1. Introduction
A diet enriched with fruits and vegetables obviates gastrointestinal manifestations, including the prevention of new gastric or duodenal ulcers and healing of already formed ulcers [
1]. Carrot (
Daucus carota L) belongs to the family Apiaceae. The edible part of a carrot is a taproot that gets its unique color due to the presence of β-carotene that is metabolized into vitamin A after human consumption. Carrot fruits are reported to cleanse the intestines as well as act as a diuretic. They are the source of nutrition and help in maintaining an acid–base balance. They are regarded as commonly used vegetables for vision maintenance. The beneficial effect of carrot and its active constituent, β-carotene, is also reported for liver function. Additionally, carrots provide relief from diarrhea, constipation, intestinal inflammation, weakness, illness, and in the treatment of rickets. In addition to β-carotene, the protective actions of carrot are also attributed to its other constituents, such as riboflavin, A-retinol, niacin, A-carotenoid, vitamins A, B
6, B
12, C, E, and K, thiamin, pantothenic acid, and folate [
2].
Although the concurrent use of herbal therapies and home remedies, along with conventional modern medicinal products, is commonly found for the management of many diseases and ailments, there is a need to standardize their combined use to overcome the possible herb–drug interaction. Their concomitant use may either decrease or increase the therapeutic value of one another [
3].
Even though carrot fruit is employed in a number of traditional medicinal systems in India for a variety of ailments in the gastrointestinal system, so far, there is no scientific report to confirm the ethnopharmacological claim. We also felt it necessary to determine the biological role of carrot in the presence of conventional antiulcer drugs, such as potent acid suppressor agent, proton pump inhibitor (PPI), and pantoprazole, as many patients use carrot with these drugs. Although PPI is a potent antiulcer agent, overdependence on this class of agent may lead to an increased risk of bone fracture [
4], mineral and vitamin deficiencies [
5], and
Clostridium difficile infection [
6]. Additionally, direct correlation is reported between the use of PPIs and development of pneumonia [
7], dementia [
8], gastric cancer [
9], and chronic kidney disease [
10]. This has led the FDA to release a number of safety guidelines and publish recommendations for PPI usage [
11]. Thus, there is a need to explore additives or substitutes that can complement or supplement the use of PPIs. Therefore, this study was carried out to validate the traditional gastroprotective claim of carrot and also to determine its interaction with pantoprazole (PZL) for antiulcer activity using different experimental models.
3. Discussion
The present work showed gastric antisecretory and gastric cytoprotective effects of
Daucus carota fruit and its additive effect with the antiulcer drug pantoprazole. The
Daucus carota plant is traditionally used as an antiulcer agent in several regions of the world [
12]. An earlier study showed that the methanolic and aqueous extract of carrot plant was found to possess a cytoprotective effect in the gastric region against gastric ulcers in rats induced by ethanol [
13]. The current study was carried out using only fruits that are traditionally used in India and the results confirmed its antiulcer effect. Furthermore, the additive effect observed with the combination of carrot and antiulcer agent suggests that it is not only safe to consume carrot fruit along with antiulcer effects, but an enhanced therapeutic effect may be achieved with these combinations.
The standard antiulcer methods used for the evaluation of antiulcer activity were followed. Only female rats of reproductive age used to minimize hormone mediated bias that would have occurred in case of mixed gender. It is observed that the ratio of men to premenopausal women for ulcer development is high, ranging from 1.9:1 to 3.1:1 [
14]. The acetic acid-induced gastric ulcer model was used to evaluate healing of gastric ulcers, wherein both gastric cytoprotective and gastric antisecretory agents as well as antioxidants are reported to increase gastric ulcer healing [
15]. Additionally, since carrot was reported for its cytoprotective effect [
16], models involving the induction of gastric ulcers by indomethacin and ethanol were used to determine the cytoprotective action of carrot and its combination. Animal models involving mental stress through cold plus restraint and pyloric ligation evaluated the gastric ulcer preventive effect. The best method used for the development of duodenal ulcers is the oral administration of cysteamine. The mechanism of induction of ulcers through the above-mentioned chemicals/methods has been described by us earlier [
17].
Carrot is used traditionally in different forms. Scientific studies on its pharmacological effects have been reported using different extracts, ranging from polar aqueous extract to non-polar solvents [
18,
19]. Some reports suggest that boiled carrot is more effective than raw carrot [
12]. We used boiled extract in this study.
Carrot is known to contain several constituents that include phenolics, flavonoids, and volatile oils. It is a rich source of β-carotene and pectins [
20]. Phenolics and flavonoids present in carrot are reported for their antioxidant properties [
21]. Moreover, carrot is known to contain C17-polyacetylenes such as falcarinol, which are a group of oxylipins that are known for anti-inflammatory, anti-neoplastic, antibacterial, serotonergic, and antifungal properties [
22]. Since falcarinol is widely believed to improve human health and protect against a variety of diseases, studies concerning its contribution to the antiulcer effect of carrot may help in identifying other plants containing this chemical for potential antiulcer actions. Volatile oils present in carrots have also been reported to possess a number of activities. Around 34 volatile constituents that include major chemicals such as carotol, β-bisabolene, and isoelemicin are reported in carrot [
23].
Since carrot contains a wide variety of constituents with varying effects, it can be assumed that one single constituent may not be responsible for its antiulcer action. Furthermore, carrot prevented the development of ulcers and increased ulcer healing by more than one mechanism, including gastric antisecretory, gastric cytoprotective, and antioxidant effects, as shown in different models used in this study. It is possible that each of the ulcer healing and ulcer preventive effects may be due to one or more constituents of the carrot preparation. We would like to emphasize that this study was not meant to identify or isolate chemical constituents responsible for the antiulcer effect, but rather to verify the traditional claim that carrot fruit possesses antiulcer action. Moreover, it is very unlikely that carrot or its isolated constituents may be used alone as antiulcer drugs, as several traditional medicines having a more potent effect than carrot have at lower dose and some of them are being used. The low dose of carrot (200 mg/kg) did not show cytoprotective potential or a weak effect in ulcer models. Hence, the effect of a combination of carrot with pantoprazole (proton pump inhibitor) was evaluated. The additive effect seen with this combination could be due to the combined antiulcer action of each agent and/or there may be some pharmacokinetic interactions. Further studies on pharmacokinetics may provide information about the potential interaction between carrot and these drugs.