1. Introduction
Diabetes is a multifaceted metabolic disorder affecting carbohydrate, fat, and protein metabolism. It is caused by increased levels of circulating blood sugar and insulin deficiency characterized by abnormal insulin secretion and insulin resistance in the body [
1]. Type-2 diabetes (T2D) affects 80% of those living with diabetes and is largely due to an unhealthy diet and a sedentary lifestyle, which might lead to persistent high glucose levels in the blood, oxidative stress, aging, and other metabolic imbalances [
1].
The use of the non-vertebrate organism
Drosophila melanogaster as a model tool for research on various human diseases is important because this fly has biochemical features and characteristics similar to those of mammals; therefore, its use is increasing [
2]. This model organism has been tested and has gained worldwide reputation for use in biomedical research, such as in diabetes studies and in other studies involving genetic manipulations [
3,
4]. Certain reports identified that disease-causing genes in humans are conserved in
Drosophila melanogaster, such as those associated with the insulin-like growth factor signaling (IGFS) pathway. About 70–75% of the brain cells in the fruit fly are insulin-producing cells (IPCs) that are similar to the vertebrate pancreatic β cells and secrete seven insulin-like peptides (ILPs) [
5,
6,
7]. In addition to this, using the fruit fly for research studies is easy and cost-effective, since it is not expensive to maintain them.
The indigenous eggplant (
Solanum anguivi lam) belongs to the Solanaceae family and is locally called “Igba Yinrin” by the Yoruba people in South-West Nigeria. It is commonly known as a forest bitter berry and a non-tuberous and highly polymorphic indigenous medicinal fruit that is widely distributed in non-arid areas of Africa and has nutritional and therapeutic potential [
8,
9]. A study reported that ripe and the unripe (green) eggplants are used in folklore medicine. These eggplants is also used in Ghana and Cameroon cuisine as one of the ingredients of a dish called “Nkwi”. Despite the benefits of the unripe fruits being known, no study has reported the properties of the ripe fruit (with an orange coloration) which is usually left to waste and rot in farms. The ripe eggplant fruits are usually discarded partly due to their low acceptability and the ignorance of their benefits and thus are among the post-harvest food crops lost after harvest in Nigeria, West Africa. Meanwhile, a study [
10] showed that ripening brings changes in the fruit content of phenolic compounds, organic acids, and carbohydrates, as well as in its color, texture, and flavor [
10].
Nigeria is facing an immense food insecurity challenge, a problem partly attributed to the increasing loss of food crops during post-harvest handling and distribution to retail markets. The reduction in post-harvest loss of this eggplant fruit and its use as a food ingredient for functional food development, such as in cookies and dumplings, could promote sustainable food security and a better health treatment/management of non-communicable diseases (NCDs) and cardiovascular diseases (CVDs), a task that requires an integrated approach (healthy diet and lifestyle). Therefore, this research was carried out on both ripe and unripe eggplants to compare their biological effects, with a focus on the anti-inflammatory, antioxidant, and anti-diabetic properties of a diet containing ripe Solanum anguivi lam fruits in diabetic Drosophila melanogaster (fruit fly).
4. Discussion
This study compared the effects of ripe and unripe fruit diets on diabetes in order to evaluate their biological potential; however, our main focus was on the effects of ripe fruits, which are not always reported in studies because ripe fruits are considered waste. Due to ripening, about 60% of indigenous eggplant
Solanum anguivi lam (SA) fruits in Nigeria are left to waste in farms, because the ripe fruit is given little or no importance. Meanwhile, this unwanted fruit is rich in viable phytochemicals, as reviewed in [
36], which explained the benefits of phyto-compounds such as hesperidin—known as a bioflavonoid with anti-inflammatory, skin-lightening, antimicrobial, and wound healing properties—and naringin—which was found to have broad pharmacological potential [
37]. In addition, myricetin was previously reported to have neuroprotective, analgesic, antihypertensive, antidiabetic. and hypolipemic potential [
38].
This clearly shows that many beneficial bioactive compounds from nature are wasted yearly due to the early ripening of fruits and vegetables as well as inadequate/poor storage facilities. This present study showed that the ripe fruit contains more vitamins and minerals than the unripe one, which are essential for the proper functioning of the body. Vitamins are essential nutrients that are needed in the body and are involved in cell regulation, body metabolism, growth, and development, physiological processes, such as iron absorption, and the immune response [
39]. We found that the levels of vitamins A, C, E, and carotenoids and of some minerals increased with ripening, which confirmed a previous report [
11]; the change in coloration of the
Solanum anguivi lam fruit could be due to the synthesis of alpha-carotene and beta-carotene, precursors of vitamin A [
40].
COX and 5-LOX metabolic products such as prostanoids and leukotrienes are implicated in degenerative diseases such as cancer progression and may represent important targets for cancer chemoprevention or treatment [
41]. From the in vitro results, the bioactive compounds present in the ripe eggplant extract could serve as dual inhibitors of inflammatory enzymes, able to block the COX and the 5-LOX metabolic pathways better than synthetic drugs (sulindac and aspirin).
The ripe eggplant extrac bioactive compounds, as shown from the results, have either additive or synergistic effects on the two major enzymes in arachidonic acid metabolic pathways, thus inhibiting their inflammatory activities. Secondly, it could be suggested that eggplant extracts and related diet also possess another advantage, as they have small or no gastric toxicity, being natural products with a balancing effect compared with synthesized non-steroidal anti-inflammatory drugs such as sulindac and aspirin, which are commonly used but cause major side effects, such as ulcerative colitis, due to non-selective COX inhibition. This study clearly shows that the eggplant, especially if ripe, could display an enhanced anti-inflammatory potency based on polyphenol structure, which contains almost the same structural and functional groups as the above-mentioned drugs. This observation confirms the need to utilize natural products such as eggplant for non-selective dual COX/5-LOX inhibition without side effects [
41,
42].
Some reports indicated that some plant products such as curcumin, tea, silymarin, resveratrol, and green and black tea, rich in polyphenols, are used as natural dual enzyme inhibitors, which means that eggplant extracts or and its related diets could exert beneficial, therapeutic effects through the modulation of COX and LOX metabolic pathways [
41,
42]. In addition, it was also confirmed that chronic inflammation is implicated in the pathophysiology of diabetes, especially type-2 diabetes, and to that end, targeting inflammation may help ameliorate diabetes, preventing its sequence and other metabolic complications, which means that an eggplant-supplemented diet could exert multiple beneficial functions.
Bioactive compounds such as vitamins, carotenoids, phenolic compounds, and flavonoids, which seem to be abundant in fruits, whether ripe or unripe, could be the reason behind the low weight gain, the increased survival, and the decreased mortality rate of the flies. This study confirmed what was reported in [
5], i.e., that diabetic fruit flies administered a high-sucrose diet show obesity-linked lipogenesis caused by the repartition of fatty acids toward esterification, away from fatty acid β-oxidation, possibly by increasing malonyl-CoA. Moreover, there is a relationship between movement and weight gain which is also linked to obesity, meaning that a healthy lifestyle involving exercise and nutritious food rich in phyto-compounds, minerals, vitamins, and fiber, and with a low GI could holistically enable body wellness, as suggested by Nwanna et al. [
12].
It was also observed that the ripe eggplant-inclusive diet was able to elicit positive effects better than the unripe fruit-inclusive diet, at the same time reducing the glucose, MDA, and thiol levels in the diabetic subjects compare to the untreated subject. There is connection between diabetes mellitus, oxidative stress, and reduced antioxidant activity [
43], while the biomarkers of oxidative stress are related to reactive oxygen species, MDA, and thiols. Thiol is an organic compound containing a sulfur atom. It is also referred to as mercaptan [
44]. Thiol acts as an antioxidant, stabilizing free radicals by accepting their unpaired electron. This means that a ripe eggplant diet, with its bioactive compounds, contains relatively more antioxidant molecules than an unripe eggplant diet [
45].
Furthermore, an increase in endogenous antioxidant enzyme activities (GSH, CAT, and SOD) was observed in the groups treated with the supplemented diet, and diabetes causes tissue injury in flies as a result of the increased production of ROS [
3]. The elevation in the activity of these enzymes might be a result of the scavenging ability of the bioactive compounds in the fruit diet, which eliminated the ROS species and exerted their effects by restoring the activity of antioxidative enzymes. SOD is an enzymatic antioxidant that defends against free radicals by converting superoxide anions to compounds with less damaging effects like hydrogen peroxide; it serves as the first-line defense mechanism against pro-oxidative injury in tissues, which is important for lifespan extension and survival of
Drosophila melanogaster [
3].
CAT is an enzyme that converts lesser damaging compounds such as peroxides and H
2O
2 to water and molecular oxygen [
46]. CAT activity was reduced in the sucrose-treated and control groups; this could also be explained by the accumulation of H
2O
2. We found that the inclusive diet increased the activities of SOD and CAT, which suggests a quick response to fight free radicals by reducing the endogenous H
2O
2 that was generated and diminishing the toxic effects it could cause [
46,
47]. GST is needed to prevent damage and serves as a defense mechanism. The ability of the
Solanum anguivi lam fruits, whether ripe or unripe, to restore the damaged antioxidant enzymes status in sucrose-induced diabetic flies cannot be overemphasized.
It is interesting that the fruit contains high levels of bioflavonoid compounds such as hesperdin, naringin, and myricetin, with high binding affinity for all the proteins of interest in this study; these compounds could serve as good inhibitors of the enzymes associated with diabetes and inflammation, although it was earlier reported that they have numerous biological properties such as anti-microbial, anti-lipidemic, anti-cancer, and antioxidant properties [
37]. Ripening increases the levels of some of these bioactive compounds, which further confirms the report of Nwanna et al. [
9] of the immerse benefit of the eggplant fruit especially, the wild species.