INTRODUCTION:

Gastrointestinal disorders can be considered one of the most common diseases in human societies. Functional digestive disorders are among the most important disorders of the body, accounting for approximately half of the referrals to gastroenterology clinics. The gastrointestinal tract is one of the most important organs

in the human body and is characterized by development of a wide variety of diseases, such as parasitic and infectious disorders, diarrhea, reflux, gastroenteritis, constipation and bloating ^1,2. Diarrhea and intestinal disorders are a major health problem around the world, especially in toddlers and children. Annually, 3-5 million deaths occur due to diarrhea across the world; diarrhea is also one of the most common causes of death in children^2,3. Digestive disorders have become widespread today. Gastrointestinal Diseases andCancer, in developed and developing countries, is the first and second leading cause of death, respectively. Gastrointestinal cancer, which can affect stomach, colon, and small intestine, is one of the common cancers among people. Although heritage plays an important role in transmission of gastrointestinal cancer, the disease can be prevented by proper lifestyle and nutrition, and inclusion of fruits and herbs in the diet as much as possible ^4,5.

Worldwide, gastric cancer is known as the fourth leading cancer and the second leading cause of death from cancer. Gastric cancer is one of the most common malignancies across the globe. The incidence of this cancer is due to the multifaceted multifactorial malignant tumor, The cause of this is cancer due to the presence of infectious, environmental and molecular genetic factors in people ^6,7. Colorectal cancer (also known as colon cancer and rectal cancer) refers to the growth of cancer cells in the colon or rectum (a part of the large intestine). This disease occurs due to abnormal growth of cells that can invade other tissues of the body (metastasis) or multiply inside them ^8,9. Infectious diarrhea is one of the main causes of morbidity and mortality in developing countries. Studies have shown that infectious diarrhea occurs in 18-93 people per 100 population each year. In duodenogastric reflux, the bile flows from the duodenum to the stomach, leading to gastritis. Gastroenteritis causes death of 5 million people across the world ^10,11. Gastrointestinal ulcers, especially in the stomach, can be due to increased secretion of acid for various reasons such as alcohol abuse and elongated hunger, etc. Increased secretion of gastric acid is the main cause of gastric mucosal injury. Therefore, the relationship between the amount of gastric acid and the secretion of gastric ulcers has been confirmed ^11,12. Gas accumulation is one of the most common disorders of the digestive system. The frequency of constipation in the Asian population is about 15-23%, and in American communities around 15-30% ¹³. Constipation refers to delayed or hard stool passage that lasts two weeks or more. Constipation is a common problem in the gastrointestinal tract that is developed in 2-28% of adults and is 3-5 times more frequent in women than in men ¹⁴. Functional dysfunction accounts for a significant proportion of gastrointestinal disorders, which indicates a relationship between psychiatric disorders and the physical symptoms of gastrointestinal disorders. Evidence suggests that mental disorders are more common among these patients ¹⁵. Due to the inevitable side effects of synthetic drugs, the discovery of new drugs that have minimal side effects has drawn great attention. The use of natural antioxidants and medicinal plants is an appropriate resource for this purpose, especially since it is more compatible with human nature and has less side effects. Obviously, the study and familiarity with these plants of natural resources has a special value, and it is therefore logical to pay attention to the medicinal plants used in traditional medicine.In addition to the people's high interest in medicinal plants, in many cases, the use of these plants has a significant effect on the reduction of complications caused by synthetic drugs or other diseases ^16-18. The present review article is aimed to report the action mechanism, antioxidant and antimicrobial activity of the most important medicinal plants occurring across the world on gastrointestinal disorders, as well as the medicinal plants used to treat common gastrointestinal diseases and disorders worldwide.

METHODS:
The data of this review article were obtained using the keywords such as gastrointestinal disorders, medicinal plants, gastrointestinal diseases, phytotherapy, gastrointestinal cancers and microbial disorders in which published in databases such as‌ IranMedex, Irandoc, ISI, PubMed, Scopus, Web of Science, SID, Magiran, and Google Scholar. In this study, 100 papers were reviewed. After the preliminary review, 11 of our papers were the subject of our study. Relevant and unrelated references were also deleted. Finally, 11 articles related to the purpose of our study were selected for study.

RESULTS:
Medicinal plants addressed in this study may play traditional and preventive therapeutic roles (Table 1). Based on the results obtained from the review of numerous articles, a number of plants have been reported to prevent digestive disorders and gastrointestinal cancers, including Glycyrrhiza glabra, Ribes nigrum ,Phyllanthus niruri , Newtonia hildebrandtii , Lantana camara, Persea , Maytenus , Streblus asper , Cordia myxa , Coriandrum sativum , Cyperus rotuntdus , Azadirachta indica , Aloe vera , Plantago asiatica , Passiflora spp. Additional information on medicinal and therapeutic plants and their details are shown in Table 1.

Glycyrrhiza glabra, Ribes nigrum ,Phyllanthus niruri , Newtonia hildebrandtii , Lantana camara, Persea , Maytenus , Streblus asper , Cordia myxa , Coriandrum sativum , Cyperus rotuntdus , Azadirachta indica , Aloe vera , Plantago asiatica , Passiflora spp.,Medicinal herbs this study contains effective ingredients. These materials are listed in Table 2.

The results of phytochemical studies of the herbs indicated that compounds such as as kobusone, and isokobusone, rotundone, auxins and phenolic compounds, isoflavene glabrene, glabridin, phytoestrogens, glycosides, flavonoids, and saponins, and etc are the most important active and active compounds of these plants (the full results are shown in Table 2).

Table 1: The most important natural antioxidants and medicinal plants effective on digestive (intestines, stomach, esophagus, etc.) diseases and disorders.

Scientific Name	Family Name	Common Name	The Effects of herbal medicine on gastrointestinal disorders	Ref.
Glycyrrhiza glabra	Fabaceae	Liquorice	This plant has significant antioxidant properties in vitro and in vivo studies. It has been shown that glabridin is one of the most important antioxidant compounds in the plant that inhibits LDL oxidation. It has been shown that doses of 60-40 μM of this compound inhibit the formation of cholesteryl linoleate hydroperoxide (CLOOH). It also has anti-inflammatory properties. In the study, the extract of this plant reduces the production of IL-6 and prostaglandin E2-. In another study, the extract of this plant causes a decrease in the levels of IL-6, IL-10 and TNF-α at concentrations of 0.2-0.5 mg/ml.	¹⁹
Ribes nigrum	Grossulariaceae	Black currant	It has been observed that this plant reduces smooth muscle contraction or spasmolytic effects of rat's ileum. The spontaneous contractions of the smooth muscle of the ileum are due to the depolarization caused by the entry of calcium ions into these cells and the activation of contractile proteins. The BC extract contains components that inhibit calcium channels. In this study, the highest concentration used was 3 mg / ml for this concentration, IC50 value of 3.23 mg/ml.	²⁰
Phyllanthus niruri	Phyllanthaceae	stonebreaker	In this study, 100,200,400 mg/kg of extract of this plant was used on rats. This plant has antioxidant properties. This plant has anti-inflammatory activity in the digestive system by inhibiting the synthesis and release of prostaglandins, proteases, lysosomal enzymes, and inhibiting the accumulation of inflammatory cells. These effects were seen in all doses. The methanolic extract of this plant also has an anti-ulcer gastrointestinal effect, which was more than 400 in 400 doses. The anti-ulcer effect of this plant may be due to a reduction in the secretion of gastric acid and the protective effect of this plant on the stomach.	²¹
Newtonia hildebrandtii	Fabaceae	Lebombo wattle	This plant has a low and moderate antimicrobial activity at concentrations of 20 mg/ml and 40 mg/ml, respectively, but Newtonia hildebrandtii has the highest antimicrobial activity at 80 mg/ml. The extract of Newtonia hildebrandtii methanol with IC50 value of 0.29 μg/ml has the most antioxidant activity. Newtonia buchananii leaves methanol extract and Newtonia buchananii stem extract showed IC50 value of 220.01μg/ml and 505.80 μg/ml acetylcholinesterase activity, respectively. Acetyl cholinesterase leads to diarrhea. In addition to acetylcholine esterase activity, the antioxidant, anti-inflammatory and antimicrobial activity of this plant also prevents diarrhea.	²²
Lantana camara	Verbenaceae	big-sage	Considering the effect of this plant on the intestine and its anti-inflammatory effects, the results of this study showed that the leaf powder of this plant and methanolic extract of this plant reduce the intestinal transfer in a dose-dependent manner. Intraperitoneal injection of methanolic extract of this plant at doses of 125, 250, 500 mg/kg significantly reduced the intestinal transfer rate. However, a dose of 1000 mg/kg completely stopped the intestinal transmission. So they can be useful to prevent diarrhea. These effects may be due to tannins, alkaloids, saponins, flavonoids, sterols and triterpenes and reducing sugars in the plant.	²³
Persea	Lauraceae	Persea plant	This study was performed to evaluate the antiulcer effect of hydroalcoholic extract of this plant (HEPM) in doses (30-300 mg/kg) in rodents. Oxidative factors like reactive oxygen species (ROS) can cause gastric ulcers, and the antioxidant compounds produced by this plant, such as polyphenols, have protective effects against gastric ulcers. In this study, HEPM shows the activity of free radical scavenging activity of HEPM. By increasing the production of mucin, HEPM accelerates the process of stomach uplift. Mucins are glycoproteins that improve and repair epithelial stomach and contribute to cell proliferation. Also, in this study, HEPM has been shown to improve the activity of superoxide dismutase oxidants (SOD) and catalase (CAT) oxidants. In this study, HEPM at 300 mg/kg dose has the most effect on gastric ulcer. HEPM does not have any toxic effects in this dose.	²⁴
Maytenus	Celastraceae	Maytenus	It has been shown that leaf extract of this type of plants has anti-ulcer and anti-inflammatory activity in rats and 70 mg/kg in rats and does not have any toxic effects. High combinations are components of the plant's extract that can reduce the secretion of hydrochloric acid in the stomach, as well as through bacteriostatic action against Helicobacter pylori (a bacterium commonly present in gastritis and ulcers) that protects mucosal The stomach is found in the study. The extract of this plant increases the pH of the stomach.	²⁵
Streblus asper	Moraceae	toothbrush tree	In this study, the methanolic extract of this plant, at doses of 100,200, 400 mg/kg, has anti-diarrheal properties. In the methanolic extract of the leaf of this plant, the activity of flavonoids anti-diarrheal is due to intestinal motility inhibition and inhibition of hydro-electrolytic secretion or gastric acid. The methanolic extract of the leaf of this plant contains compounds such as glycosides, flavonoids, and saponins, which may be due to the presence of these compounds in the anti-diarrheal activity of this plant. Anti-diarrheal activity These compounds may be due to the activation of Na + / K + -ATPase activity.	²⁶
Cordia myxa	Boraginaceae	Assyrian plum	The extract of this plant acts on the stomach, the effective dose of the extract of this plant is 125 mg/kg. The extract of this plant reduces the mucosal damage of the stomach, decreases malondialdehyde (MDA) (oxidative stress marker) and TNFα, and increases the level of mucin and catalase in the gastric mucosa.	²⁷
Coriandrum sativum	Apiaceae	Coriander	The aqueous extract of this plant affects the stomach, the aqueous extract of this plant at doses of 250 mg/kg and 500 mg/kg reduces the secretion of gastric acid. One of the most beneficial effects of the aqueous extract of this plant on different doses is through the effect on 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) and thus inhibition of various stages of gastric cancer from hyperplasia to adenoma.	²⁷
Cyperus rotuntdus	Cyperaceae	coco-grass	The extract of this plant acts on the stomach, at the dose of 100 mg/kg or 200 mg/kg extract of this plant increases the activity of antioxidant enzymes such as glutathione peroxidase and prevents ulceration of the stomach. Doses of 250 mg/kg and 500 mg/kg of methanolic extract of this plant increase the activity of superoxide dismutase, glutathione peroxidase, increase in glutathione level and inhibit lipid peroxidation in gastric mucosa, which are dose-dependent effects.	²⁷
Azadirachta indica	Meliaceae	neem, nimtree	Aqueous extract of this plant was used in the concentration of 0.01-10 mg/ml in rats. The maximum effect of this extract was to reduce the contraction of the ileum muscles of 5 mg/ml, which had no special effects. In this study, SNF inhibited the acetylcholine stimulatory effect. This may be due to the fact that SNF acts as a calcium channel blocker or acetylcholine antagonist. Flavonoids in this plant, such as galetin 3,6-dimethyl ether, have been shown to reduce the ileum contraction in the tested rats by activating the potassium channel and decreasing cytosolic concentrations.	²⁸
Aloe vera	Asphodelaceae	Aloe vera	This plant has anti-inflammatory activity. Antisecretory, cytoprotective and antioxidant activity of this plant has protective effects on the gastric mucosa. In this study, a combination of three high-dose 300 mg/kg doses in albino rats was effective in improving gastric and duodenal ulcers.	²⁹
Plantago asiatica	Plantaginaceae	Chinese plantain	The extract of this plant contains butyric acid, which can prevent and control colon carcinogenesis, protect against mucosal oxidative stress, and reduce inflammation. Butyric acid stimulates enteroendocrine cells by increasing serum levels of GLP-1. Polysaccharides in these plants increase the production of Short-Chain Fatty Acid (SCFA), which can reduce the amount of free fatty acids (FFAs) and cholesterol, prevent dysfunction of pancreatic beta cells and prevent The apoptosis of these cells is shown to be a high fat diet with increased TNF-α expression and NF-κB activation in the ileum. Also, SCFAs can inhibit IL-6 expression.	³⁰
Passiflora spp.	Passifloraceae	passion flowers	Weed extracts are also used for the treatment of gastrointestinal disorders from with neurological origin, and also have anti-inflammatory and antibacterial activities. All of these plant extracts inhibit the growth of Helicobacter pylori. Weed extracts are also used for the treatment of gastrointestinal disorders from the origin of nervous system, as well as anti-inflammatory and antibacterial activity. All of these herbal extracts, growth H. pylori inhibits.	³¹

Table 2. Effective material of the herbal plants

Scientific Name	Effective material	Ref.
Glycyrrhiza glabra	Anethole, glycyrrhizin, isoflavene glabrene, glabridin, phytoestrogens.	¹⁹
Ribes nigrum	delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-glucoside, and cyanidin-3-O-rutinoside, polyphenols.	²⁰
Phyllanthus niruri	Hypophyllanthin, phyllanthin	²¹
Newtonia hildebrandtii	2,3,4-trihydroxybutylpentatriacontanoate (newtonoate), glyceryl monotetracosanoate, bergenin, tri- O -methylnorbergenin.	²²
Lantana camara	tannins, alkaloids, saponins, flavonoids, sterols and triterpenes and reducing sugars	²³
Persea	estragole, α-farnesene, β-caryophyllene, germacrene D, α-cubebene and eugenol.	²⁴
Maytenus	Tannins (epigallocatechin) and terpenes (fridenelol)	²⁵
Streblus asper	glycosides, flavonoids, and saponins	²⁶
Cordia myxa	flavonoid glycosides, robinin, rutin, datiscoside and hesperidin, chlorogenic and caffeic acid	²⁷
Coriandrum sativum	carbohydrates, phenolic compounds,	²⁷
Cyperus rotuntdus	α-cyperone, β-selinene, cyperene, patchoulenone, sugeonol, kobusone, and isokobusone , rotundone, auxins and phenolic compounds.	²⁷
Azadirachta indica	tannin, phenolic compounds.	²⁸
Aloe vera	polymannans, anthraquinone C-glycosides, anthrones, emodin and various lectins.	²⁹
Plantago asiatica	dibenzylbutane lignin, plasiaticine, an acetylenic glycoside, plasiaticine, an indole alkaloid, plasiaticine, plasiaticine I	³⁰
Passiflora spp.	Maltol, cyanogenic glycosides, flavonoids, glycosides, apigenin, benzoflavone, homoorientin, 7-isoorientin, isoshaftoside, isovitexin (or saponaretin), kaempferol, lucenin, luteolin, n-orientin, passiflorine, quercetin, rutin, saponarin, shaftoside, vicenin and vitexin	³¹

DISCUSSION:

Most clinical trials have clearly demonstrated the beneficial effects of dietary antioxidants and medicinal plants on various types of cancers. Today, phytotherapy, i.e., the use of herbal products and/or herbal extracts is common around the world, even in industrialized countries where pioneers of technology and science and the use of artificial drugs live. Many of the herbs used in foods include a large amount of phenolic compounds that exert an appropriate antioxidant activity ^32-39. The presence of phenolic and antioxidant compounds in various organs of medicinal plants produces strong antioxidant, anti-inflammatory, antispasmodic, anti-digestive cancer and antimicrobial effects ^40-42. Studies have shown that Zingiber officinale, Pinellia ternate, Trigonella foenum-graecum, Achillea millefolium, and Myristica fragrans play significant part in treating parasitic and infectious diseases such as diarrhea, reflux, gastroenteritis, peptic ulcer, digestive cancer, constipation, flatulence and other digestive disorders and cancers ^43-48. As the phytochemical and pharmacological investigations of medicinal plants cited in this review suggest, they contain phenolic and antioxidant compounds, and are very important for gastrointestinal diseases; however, the precise mechanism of these plants remains to be clarified ^49-53. If these main compounds are effective in gastrointestinal disorders, these plants most probably are effective in these disorders. It should be noted that gastrointestinal disorders are developed due to different causes ^54-57.A number of plants in this study are important for the evaluation of antimicrobial activity in infectious diseases .Therefore, different medicinal plants may act through more than one specific mechanism ^58,65.

CONCLUSION:

In this review, the medicinal plants used for the treatment of parasitic and infectious diseases, diarrhea, gastroenteritis, gastric ulcer, constipation and other digestive disorders were addressed. The results of phytochemical studies of the herbs indicated that compounds such as kobusone, and isokobusone, rotundone, auxins and phenolic compounds, isoflavene glabrene, glabridin, phytoestrogens, glycosides, flavonoids, and saponins ,and etc are the most important active and active compounds of these plants. Therefore, these findings are important for the management of gastrointestinal disorders and future studies on traditional medicine for the development of medications.

LIST OF ABBREVIATIONS DIABETES:

Gasterointestinal disorders: GI

COMPETING INTERESTS:

The authors declare no conflict of interest.

AUTHORS’ CONTRIBUTIONS:

All authors searched, studies, reviewed and contributed to the design of the research. All authors reviewed, commented and approved the final draft.

ACKNOWLEDGMENTS:

The present study was supported by Lorestan University of Medical Sciences. We cordially thank of Lorestan University of Medical Sciences, Iran.

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Received on 22.11.2018 Modified on 10.12.2018

Research J. Pharm. and Tech 2019; 12(2):841-847.

DOI: 10.5958/0974-360X.2019.00145.8