Diabetes mellitus (DM) affects essential pathways of carbohydrate, protein, and lipid metabolism consequent to a deficiency of insulin secretion, insulin action, or both . Hyperglycemia is the major hallmark of both type 1 and type 2 DM and it is the principal etiological factor for the pathogenesis of both macro- and microvascular complications. About 80% of type 2 DM is reported to be associated with obesity, dyslipidemia and hypertension in addition to insulin resistance . Dyslipidemia of diabetes mellitus has been linked with an increased risk of cardiovascular disease (CVD) development. However, the most common form of dyslipidemia associated with DM is hyperlipidemia; characterized by an elevated plasma triglyceride, cholesterol, small dense LDL, and low HDL cholesterol levels. Previous studies have indicated a strong positive correlation between high plasma lipids; notably of low-density lipoprotein (LDL) and incidence of CVD . Increased lipid peroxidation that can damage cell membranes, lipoproteins and lipid containing structures is also linked with an increased CVD risk . Potential mechanisms reported to most likely be responsible for diabetic dyslipidemia include defect in insulin action, hyperglycemia, and peripheral actions of insulin on adipose tissue, changes in liver apoprotein production, defective regulation and action of lipoprotein lipase (LPL), and cholesteryl ester transfer protein (CETP) . In addition, increased adipocyte lipolysis due to poor insulinization results in increased free fatty acid flux from the adipocytes and transport to the liver which eventually causes an increased very low-density lipoprotein (VLDL) and triglyceride secretion in blood [6, 7].
While glycemic control tends to dominate the management of type 1 DM, the care for individuals with type 2 DM emphases the treatment of other co-morbid conditions associated with the disease such as life style modification, detection/management of obesity, hypertension, dyslipidemia, and related microvascular and macrovascular complications . Diabetes thus, requires a multiple therapeutic approach to adequately control the multiple metabolic abnormalities and progressive nature of the disease. Recent therapeutic trends in the treatment of DM therefore use combination therapies involving different hypoglycemic drugs and/or insulin . Furthermore, many diabetic patients have opted for alternative plant-based therapies alone or in combination to the conventional hypoglycemic drugs due to their increased cost, non-availability, contraindications, and the assumed safety of medicinal plants. As such, the use of medicinal plants would continue to be popular and common, hence the need to scientifically validate medicinal plants as safer alternatives to the conventional ones. Traditional herbal healers use different plant parts in combination with other plants for the treatment of diabetes with the hope that the combined plants would target different pathologies of the disease, despite that the safety and probable mechanism of action is unknown in addition to the consequences which could be increased morbidity and mortality.
Ethnobotanic surveys have shown that plants such as Leptadenia hastata and Momordica balsamina used most commonly for dietary purposes have gained popularity as ingredients of polyherbal anti-diabetic formulations used by traditional herbal healers in Northern Nigeria [9,10,11]. Leptadenia hastata (Pers.) Decne, which belongs to the family Asclepiadaceae , and Mormodica balsamina Linn, belonging to the family of Cucurbitaceae, are both used for multiple medicinal purposes in Africa [13, 14]. L. hastata and M. balsamina have both been reported as important sources of dietary nutrients including fatty acids, beta carotene, protein and minerals, and pharmacologically active phytoconstituents such as phenolic compounds, triterpenoids, and glycosides [15, 16]. Phytochemical screening of the leaves of L. hastata confirmed the presence of major chemical compounds such as alkaloids, flavonoids, tannins, phenolic glycosides, triterpenes, and saponins . The bark and leaves of L. hastata were found to contain mixtures of polyoxypregnane ester derivatives such as ester 12-O-aceylsarcostin, gagaminin, kidjolanin, metaplexigenin, and cynanforidin as well as tritepenes like lupeol, lupeol acetate, and lupeol palmitate [17, 18]. In a study by Bello et al. , the aqueous and methanolic leaf extracts of L. hastata reduced the level of blood glucose and blood lipids in both normal and alloxan-induced diabetic rats with a 37.02% and 69.81% alpha glucosidase inhibitory effect, respectively. In another study conducted by Gwarzo and Ameen , 3-week supplementation of the diet of hyperlipidemia-induced Wistar albino rats with the leaf powder of L. hastata was associated with a reduction in serum lipid profile and blood glucose level. Further to this, we conducted a bioassay-guided fractionation and characterization of the methanolic leaf extract of L. hastata and our results revealed 5-methyl genistein as one of the major bioactive compounds responsible for its anti-diabetic effect (unpublished).
In the same way, studies of the potential health benefits of the different plant parts of M. balsamina have indicated that it possesses activities like anti-microbial, anti-spasmodic, anti-inflammatory, analgesic, anti-HIV, anti-diabetic, anti-diarrheal, hepato-protective, anti-malarial, antioxidant, anti-cancer, and wound-healing properties . These activities could be as a result of the presence of cucurbitane-type triterpenoids from the leaves of M. balsamina including balsaminapentaol, balsaminol A and B, cucurbalsaminol A and B , and a novel ribosome-inactivating protein (RIP), balsamin from the seeds of the balsam apple . In our newly conducted work, we isolated a pentane type triterpenoid (betulinic acid) from the ethylacetate fraction of the leaves of M. balsamina which was found to contribute to its antidiabetic activity (unpublished). Combination of the plant leaves of L. hastata and M. balsamina could therefore provide a multi-therapeutic approach for the treatment of diabetes mellitus and its complications. Our previous study had demonstrated the acute and sub-acute anti-hyperglycemic effect of the aqueous leaf extracts of L. hastata and M. balsamina at a dose of 400 and 200 mg/kg body weight respectively (doses obtained from anti-hyperglycemic screening of the 1/5th, 1/10th, and 1/20th of the LD50 dose; 2000 mg/kg) in STZ-induced diabetic . The dose combination was therefore selected and used in the present study to further evaluate its effect on serum lipid profile in STZ-induced diabetic rats.