de Farmacognosia xxx (2015) xxx-xxx w w w . s b f g n o s i a . o r g . b r / r e v i s t a a b s t r a c t In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf teas are used in folk medicine to treat several inflammatory illnesses. In order to validate this medicinal application, we analyzed the acute toxicity and antioxidant, antiedematogenic and antinociceptive potentials of an aqueous extract of this species, using culture cells and animal models. The aqueous extract did not cause toxic effects on human lymphocytes in high concentration (400 g/mL), neither on mice treated with high doses (5000 mg/kg) in an acute toxicity analysis by oral route, and also did not cause lesions in the gastric mucosa of animals treated with 300 mg/kg, which was the maximal dose used in the anti-inflammatory screening. The aqueous extract caused inhibition of inflammatory pain in formalin-induced paw licking test with all tested doses, 30, 100 and 300 mg/kg, and antiedematogenic activity at 100 and 300 mg/kg. Additionally, the aqueous extract presented statistically significant action on the release of nitric oxide by lipopolysaccharide-activated macrophages. These results and other previously observed preliminarily Q2 studies support the folk use of this species, and further investigation of its action mechanism by inhibition of COX-2 or related metabolite would be interesting.

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Section: Resultssupporting

confidence: 77%

Anti-inflammatory action of Justicia acuminatissima leaves

Verdam

Guilhon-Simplicio

Barbosa

et al. 2015

Revista Brasileira de Farmacognosia

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“…In addition, efforts to obtain drugs able to inhibit both 5-lipoxygenase and COX, the so-called dualacting anti-inflammatory drugs [19], have continued because dual-acting anti-inflammatory drugs retain the activity of classic NSAIDs, while avoiding their main drawbacks [20]. Currently, various structural families of dual-acting anti-inflammatory drugs have been designed, and several compounds are under clinical investigation [21], although humans have taken almost 2,000 years to develop coxibs, starting from willow tree bark to the development of aspirin [22] (Figs. 1, 3).…”

Section: Safer Nsaids To Cover the Aforementioned Adverse Effectsmentioning

confidence: 99%

Omega-3 polyunsaturated fatty acids as an angelus custos to rescue patients from NSAID-induced gastroduodenal damage

et al. 2015

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Nonsteroidal anti-inflammat ory drugs (NSAIDs) are one of the drug types frequently prescribed for their analgesic, anti-inflammatory, and antithrombotic actions, but carry a risk of major gastroduodenal damage from mild erosive changes to serious ulceration leading to fatal outcomes. From the long history of willow tree bark and its extracts being applied for the relief of pain and fever, the synthesis of acetylsalicylic acid, the development of selective cyclooxygenase 2 inhibitors (coxibs), and the identification of a G-protein-coupled receptor for prostaglandin, the popular combination regimen of an NSAID and a proton pump inhibitor was invented, but development was continued for further improvement. With regard to major NSAID adverse effects, gastrointestinal (GI) and cardiovascular (CV) risks still remained as problems to be solved. In this review, it is shown that n-3 polyunsaturated fatty acid (PUFA) based NSAIDs can be an angelus custos, supported with facts that an intake of essential n-3 PUFAs orchestrates concerted protective actions against two notorious side effects of NSAIDs, the aforementioned GI risk and CV risk of NSAIDs. Since pills containing n-3 PUFAs, omega-3-acid ethyl ester capsules (Lovaza, Omarcor), have already been safely prescribed to prevent atherosclerosis through lessening lipid burdening, the introduction of a drug delivery system such as a gastroretentive form of n-3 PUFA based NSAIDs will highlight newer hope for GI safety under the guarantee of reduced CV risk. Because n-3 PUFAs have been proven to attenuate cytotoxicity, inhibit lipid-raft-associated harmful signaling, and relieve oxidative stress relevant to NSAIDs, n-3 PUFA based NSAIDs will be next-generation GI-safe NSAIDs.

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“…Currently, the main pharmacological treatment for this disease is antisecretory drugs including, histamine type 2 receptor antagonists such as cimetidine and congeners, and irreversible proton pump inhibitors such as omeprazole, famotidine and congeners. Although effective, long-term treatment with these drugs is associated with several side effects and poor gastric healing, leading to ulcer recurrence [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat

et al. 2017

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BackgroundMassive alcohol drinking can lead to gastric ulcer. In the present study we investigated the gastroprotective effect of Citrus sinensis peel aqueous extract (CSPE) and Hesperidin (H) in ethanol (EtOH) induced oxidative stress and peptic ulcer in rats.MethodsSeventy adult male Wistar rats were divided into seven groups of 10 each: control, EtOH (4 g/kg b.w.), EtOH + various doses of CSPE (100, 200 and 400 mg/kg, b.w.), EtOH + Hesperidin (50 mg/kg, p.o.) and EtOH + Omeprazole (OM, 20 mg/kg, p.o.). Animals were perorally (p.o.) pre-treated with CSPE during 15 days and intoxicated with a single oral administration of EtOH (4 g/kg b.w.) during 2 h. Gastric ulcer was induced in rats with a single dose of ethanol (EtOH). Ulcer index, gene expression of gastric cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), malondialdhyde (MDA), hydrogen peroxide H2O2 and Thiol groups (−SH) content in stomach and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and gluthation peroxidise (GPx) were measured. Furthermore, histopathological examinations were performed.ResultsThe results showed that ethanol induced gastric damage, improving oxidative stress markers level such as MDA (121 ± 4.45 nmol/mg proteins) and H2O2 (24.62 ± 1.04 μmol/mg proteins), increased pro-inflammatory cytokine (TNF-α level), as well as the expression of COX-2 in the ethanol group. However, a significant depletion of enzymatic and non-enzymatic antioxidants were observed, such as, GPx (72%), SOD (57.5%), CAT (41.6%) and -SH (50%). The lesions were associated with severe histopathological damage. The both Citrus sinensis peel aqueous extract (CSPE) and hesperidin significantly protect against all gastric damages caused by ethanol administration in rats.ConclusionsWe propose that CSPE and hesperidin exhibit protective effects in EtOH-induced peptic ulcer in rat. This protection might be related in to part its antioxidant properties as well as its opposite effects on some studied intracellular mediators.

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Development of GI-safe NSAID; progression from the bark of willow tree to modern pharmacology

Cited by 19 publications

References 46 publications

Anti-inflammatory action of Justicia acuminatissima leaves

Anti-inflammatory action of Justicia acuminatissima leaves

Omega-3 polyunsaturated fatty acids as an angelus custos to rescue patients from NSAID-induced gastroduodenal damage

Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat

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