**6. Some selected medicinal plants with antiulcerogenic properties in Nigeria**

In Nigeria, SU remains a significant public health challenge affecting people of all ages. While its management through orthodox medicine has recorded substantial successes over the years, a considerable proportion of the populace still rely exclusively on complementary and alternative medicine (CAM) in seeking aid to treat and manage SU. This may be due to the ease of accessibility, affordability and minimal side effect associated with the use of medicinal plants [22]. A compilation of selected antiulcerogenic medicinal plants in Nigeria revealed that the most widely used plants in the management of SU are *Occimum basillicum*, *M. paradisiaca*, *Aloe vera*, *Azadiracter indica*, *Brassica oleracae* and *Carica papaya* [78]. Others include but not limited to the following: *Diodia sarmentosa*, *Cassia nigricans*, *Ficus exasperate*, *Synclisia*  *scabrida*, *Artocarpus heterophyllus* Lam., *Blighia sapida* Konig., *Dialium guineense* Willd., *Emblica officinalis* Gaertn., *Gongronema latifolium*, *Ageratum conyzoides*, *Aloe vera*, *Artocarpusaltilis*, *Aspilia africana*, *Bryophyllum pinnatum*, *Fluerya aestuans*, *Musa paradiasiaca*, *Musa sapientum*, *Persea Americana*, *Talinum triangulare*, *Fluerya aetuans*, *Brassica oleracae, Acacia nilotica* L.*, Alchornea cordifolia Schum & thonn, Anacardium occidentale* L., *Balanites aegyptiaca* L., *Bridelia ferruginea* Benth, *Carica papaya* Linn, *Ficus thonningii* Blume, *Guiera senegalensis* J. F. Gmel, *Hibiscus sabdariffa* L., *Mangifera indica* L., *Momordica charantia* L., *Ocimum gratissium* L., *Piliostigma reticulatum* (DC) Hochst, *Pisidium guajava* L., *Scoparia dulcis*, *Vernonia kotschyana* Sch. Bip., *Zingiber officinale* Rosc [79].

## **7. The role of medicinal plants in oxidative gastropathy**

Following the experimental demonstration that many medicinal plants are endowed with good antiulcerogenic activity with relatively lesser adverse effect compared with the conventional drugs, further steps have been taken in presenting a good number of them for clinical trials. Despite this giant stride, not many of the medicinal plants have passed market entry stage. To the best of our knowledge, of the many presented for developmental evaluations in 2004, only *Azadirachta indica* (Family: Meliaceae) received remarkable attention at its advance stage of clinical trial. It exhibited significant therapeutic potency by reducing gastric hyperse-

Several phytonutrients have proven health benefits and have been reported to elicit significant antiulcerogenic potential in both humans and experimental animal models [73]. While steroid glycosides, tannins, terpenoids and flavonoids have been shown to preserve gastric mucosal against oxidative insults of reactive metabolites and oxidative stress [22, 59], the tendency of phenolic compounds and alkaloids to regulate gastric acid secretion and protect the gastric mucosal epithelia against erosion and other aggressive factors in different ulcer models have been demonstrated [77]. While **Table 1** also presents some of these phytonutrients as being responsible for the elicited antiulcerogenic properties of the plants, several others have also been identified and isolated from diverse plants. Some of these include; saponins, phobaphenes, glucose, luvangetin, tartarate, potash, nimbidin, quercetin, apigenin, papain, chymopapain, pectin, carposide, carotenoids, antheraxanthin, carpaine, resin, euphorbon, caoutchouc, rutin, anthocyanins, cyanindin, kaempferol, sterols, mucilage, terpenoids, kaepferom, ash, starch, fats, proteins, glycosides, ellagic acid, beta sitosterol, gallic acid, limonene, pinene, albuminous matter, cellulose, chlorophyll, mineral salts, myricitin, triterpenes, and sorbitol [37]. These compounds have either been elucidated to decrease acid/pepsin secretion or confer cytoprotection via effective modulation on mucosal

**6. Some selected medicinal plants with antiulcerogenic properties in** 

In Nigeria, SU remains a significant public health challenge affecting people of all ages. While its management through orthodox medicine has recorded substantial successes over the years, a considerable proportion of the populace still rely exclusively on complementary and alternative medicine (CAM) in seeking aid to treat and manage SU. This may be due to the ease of accessibility, affordability and minimal side effect associated with the use of medicinal plants [22]. A compilation of selected antiulcerogenic medicinal plants in Nigeria revealed that the most widely used plants in the management of SU are *Occimum basillicum*, *M. paradisiaca*, *Aloe vera*, *Azadiracter indica*, *Brassica oleracae* and *Carica papaya* [78]. Others include but not limited to the following: *Diodia sarmentosa*, *Cassia nigricans*, *Ficus exasperate*, *Synclisia* 

cretion, gastroesophageal and gastroduodenal ulcers [76].

defensive factors.

**Nigeria**

32 Stomach Disorders

**5. Phytonutrients associated with antiulcerogenic activity**

Reactive oxygen species (ROS) are a by-product of normal metabolism and have roles in cell signaling and homeostasis [80]. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipids [81]. A good number of NSAIDS have been implicated in cellular toxicity leading to oxidative gastropathy [82]. Despite the use of NSAIDS as antipyretic and antiinflammation agents, and in the treatment of rheumatic, musculoskeletal, and cardiovascular diseases [83], gastrointestinal toxicity through ROS formation has limited their application [84, 85]. It has been proposed that NSAID-mediated gastrointestinal lesions involve the uncoupling of oxidative phosphorylation and inhibition of electron transport chain causing incomplete reduction of oxygen [82]. This they do by tenaciously binding to a site near complex I and ubiquinone, thus facilitating events leading to ROS generation [86, 87]. Subsequently, when the gastric antioxidant capacity is overwhelmed, the epithelia mitochondrial aconitase is inhibited, resulting in the release of iron that reacts with H<sup>2</sup> O2 , producing hydroxyl radical. These cascades of event amplify gastric oxidative stress whose consequential effect is manifested as gastropathy [88]. Oxidative stress-induced functional loss is well correlated with numerous disease states including cardiovascular, neurological, cancer, aging processes and gastropathy [83] and is also implicated in a variety of drug-induced toxicities such as SU [2]. Antioxidative and free radical scavenging mechanisms play an important role in the protection against ROS mediated toxicities [89]. Over the past decades, interests in medicinal plants, especially the antioxidative ones, have increased appreciably and they have been elucidated to significantly either protect against or ameliorate ROS-mediated oxidative gastropathy [22, 90]. Such annihilation of ROS in SU diseases have been achieved through induction of enzymic antioxidants (superoxide dismutase, catalase, glutathione reductase and peroxidase) and optimization of reduced glutathione (GSH) contents [2, 22, 59]. Harmonizing the foregoing, a probable mechanism of antioxidative and gastroprotective activities of medicinal plants may be idealized as illustrated in **Figure 1**. This ultimately involves induction and optimization of preventive (catalase, glutathione peroxidase) and chain-breaking (superoxide dismutase, glutathione reductase) antioxidants that subsequently improve gastric GSH level, annihilate liberated reactive metabolite and effectively scavenge ROS (O<sup>2</sup> − , OH− ) (**Figure 1**). This may also be opined to regulate mucosal fluidity and strengthens defensive mechanisms against oxidative gastric damage.

**Figure 1.** Probable mechanism of antioxidative and gastroprotective capabilities of medicinal plants. The dotted arrows represent sites of induction and optimization by the plants that consequently promote scavenging of O<sup>2</sup> − and OH− . This will normalize and increase gastric reduced glutathione (GSH) content and promotes its mobilization toward detoxification of the liberated reactive metabolites. NSAIDS, nonsteroidal anti-inflammatory drugs; MP, medicinal plants; GPx, glutathione peroxidase; GRx, glutathione reductase; GSSG, oxidized glutathione.

## **8. Conclusion**

Globally, SU is a devastating disease posing serious threat to the quality of life of humans. It affects significant proportion of the populace in both developed and developing countries. Although, conventional drugs have been used to manage and treat SU sufferers, affordability and inherent side effects have limited their application. Consequently, alternatives are being sought in medicinal plants, which provide a potential source of antiulcerogenic drugs and are widely used in traditional systems of medicine. Several medicinal plants have been investigated for their proven health benefits in SU management with their phytonutrients playing significant roles. Of the phytonutrients, tannins seem to top the list and has suggested probable focus on their characterization for antiulcer therapy. In spite of the impressive experimental evaluation of medicinal plants for the treatment of SU, very few have reached clinical trials and not very many have been marketed. This indicates that the intended benefits of CAM research are not yet having far-reaching effect. Nevertheless, the continuous search for antiulcerogenic agents of plant origin (available as gifts of nature) is imperative. This will ultimately and eventually present effective and globally competitive exciting opportunities for the development of new lead therapeutics for SU and other related disorders.
