Abstract
The purpose of this review is to summarize the available antidiabetic medicinal plants in the Kingdom of Saudi Arabia with its phytoconstituents and toxicological findings supporting by the latest literature. Required data about medicinal plants having antidiabetic activities and growing in the Kingdom of Saudi Arabia were searched/collected from the online databases including Wiley, Google, PubMed, Google Scholar, ScienceDirect, and Scopus. Keywords used in search are in vivo antidiabetic activities, flora of Saudi Arabia, active ingredients, toxicological evaluations, and medicinal plants. A total of 50 plant species belonging to 27 families were found in the flora of Saudi Arabia. Dominant family was found Lamiaceae with 5 species (highest) followed by Moraceae with 4 species. β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic acid, rutin, chlorogenic acid, quercetin, and kaempferol are the very common bioactive constituents of these selected plant species. This paper has presented a list of antidiabetic plants used in the treatment of diabetes mellitus. Bioactive antidiabetic phytoconstituents which showed that these plants have hypoglycemic effects and highly recommended for further pharmacological purposes and to isolate/identify antidiabetes mellitus (anti-DM) active agents also need to investigate the side effects of active ingredients.
1. Introduction
Medicinal plants are used for the treatment of different infections [1, 2]. These plants contributed as a source of inspiration for novel therapeutic compounds [3]. The medicinal value of plants is due to the presence of a wide variety of secondary metabolites including alkaloids, glycosides, tannins, volatile oil, and terpenoids [4, 5]. Medicinal plants and their extracts represent a rich source of crude medications that possess therapeutic properties. Indeed, the World Health Organization reports that various plant fractions and their dynamic constituents are utilized as traditional medicines by 80% of the world population [6]. Plants are the primary source for different pharmaceutical, perfumery, flavor, and cosmetics industries; the use of modern drugs dramatically resulted into resistant microorganisms toward different modern drugs; the researchers are now in search for alternate source of treatment of various disorders [7, 8]. For this purpose, the medicinal herbs are the best alternate to various drugs. Most of natural products possess interesting biological activities and medicinal potential. Various herbs, fruits, and grains have been found to have different important biological activities such as antioxidant, [9] antitumor, antimutagenic, antidiabetes, antianalgesic, [10] antidementia, inflammation inhibitory effect, [9] antitumor, [11] anticancer, [12] antimicrobial, antileishmanial, and antimalarial properties [13, 14]. The consumption of natural antioxidants will reduce risk of many diseases including cancer, cardiovascular disease, diabetes, and other diseases allied with aging [15]. For natural antioxidants, a larger number of medicinal herbs have been evaluated by applying laboratories’ developed procedures. Plants derived substances, collectively called phytonutrients or phytochemicals, been recognized as good source of natural antioxidants [16, 17].
The Kingdom of Saudi Arabia is a huge arid land with an area of about 2,250,000 km2 covering the major part of the Arabian Peninsula, characterized by different ecosystems and diversity of plant species. The climate in Saudi Arabia differs greatly between the coast and the interior. High humidity coupled with more moderate temperatures is prevalent along the coast, whereas aridity and extreme temperatures characterize the interior. The flora of Saudi Arabia is one of the richest biodiversities in the Arabian Peninsula and comprises very important genetic resources of crops and medicinal plants. Saudi Arabia contains 97 trees, 564 shrubs, and about 1620 herbs, which cover, respectively, 4.25%, 24.73%, and 71.02% of higher plant diversity of the country [18].
Diabetes mellitus is one of the most prevalent diseases in endocrine gland system with an increasing incidence in human community [19]. Type I diabetes is caused by insulin secretion deficit, while type II diabetes is accompanied with progressive rate of insulin resistance in liver and peripheral tissues, reducing β-cell mass, and deficient insulin secretion [20, 21]. This disease brings about acute metabolic side effects including ketoacidosis, hyperosmolar coma accompanied with chronic disorders, and long term, adverse side effects such as retinopathy, renal failure, neuropathy, skin complications, as well as increasing cardiovascular complication risks [22, 23]. Also, common symptoms of diabetes are frequent urine, thirsty, and overeating [24]. Diabetes inflicts 100 million people yearly and is recognized as the seventh cause of death in the world [25]. It has been estimated that the number of diabetic people will increase from 150 million individuals in 2003 to 300 million by 2025 [26]. The essential and effective drugs for diabetes mellitus are insulin injection and hypoglycemic agents, but these compounds possess several adverse effects and have no effects on diabetes complications in long term. Therefore, it is important to find effective compounds with lower side effects in treating diabetes [27]. Medicinal plants are good sources as alternative or complementary treatments for this and other diseases [28–30]. Although various plants have been traditionally used throughout history to reduce blood glucose and improve diabetes complications, there is not enough scientific information about some of them. Herbal medicines are commonly prescribed throughout the world because of low side effects, availability, roughly low cost, and also its effectiveness [31, 32].
In Saudi Arabia, the number of people who suffer from DM increased from 890,000 in 2000 to a staggering projection of 2,523,000 in 2030. In 2011, Saudi Arabia reported a prevalence of DM at 30% of the total population, with a rate of 27.6% in women and 34.1% in men [33]. According to 2010 data from several sources (WHO, World Bank, UNESCO, CIA, and individual country databases), DM is the number three disease-related cause of death in Saudi Arabia [34].
In the present situation, herbal medicines’ usage has significantly increased and published studies from developed countries emphasize that a paramount proportion of medicines supplied by them have herbal origins, so growing and producing the herbal medicines could be helpful to both economic development and community’s health [35]. Keeping in mind the importance of medicinal plants, in the current review various medicinal plants used for antidiabetic treatment around the world, native to or cultivated in Saudi Arabia, are documented for the purpose to provide up-to-date insight on medicinal plant used for DM, so that researcher easily selects plant for bioscreening and active constituents’ identification purposes. Therefore, we invite researchers' attention to carry out detailed ethnopharmacological and toxicological studies on unexplored antidiabetic plants in order to provide reliable knowledge to the patients and develop novel antidiabetic drugs.
2. Methods
Required data about medicinal plants having antidiabetic activities and growing in the Kingdom of Saudi Arabia were searched/collected from the online databases including Wiley, Google, PubMed, Google Scholar, ScienceDirect, and Scopus. Keywords used in search are in vivo antidiabetic activities, flora of Saudi Arabia, active ingredients, toxicological evaluations, and medicinal plants. Latest published data approximately in the last ten years with the key outcome of change in blood glucose level in animal model were included. One or two articles are selected as references for each plant’s species on priority basis from the journals found in web of science and latest years.
3. Results
The names, families, used parts, location, and antidiabetic properties in animal model of the native/cultivated Saudi medicinal plants are summarized in Table 1. The active ingredients and toxicological effect of these plants in animal model are given in Table 2. A total of 50 plant species belong from 27 families were found in the flora of Saudi Arabia. Dominant family was found Lamiaceae with 5 species (highest) followed by Moraceae with 4 species.
4. Discussion
The majority of the experiments confirmed the benefits of medicinal plants with hypoglycemic effects in the management of diabetes mellitus. From Table 1, it can be concluded that among the plants used for the treatment of diabetes, H. salicornicum, T. oliverianum, A. cepa, A. herba-alba, Teucrium polium, Sesamum indicum, Z. spina-christi, and U. dioica seem to be most common plants used to treat diabetes and are available everywhere in the world. The leaves were most commonly used plant part, and other parts (root, stem, bark, flower, seed, and whole plant) were also useful for curing. The most common diabetic model that was used was the streptozotocin and alloxan-induced diabetic mouse or rat as diabetic models. The most commonly involved active constituents are flavonoid, alkaloid, saponin, carbohydrate, vitamins, amino acid and its derivatives, phenol and its derivatives, and benzoic acid derivatives. The very common phytoconstituents, targeted metabolic pathways, and its structure are given in Table 3 [194, 195]. The native to or cultivated plant species of the kingdom given in Table 1 are selected from the published literature about ethnobotanical value and antidiabetic potential of medicinal plants around the world. The ethnobotanical information reports about 800 plants that may possess antidiabetic potential [196, 197]. Jeeva and Anlin also reported 177 plants belonging to 156 genera and 76 families used traditionally for antidiabetic treatment [198]. In the Middle East countries, there are 129 plant species still in use in traditional Arabic medicine. This indicates that the medicinal plant species require preservation as well as the ethnobotanical and ethnopharmacological knowledge. The preservation of the herbs is an essential requirement for maintaining traditional Arabic medicine as a medicinal and cultural resource [199]. The selected plant species H. salicornicum, T. oliverianum, A. cepa, A. herba-alba, Teucrium polium, Sesamum indicum, Z. spina-christi, and F. religiosa are the native Saudi medicinal plants traditionally used for the treatment of DM [200]. Similarly published data showed that 20 medicinal plants are traditionally used in Tabuk region of Saudi Arabia [201]. Anisotes trisulcus, Artemisia judaica, and Moringa peregrine are used in Al Khobah village, Saudi Arabia, for DM treatment [202]. O. europaea is used in Al Bahah region of KSA for DM treatment [203]. C. roseus, A. cepa, U. dioica, A. aspera, C. intybus, C. cyminum, F. bengalensis, C. colocynthis, and T. polium are the highly investigated medicinal plants for antidiabetic potential [204–206].
Desiring to contribute to the conservation priorities of traditional medicine knowledge of various medicinal plants native to or cultivated in Saudi Arabia and to make it easy and familiarized with disease treatment, the present compilation was conducted. According to the International Union for Conservation of Nature and the World Wildlife Fund, there about 15,000 medicinal plant species are threatened with extinction from overharvesting and habitat destruction and 20% of their wild resources have already been nearly exhausted with the increasing human population and plant consumption [207]. Each plant species lost due to extinction phenomena could represent not only the loss of healthcare saving cures for special diseases but also the loss of probable primary metabolite liker protein- or vitamin-rich foods [208]. Medicinal plants have been cited as a potential source of heavy metal toxicity to both man and animals. The most common heavy metals implicated in human toxicity include lead, mercury, arsenic, and cadmium, although aluminum and cobalt may also cause toxicity. From the study, the levels of these metals differed in the same plant collected from different geographical locations. A study conducted showed that the levels of lead in Cassia alata varied from 17.7 to 4.45 μg/g for the 5 collection sites. Similarly for Cassia occidentalis and Rauvolfia vomitoria, the level is varied between 7.85-4.35 and 9.25–1.55 μg/g, respectively. Similarly, that of aluminum varied between 105.53 and 23.3 for Rauvolfia vomitoria and 104.25–12.4 μg/g for Paullinia pinnata. The levels of heavy metals also varied for different plants collected from the same location. Uptake of metals by plants is influenced by a number of factors including metal concentrations in soils, cation exchange capacity, soil pH, organic matter content, types and varieties of plants, and plant age. However, the prevailing factor is the concentration of the metal in the soil and thus the existing environmental conditions [209]. Another study conducted on onion bulb showed that the concentrations of Cr in onion bulb and Fe in onion leaf were above the permissible level (2.3 mg/kg, 425.5 mg/kg) set by FAO/WHO at Mojo (4.87 mg/kg, 1090.40 mg/kg), Meki (4.13 mg/kg, 1836.47 mg/kg), and Ziway (3.33 mg/kg, 764.33 mg/kg), respectively. The results generally indicate that the consumption of these onion bulbs could be the health risk respective to Cr [210]. Therefore, it is suggested that the medicinal plant source for the treatment of diabetes must not be taken from heavy metal contaminated areas to avoid their uptake by the plants because migration of these contaminants into noncontaminated areas (or leaching through the soil and spreading of heavy metal contaminated sewage sludge) are a few examples of events contributing to contamination of the ecosystem.
5. Conclusion and Recommendations
The present review provides a picture of medicinal plants that have been studied as anti-DM drugs, which can be grown either in combination with other medicinal plants or alone as treatment for diabetes and drawbacks should be properly addressed so that medicinal plants can be effectively utilized as anti-DM drugs. Diabetes is a metabolic disorder which can be considered as a major cause of high economic loss which can in turn impede the development of nations. Moreover, uncontrolled diabetes leads to many chronic complications such as blindness, heart failure, and renal failure. In order to prevent this alarming health problem, the development of research into new hypoglycemic and potentially antidiabetic agents is of great interest. In conclusion, this paper has presented a list of anti-DM plants used in the treatment of diabetes mellitus. Bioactive antidiabetic phytoconstituents which showed that these plants have hypoglycemic effects and highly recommended for further pharmacological purposes and to isolate/identify anti-DM active agents also need to investigate the side effects of active ingredients.
Data Availability
This is a review article. All data are taken from published research papers and available online.
Conflicts of Interest
The authors declare no conflicts of interest.
Authors’ Contributions
All three authors contributed equally.
Acknowledgments
The authors wish to thank Research Center College of Pharmacy at King Saud University, Riyadh, Saudi Arabia for their financial support and for providing free access to digital library and laboratory.