Open access peer-reviewed chapter

Medicinal Plants, Bioactive Compounds, and Dietary Therapies for Treating Type 1 and Type 2 Diabetes Mellitus

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Chinaza Godswill Awuchi

Submitted: December 18th, 2020 Reviewed: February 7th, 2021 Published: February 25th, 2021

DOI: 10.5772/intechopen.96470

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Medicinal plants, bioactive compounds, and dietary measures have been found to be effective in the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). About 463 million people have diabetes worldwide; estimates project 700 million people by 2045. While T1DM is caused by the loss of beta cells of pancreatic islets that produce insulin, resulting in the deficiency of insulin, T2DM, which constitutes over 90 to 95% of all DM cases, is caused by insulin resistance, and could relatively combine reduction in the secretion of insulin. Aloe vera, Terminalia chebula, Perilla frutescens, Curcuma longa, Zingiber zerumbet, Nigella sativa, Gongronema latifolium, Pachira aquatic, Caesalpinioideae, Azadirachta indica, Artemisia dracunculus, Artemisia herbaalba, Vachellia nilotica, Abelmoschus moschatus, Cinnamomum verum, Salvia officinalis, Tinospora cordifoli, Pterocarpus, Ocimum tenuiflorum, Mangifera indica, Syzygium cumini, Coccinia grandis, Caesalpinia bonduc, Gymnema sylvestre, Carthamus tinctorius, Allium sativum, and Trigonella foenum-graecum are among the medicinal plants shown to be effective in controlling and treating T1DM and T2DM. Bioactive compounds such as lycopene, vitamin E, vitamin D, genistein, quercetin, resveratrol, epigallocatechin-3-gallate, hesperidin, naringin, anthocyanin, etc. are useful in treating T1DM and T2DM.


  • medicinal plants for treating diabetes type 1 and 2
  • bioactive compounds for treating diabetes type 1 and 2
  • dietary measures for managing diabetes
  • diabetes mellitus
  • herbal therapy for diabetes

1. Introduction

Diabetes mellitus (DM), simply called diabetes, are metabolic disorders characterized by varying or persistent hyperglycemia (high levels of sugar in the blood) over an extended time period. The most common symptoms of DM usually include increased appetite, increased thirst, and frequent urination. If not treated or when poorly managed, DM can result in several complications. While acute complications of DM often include hyperosmolar hyperglycemic state, diabetic ketoacidosis, or even death, severe chronic complications include cognitive impairment, damage to the eyes, damage to the nerves, foot ulcers, chronic kidney disease, stroke, and cardiovascular disease [1]. Diabetes mellitus (DM) manifest by hyperglycemia, defects in insulin secretion, glucose intolerance, and/or failure of insulin activity to boost uptake of glucose. Diabetes mellitus (DM) causes global burden as a result of its high morbidity/mortality rates, as well as the capital intensity required for its treatment and management. About 463 million people have DM worldwide, while estimates project 700 million people by 2045 [2].

Globally, epidemiological studies showed that diabetes is more prevalent in middle- and low-income countries with about 50 percent of cases unreported and undiagnosed [2, 3]. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are the most common types of DM. Over 90 to 95% of DM cases are T2DM [2, 4], while the remain 5 to 10% are other types of DM, including T1DM, the gestational diabetes, and other minor specific types rarely encountered. Worldwide, there has been serious search for cost effective and potent drug against T1DM and T2DM in order to reduce the annual death rate [5]. Various antidiabetic therapeutics and treatments that make use of conventional medications are often laborious as they are not single-dose treatment regimen; some are taken throughout lifetime. In recent years, medicinal plants, bioactive compounds, and dietary measures have been found to be effective in the treatment of T1DM and T2DM.

The increasing awareness of the safety and efficacies of medicinal plants, dietary therapy, and bioactive compounds in treatment of various metabolic diseases is gradually reshaping treatment measures for many metabolic diseases [6, 7, 8], including DM. Medicinal plants and their bioactive constituents play important role in regulating metabolisms in humans, usually resulting in improved health and general wellbeing. They can be largely found in fruits and vegetables, medicinal plants [9, 10, 11, 12, 13, 14, 15, 16], whole grains [11], etc., and could be consumed every day. The health benefits of bioactive compounds are commonly reported in animal and cell studies, which often include regulating cell signaling pathway, scavenging free radicals, and decreasing inflammation [17, 18]. Natural materials containing bioactive compounds have been traditionally employed in the treatment of diabetes mellitus (DM). Due to their safety, availability, and tolerable side effects, bioactive compounds applications have been suggested for reducing incidences or delaying progression of many diseases, such as T1DM and T2DM, constipation, Alzheimer’s disease, etc. [19, 20]. This chapter provides detailed descriptions and efficacies of the medicinal plants, bioactive compounds, and dietary nutrients shown to be effective in treating T1DM and T2DM. Although the medicinal plants, bioactive compounds, and dietary nutrients discussed in this chapter are mainly focused on T1DM and T2DM, they could also be effective against the less common types of DM such as the gestational diabetes and other minor specific types rarely encountered.


2. Causes and complications of T1DM and T2DM

Type 1 diabetes mellitus (T1DM) is caused by the loss of beta cells of pancreatic islets that produce insulin, resulting in the deficiency of insulin. T1DM can be additionally classified as idiopathic or immune-mediated. Most T1DM has the nature of the immune mediation, where an autoimmune attack mediated by T-cell results in loss of beta cells and consequently insulin [21]. The majority of the affected individuals are otherwise mostly healthy, with healthy weight during the onset occurrence. Responsiveness and sensitivity to insulin are often normal, particularly in initial stages. Though T1DM is often referred to as “juvenile diabetes” due because of the regular onset in children, most people with T1DM are currently adults. T1DM could be accompanied by unpredictable, irregular high levels of blood sugar, and potentials for serious low levels of blood sugar or diabetic ketoacidosis. Other T1DM complications are endocrinopathies (such as Addison’s disease), gastroparesis (that results in irregular dietary carbohydrates absorption), infection, and impairment in the counterregulatory responses to low levels of blood sugar. These usually occur in 1–2% of those with T1DM [22]. T1DM is in part hereditary, with several genes, such as some HLA genotypes, having influence on T1DM risks. In those with genetic susceptibility, the onset of DM could be caused by at least environmental factors, including diet, stress, or viral infection [23]. Although many viruses have been reported, however, no reliable evidence has supported their potentials to cause DM in humans [23, 24]. Among dietary factors, it has been reported that gliadin (a gluten protein) can be a factor in the development of T1DM, although the mechanism has not been established, at least not entirely. T1DM occurs at any stage of life; significant percentage has been detected in adulthood. Latent autoimmune diabetes of adults (LADA) is a term used when T1DM occurs in adulthood, and has slower onset than T1DM in children. Due to this difference, few people make use of the unofficial term “type 1.5 diabetes” in place of T1DM in adults. Adults with latent autoimmune diabetes of adults are often misdiagnosed as having T2DM initially, due to age instead of cause [25].

On the other hand, type 2 diabetes mellitus (T2DM), which constitutes over 90 to 95% of all DM cases, is caused by insulin resistance, and could combine relative reduction in the secretion of insulin. The defects in body tissues response to insulin is considered to be related the insulin receptors. Cases of DM with known defects are categorized separately. Many individuals with T2DM present clinical prediabetes evidence (such as impaired glucose tolerance and/or impaired fasting glucose) prior to developing T2DM [26]. Prediabetes progression to overt T2DM could be reversed or slowed by lifestyle medications/changes, which enhance sensitivity to insulin or decrease the production of glucose in the liver [27]. T2DM is mostly because of lifestyle and environmental factors, as well as genetics [28]. Some lifestyle factors result in T2DM development, such as obesity (body mass index ≥30), urbanization, stress, poor diet, and lack of physical activities. Dietary factors, including sugar-sweetened drinks, have been correlated with increased risks of T2DM. Fat types in the food are also significant; trans fats and saturated fat increase the risks, while monounsaturated and polyunsaturated fat reduce the risks [28]. Excessive consumption of carbohydrates dense foods such as white rice may increase risks of DM [29]. Lack or insufficient physical activities can increase risks of DM in some individuals. Adverse childhood experiences (ACEs), such as neglect, abuse, and household challenges, increase possibility of T2DM by 32% later in life, with neglect reported to have the most significant effects [30].


3. Medicinal plants for T1DM and T2DM treatment

Several medicinal plants have been shown to be effective in treating and managing DM. Aloe vera, Terminalia chebula, Perilla frutescens, Symplocos, Symphytum, Cactaceae, Zingiber zerumbet, Chrysanthemum morifolium, Tinospora cordifolia (guduchi), Nigella sativa, Gongronema latifolium, Pachira aquatic, Caesalpinioideae, Azadirachta indica, Artemisia dracunculus, Artemisia herbaalba, Andrographis paniculata L, Asphodelaceae, Mentha, Fabaceae, Achyranthes, Vachellia nilotica, Abelmoschus moschatus, Cinnamomum verum, Panax, Salvia officinalis, Tinospora cordifoli, Pterocarpus, Ocimum tenuiflorum, Momordica charantia, Mangifera indica, Syzygium cumini, Coccinia grandis, Caesalpinia bonduc, Liriope, Sarcopoterium, Swertia, Combretum, Gymnema sylvestre, Bauhinia, Ferula assafoetida, Carthamus tinctorius, Allium sativum,and Trigonella foenum-graecumare among the medicinal plants shown to be effective in controlling and treating T1DM and T2DM [31]. Table 1 shows the list of plants known to be effective in treating T1DM and T2DM.

Scientific name of plantCommon nameParts usedEffectiveness and mechanisms against T1DM and T2DMType of studyReference
Allium sativumGarlicBulbAntihyperlipidemic and antihyperglycemic effects. Lowers FBG, improves glycemic control via increased secretion of insulin and improved sensitivity to insulinIn vivo[32]
Aloe veraAloe veraLeavesPrevents changes in insulin levels. Diabetic kidney shows distinctive changes resulting in kidney failure or renal insufficiency. Major alteration was mostly reported in kidney tissue proximal tubules in diabetic animal modelsIn vitro[33]
Bauhinia forficateBrazilian orchid treeLeavesAfter treatment for 31 days using decoction, in T2DM group, urinary glucose and plasma glucose levels reduced significantlyIn vitro[31]
Gray NickerSeedsThe 50% ethanolic and aqueous extracts of seeds of Caesalpinia
bonducellahad hypolipidemic and antihyperglycemic activities in streptozotocin-induced diabetic rats. Both ethanolic and aqueous extracts indicated potent hypoglycemic properties in chronic T2DM rats. The antihyperglycemic properties of the seed extracts could be because of the glucose absorption blockage
In vitro[31]
Carthamus tinctoriusSafflowerFlowerThe hydroalcoholic extracts from flower of Carthamus tinctoriuscan treat T1DM and T2DM. The flower of Carthamus tinctoriusis rich in flavonoids, including kaempferol and quercetin, with hypoglycemic and antioxidant effectsIn vivo[34]
Cinnamomum verumCinnamonWhole plantCinnamomum verumin diet reduces risks of cardiovascular diseases and DM. Cinnamomum verumreduced HbA1C (hemoglobin A1c) by 0.83% in comparison to the usual care alone, which reduced hemoglobin A1c by 0.37% in T2DM patients in a controlled, randomized trialIn vivo[32]
Combretum MicranthumKinkeliba,
LeavesHypoglycemic properties of Combretum Micranthumextracts were studied using fasting blood sugar and glucose tolerance in healthy rats. The aqueous extracts from leaf of Combretum Micranthumhas antidiabetic properties against T1DM and T2DMIn vitro[31, 35]
Ferula asafoetidaAsafoetidaGumWith the presence of antioxidants, gum of Ferula assafoetidadecrease the free radical levels in cells, and stimulates insulin secretion and synthesis in T2DM, and residual pancreatic cells hyperplasia and reduction of glucose level in bloodIn vivo[35]
GinsengGinsengRoot, berries, stalk, leavesGinseng significantly reduced fasting blood glucose (FBG) and insulin resistance in patients with T2DM. Amongst 30 T2DM patients treated using Renshen tangtai (injection containing Ginseng polysaccharides and polypeptide), 86.7% presented significant effects on symptoms of T1DM and T2DMIn vivo and in vitro[31, 32]
Gymnema sylvestreCowplantLeafThe crude extracts of Gymnema sylvestreand dihydroxy gymnemic triacetate (a compound obtained from Gymnema sylvestre) have hypoglycemic effects in streptozotocin-induced diabetic rats in time- and dose-dependent mannersIn vitro[35]
Liriope spicataMonkey grassLeavesAqueous extracts of Liriope spicataresulted in significant reduction in levels of fasting blood sugar and significantly improved glucose tolerance and insulin in streptozotocin-induced diabetic mice.In vitro[35]
Mangifera indicaMangoLeavesExtracts of mango leaves have hypoglycemic properties, possibly because of decrease in intestinal glucose absorptionIn vitro[31]
Momordica charantiaBitter melonFruitMomordica charantiareduced postprandial and fasting serum levels of glucose in patients with T2DM. Bitter melon showed antihyperglycemic effects by increasing the expression of glucose transporter type 4 (GLUT4), activating AMPK, inhibiting protein tyrosine phosphatase 1B (PTP1B), promoting beta cells recovery and insulin-mimicking actionIn vivo[32]
Sarcopoterium spinosumS. spinosumRootSarcopoterium spinosumroot aqueous extracts induce antidiabetic effects on progressive hyperglycemia in mice with T1DM and T2DM. Aqueous root extracts of Sarcopoterium spinosumhas insulin-like action in target tissuesIn vitro[35]
Swertia puniceaSwertiaWhole plantMechanism Swertia puniceahypoglycemic effects has been established by ameliorating insulin resistance in mice with T1DM and T2DMIn vitro[35]
Trigonella foenum graecumFenugreekSeedPowdered fenugreek (15 g) administered to T2DM patients decreased Darqndkhvn senseIn vivo[36]
Urtica dioicaStinging nettleLeavesUrtica dioicaleaves’ aqueous extracts enhanced glycemia levels in rats with T2DM, and is mediated by essential effects on the pancreatic beta-cells functional statusIn vivo[37]
Zingiber zerumbetBitter gingerRootEthanol extracts of bitter ginger rhizome were administered to streptozotocin-induced diabetic rats. After 3 months of diabetic conditions, weight gain in streptozotocin-induced diabetic rats was significantly less in comparison with healthy rats, while the glucose levels in the blood were significantly higher. Body weight reduction was unnoticeable in streptozotocin-induced diabetic rats receiving ethanol extracts of bitter ginger rhizome during study periodIn vitro[38]

Table 1.

Medicinal plants effective against T1DM and T2DM.


4. Bioactive compounds and dietary nutrients with effectiveness against T1DM and T2DM

Many dietary nutrients and bioactive compounds have effectiveness in the treatment of T1DM and T2DM. This section discusses the most common bioactive compounds and dietary nutrients for treating DM, with more focus on type 1 and type 2 DM. Figure 1 shows the complex mechanisms of cell signaling targeted by T1DM and T2DM therapeutic strategies and bioactive compounds of plants.

Figure 1.

Few complex mechanisms of cell signaling targeted by T1DM and T2DM therapeutic strategies and bioactive compounds of plants.

4.1 Vitamins

Vitamins are bioactive organic compounds which are essential micronutrients organisms required in small quantities, usually within micrograms to milligrams, for the proper functioning of body metabolisms [39]. Here are some vitamins for treating T1DM and T2DM.

4.1.1 Vitamin A for T1DM and T2DM treatment

Vitamin A has been known to be important in treating DM. it is a group of unsaturated organic compounds essential to organisms, e.g. retinol, retinal, as well as many provitamin A carotenoids [39]. Retinol (or Vitamin A) is essential nutrient required for vision, normal growth, and reproduction. Retinoic acid (RA) is a metabolite of vitamin A with physiological importance. Retinol is converted intracellularly to 9-cis-retinoic acid or retinal all-trans-RA [40]. Mechanisms by which vitamin A influence T1DM and T2DM include adipose and obese biology regulation, increasing insulin sensitivity, βcells regeneration, and oxide radicals’ chelation [40]. It has been reported that all-trans-retinoic acid may enhance insulin signaling through preventing the activity of protein kinase C (PKC) by binding to isozymes of PKC [40]. Protein kinase C was reportedly high in DM and blocked insulin signaling [40]. Retinoic acid increases secretion of insulin and levels of insulin mRNA in cultured islets, through raising pancreatic glucokinase by the glucokinase promoter activation. Retinol and retinoic acid are uncoupling protein 1 (UCP-1) positive regulators, and the UCP-1 overexpression may enhance insulin resistance and glucose transport of skeletal muscle [41]. For diabetic patients that have altered retinoid biology, vitamin A could not be effective intervention; it has been reported that insulin treatment may reverse retinoid metabolic availability. Also, intakes of vitamin A in large doses interfere with bone metabolisms and have been associated with osteoporosis [40]. Berry and Noy [42] showed that all-trans-RA has suppressive effects on insulin resistance and obesity through inducing retinoid acid receptor (RAR) gene expression and PPARβ/δgene expression. In 2018, a study carried out by [43] reported that rats with vitamin A deficiency that were fed with diets had decreased monounsaturated fatty acid and stearoyl-CoA desaturase 1 (SCD1) levels, which alter function and structure of pancreas and increase ER stress-induced apoptosis.

4.1.2 Vitamin E for T1DM and T2DM treatment

Vitamin E is a significant constituent of antioxidant systems in every body tissue. α-tocopherol is most active type of vitamin E. Vitamin E is a group of about 8 fat soluble vitamins which four tocotrienols and four tocopherols. Vitamin E, because of its antioxidant activity, is believed to be promising therapeutic alternative T1DM and T2DM. Supplementation with vitamin E has been reported to ameliorate mouse hyperglycemia through improving secretion of insulin from alloxan-treated islet [44]. In vivo, rats with streptozotocin-induced DM were shown to present significant decrease in glucose level and improved antioxidant enzymes activities, including glutathione reductase, glutathione peroxidase, and catalase, after vitamin E supplementation. However, results obtained from human studies have been inconsistent. Vitamin E only showed effectiveness in patients that have insufficient glycemic control baseline or low-serum concentrations of vitamin E [45]. Vitamin E plays significant role in the treatment of T1DM and T2DM.

4.1.3 Vitamin D for T1DM and T2DM treatment

The most important forms of Vitamin Ds in humans are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D is a group of fat soluble secosteroids responsible for various biological functions, including intestinal absorption of calcium, phosphate, magnesium, and other biological functions. Vitamin D3 is obtained from diets and also synthetically made in skin from 7-dehydrocholesterol when exposed to radiation of solar UVB. It is converted in the kidney to the active vitamin D, 1,25-(OH)2 VD3 [46]. Vitamin Ds are mediated by vitamin D receptor (VDR), their nuclear receptor. Vitamin D plays significant roles in modulating T1DM and T2DM risks through having influence on inflammation, insulin sensitivity, and β-cell function [47]. Vitamin D can promote the survival of β-cell through modulating the activity and generation of cytokines via downregulation of Fas or NF-κB-related pathways. Currently, one study reported that vitamin D has increasing effects on insulin secretion stimulated by glucose through improving influx of calcium through upregulating the expression of “R-type voltage-gated calcium channel” (VGCC) genes in human and mouse islets. Treating STZ-induced diabetic rat using diet with vitamin D supplementation increased levels of insulin, decreased fasting blood glucose levels, as well as restored pancreatic islets injured by streptozotocin [48]. Meerza et al. [49] showed that treating 1,25-(OH)2 VD3 has significant changing effects on the concentrations of blood glucose and calcium, and glucose metabolic enzymes activities, such as fructose 1,6-bisphosphatase (FBPase), hexokinase, and glucose-6-phosphatase (G6Pase) in mice with induced DM. Vitamin D can have effect on insulin sensitivity in peripheral insulin-target cell through stimulating insulin receptor expression via VDR interaction or by other channels [50]. Calcium plays crucial role for any insulin-mediated intracellular process, and the extracellular and intracellular concentrations of calcium are, to a large extent, regulated by vitamin D to influence sensitivity of insulin [51].

4.2 Lycopene

Lycopene, a natural occurring carotenoid, is commonly found in tomatoes, pink grapefruit, etc.; it gives the red color. Several in vivo examinations indicated the health benefits of lycopene on T1DM and T2DM, and its accompanying complications [52, 53]. The antioxidant and anti-inflammatory properties of lycopene may be connected with its antidiabetic functions. Ali and Agha [54] carried out study with diabetic rats where lycopene supplementation resulted in a dose-dependent reduction of hydrogen peroxide (H2O2), lipid peroxidation, and NO, and also increased antioxidant enzymes activities, which led to decreased levels of glucose, increased levels of insulin, and enhanced profiles of serum lipids. Lycopene antioxidant properties have also indicated to solve diabetic endothelial dysfunctions in rats with induced diabetes [52]. Lycopene was evaluated for its capability to reduce cognitive decline associated with T2DM. Kuhad [55] showed dose-dependent responses to chronic treatments using lycopene, which eased cognitive impairments, decreased TNF-αand NO, alleviated cholinergic dysfunctions, and increased activity of acetylcholinesterase in rats on streptozotocin-induced diabetes. Endothelial progenitor cells (EPCs) dysfunctions are implicated in vascular complications associated with diabetes [56]. Zeng et al. [57] reported that lycopene improved AGE-induced oxidative autophagy and endothelial progenitor cells apoptosis, thereby damaging EPCs functions and number. Based on the knowledge about lycopene and T2DM, it is clear that lycopene could have promising potentials for improving T2DM vascular complications. Li et al. [53] carried out a study on rats with streptozotocin- (STZ) induced diabetes for studying lycopene specific therapeutic effects on diabetic nephropathy. They reported that lycopene has protective effects on kidney against DM-induced morphological destructions as well as impairments of functions through regulating growth factor of connective tissue, increasing protein kinase B (Akt) phosphorylation, and improving oxidative status. A different study showed that lycopene ameliorates renal functions through interruption of the Advanced glycation end products (AGE)-receptor for advanced glycation end-products (RAGE) (AGE-RAGE) axis [58].

Table 2 shows bioactive compounds, dietary nutrients, and their sources for T1DM and T2DM treatment.

Plants and sources of the compoundsBioactive CompoundPhytochemical classT1DM and T2DM propertiesReferences
Asparagus, buckwheat, figs, apples, etc.RutinPolyphenol (flavonoid)Rutin reduced levels of blood glucose in insulin-resistant mouse by improving GLUT4 translocation and activities of insulin-dependent receptor kinase[59]
Vitamin D3 (Cholecalciferol) is obtained from diets (fatty fishes, cooked egg yolk, liver, fungi) or synthetically made in skin when exposed to solar UVB.Vitamin DVitaminTreating streptozotocin-induced diabetic rat using diet with vitamin D supplements decreased fasting blood glucose levels, increased levels of insulin, as well as restored pancreatic islets injured by STZ[48]
Citrus fruits, such as lemons, oranges, etc., and few plantsHesperidinPolyphenol (flavonoid glycoside)It has protective effects in diabetic nephropathy, often through inhibiting transforming growth factor-β1- (TGF-β1-) integrin-linked kinase- (ILK-) Akt signalling[60, 61]
Cod liver oil, carrots, broccoli leaf, liver (fish, pork, beef), sweet potato, spinach, etc.Vitamin A, including provitamin A compoundsVitaminIncreases levels of insulin mRNA and secretion of insulin in cultured islets, through raising pancreatic glucokinase by activating glucokinase promoter. Retinol and retinoic acid are uncoupling protein 1 (UCP-1) positive regulators; UCP-1 overexpression could enhance insulin resistance and glucose transport[41]
Fruits, flowers, vegetables, etc.AnthocyaninPolyphenol (flavonoid)In STZ-induced diabetic rats, pelargonidin (an anthocyanin) injection improved glucose tolerance, normalized elevated levels of blood glucose, and improved serum insulin level[62]
Grapefruit, pumelo, tomatoes, grapefruit juices, etc.NaringinPolyphenol (flavonoid)Naringin protects cells against high glucose-induced destruction. Naringin inhibits high inflammatory reaction induced by glucose through mediating oligomerization and nucleotide-binding domain-related receptors family of inflammasome of pyrin domain-containing 3 in mesangial cells of rat[63]
Grapefruit, oranges, lemon, tomatoes, etc.NaringeninPolyphenol (flavonoid)Naringenin ameliorated structural changes and renal damages, including glomerulosclerosis in STZ-induced diabetic rats, possibly via downregulating IL-1 and TGF-β1 through decreasing oxidative stress, modulating production of proinflammatory cytokines and apoptotic events[64]
Green tea, black tea, white tea, onions, apple skin, plums, etc.Epigallocatechin gallatePolyphenol
Epigallocatechin gallate supplementations have influence on expression of the genes involved in metabolism of lipid and glucose in liver, such as through increasing glucose kinase by mRNA expression and reducing mRNA expressions of G6Pase, fatty acid synthases, as well as PEPCK[65]
Turmeric plant (Curcuma longa)CurcuminPolyphenolCurcumin oral administration reduced blood glucose levels, increased levels of plasma insulin, and reduced body weight[66]
Red onions, apples, tea, broccoli, etc.QuercetinPolyphenol (flavonoid)Quercetin increased glucose uptakes in cultured skeletal muscle cell by stimulating GLUT4 translocation through 5’ AMP-activated protein kinase activation. Quercetin has activities on homeostasis of glucose in skeletal muscle and liver.[67]
Red wines, grape skins, seeds, groundnut skins, etc.ResveratrolPolyphenolIn insulin-secreting cell, treatment with resveratrol improved mitochondrial activity, improved insulin secretion stimulated by glucose, and enhanced glucose metabolism.[68]
Soybeans, fava beans, chickpeas, etc.GenisteinPolyphenol (isoflavone)Supplementation with genistein alleviated hyperglycemia induced by streptozotocin and improved insulin levels and glucose tolerance[69]
Tomatoes, pink grapefruit, etc.LycopeneCarotenoidLycopene antioxidant activities have demonstrated to solve diabetic endothelial dysfunctions in diabetic rats[52]
Wheat germ oil, sunflower oil, rapeseed/canola oil, almonds, g hazelnut oil, etc.Vitamin EVitaminAfter vitamin E supplementation, rats with streptozotocin-induced DM, in vivo, were shown to present significant reduction in glucose level and improved antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase.[44]

Table 2.

Medicinal plants, bioactive compounds, nutrients with effectiveness against T1DM and T2DM.

4.3 Polyphenolic compounds and their properties against T1DM and T2DM

Several polyphenols have been directly linked to treatment of T1DM and T2DM, including resveratrol, epigallocatechin-3-gallate (EGCG), quercetin, genistein, hesperidin, naringin, anthocyanins, curcumin, rutin, naringenin, etc.

4.3.1 Resveratrol properties against T1DM and T2DM

This polyphenol occurs naturally in red wines, seeds, grape skins, and groundnut (peanut) skins. In insulin-secreting cell, treatment with resveratrol improved insulin secretion stimulated by glucose, improved mitochondrial activity, and enhanced glucose metabolism [68]. The effects depend on active Sirtuin 1-induced key genes upregulation for β-cell functions [68]. Resveratrol exhibits anti-inflammatory and antioxidant properties, and also maintains metal homeostasis and increases mitochondrial function [70]. Resveratrol lower production of hepatic glucose, improve insulin sensitivity, and normalize hyperglycemia through Sirtuin 1 activation [71]. A study done recently suggest that T2DM was improved by resveratrol through the regulation of lipid metabolism, mitochondrial biogenesis, and βcells via SIRT1 activation [72]. Animal and cell studies suggest that resveratrol could have potentials in T1DM and T2DM treatment [73]. A NAD + -dependent deacetylase known as Sirtuin 1 (SIRT1) is known to be involved in regulating several factors which affect T2DM; resveratrol has been shown to be SIRT1 activator [71].

4.3.2 Epigallocatechin-3-Gallate (EGCG) properties against T1DM and T2DM

Epigallocatechin-3-gallate, a polyphenol, is obtained from numerous plants, especially green teas, black tea, white tea, and apple skin. Studies have been done on green tea health benefits, with the benefits associated with epigallocatechin-3-gallate, which is most abundant constituent. EGCG has strong antioxidant activities. Han [74] reported that epigallocatechin-3-gallate protected cells of RINn5F against β-cell damage caused by cytokines. The molecular mechanisms may include suppressing expression of iNOS via the inhibition of the activation of NF-κB. Consequently, epigallocatechin-3-gallate can improve pancreatic functions. Cytokines made by immune cell might cause damage of β-cell in insulin-dependent DM, and have been attributed to NO and iNOS generation in the cells. EGCG antioxidant effects are contentious; some evidence suggested that EGCG is prooxidant [75]. A typical example is the report of the work done by [75] showed that EGCG mediated the H2O2 production and triggered the formation of Fe2 + −dependent toxic radicals, which caused cell apoptosis and reduced the viability of cell in pancreatic βcells of HIT-T15.

4.3.3 Quercetin properties against T1DM and T2DM

Quercetin is a flavonoid which occurs naturally in many foods such as red onions, tea, apples, etc. A study indicated that treatment with quercetin enhanced lipid and glucose metabolism, as well as eased hepatic histomorphological damage in rats with STZ-induced DM, which possibly connected to the SIRT1 activity upregulation by quercetin and its impacts on Akt signaling pathways [76]. Vascular complications have been associated with most mortality and morbidity in T1DM and T2DM patients [77]. Youl et al. [78] carried out research and reported that quercetin improved secretion of glucose-induced insulin and protected β-cell viability/function from hydrogen peroxide-induced oxidative damages in cells of INS-1. The effects are mediated by extracellular signal regulated kinase (ERK1/2) phosphorylation, which suggest that activation of extracellular signal regulated kinase take part in quercetin action [78]. Quercetin has antiapoptotic, anti-inflammatory, and antioxidant effects, and has been shown to have potentials for diabetes treatment, as well as its health complications [67, 76, 77]. Quercetin also has influence on homeostasis of glucose in skeletal muscle and liver; quercetin increased glucose uptakes in cultured skeletal muscle cell by stimulating GLUT4 translocation through 5’ AMP-activated protein kinase (AMPK) activation [67]. In the same way, quercetin in hepatocytes activated 5’ AMP-activated protein kinase, and was associated with glucose-6-phosphatase suppression, finally reducing the production of hepatic glucose [67].

4.3.4 Genistein properties against T1DM and T2DM

Genistein, a naturally occurring compound, structurally belongs to a group of compounds known as isoflavone. Genistein is found in many plants such as soybeans, chickpeas, etc. [79]. Evidence support genistein as a therapeutic potential and preventive treatment for T1DM and T2DM [69, 80, 81]. Genistein dietary supplementation enhanced mass of β-cell through reducing apoptosis and increasing the proliferation of β-cell [69]. The genistein supplementation alleviated hyperglycemia induced by streptozotocin (STZ) and improved insulin levels and glucose tolerance [69]. Recently, [82] showed that genistein decreased fasting glucose levels, prevented cytosolic phosphoenolpyruvate carboxy kinase (PEPCK), and activated ERK1/2 and AMPK pathways in mice with alloxan-induced diabetes, which could, as a result, improve dysfunctions in T1DM and T2DM associated hepatic gluconeogenesis. Mass loss in functional β-cell, which reduces secretion of insulin, is important for T2DM development. The βcells mass is regulated by balance between apoptosis, proliferation, transdifferentiation, and neogenesis [80]. Ae Park et al. [81] studied genistein antidiabetic effects on C57BL/KsJ-db/db mice that share human-like T2DM metabolic features. HbA1c and blood glucose were reported to be significantly lower in groups of genistein, whilst glucagon-insulin ratio and glucose tolerance were also enhanced in the group of genistein in comparison with control group [81]. Also, the supplements of genistein improved the total cholesterol, free fatty acid, HDL-cholesterol, and plasma triglyceride levels in the mice. The effects could be due to increased activities of hepatic glucokinase, and also due to the decreased activities of G6Pase, β-oxidation, and hepatic fatty acid synthase [81]. Consequently, genistein could have antidiabetic effects against T1DM and T2DM through improving the metabolism of glucose and lipid. Fu et al. [69] showed that incubation of genistein induced increase in the proliferation of human islet β-cell and INS-1 through activating cAMP/PKA-dependent extracellular signal regulated kinase (ERK1/2) signaling pathway. Studies involving animal models showed that genistein has antidiabetic effects; particularly, [69] showed that STZ-induced diabetes reduced mass of β-cell and caused cell architecture disruption.

4.3.5 Hesperidin properties against T1DM and T2DM

Hesperidin, a flavonoid glycoside, is commonly found in citrus fruits, e.g. lemons and oranges, in rich quantity. Hesperidin oral administration significantly decreased HbA1c and glucose levels and raised serum insulin, vitamin E, and vitamin C levels in rats with HFD/STZ-induced diabetes [83]. The effects were most likely as a result of decline in producing oxidants and proinflammatory cytokines, including IL-6 and TNF-α[83]. In vivo and in vitro studies showed that hesperidin helps in T2DM treatment and prevention, and complications associated with T1DM and T2DM, via its antidepressant, anti-inflammatory, and antioxidant properties [61, 83, 84]. In pancreatic islet cells of rat, hesperidin has been reported to protect against IL-1β-induced oxidative stress, thus improving islet cells function and restoring insulin secretion and biosynthesis [84]. Hesperidin treatment in rats with STZ-induced diabetes attenuated plasma and retina abnormalities, such as increased breakdown of blood retina and decreased retina thickness, through its anti-inflammatory and antioxidant properties, and the inhibition of AGEs production and high aldose reductase [85]. Hesperidin treatment in rats on high fat diet (HFD)/STZ-induced diabetes decreased hyperglycemia through increasing the uptake of peripheral glucose, which may be attributed to GLUT4 mRNA expression upregulation [84].

4.3.6 Naringin properties against T1DM and T2DM

Naringin, also a flavonoid, is commonly seen in some grapefruits and citrus species. It is known for its antihyperglycemic, antioxidant, and anti-inflammatory properties [86]. Numerous studies recently conducted demonstrated that naringin may improve T1DM and T2DM and ameliorate the severity of their associated health complications; their mechanism is understood [63, 86]. In vitro studies showed that naringin protects cells against high glucose-induced destruction. A typical example is the work done by [63], which showed that naringin inhibits high inflammatory reaction induced by glucose through mediating the oligomerization and nucleotide-binding domain-related receptors family of inflammasome of pyrin domain-containing 3 (NLRP3) in mesangial cells of rat. Sharma et al. [87] showed that naringin ameliorated kidney damage and hepatic steatosis, and attenuated β-cell dysfunction and insulin resistance through reducing inflammation and oxidative stress by upregulating PPARγ, heat shock protein-72, as well as heat shock protein-27. Li et al. [88] showed that naringin can protect the endothelial cells of humans against high damage induced by glucose through improving mitochondrial function, downregulating chemokine (C-X3-C motif) ligand 1 (CX3CL1), and inhibiting oxidation. In addition, many studies have showed naringin beneficial effects on complications of diabetes such as diabetes-associated anemia, atherosclerosis, cognitive decline, and kidney damage [89, 90]. Mahmoud [89] showed that naringin protected rats with HFD/STZ diabetes from diabetes-induced anemia through stimulation of adiponectin expression and reducing the production of proinflammatory cytokine. In rats with NA/STZ-induced DM, naringin significantly ameliorated the serum glucose levels and profile of the lipid, including low density lipoprotein cholesterol (LDL), and free fatty acids (FFAs) [86]. The effects could be potentiated through elevation in glycogen phosphorylase and liver G6Pase activities, enhancing response to insulin secretion, and improving GLUT4 expression, adiponectin, and insulin receptor, in addition to reducing oxidative stress [86].

4.3.7 Anthocyanins properties against T1DM and T2DM

Anthocyanins (ANTs) are flavonoids mostly responsible for purple, blue, and red colors of fruits, flowers, and vegetables [91]. Most anthocyanins have strong antioxidant properties which may play role in their antidiabetic activities against T1DM and T2DM. In rats with STZ-induced diabetes, pelargonidin (an anthocyanin) injection improved serum insulin level, improved glucose tolerance, and normalized elevated levels of blood glucose [62]. Yan et al. [92] reported that anthocyanins pre-treatment attenuated β-cell autophagy mediated by H2O2 through antioxidant transcription factor Nrf2 activation. In cells of HepG2, mulberry anthocyanins extracts were reportedly found to alleviate insulin resistance through PI3K/Akt pathways activation [93]. Zhang et al. [94] indicated that anthocyanins from extracts of Chinese bayberry upregulated expression of HO-1 through activating ERK1/2 and PI3K/Akt signaling in cells of INS-1. Consequently, anthocyanins protected the cells against β-cell injury induced by H2O2.

4.3.8 Curcumin properties against T1DM and T2DM

Curcumin, a polyphenol, is extracted from dried root of turmeric plant (Curcuma longa). Curcumin has numerous pharmacological activities in which anti-inflammatory and antioxidant properties are most notable properties [95]. The main factors in T1DM- and T2DM-related hepatic fibrogenesis are hepatic stellate cells (HSCs) [96]; in HSCs, AGEs induce gene expression of RAGE that may stimulate HSCs activation [96]. Lin et al. [95] showed that curcumin inhibited AGE stimulation possibly through increasing PPARγgene expression which ameliorated RAGE expression, and eased oxidative stress. A study showed that curcumin oral treatment increased levels of plasma insulin, reduced blood glucose levels, and reduced body weight [63]. Study indicated that curcumin ameliorated glucose/lipid metabolic disorder and enhanced insulin resistance in diabetic rats; the effects may be attributed to the decrease in the TNF-αand free fatty acid in serum [97]. Curcumin has significant effects against T1DM and T2DM. Through scavenging free radicals, curcumin protects pancreatic islet against oxidative stress induced by streptozotocin. Curcumin increased insulin secretion, increased islet viability, reduced concentration of ROS, reduced NO generation, and inhibited poly ADP-ribose polymerase-1 overactivation. Oral curcumin in db/db mice alleviated hyperglycemia-induced kidney/liver damage via mitochondrial function normalization, by suppressing lipid peroxidation and NO synthesis [98].

4.3.9 Rutin properties against T1DM and T2DM

Rutin is a flavonoid commonly found in several fruits and vegetables, including asparagus, buckwheat, figs, and apples. Rutin is known to have many biological properties such as antioxidant, neuroprotective, antihyperglycemic, and anti-inflammatory properties [99], and all support its potential applications in the prevention and treatment of T1DM and T2DM and their associated health complications. Rutin reduced glycogen phosphorylase and G6Pase activities and increased hepatic hexokinase activities [47]. To this effect, rutin might decrease output of hepatic glucose. In rats with nicotinamide-STZ-induced diabetes, rutin administration decreased serum glucose levels, ameliorated glucose tolerance significantly, ameliorated oxidative stress, and also improved serum lipid variables, including serum total lipids, triglycerides, VLDL-cholesterol, and LDL-cholesterol. Rutin antihyperglycemic effects could be accomplished through increasing the uptake of glucose by peripheral tissue, stimulating secretion of insulin, suppressing gluconeogenesis in liver, and improving insulin resistance. Hsu et al. [59] showed that rutin decreased levels of blood glucose in insulin-resistant mouse by improving GLUT4 translocation and activities of IRK (insulin-dependent receptor kinase).

4.3.10 Naringenin properties against T1DM and T2DM

Naringenin, another flavonoid, naturally occur in citrus fruits, including oranges, tomatoes, grapefruits, and lemons [100]. Due to its beneficial effects in treating T1DM and T2DM and their associated health complications, naringenin has recently gained more attention. Several studies have evaluated naringenin role in complications associated with T1DM and T2DM, including vascular disease, neuropathy, hepatotoxicity, cardiac hypertrophy, and nephropathy [101, 102]. Kapoor and Kakkar [101] showed that increased apoptotic proteins expression, mitochondria dysfunction, increased ROS generation, altered antioxidant status, and altered activities of kidney and liver enzymes; may induce diabetic hepatopathy and liver damage in rats with T2DM; all the effects were completely rescued after treatment with naringenin. Consequently, naringenin has promising potentials for diabetic hepatopathy treatment. Naringenin functioned as cholinesterase inhibitor and as antioxidant, ameliorating diabetes-induced dysfunctions in memory of rats [103]. Roy et al. [64] reported that naringenin ameliorated renal damage and structural changes, including glomerulosclerosis in rats with STZ-induced diabetes, likely via downregulating IL-1 and TGF-β1 through decreasing oxidative stress, modulating the production of proinflammatory cytokines and apoptotic events. They reported that naringenin ameliorated endothelial dysfunctions induced by glucose through reducing apoptosis and oxidative stress through NO and ROS/caspase-3 pathways in endothelial cell [64, 102]. In rats with STZ-induced diabetes, naringenin oral administration improved VLDL concentrations, normalized LDL, and reduced blood glucose levels, as well normalized oxidative stress in pancreas and liver; the effects have been associated with increased mRNA expression and increased protein levels of PPARγand GLUT4 by naringenin [104].


5. Epigenetic modification actions of bioactive compounds and dietary nutrients in T1DM and T2DM

Epigenetic modification is heritable and persistent changes in DNA which regulate how the expression of genes are done, with no effects on the sequence of the nucleotide itself. Epigenetic modification includes DNA methylation, microRNA regulation, and histone modification. It has been generally acknowledged that epigenetic and genetic factors predispose to T1DM and T2DM. The main genes which regulate the differentiation of β-cell, including GLP1 receptor, PDX1, and PAX4, are epigenetically regulated. To prevent or alleviate symptoms of hyperglycemia, preventive strategies using nonpharmacological measures have been employed. Weight loss, regular exercise, and healthy diet can help manage glucose serum level and also enhance normal metabolism of glucose. Pancreatic islets can be transplanted [105]. Epigenetic modification encourages insulin resistance via having pro-inflammatory effects on numerous biological factors, such as osteopontin, NF-kB, and Toll-like receptors [106, 107]. Some of the bioactive compounds and dietary nutrients associated with the epigenetic modification in T1DM and T2DM are shown in Table 3.

Plants and natural sources of the compoundsBioactive compoundPhytochemical groupEpigenetic modification effectReference
Apples, black tea, grapes, blackberries, etc.Epigallocatechin gallatePolyphenol (flavonoids)Chromatin remodelling, histone acetylation, DNA methylation[108, 109]
Broccoli, cabbages, Brussels sprouts, etc.SulforaphaneIsothiocyanateDNA methylation[110]
Cod liver oil, liver, carrots, broccoli leaf, sweet potato, spinach, etc.Vitamin AVitaminChanges chromatin structure[111]
Fatty fishes, liver, fungi, cooked egg yolk. Synthetically made in skin when exposed to solar UVBVitamin DVitaminChanges chromatin structure[112]
Grapes, chocolate, grape skins, red wines, seeds, peanut skins, etc.ResveratrolPolyphenolmiRNA levels modifications, chromatin remodelling, histone modifications[113]
Turmeric plant (Curcuma longa)CurcuminPolyphenolmiRNA levels modifications, chromatin remodelling, histone modifications[114]
Red onions, broccoli, apples, tea, etcQuercetinPolyphenol (flavonoid)Histone modifications[67]
Rice, fat fraction of bran, rice bran oil, etc.ϒ-oryzanolLipidDNA methylation[115]
Soybeans, chickpeas, beans, fava, etc.GenisteinPolyphenol (isoflavone)Histone modifications, DNA methylation[116]
Soybeans, chickpeas, fava, etc.GenisteinPolyphenol (isoflavone)DNA methylation[116]
Tomatoes, pink grapefruit, etc.LycopeneCarotenoidDNA methylation[117]

Table 3.

Medicinal plants, nutrients, and bioactive compounds in epigenetic modification in T1DM and T2DM.

Bioactive compounds, including EGCG, resveratrol, curcumin, sulforaphane, lycopene, etc., have been reported to modify epigenetic mechanisms, which could result in increased cells sensitivity to conventional agents [118]. Quercetin is a bioactive compound in buckwheat and citrus fruits. The bioactive compound functions as DNMT1 inhibitor through repressing TNF-induced NFkappa transcription factor and also encourages Fas ligand associated apoptosis through histone H3 acetylation, in addition to potential inhibition of HDAC [119]. Quercetin has been reported to take part in glucose uptake stimulation via MAPK insulin-dependent mechanisms. This is achieved in muscles through translocating GLUT4 transporters and in the liver through downregulating key enzymes of gluconeogenesis [67]. Resveratrol is a polyphenol which naturally occurs in grapes, chocolate, etc. Resveratrol activates a NAD-dependent HDAC, called sirtuin 1 (SIRT1); administration of SIRT1 to animals with insulin resistance regulates insulin sensitivity and improves glucose homeostasis [113]. Curcumin inhibits DNMTs, HDACs, and HATs. It inhibits or activates many miRNAs [120]. Epigallocatechin gallate (EGCG), an abundant catechin in green tea, is known to affect T1DM and T2DM. Epigenetic action mechanism of EGCG involves DNA methylation, histone acetylation, and deacetylation. Epigallocatechin gallate upregulates activities of anti-inflammation of regulatory T cell [108]. Genistein, a polyphenol obtained from soybean, induces active histone modifications and reverses hypermethylation [121]. Genistein appears to modulate on T1DM and T2DM through having direct effects on protection against apoptosis, glucose-stimulated insulin secretion, and β-cell proliferation. These have been reported to modulate through epigenetic mechanisms and to involve cascades of cAMP/PKA signaling [116]. Sulforaphane obtained from broccoli is a bioactive compound with epigenetic effects. Sulforaphane was reported to inhibit HDACs, decrease promoter methylation, and inhibit expression of DNMT1 in T2DM [122]. in vivostudies of cell culture, co-expression network analysis, and analysis of genetic data of liver tissues indicated that sulforaphane inhibits production of glucose via nuclear translocation mechanisms of “nuclear factor erythroid 2-related factor 2” (NRF2) as well as inhibiting gene expression of essentials enzymes involved in gluconeogenesis [110]. Lycopene in tomatoes and organosulfur compounds in allium and garlic have anti-diabetic effects, especially against T2DM. These bioactive substances were reported to modulate through inducting histone acetylation in numerous malignancies. Lycopene is a carotenoid in tomatoes which has potent antioxidant properties. Studies reported a usefulness in using lycopene to ameliorate oxidative stress in patients with T1DM and T2DM [117]. Lycopene was reported to act through gene methylation. Bioactive compounds have epigenetic modification role in T1DM and T2DM.


6. Conclusion and future perspective

Diabetes mellitus (DM), simply called diabetes, are metabolic disorders characterized by varying or persistent hyperglycemia (high levels of sugar in the blood) over an extended time period. About 463 million people have diabetes worldwide; estimates project 700 million people by 2045. Over 90 to 95% of DM cases are T2DM, while the remain 5 to 10% are other types of DM, including T1DM, the gestational diabetes, and other minor specific types rarely encountered. Medicinal plants, bioactive compounds, and dietary measures have been found to be effective in the treatment of T1DM and T2DM. While T1DM is caused by the loss of beta cells of pancreatic islets that produce insulin, resulting in the deficiency of insulin, T2DM is caused by insulin resistance, and could combine relative reduction in the secretion of insulin. Aloe vera, Terminalia chebula, Perilla frutescens, Curcuma longa, Zingiber zerumbet, Nigella sativa, Gongronema latifolium, Pachira aquatic, Caesalpinioideae, Azadirachta indica, Abelmoschus moschatus, Cinnamomum verum, Salvia officinalis, Tinospora cordifoli, Pterocarpus, Ocimum tenuiflorum, Mangifera indica, Syzygium cumini, Coccinia grandis, Caesalpinia bonduc, Gymnema sylvestre, Carthamus tinctorius, Allium sativum,and Trigonella foenum-graecumare among the medicinal plants shown to be effective in controlling and treating T1DM and T2DM. Bioactive compounds such as lycopene, vitamin E, vitamin D, genistein, quercetin, resveratrol, epigallocatechin-3-gallate, hesperidin, naringin, anthocyanin, etc. are useful in treating T1DM and T2DM. There is need to explore other treatment measures, both medicine and alternative medicine, for T1DM and T2DM treatment. Medicinal plants and their bioactive constituents provide excellent potentials for the development of drugs and therapeutic measures for treating diabetes mellitus in general.



The author acknowledge the effort of his colleagues at School of Natural and Applied Sciences, Kampala International University, Uganda, for helping through one way or the other.


Conflict of interest

The author declares no conflict of interest.


  1. 1. Saedi, E; Gheini, MR; Faiz, F; Arami, MA. “Diabetes mellitus and cognitive impairments”. World Journal of Diabetes. 2016;7(17);412–22. doi:10.4239/wjd.v7.i17.412
  2. 2. International Diabetes Federation, IDF Diabetes Atlas 2020, 9th edition, 2020. Available at htt://
  3. 3. Cho N. H., J. E. Shaw, S. Karuranga et al. “IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045,” Diabetes Research and Clinical Practice, vol. 138, pp. 271–281, 2018.
  4. 4. Ogurtsova K., J. D. da Rocha Fernandes, Y. Huang et al., “IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040,” Diabetes Research and Clinical Practice, vol. 128, pp. 40–50, 2017.
  5. 5. Brahmachari G., “Bio-flavonoids with promising antidiabetic potentials: a critical survey,” Opportunity, Challenge and Scope of Natural Products in Medicinal Chemistry, pp. 187–212, 2011.
  6. 6. Andrade, C., Gomes, N.G.M., Duangsrisai, S., Andrade, P.B., Pereira, D.M., Valentão, P. Medicinal plants utilized in Thai Traditional Medicine for diabetes treatment: ethnobotanical surveys, scientific evidence and phytochemicals, Journal of Ethnopharmacology, 2020;S0378–8741(20)33059–2.
  7. 7. Yuan, H., Ma, Q., Ye, L., Piao, G. The traditional medicine and modern medicine from natural products. Molecules 2016;21;559.
  8. 8. Peltzer, K., Pengpid, S., Puckpinyo, A., Yi, S., Anh, L.V. The utilization of traditional, complementary and alternative medicine for non-communicable diseases and mental disorders in health care patients in Cambodia, Thailand and Vietnam. BMC Complement. Altern. Med. 2016;1–11.
  9. 9. Galanakis C. M., Nutraceutical and Functional Food Components, Academic Press, 2017.
  10. 10. Chinaza GA, Chinelo KE, Obinna CA, Nwabgaoso O, and Ikechukwu OA. Medicinal Plant Phytochemicals: The Biochemistry and Uses of the Pharmacologically Active Alkaloids, Terpenes, Polyphenols, and Glycosides. Agro and Food Processing for Wealth Creation - The Nigerian Experience. Proceedings of the Nigerian Institute of Food Science and Technology. 15–18 October, 2020a.
  11. 11. Chinaza Godswill Awuchi, Ebere Udeogu, Amagwula Otuosorochi Ikechukwu. Hemagglutinin Activities of Lectin Extracts from Selected Legumes. Submitted to Abia State University, Uturu, Nigeria. 2020b.
  12. 12. Ahaotu Ndidiamaka Nnennaya; Ibeabuchi Chidi Julian; Agunwa Ijeoma; Echeta, Chinelo Kate; Awuchi, Chinaza Godswill; Ohia Promise. Antinutritional and phytochemical composition of fermented condiment (Ogiri) made from Sandbox (Hura crepitan) Seed. European Academic Research, 2020a;8 (4): 1871–1883.
  13. 13. Ahaotu NN, Echeta CK, Bede NE, Awuchi CG, Anosike CL, Ibeabuchi CJ, and Ojukwu M. Study on the nutritional and chemical composition of “Ogiri” condiment made from sandbox seed (Hura crepitans) as affected by fermentation time. GSC Biological and Pharmaceutical Sciences, 2020b;11(2), 105–113. doi:10.30574/gscbps.2020.11.2.0115.
  14. 14. Twinomuhwezi H, Awuchi CG, and Kahunde, D. Extraction and Characterization of Pectin from Orange (Citrus sinensis), Lemon (Citrus limon) and Tangerine (Citrus tangerina).American Journal of Physical Sciences, 2020; 1; 17–30.
  15. 15. Awuchi CG, CK Echeta, and VS Igwe. Diabetes and the Nutrition and Diets for Its Prevention and Treatment: A Systematic Review and Dietetic Perspective. Health Sciences Research. 2020; 6(1); 5–19.
  16. 16. Awuchi, Chinaza Godswill. Medicinal Plants: The Medical, Food, and Nutritional Biochemistry and Uses. International Journal of Advanced Academic Research, 2019; 5 (11); 220–241.
  17. 17. Huang T.-C., K.-T. Lu, Y.-Y. P. Wo, Y.-J. Wu, and Y.-L. Yang, “Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation,” PLoS One, vol. 6, no. 12, article e29102, 2011.
  18. 18. Mahmoud M. F., N. A. Hassan, H. M. El Bassossy, and A Fahmy, “Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation,” PLoS One, vol. 8, no. 5, article e63784, 2013.
  19. 19. Gothai S., P. Ganesan, S. Y. Park, S. Fakurazi, D. K. Choi, and P. Arulselvan, “Natural phyto-bioactive compounds for the treatment of type 2 diabetes: inflammation as a target,” Nutri- ents, vol. 8, no. 8, 2016.
  20. 20. McAnany B. and D. Martirosyan, “The effects of bioactive compounds on Alzheimer’s disease and mild cognitive impairment,” Functional Foods in Health and Disease, vol. 6, no. 6, pp. 329–343, 2016.
  21. 21. Rother KI. “Diabetes treatment—bridging the divide”. The New England Journal of Medicine. 2007;356 (15): 1499–501. doi:10.1056/NEJMp078030
  22. 22. Dorner M, Pinget M, Brogard JM. “Essential labile diabetes”. MMW, Munchener Medizinische Wochenschrift (in German). 1977; 119 (19): 671–74.
  23. 23. Petzold A, Solimena M, Knoch KP. “Mechanisms of Beta Cell Dysfunction Associated With Viral Infection”. Current Diabetes Reports (Review). 2015;15 (10): 73. doi:10.1007/s11892-015-0654-x
  24. 24. Butalia S, Kaplan GG, Khokhar B, Rabi DM. “Environmental Risk Factors and Type 1 Diabetes: Past, Present, and Future”. Canadian Journal of Diabetes(Review). 2016;40 (6): 586–93. doi:10.1016/j.jcjd.2016.05.002
  25. 25. Laugesen E, Østergaard JA, Leslie RD. “Latent autoimmune diabetes of the adult: current knowledge and uncertainty”. Diabetic Medicine. 2015;32 (7): 843–52. doi:10.1111/dme.12700
  26. 26. American Diabetes Association. “2. Classification and Diagnosis of Diabetes”. Diabetes Care. 2017;40 (Suppl 1): S11–S24. doi:10.2337/dc17-S005
  27. 27. Carris NW, Magness RR, Labovitz AJ. “Prevention of Diabetes Mellitus in Patients With Prediabetes”. The American Journal of Cardiology. 2019;123 (3): 507–512. doi:10.1016/j.amjcard.2018.10.032
  28. 28. Risérus U, Willett WC, Hu FB. “Dietary fats and prevention of type 2 diabetes”. Progress in Lipid Research. 2009;48 (1): 44–51. doi:10.1016/j.plipres.2008.10.002
  29. 29. Hu EA, Pan A, Malik V, Sun Q. “White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review”. BMJ. 2012;344: e1454. doi:10.1136/bmj.e1454
  30. 30. Huang, Hao; Yan, Peipei; Shan, Zhilei; Chen, Sijing; Li, Moying; Luo, Cheng; Gao, Hui; Hao, Liping; Liu, Liegang. “Adverse childhood experiences and risk of type 2 diabetes: A systematic review and meta-analysis”. Metabolism – Clinical and Experimental. 2015; 64 (11): 1408–1418. doi:10.1016/j.metabol.2015.08.019
  31. 31. Moradi B, Saber A, Somayeh S, Mohsen A, Fatemeh B. The most useful medicinal herbs to treat diabetes. Biomedical Research and Therapy 2018, 5(8): 2538–2551. DOI: 10.15419/bmrat.v5i8.463
  32. 32. Xie W, Zhao Y, Zhang Y. Traditional chinese medicines in treatment of patients with type 2 diabetes mellitus. Evidence-Based Complementary and Alternative Medicine. 2011;2011.
  33. 33. Rao NK, Nammi S. Antidiabetic and renoprotective effects of the chloroform extract ofTerminalia chebulaRetz. seeds in streptozotocin-induced diabetic rats. BMC complementary and alternative medicine. 2006;6:17
  34. 34. Salahi M, 2012. Medical Climatology of Iran. Journal of Army University of Medical Sciences. 2012;2:49. null.
  35. 35. Rao MU, Sreenivasulu M, Chengaiah B, Reddy KJ, Chetty CM. Herbal medicines for diabetes mellitus: a review. Int J PharmTech Res. 2010;2:1883–1892.
  36. 36. Huseini HF, Fakhrzadeh H, Larijani B, Samani AS. Review of anti-diabetic medicinal plant used in traditional medicine. Journal of Medicinal Plants. 2006;1:1–8.
  37. 37. Das M, Sarma BP, Khan AK, Mosihuzzaman M, Nahar N, Ali L, et al. The antidiabetic and antilipidemic activity of aqueous extract ofUrtica dioicaL. on type2 diabetic model rats. Journal of Bio-Science. 2009;17:1–6. null.
  38. 38. Yu Z, Gong C, Lu B, Yang L, Sheng Y, Ji L, et al. Dendrobium chrysotoxum Lindl. alleviates diabetic retinopathy by preventing retinal inflammation and tight junction protein decrease. Journal of diabetes research. 2015;2015
  39. 39. Godswill CA, Igwe VS, Amagwula IO, Echeta CK. Health Benefits of Micronutrients (Vitamins and Minerals) and their Associated Deficiency Diseases: a Systematic Review.International Journal of Food Sciences, 2020;3(1): 1–32.
  40. 40. Iqbal S., I. Naseem. “Role of vitamin A in type 2 diabetes mellitus biology: effects of intervention therapy in a deficient state,” Nutrition, 31, 7–8, 901–907, 2015.
  41. 41. Poher A.-L., C. Veyrat-Durebex, J. Altirriba et al. “Ectopic UCP1 overexpression in white adipose tissue improves insulin sensitivity in Lou/C rats, a model of obesity resistance,” Diabetes, vol. 64, no. 11, pp. 3700–3712, 2015.
  42. 42. Berry D. C. and N. Noy, “All-trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor β/δ and retinoic acid recep- tor,” Molecular and Cellular Biology, vol. 29, no. 12, pp. 3286–3296, 2009.
  43. 43. Raja M. Gopal Reddy, S. Mullapudi Venkata, U. K. Putcha, and S. M. Jeyakumar. “Vitamin A deficiency induces endoplasmic reticulum stress and apoptosis in pancreatic islet cells: implications of stearoyl-CoA desaturase 1- mediated oleic acid synthesis,” Experimental Cell Research, vol. 364, no. 1, pp. 104–112, 2018.
  44. 44. Takemoto K., W. Doi, N. Masuoka, “Protective effect of vitamin E against alloxan-induced mouse hyperglycemia,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1862, no. 4, pp. 647–650, 2016.
  45. 45. Suksomboon N., N. Poolsup, S. Sinprasert, “Effects of vitamin E supplementation on glycaemic control in type 2 diabetes: systematic review of randomized controlled trials,” Journal of Clinical Pharmacy and Therapeutics, vol. 36, no. 1, pp. 53–63, 2011.
  46. 46. Rege S. D., T. Geetha, T. L. Broderick, J. R. Babu, “Can diet and physical activity limit Alzheimer’s disease risk?,” Current Alzheimer Research, vol. 14, no. 1, pp. 76–93, 2017.
  47. 47. Ahmed O. M., A. A. Moneim, I. A. Yazid, A. M. Mahmoud, “Antihyperglycemic, antihyperlipidemic and antioxidant effects and the probable mechanisms of action of Ruta graveo- lens infusion and rutin in nicotinamide-streptozotocin- induced diabetic rats,” Diabetologia Croatica, vol. 39, no. 1, pp. 15–35, 2010.
  48. 48. Wang G., C. Hu, C. Hu, L. Ruan, Q. Bo, L. Li, “Impact of oral vitamin D supplementation in early life on diabetic mice induced by streptozotocin,” Life, Earth & Health Science, vol. 42, no. 3, pp. 455–459, 2014.
  49. 49. Meerza D., I. Naseem, J. Ahmed, “Effect of 1, 25(OH)2 vitamin D3 on glucose homeostasis and DNA damage in type 2 diabetic mice,” Journal of Diabetic Complications, vol. 26, no. 5, pp. 363–368, 2012.
  50. 50. Mitri J., A. G. Pittas, “Vitamin D and diabetes,” Endocri- nology and Metabolism Clinics of North America, vol. 43, no. 1, pp. 205–232, 2014.
  51. 51. Ojuka E. O., “Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle,” Proceedings of the Nutrition Society, vol. 63, no. 02, pp. 275–278, 2004.
  52. 52. Zhu J., C. G. Wang, Y. G. Xu, “Lycopene attenuates endo- thelial dysfunction in streptozotocin-induced diabetic rats by reducing oxidative stress,” Pharmaceutical Biology, vol. 49, no. 11, pp. 1144–1149, 2011.
  53. 53. Li W., G. Wang, X. Lu, Y. Jiang, L. Xu, and X. Zhao, “Lyco- pene ameliorates renal function in rats with streptozotocin- induced diabetes,” International Journal of Clinical and Experimental Pathology, vol. 7, no. 8, pp. 5008–5015, 2014.
  54. 54. Ali M. M., F. G. Agha, “Amelioration of streptozotocin- induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 69, no. 3, pp. 371–379, 2009.
  55. 55. Kuhad A., R. Sethi, K. Chopra, “Lycopene attenuates diabetes-associated cognitive decline in rats,” Life Sciences, vol. 83, no. 3–4, pp. 128–134, 2008.
  56. 56. Lombardo M. F., P. Iacopino, M. Cuzzola et al., “Type 2 diabetes mellitus impairs the maturation of endothelial progenitor cells and increases the number of circulating endothelial cells in peripheral blood,” Cytometry Part A, vol. 81A, no. 10, pp. 856–864, 2012.
  57. 57. Zeng Y.-C., L.-S. Peng, L. Zou et al., “Protective effect and mechanism of lycopene on endothelial progenitor cells (EPCs) from type 2 diabetes mellitus rats,” Biomedicine & Pharmacotherapy, vol. 92, pp. 86–94, 2017.
  58. 58. Tabrez S., K. Z. Al-Shali, S. Ahmad, “Lycopene powers the inhibition of glycation-induced diabetic nephropathy: a novel approach to halt the AGE-RAGE axis menace,” Bio-Factors, vol. 41, no. 5, pp. 372–381, 2015.
  59. 59. Hsu C. Y., H. Y. Shih, Y. C. Chia et al., “Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose transporter 4 translocation,” Molecular Nutrition & Food Research, vol. 58, no. 6, pp. 1168–1176, 2014.
  60. 60. Zhang Q., H. Yuan, C. Zhang et al., “Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviat- ing inflammation and lipotoxicity,” Diabetes Research and Clinical Practice, vol. 142, pp. 363–373, 2018a.
  61. 61. Zhang Y., B. Wang, F. Guo, Z. Li, G. Qin, “Involvement of the TGFβ1- ILK-Akt signaling pathway in the effects of hesperidin in type 2 diabetic nephropathy,” Biomedicine & Pharmacotherapy, vol. 105, pp. 766–772, 2018b.
  62. 62. Luna-Vital D. A., E. Gonzalez de Mejia, “Anthocyanins from purple corn activate free fatty acid-receptor 1 and glucokinase enhancing in vitro insulin secretion and hepatic glucose uptake,” PLoS One, vol. 13, no. 7, article e0200449, 2018.
  63. 63. Chen F., G. Wei, J. Xu, X. Ma, Q. Wang, “Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 inflammasome,” BMC Complementary and Alternative Medicine, vol. 18, no. 1, p. 192, 2018.
  64. 64. Roy S., F. Ahmed, S. Banerjee, U. Saha, “Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events,” Pharmaceutical Biology, vol. 54, no. 9, pp. 1616–1627, 2016.
  65. 65. Oršolić N., D. Sirovina, G. Gajski, V. Garaj-Vrhovac, M. Jazvinšćak Jembrek, I. Kosalec, “Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG),” Mutation Research/Genetic Toxicology and Environmental Mutagene- sis, vol. 757, no. 1, pp. 36–44, 2013.
  66. 66. Rashid K., P. C. Sil, “Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats,” Toxicology and Applied Pharmacology, vol. 282, no. 3, pp. 297–310, 2015.
  67. 67. Eid H. M., A. Nachar, F. Thong, G. Sweeney, P. S. Haddad, “The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes,” Pharmacognosy Magazine, vol. 11, no. 41, pp. 74–81, 2015.
  68. 68. Vetterli L., T. Brun, L. Giovannoni, D. Bosco, P. Maechler, “Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E β-cells and human islets through a SIRT1-dependent mechanism,” Journal of Biological Chemistry, vol. 286, no. 8, pp. 6049–6060, 2011.
  69. 69. Fu Z., W. Zhang, W. Zhen et al., “Genistein induces pan- creatic β-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice,” Endocrinology, vol. 151, no. 7, pp. 3026–3037, 2010.
  70. 70. Granzotto A., P. Zatta, “Resveratrol and Alzheimer’s disease: message in a bottle on red wine and cognition,” Frontiers in Aging Neuroscience, vol. 6, p. 95, 2014.
  71. 71. Kitada M., D. Koya, “SIRT1 in type 2 diabetes: mechanisms and therapeutic potential,” Diabetes & Metabolism Journal, vol. 37, no. 5, pp. 315–325, 2013.
  72. 72. Cao M.-M., X. Lu, G. D. Liu, Y. Su, Y. B. Li, J. Zhou, “Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via sirtuin type 1,” Experimental and Therapeutic Medicine, vol. 15, no. 1, pp. 576–584, 2018.
  73. 73. Szkudelski T., K. Szkudelska, “Resveratrol and diabetes: from animal to human studies,” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, vol. 1852, no. 6, pp. 1145–1154, 2015.
  74. 74. Han M. K., “Epigallocatechin gallate, a constituent of green tea, suppresses cytokine-induced pancreatic β-cell damage,” Experimental & Molecular Medicine, vol. 35, no. 2, pp. 136–139, 2003.
  75. 75. Suh K. S., S. Chon, S. Oh et al., “Prooxidative effects of green tea polyphenol (−)-epigallocatethin-3-gallate on the HIT-T15 pancreatic beta cell line,” Cell Biology and Toxi- cology, vol. 26, no. 3, pp. 189–199, 2010.
  76. 76. Peng J., Q. Li, K. Li et al., “Quercetin improves glucose and lipid metabolism of diabetic rats: involvement of Akt signal- ing and SIRT1,” Journal of Diabetes Research, vol. 2017, Article ID 3417306, 10 pages, 2017.
  77. 77. Ergul A., “Endothelin-1 and diabetic complications: focus on the vasculature,” Pharmacological Research, vol. 63, no. 6, pp. 477–482, 2011.
  78. 78. Youl E., G. Bardy, R. Magous et al., “Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway,” British Journal of Pharmacology, vol. 161, no. 4, pp. 799–814, 2010.
  79. 79. Oh Y. S., H. S. Jun, “Role of bioactive food components in diabetes prevention: effects on beta-cell function and preser- vation,” Nutrition and Metabolic Insights, vol. 7, pp. 51–59, 2014.
  80. 80. Tarabra E., S. Pelengaris, M. Khan, “A simple matter of life and death—the trials of postnatal beta-cell mass reg- ulation,” International Journal of Endocrinology, vol. 2012, Article ID 516718, 20 pages, 2012.
  81. 81. Ae Park S., M. S. Choi, S. Y. Cho et al., “Genistein and daid- zein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice,” Life Sciences, vol. 79, no. 12, pp. 1207–1213, 2006.
  82. 82. Dkhar B., K. Khongsti, D. Thabah, D. Syiem, K. Satyamoorthy, B. Das, “Genistein represses PEPCK-C expression in an insulin-independent manner in HepG2 cells and in alloxan-induced diabetic mice,” Journal of Cellular Biochemistry, vol. 119, no. 2, pp. 1953–1970, 2018.
  83. 83. Mahmoud A. M., M. B. Ashour, A. Abdel-Moneim, O. M. Ahmed, “Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflamma- tory cytokine production in high fat fed/streptozotocin- induced type 2 diabetic rats,” Journal of Diabetes and its Complications, vol. 26, no. 6, pp. 483–490, 2012.
  84. 84. Mahmoud A. M., O. M. Ahmed, M. B. Ashour, A. Abdel- Moneim, “In vivo and in vitro antidiabetic effects of citrus flavonoids; a study on the mechanism of action,” International Journal of Diabetes in Developing Countries, vol. 35, no. 3, pp. 250–263, 2015.
  85. 85. Shi X., S. Liao, H. Mi et al., “Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats,” Molecules, vol. 17, no. 11, pp. 12868–12881, 2012.
  86. 86. Ahmed O. M., M. A. Hassan, S. M. Abdel-Twab, M. N. Abdel Azeem, “Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats,” Biomedicine & Pharmacotherapy, vol. 94, pp. 197–205, 2017.
  87. 87. Sharma A. K., S. Bharti, S. Ojha et al., “Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes,” The British Journal of Nutrition, vol. 106, no. 11, pp. 1713–1723, 2011.
  88. 88. Li G., Y. Xu, X. Sheng et al., “Naringin protects against high glucose-induced human endothelial cell injury via antioxida- tion and CX3CL1 downregulation,” Cellular Physiology and Biochemistry, vol. 42, no. 6, pp. 2540–2551, 2017.
  89. 89. Mahmoud A. M., “Hematological alterations in diabetic rats - role of adipocytokines and effect of citrus flavonoids,” EXCLI Journal, vol. 12, p. 647, 2013.
  90. 90. Qi Z., Y. Xu, Z. Liang et al., “Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in a type 2 diabetic rat model,” Molecular Medicine Reports, vol. 12, no. 5, pp. 7093–7101, 2015.
  91. 91. Sancho R. A. S., G. M. Pastore, “Evaluation of the effects of anthocyanins in type 2 diabetes,” Food Research International, vol. 46, no. 1, pp. 378–386, 2012.
  92. 92. Zhang B., M. Buya, W. Qin et al., “Anthocyanins from Chinese bayberry extract activate transcription factor Nrf2 in β cells and negatively regulate oxidative stress-induced autophagy,” Journal of Agricultural and Food Chemistry, vol. 61, no. 37, pp. 8765–8772, 2013.
  93. 93. Yan F., G. Dai, X. Zheng, “Mulberry anthocyanin extract ameliorates insulin resistance by regulating PI3K/AKT pathway in HepG2 cells and db/db mice,” The Journal of Nutritional Biochemistry, vol. 36, pp. 68–80, 2016.
  94. 94. Zhang B., M. Kang, Q. Xie et al., “Anthocyanins from Chinese bayberry extract protect β cells from oxidative stress- mediated injury via HO-1 upregulation,” Journal of Agricultural and Food Chemistry, vol. 59, no. 2, pp. 537–545, 2011.
  95. 95. Lin J., Y. Tang, Q. Kang, A. Chen, “Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro,” Laboratory Investigation, vol. 92, no. 6, pp. 827–841, 2012a.
  96. 96. Lin J., Y. Tang, Q. Kang, Y. Feng, A. Chen, “Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress,” British Journal of Pharmacology, vol. 166, no. 8, pp. 2212–2227, 2012b.
  97. 97. Su L.-q., Y.-d. Wang, H.-y. Chi, “Effect of curcumin on glucose and lipid metabolism, FFAs and TNF-α in serum of type 2 diabetes mellitus rat models,” Saudi Journal of Biological Sciences, vol. 24, no. 8, pp. 1776–1780, 2017.
  98. 98. Soto-Urquieta M. G., S. López-Briones, V. Pérez-Vázquez, A Saavedra-Molina, G. A. González-Hernández, J. Ramírez-Emiliano, “Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice,” Biological Research, vol. 47, no. 1, p. 74, 2014.
  99. 99. Ghorbani A., “Mechanisms of antidiabetic effects of flavo- noid rutin,” Biomedicine & Pharmacotherapy, vol. 96, pp. 305–312, 2017.
  100. 100. Rao V., S. Venkateswara, S. Vinu Kiran, “Flavonoid: a review on naringenin,” Journal of Pharmacognosy and Phytochemistry, vol. 6, no. 5, pp. 2778–2783, 2017.
  101. 101. Kapoor R., P. Kakkar, “Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modu- lating mitochondrial dysfunction and apoptotic signaling cascade,” Toxicology Reports, vol. 1, pp. 569–581, 2014.
  102. 102. Qin W., B. Ren, S. Wang et al., “Apigenin and naringenin ameliorate PKCβII-associated endothelial dysfunction via regulating ROS/caspase-3 and NO pathway in endothelial cells exposed to high glucose,” Vascular Pharmacology, vol. 85, pp. 39–49, 2016.
  103. 103. Rahigude A., P. Bhutada, S. Kaulaskar, M. Aswar, and K. Otari, “Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes- induced memory dysfunction in rats,” Neuroscience, vol. 226, pp. 62–72, 2012.
  104. 104. Singh A. K., V. Raj, A. K. Keshari et al., “Isolated mangiferin and naringenin exert antidiabetic effect via PPARγ/ GLUT4 dual agonistic action with strong metabolic regula- tion,” Chemico-Biological Interactions, vol. 280, pp. 33–44, 2018.
  105. 105. Poradzka A., J. Wro’nski, M. Jasik, W. Karnafel, and P. Fiedor, “Insulin replacement therapy in patients with type 1 diabetes by isolated pancreatic islet transplantation,” Acta Poloniae Pharmaceutica. Drug Research, vol. 70, no. 6, pp. 943–950, 2013.
  106. 106. Sommese L., A. Zullo, F. P. Mancini, R. Fabbricini, A. Soricelli, and C. Napoli, “Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus,” Epigenetics, vol. 12, no. 6, pp. 401–415, 2017.
  107. 107. Saad B., H. Zaid, S. Shanak, S. Kadan, Anti-diabetes and Anti-obesity Medicinal Plants and Phytochemicals, Springer, 2017.
  108. 108. Yun J.-M., I. Jialal, S. Devaraj, “Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers,” British Journal of Nutrition, vol. 103, no. 12, pp. 1771–1777, 2010.
  109. 109. Crescenti A, Sola R, Valls RM, et al. Cocoa con-sumption alters the global DNA methylation of pe-ripheral leukocytes in humans with cardiovascular disease risk factors: A randomized controlled trial. PloS One 2013; 8(6): e65744.
  110. 110. Axelsson A. S., E. Tubbs, B. Mecham et al., “Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes,” Science Translational Medicine, vol. 9, no. 394, 2017.
  111. 111. Kashyap V, Gudas LJ. Epigenetic regulatory mechanisms distinguish retinoic acid-mediated transcriptional responses in stem cells and fibro-blasts. J Biol Chem 2010; 285(19): 14534–48.
  112. 112. Yao Y, Zhu L, He L, et al. A meta-analysis of the relationship between vitamin D deficiency and obesi-ty. Int J Clin Exp Med 2015; 8(9): 14977–84.
  113. 113. Timmers S., M. K. C. Hesselink, P. Schrauwen, “Therapeutic potential of resveratrol in obesity and type 2 diabetes: New avenues for health benefits?” Annals of the New York Academy of Sciences, vol. 1290, no. 1, pp. 83–89, 2013.
  114. 114. Boyanapalli SS, Tony KAN. “Curcumin, the king of spices”: Epigenetic regulatory mechanisms in the prevention of cancer, neurological, and inflammatory diseases. Curr Pharmacol Rep 2015; 1(2): 129–39.
  115. 115. Kozuka C, Yabiku K, Takayama C, Matsushita M, Shimabukuro M. Natural food science based novel approach toward prevention and treatment of obesity and type 2 diabetes: Recent studies on brown rice and gamma-oryzanol. Obes Res Clin Pract 2013; 7(3): e165–72.
  116. 116. Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic beta-cell function. Food Funct 2013; 4(2): 200–12.
  117. 117. Valero M. A., A. Vidal, R. Burgos et al., “Meta-analysis on the role of lycopene in type 2 diabetes mellitus,” Nutrición Hospitalaria, vol. 26, no. 6, pp. 1236–1241, 2011.
  118. 118. Li Y., D. Kong, Z. Wang, F. H. Sarkar, “Regulation of microRNAs by natural agents: an emerging field in chemopre- vention and chemotherapy research,” Pharmaceutical Research, vol. 27, no. 6, pp. 1027–1041, 2010.
  119. 119. Lee W.-J., Y.-R. Chen, T.-H. Tseng, “Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells,” Oncology Reports, vol. 25, no. 2, pp. 583–591, 2011.
  120. 120. Reuter S., S. C. Gupta, B. Park, A. Goel, B. B. Aggarwal, “Epigenetic changes induced by curcumin and other natural compounds,” Genes & Nutrition, vol. 6, no. 2, pp. 93–108, 2011.
  121. 121. Majid S., A. A. Dar, V. Shahryari et al., “Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-cell translocation gene 3 in prostate cancer,” Cancer, vol. 116, no. 1, pp. 66–76, 2010.
  122. 122. Meeran S. M., S. N. Patel, T. O. Tollefsbol, “Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines,” PLoS ONE, vol. 5, no. 7, Article ID e11457, 2010.

Written By

Chinaza Godswill Awuchi

Submitted: December 18th, 2020 Reviewed: February 7th, 2021 Published: February 25th, 2021