Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.5926
Peer-review started: April 28, 2019
First decision: July 22, 2019
Revised: August 16, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: October 21, 2019
Nonsteroidal anti-inflammatory drugs (NSAIDs), like diclofenac, are prone to induce gastro-duodenal injury on prolonged use, a fact that compromises their clinical usefulness. Continued efforts are being exerted to find agents that could be given alongside the NSAIDs to guard against such injury.
Whereas proton pump inhibitors (PPIs), like omeprazole, are often used to protect against such injury, they are not always effective in protecting against both gastric and duodenal lesions. Moreover, they often exert side effects on their own. Accordingly, the search continues to find agents, such as natural products, that could be safer than PPIs and prove effective against both gastric and duodenal lesions induced by NSAIDs. The herbal preparation, STW 5, has been the focus of our studies for many years, particularly in the field of gastro-intestinal ailments. The preparation has proved to be clinically effective in functional dyspepsia and irritable bowel syndrome, as well as experimentally effective against gastric ulcers, ulcerative colitis, and other gastro-intestinal disorders. STW 5 has a wide safety profile. We were therefore highly motivated to test its efficacy in protecting against the gastro-duodenal lesions induced by diclofenac, as an example of a widely used NSAID.
It was important not only to show the efficacy of the herbal preparation in protecting against diclofenac induced lesions, but also to compare its efficacy with that of omeprazole, as an example of a widely used PPI. This would then lead to its clinical trial and possible application as adjuvant therapy for patients who may be sensitive to the use of NSAIDs. STW 5 could then become a valuable and much safer substitute for PPIs.
To achieve these aims experiments were designed to induce gastro-duodenal lesions in rats by feeding them orally with diclofenac for 6 d. The rats were allocated into groups, some receiving concomitantly omeprazole, and others receiving STW 5. At the end of the experimental period, the animals were sacrificed, samples of blood were taken to determine levels of relevant mediators of inflammation, oxidative stress, and apoptosis using ELISA techniques. Sections of gastric and duodenal tissue were prepared for histological examination. All the chosen parameters were considered relevant to the study in question.
Diclofenac led to marked histological changes in both the stomach and duodenum, associated with significant changes in inflammatory cytokines (tumor necrosis factor α, interleukins-1β and 10), in the oxidative stress enzyme, heme oxygenase 1, and in the apoptotic regulator, B-cell lymphoma 2. Both omeprazole and STW 5 in the given doses were comparable in their effects in counteracting the changes in all the biochemical parameters, but STW 5 was much more effective in preventing the histological changes in both the stomach and duodenum. The present results lend further support to the beneficial use of STW 5 in gastro-intestinal disorders. It would be of value to extend the study to other NSAIDs and to further prolong the administration of the NSAID for more than one week. In the present study, giving diclofenac for longer than 6 d led to animal mortality.
STW 5 may offer a much safer alternative to PPIs to help protect the stomach and duodenum from damage in patients under prolonged treatment with NSAIDs. The good clinical tolerability of the herbal preparation which has already been well established in functional dyspepsia and irritable bowel syndrome may pave the way to introducing it in preliminary clinical trials as adjuvant therapy in patients undergoing therapy with NSAIDs.
The study is a good example of developing new therapeutic indications for drugs already established on the market, based on well-designed experiments to show their potential efficacy in a new domain. The results obtained warrant further investigations and placebo-controlled studies before being clinically introduced as adjuvant therapy in patients under treatment with drugs that could potentially injure the gastro-intestinal tract.