**1. Introduction**

Diabetes mellitus (DM) is one of the most common metabolic disorders with significant morbidity and mortality rates around the world. It is caused either by deficiency in insulin secretion or degradation of secreted insulin [1], which is the result of cell alterations caused by many internal and external factors, such as obesity, sedentary lifestyle, and oxidative stress [2,3]. However, oxidative stress occurs when the production of free radicals, such as reactive oxygen species (ROS), overwhelms the detoxification capacity of the cellular antioxidant system, resulting in biological damages [4]. It plays a central role in the development of diabetes, such as microvascular and cardiovascular complications [5]. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction, which is the main mediator of diabetes tissue damage, insulin resistance, β-cell dysfunction, and impaired glucose tolerance [6].

The prevalence of diabetes reported by the International Diabetes Federation (IFD) indicates that the number of adult diabetic patients globally was 366 million in November 2011, and it is projected to increase to 552 million by the 2030 [7]. In Africa, more than 14 million people have diabetes, accounting for about 4.3% of adults, and it caused about 401,276 deaths in 2012 [8]. Numerous synthetic anti-diabetic agents, such as acarbose, miglitol, sulfonylurea, metformin, and thiozolidinedione, are readily available on the market, but the effectiveness of these products is limited due to non-availability, cost, and high side effects, such as hypoglycaemia, damage to the liver, flatulence, diarrhea, abdominal pain, dropsy, drug-resistance, weight gain, and heart failure [9,10]. Therefore, due to the above-mentioned detrimental effects, there is a grea<sup>t</sup> need for developing alternative natural anti-diabetic products with a high safety margin.

Natural plants have been used as a source of medicine since time immemorial for the purpose of curing numerous human afflictions. Plants are known to be the main source of health-promoting substances because they are comprised of secondary metabolites, such as polyphenols, flavonoids, terpenoids, alkaloids, carotenoids, vitamins, and several other constituents, which are responsible for anti-diabetic, antioxidant, anti-hypertensive, and other health promoting effects [11].

*Salvia africana-lutea*, commonly known as *Bruinsalie* or beach sage, is distributed from Namaqualand to the Eastern Cape Province of South Africa (in the South-Western part of South Africa). It is traditionally used for the treatment of different kinds of ailments and/or diseases, such as coughs, sexual debility, mental and nervous conditions, throat inflammation, chronic bronchitis, tuberculosis, influenza, stomach ache, diarrhea, and urticarial [12]. A preliminary phytochemical and biological evaluation of *S. africana-lutea*, collected from Pretoria, South Africa, indicated a grea<sup>t</sup> potential of *S. africana-lutea* methanolic extract as a source of abietane diterpenes [13,14]. The ethno-medicinal report of the plant in controlling different symptoms related to ageing diseases justifies the present study to isolate and identify the chemical constituents and explore their in vitro bio-activities. Terpenoids isolated from Lamiaceae, especially abietane diterpenes and some classes of triterpenes, play a crucial role as eco-physiological mediators and are of interest for potential application as therapeutic agents in the treatment of diabetes [15,16]. Recent reports indicate the efficiency of carnosic acid derivatives in controlling the detrimental effects of diabetes by improving glucose and insulin secretion [17], improving glucose homeostasis, or stimulating glucose uptake through intensifying peripheral glucose clearance in tissues, thereby alleviating pathological effects related with the hyperglycaemic state [18]. Carnosol improved diabetes and its complications by modulation of oxidative stress and inflammatory responses [19] and stimulated glucose uptake [20]. Several triterpenes including ursolic acid, oleanolic acid, lupeol, and betulinic acid, have been reported to be potential anti-diabetic candidates with different mechanisms of action [21–23].

This work primarily examines the phytochemical isolation of different constituents present in the methanolic extract of *S. africana-lutea* as well as the anti-diabetic and the antioxidant activities of its isolated compounds.

## **2. Experimental Section**
