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Potential Application of Some Lamiaceae Species in the Management of Diabetes

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Potential Application of Some Lamiaceae Species in the Management of Diabetes plants Review Potential Application of Some Lamiaceae Species in the Management of Diabetes Ninon G.E.R. Etsassala 1 , Ahmed A. Hussein 2 and Felix Nchu 1,* 1 Department of Horticultural Sciences, Faculty of Applied Sciences, Cape Peninsula University of Technology, Symphony Road, Bellville 7535, South Africa; [email protected] 2 Chemistry Department, Cape Peninsula University of Technology, Bellville Campus, Symphony Road, Bellville 7535, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-219-596-473 Abstract: Diabetes is one of the most dangerous metabolic disorders, with high rates of mortality worldwide. Since ancient times, medicinal plants have been used in traditional medicine to treat many diseases, including diabetes and its related complications. Plants are widely accepted, affordable, and perceived to have minimal adverse side effects. The Lamiaceae family is a potential source of therapeutic agents for the management of metabolic disorders, including diabetes. Hence, this review paper summarizes the antidiabetic use of Lamiaceae species in folk medicine globally. Furthermore, we present the antidiabetic activities and phytochemical constituents of twenty-three (23) Lamiaceae species and the antidiabetic activity of some notable chemical constituents isolated from some of these Lamiaceae species. Keywords: Lamiaceae species; diabetes mellitus; oxidative stress; secondary metabolites Citation: Etsassala, N.G.E.R.; Hussein, A.A.; Nchu, F. Potential Application of Some Lamiaceae 1. Introduction Species in the Management of Diabetes mellitus (DM) is one of the most dangerous metabolic disorders, causing high Diabetes. Plants 2021, 10, 279. mortality rates worldwide [1]. It is well known that insulin plays a crucial role in glucose https://doi.org/10.3390/plants homeostasis, as it activates the transport of blood glucose inside the skeletal muscle [2]. 10020279 However, insulin resistance in target tissues and the shortage of insulin production from pancreatic β-cells are the principal attributes of type 2 diabetes. Additionally, type 2 DM Academic Editors: Ana characterization also encompasses a decrease in peripheral glucose uptake within the Maria Carvalho and Laura Cornara muscle, adipose, or liver cells and an increase in endogenous glucose secretion, causing Received: 17 November 2020 increased blood glucose concentration [3–5]. Therefore, agents with the ability to activate Accepted: 26 January 2021 Published: 1 February 2021 glucose uptake in these tissues can ameliorate insulin resistance and treat diabetes [6]. Many synthetic antidiabetic drugs such as acarbose, sulfonylurea, miglitol, metformin, and thiazolidinedione are already present in the market. However, their effectiveness Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in is restricted because of their high cost and adverse side effects [7,8], which incentivize published maps and institutional affil- the development of powerful natural antidiabetic products/drugs with minimal adverse iations. side effects. Lamiaceae, commonly known as the mint family, is a cosmopolitan flowering plant family with approximately 7136 species assigned to 236 genera. Most of the species are herbaceous or shrubby, and trees are scarce. The most well-known genus is Salvia (900), followed by Scutellaria (360), Stachys (300), Plectranthus (300), Hyptis (280), Teucrium (250), Copyright: © 2021 by the authors. Vitex (250), Thymus (220), Nepeta (200), and Clerodendrum (150) [9]. Licensee MDPI, Basel, Switzerland. This article is an open access article The family possesses significant economic value, as it contains some horticultural distributed under the terms and species and culinary herbs, such as rosemary, salvia, ocimum, and leonotis. They are well conditions of the Creative Commons reputed because of the high level of aromatic compounds within their leaves, flowers, Attribution (CC BY) license (https:// and essential oils. These compounds are pharmacologically active terpenoids that play creativecommons.org/licenses/by/ vital roles in developing new bioactive products within the cosmeceuticals, nutraceuticals, 4.0/). Plants 2021, 10, 279. https://doi.org/10.3390/plants10020279 https://www.mdpi.com/journal/plants Plants 2021, 10, 279 2 of 22 and pharmaceutical industries [10]. People use many species in this family for culinary, fragrance, flavour, and aromatherapy purposes. Additionally, Lamiaceae species have antispasmodic, antiseptic, antimicrobial, cal- mative, and antidiabetic activities [11]. Lamiaceae species have been used as antidiabetic agents since time immemorial for their curative abilities within the folk medicine of diver- gent communities, regions, and tribes in the African sub-region and worldwide [12]. This study reviews the traditional use of the Lamiaceae species to treat diabetes globally and reports on the isolated antidiabetic compounds and their pharmacological actions from Lamiaceae species. 2. Method This review summarized previous research works (1986–2020) conducted on plants of the Lamiaceae species that have been traditionally used to treat diabetes worldwide and the antidiabetic bioactivities of their extracts and pure compounds. The keywords “Lamiaceae species” and “treatment of diabetes” as well as scientific databases such as SciFinder, Science Direct, and Google Scholar were used to source primary and secondary data for this review. Additionally, we used a database of plants (http://www.theplantlist.org/) to check the scientific names of plants and their authority. Furthermore, Quantum GIS was used to produce a map of the traditional use of the Lamiaceae species to manage diabetes in different countries and regions of the world. 3. Lamiaceae Species Used for Diabetes 3.1. Ajuga iva (L.) Schreb 3.1.1. Traditional Uses Ajuga iva is widely distributed in the South European and North African countries [13]. In Morocco and Algeria, a decoction of A. iva is utilized in traditional medicine to treat different kinds of diseases, including diabetes. Additionally, many Moroccans use its decoction to alleviate diabetes [13–15]. 3.1.2. Phytochemical Constituents The phytochemical investigation of the extracts derived from different parts of A. iva showed the presence of diverse classes of bioactive secondary metabolites such as flavonoids, steroids, terpenoids, and fatty acids [16]. Five terpenoids such as ivain I-V were isolated from the diethyl ether extract of the whole plant of A. iva, in addition to 6- desoxyharpagide, 3-8-O-acetylharpagide, 8-O-acetylharpagide, and harpagide. Flavonoids, such as apigenin hexoside-pentoside, apigenin dihexoside, apigenin 7-O-neohesperidoside, naringenin-hexoside, apigenin 7-O-glucoside, and naringenin-7-O-α-L-rhamnopyranosyl, were reported from A. iva [13,17]. Other compounds, including 5-caffeoylquinic acid, apigenin 6,8-di-C-glucoside, 3,5-dicaffeoylquinic acid, and naringin were predominantly found in the infusion of A. iva [18]. 3.1.3. Antidiabetic Activity In vitro and in vivo biological investigations revealed that the methanolic extract of A. iva has antidiabetic activity [16,19]. A. iva possesses hypoglycaemic and hypolipidemic activities [19]. The bio-evaluation of the alpha-amylase and alpha-glucosidase inhibitory activities of the aqueous and methanolic extracts of the aerial parts of A. iva showed a good inhibition of alpha-amylase, with IC50 values of 0.210 ± 0.003 and 0.180 ± 0.005 µg/mL, as well as of alpha-glucosidase, with IC50 values of 0.172 ± 0.012 and 0.130 ± 0.008 µg/mL, respectively [17]. The whole plant of A. iva has been reported to increase the hepatic glycogen concen- tration and prevent diabetic complications in the kidneys, pancreas, and liver. Additionally, the extract of A. iva showed a preventive effect against the deleterious effects of diabetes on oxidative stress [18]. The administration of the extract of A. iva significantly reduced the plasma glucose concentration and consequently resulted in the rapid normalization of Plants 2021, 10, 279 3 of 22 glucose levels in diabetic animals [18]. The aqueous extract of A. iva significantly decreased the plasma glucose level in STZ-diabetic rats, with no effect on insulin production. Addi- tionally, A. iva upgraded the glycaemic value (41%) in hyperglycaemic rats and lessened the glycosylated haemoglobin (HbA1c) [19]. The lyophilized aqueous extract of A. iva (whole plant) displayed significant hypoglycaemic activity and was relatively non-toxic to normal (normoglycemic) and streptozotocin (STZ)-diabetic rats [19]. An aqueous extract of the whole plant of A. iva showed hypolipidemic and hypoglycaemic effects in both normo- glycemic and diabetic rats [19]. Additionally, the aqueous extract of A. iva is a rich source of phytoecdysteroids, which are potential therapeutic candidates for alloxan-induced diabetic male albino rats [20]. A. iva aqueous extract demonstrated significant hypolipidemic activity after a single dose and repeated treatments on STZ-diabetic rats [15]. 3.2. Ballota nigra L. 3.2.1. Traditional Uses Ballota nigra is native to the Mediterranean region and predominantly found in Europe and Asia [21]. People in many parts of Turkey use the aerial parts of B. nigra traditionally to treat haemorrhoids, wounds, ulcers, animal bites, sores, flu, colds, and flatulence, and as an antiseptic for inflamed skin, wounds, burns, and diabetes mellitus [21,22]. 3.2.2. Phytochemical Constituents Numerous compounds such as 7α-acetoxymarrubiin, ballonigrin, ballotenol, balloti- none,
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