Obesity and Clinical Riskiness Relationship: Therapeutic Management by Dietary Antioxidant Supplementation—a Review
Obesity is a global health problem affecting all age groups, leading to many complications such as type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, atherosclerosis, and stroke. Physiologically, obesity arises from metabolic changes in the tissues and organs of the human body; these changes result in an imbalance between energy intake and energy expenditure, which in turn results in increased fat accumulation in adipose tissue. Such fat accumulation predisposes individuals to development of several health problems. Two different obesity treatment drugs are currently on the market; Orlistat, which reduces intestinal fat absorption via inhibiting pancreatic lipase, and Sibutramine, an anorectic or appetite suppressant. Both drugs have hazardous side effects, including increased blood pressure, dry mouth, constipation, headache, and insomnia. For this reason, a wide variety of natural materials have been explored for their obesity treatment potential. Therefore, the present review focuses on the safety and efficacy of some herbal medicines in the management of obesity through covering their beneficial effects and mechanism of action.
KeywordsObesity Diseases-associated obesity Diabetes Cardiovascular disease Atherosclerosis Dietary natural antioxidants Herbal medicine
Obesity is the most prevalent health problem. It is also known to be a risk factor for the development of metabolic disorders such as type 2 diabetes, systemic hypertension, cardiovascular disease, dyslipidemia, and atherosclerosis. Obesity is a pathological condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems . Also, obesity is generally defined as the abnormal or excessive accumulation of fat in adipose tissue to the extent that health may be impaired . Obesity comes about when energy intake, principally stored as triglycerides, exceeds energy expenditure . It is a complex trait influenced by diet, developmental stage, age, physical activity, and genes . Obesity is currently considered an epidemic in developed and developing countries causing a major health concern that has become a priority in public health policies. The World Health Organization (WHO) estimates that over 1.6 billion adults worldwide are considered overweight, and 400 million of these are considered obese . Overweight and obesity are directly related to increase risk of several chronic diseases and impaired physical function.
Overweight: Overweight is defined as having a BMI between 25.0 and 30.0 kg/m2.
Obese: Obese is defined as having a BMI greater than or equal to 30.0 kg/m2.
Physiology of Obesity
Research over the past two decades has provided an unprecedented expansion in our knowledge about the physiological and molecular mechanisms regulating body fat . Perhaps, the greatest impact has resulted from the cloning of genes corresponding to the five mouse monogenic obesity syndromes and the subsequent characterization of pathways identified by these genetic entry points. The description of three of these genes (ob, db, and Ay) has already led to potential drugs or drug targets currently in pharmaceutical development: leptin, leptin receptor, and melanocortin-4 (MC4) receptor. In addition, extensive molecular and reverse genetic studies (mouse knockouts) have helped to identify other critical players in energy balance, as well as validate or refute the importance of previously identified pathways . In such a system, afferent signals tell central controls in the brain about the state of the external and internal environment as they relate to food. In turn, this central controller transducers these messages into efferent control signals governing the search for and acquisition of food, as well as modulates the subsequent disposal of food once inside the body . Finally, there is a control system that ingests, digests, absorbs, transports, stores, metabolizes, and excretes waste from the ingested food.
Causes of Obesity
Obesity results from an imbalance of energy homeostasis, over an extended period of time, caused by the consumption of more calories than the body is able to burn. The cause of this imbalance is complex and is influenced by the convergence of various environmental, behavioral, and genetic factors . No single cause can account for obesity; instead, obesity is due to a combination of contributing factors. Obesity reflects the associations of genetic, metabolic, cultural, environmental, and behavioral factors .
Regulation of Energy Homeostasis and Obesity
Obesity is characterized by an excess of adipose tissue. The increase of food intake (hyperphagia) triggered by a period of fasting is a simple but compelling example of food-intake regulation. The balance between energy intake (food consumption) and energy expenditure (basal metabolic rate, i.e., biochemical processes required to maintain cellular viability, physical activity, and adaptive thermogenesis) is tightly regulated. A homeostatic network maintains energy stores through a complex interplay between the feeding regulatory centers in the central nervous system (CNS), particularly in the hypothalamus and the regulated storage and mobilization of fat stores that maintains the body energy stores. Thus, genes that encode the molecular components of this system may underlie obesity and related disorders. A number of recent research groups have encoded the molecular and genetic mysteries that underlie obesity and its related disorders .
Obesity and Clinical Riskiness Relationship
Obesity, while carrying a health risk itself, also increases the risk for developing a wide variety of other diseases  and has assessed the prevalence of major obesity-associated co-morbidities as type 2 diabetes mellitus, gallbladder disease, coronary heart disease, high blood pressure, high blood cholesterol level, and osteoarthritis. The prevalence of type 2 diabetes mellitus increased sharply in both overweight and obese men and women. Moreover, the incidence of type 2 diabetes increased with increasing weight class. Likewise, the incidence of high blood pressure increased with increasing weight class category in both genders. High blood cholesterol was found to be more prevalent in overweight individuals than in normal or underweight individuals .
Obesity and Diabetes
The condition most strongly influenced by body weight is type 2 diabetes. In the Nurses’ Health Study, which followed by 114,000 middle-aged women for 14 years, the risk of developing diabetes was 93 times higher among women who had a body mass index of 35 or higher at the start of the study, compared with women with body mass index lower than 22 . Weight gain during adulthood also increased diabetes risk, even among women with body mass index in the healthy range. The Health Professionals Follow-Up Study found a similar association in men .
More investigators conducted a systematic review of 89 studies on weight-related diseases and then did a statistical summary or meta-analysis of the data. Of the 18 weight-related diseases studied, diabetes was at the top of the risk list compared with men and women in the normal weight range (body mass index lower than 25). Men with body mass index of 30 or higher had a sevenfold higher risk of developing type 2 diabetes, and women with BMI of 30 or higher had a 12-fold higher risk .
Obesity, type 2 diabetes, and hyperlipidemia often coexist and associate with significantly increased morbidity and mortality . A significant increase in total refined carbohydrate intake and fructose has paralleled recent increase in incidence of obesity and diabetes . Metabolism of sugars, particularly fructose, occurs mainly in the liver, and high-fructose flux leads to enhanced hepatic triglyceride accumulation resulting in impaired glucose and lipid metabolism and increased pro-inflammatory cytokine expression . Fat cells especially those stored around the waist-secrete hormones and other substances that fire inflammation. Although inflammation is an essential component of the immune system and part of the healing process, inappropriate inflammation causes a variety of health problems. Inflammation can make the body less responsive to insulin and change the way the body metabolizes fats and carbohydrates, leading to higher blood sugar levels and, eventually, to diabetes and its many complications . Several large trials have shown that moderate weight loss can prevent or delay the start of diabetes in people who are at high risk .
Obesity and Cardiovascular Disease
The growing epidemic of obesity and other metabolic disorders, associated with insulin resistance, cardiovascular diseases, and cancer, has made adipose tissue an important subject of scientific study and a target of therapeutic intervention . In addition to its function as strong depot of excess energy, adipose tissue is active endocrine organ. It secretes protein as adipokines . Adipose tissue from obese mice shows signs of endoplasmic reticulum stress . However, the exact physiology of endoplasmic reticulum stress in obese tissue is unknown; it may result from various physiological conditions like nutrient overload , high demand for protein synthesis , low glucose in setting of insulin resistance, and decreased adipose tissue revascularization . Body weight is directly associated with various cardiovascular risk factors. As body mass index increases, so do blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, blood sugar, and inflammation. These changes increased risk for coronary heart disease, stroke, and cardiovascular death.
Obesity and Coronary Artery Disease
Numerous studies have demonstrated a direct association between excess body weight and coronary artery disease (CAD). CAD collaboration investigators conducted a meta-analysis of 21 long-term studies that were followed by more than 300,000 participants for an average of 16 years. Study participants who were overweight had a 32 % higher risk of developing CAD, compared with participants who were at a normal weight; those who were obese had an 81 % higher risk . Although adjustment for blood pressure and cholesterol levels slightly lowered the risk estimates, they remained highly significant for obesity. The investigators estimated that the effect of excess weight on blood pressure and blood cholesterol accounts for only about half of the obesity-related increased risk of coronary heart disease.
Obesity and Stroke
Ischemic (clot-caused) stroke and coronary artery disease share many of the same disease processes and risk factors. A meta-analysis of 25 prospective cohort studies with 2.3 million participants demonstrated a direct, graded association between excess weight and stroke risk . Overweight increased the risk of ischemic stroke by 22 %, and obesity increased it by 64 % . There was no significant relationship between overweight or obesity and hemorrhagic (bleeding-caused) stroke . A repeat analysis that statistically accounted for blood pressure, cholesterol, and diabetes weakened the associations, suggesting that these factors mediate the effect of obesity on stroke. In a meta-analysis of 26 observational studies that included 390,000 men and women and several racial and ethnic groups and samples from the US and other countries, obesity was significantly associated with death from CAD and cardiovascular disease. Women with body mass index of 30 or higher had a 62 % greater risk of dying early from CAD and also had a 53 % higher risk of dying early from any type of cardiovascular disease, compared with women who had body mass index in the normal range (18.5 to 24.9). Men with body mass index of 30 or higher had similarly elevated risks .
Obesity and Cancer
In an exhaustive review of the data released in 2007, an expert panel assembled by the World Cancer Research Fund and the American Institute for Cancer Research concluded that there was convincing evidence of an association between obesity and cancers of the esophagus, pancreas, colon and rectum, breast, endometrium, and kidney and a probable association between obesity and gallbladder cancer . Abdominal obesity and weight gain during adulthood were also linked with several cancers. A later systematic review and meta-analysis confirmed direct associations between obesity and cancers of the breast, colon and rectum, endometrium, esophagus, kidney, ovary, and pancreas . Encouragingly, the Nurses’ Health Study has found that for overweight women who have never used hormone replacement therapy, losing weight after menopause and keeping it off cut their risk of post-menopausal breast cancer in half .
Obesity and Inflammation
Cardiovascular disease, diabetes, and obesity are interrelated in that they are each associated with chronic low-grade inflammation. Obesity refers to an accumulation of adipose tissue and is a major contributor to inflammation. Recent studies have exposed the biologically active nature of adipocytes and their ability to modulate the inflammatory response by functioning as an endocrine organ that secretes adipokines, chemokines, and cytokines . In a review article , mammalian adipose tissue is characterized as white adipose tissue (WAT) or brown adipose tissue (BAT). These two forms are similar metabolically but differ in that WAT primarily stores energy, while BAT dispels energy as heat. WAT plays an active role in the pathophysiological processes leading to the development of inflammatory diseases and is composed of both subcutaneous and visceral adipose tissue. Subcutaneous adipose tissue stores most of the body’s energy reserves and resides in the upper and lower body, while visceral adipose tissue surrounds and supplies the internal organs with energy. Adipose tissue is composed of mature adipocytes and a group of smaller cells that include pre-adipocytes, fibroblasts, and macrophages among many others . The adipocyte is a multifunctional cell engaging in lipid synthesis, lipid storage, and the secretion of both pro-inflammatory and anti-inflammatory factors . Under normal circumstances, adipose tissue primarily secretes anti-inflammatory molecules, but as lipid accumulates and cells hypertrophy, the adipoctyes, preadipocytes, and macrophages within the adipose tissue can secrete a variety of inflammatory cytokines and hormones such as C-reactive protein (CRP), resistin, inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6) , and monocyte chemotactic protein-1 (MCP-1) . Enlarged adipocytes also secrete the hormone leptin, which is pro-inflammatory and decreases the secretion of adiponectin, a hormone with anti-inflammatory properties . Some of the primary cytokines and chemokines involved in inflammation include tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and monocyte chemotactic protein-1 (MCP-1). Visceral adipose tissue has a higher rate of lipolysis (fatty acid turnover), an increased infiltration of inflammation-inducing macrophages, and a higher expression of IL-6, MCP-1, and additional inflammatory-related markers than subcutaneous adipose tissue . With increasing adiposity, monocytes move from the blood to adipose tissue where they differentiate into inflammatory macrophages and are activated to express inflammatory cytokines such as MCP-1, IL-6, and TNF-α . There is evidence to suggest that macrophages may be attracted to high levels of necrotic tissue induced by hypoxia in the expanding adipocytes . The inflammation associated with obesity also exerts a negative effect on the vasculature within the body, leading to an increased risk of atherosclerosis and CVD.
Obesity and Lung Function/Respiratory Disease
Excess weight impairs respiratory function via mechanical and metabolic pathways. The accumulation of abdominal fat, for example, may limit the descent of the diaphragm and in turn lung expansion, while the accumulation of visceral fat can reduce the flexibility of the chest wall, sap respiratory muscle strength, and narrow airways in the lungs . Cytokines generated by the low-grade inflammatory state that accompanies obesity may also impede lung function. Asthma and obstructive sleep apnea are two common respiratory diseases that have been linked with obesity. In a meta-analysis of seven prospective studies that included 333,000 subjects, obesity was found to increase the risk of developing asthma in both men and women by 50 % . Obesity is also a major contributor to obstructive sleep apnea (OSA), which is estimated to affect approximately one in five adults; one in 15 adults has moderate or severe obstructive sleep apnea. This condition is associated with daytime sleepiness, accidents, hypertension, cardiovascular disease, and premature mortality. Between 50 and 75 % of individuals with OSA are obese . Clinical trials suggest that modest weight loss can be helpful when treating sleep apnea [37, 38].
Obesity, Memory, and Cognitive Function
Alzheimer’s disease and dementia are scourges of populations that enjoy a long life span. In the US, these diseases affect more than 7.5 million people and most of them over age of 65. At 65, the estimated lifetime risk for Alzheimer’s disease is 17.2 % in women and 9.1 % in men . Body weight is a potentially modifiable risk factor for Alzheimer’s disease and dementia. A meta-analysis of ten prospective cohort studies that included almost 42,000 subjects followed for three to 36 years demonstrated a U-shaped association between body mass index and Alzheimer’s disease. Compared with being in the normal weight range, being underweight was associated with a 36 % higher risk of Alzheimer’s disease while being obese was associated with a 42 % higher risk . The associations were stronger in studies with longer follow-up. A more recent meta-analysis demonstrated a similarly strong association between obesity and Alzheimer’s disease .
Obesity and Mortality
Obesity is a global health concern associated with high morbidity and mortality, given the adverse consequences of obesity on multiple aspects of health; it makes sense that the condition also shortens survival or increases premature mortality. However, pinning down the contribution of obesity to premature mortality has been fraught with methodological problems and controversy.
Therapeutic Management by Dietary Antioxidant Supplementation
Multiple factors have contributed to the obesity epidemic. Social, sensory, cultural, medical, perceptual, conditioning, and developmental influences have combined to disrupt well-established feeding controls. Recent research suggests that the rise in obesity is primarily due to altered, sedentary lifestyles, energy-dense diets, and low levels of physical activity. Currently, more than one billion adults worldwide are overweight, and at least 300 million of them are clinically obese Therapeutic strategies include synthetic drugs and surgery and may entail high costs and serious complications. Nowadays, the broad commercial production of many antioxidants formulae by the pharmaceutical companies and its use for treating many diseases, improving health, and increasing body immunity has acted as a great stimulus to research on its role in the body. However, medication from natural sources would be a wise option as a substitute to the chemical remedies in controlling many diseases. Plant-based medicinal agents offer an alternative approach. Number of plants, such as green tea, bitter orange, kidney bean, ginger, cherries, and curcumin , helps in the treatment of obesity. Herbs, spices, and medicinal plants have been cherished by many ancient cultures for their use in curing common ailments and promoting good health . Dietary spices are a heterogeneous collection of a wide variety of volatile and non-volatile chemicals obtained from dried aromatic parts of plants—generally the seeds, berries, roots, pods, and sometimes leaves. Populations that use spices and/or herbs in their diets have been shown to have lower incidences of chronic disease . Naturally occurring phytochemicals present an exciting opportunity for the discovery of newer antiobesity agents. As per literature indicates numerous bioactive components from nature are potentially useful in obesity treatments. Antiobesity pharmacological treatment should be administered only when considered safe and effective for obese subject. Among treatments for obesity, the most promising strategies in the effort to reduce energy intake through different mechanisms including the following: lipase inhibitory effect, suppressive effect on food intake, inhibitory effect on adipocyte differentiation, stimulatory effects on energy expenditure, and regulatory effect on lipid metabolism.
Therefore, in this review, some herbal plants with antiobesity potential and the scientific data, including their active components, beneficial therapeutic effects, and mechanisms of action against obesity, were reviewed.
Curcumin (Curcuma longa) is a yellow orange dye derived from the rhizomes of Curcuma longa plant which is used as a spice and food-coloring agent . It is a lipophilic molecule  characterized by its phenolic contents (two orthomethoxylated phenols) besides the three-diketone moiety , which provides the free radical trapping capacity of curcumin. Curcumin has shown to be a powerful scavenger of the superoxide anion, the hydroxyl radical, and nitrogen dioxide .
Therapeutic Benefits of Curcumin
Curcumin has many pharmacologic activities, including anti-inflammatory properties, powerful antioxidant activity, and cancer preventive properties . Also, it has been demonstrated in modern medicinal practice as a neuroprotective, cardioprotective, hypoglycaemic, and lipid-lowering agent [49, 50]. Curcumin has the ability to inhibit angiogenesis in adipose tissues and hence aid in lowering body weight and obesity. Curcumin at cellular and whole organism levels shows remarkable health benefits for prevention of obesity and associated metabolic disorders by suppressing angiogenesis in adipose tissues . Curcumin therapeutic benefits have also been demonstrated in cyclosporine-induced renal dysfunction , cadmium-induced oxidative damage , ethanol-induced oxidative injury in brain , and CC14-induced hepatic injury . Moreover, experimental studies with diabetic animals demonstrated that curcumin supplementation can suppress cataract development and collagen cross-linking, promote wound healing ameliorate renal lesions, and lower blood lipids and glucose levels . Curcumin has also shown to be effective against atherosclerosis. The proliferation of peripheral blood mononuclear cells (PBMCs) and vascular smooth muscle cells (VSMCs), which are hallmarks of atherosclerosis, is inhibited by curcumin. Besides, curcumin has also demonstrated to prevent myocardial infarction and other cardiovascular diseases . The effects of curcumin in cardiovascular diseases are linked to its ability to (1) inhibit platelet aggregation , (2) inhibit inflammatory response , (3) lower LDL and elevate HDL , (4) inhibit fibrinogen synthesis , and (5) inhibit oxidation of LDL . A review on the effect of curcumin on number of CVD risk factors is provided, which attempts to explain how this plant product acts to prevent development of CVD in the obese states .
Green tea (Camellia sinensis) is produced from steaming fresh leaves at high temperatures, thereby inactivating the oxidizing enzymes and leaving the polyphenol content intact. The polyphenols found in tea are more commonly known as flavanols or catechins and comprise 30–40 % of the extractable solids of dried green tea leaves . The main catechins in green tea are epicatechin, epicatechin-3-gallate, epigallocatechin, and epigallocatechin-3-gallate (EGCG) with the latter being the highest in concentration. Green tea polyphenols have demonstrated a significant antioxidant, anticarcinogenic, anti-inflammatory, thermogenic, probiotic, and antimicrobial properties in numerous human, animal, and in vitro studies .
Therapeutic Benefits of Green Tea
Green tea is one of the most popular beverages consumed worldwide. It has been reported that green tea and its components have many biological and biochemical effects such as antimutation, anticarcinogenesis , antioxidation , apoptosis-inducing , and antiangiogenesis . Moreover, epidemiological studies have implied that drinking green tea reduces blood cholesterol . Green tea has many components such as catechins, caffeine, theanine, and vitamins . Catechins are present from 15 to 20 % by weight in green tea. Green tea catechins have a hypocholesterolemic effect and suppress the intestinal absorption of cholesterol . Moreover, it was reported that epigallocatechingallate (EGCG), a kind of catechin, had an inhibitory effect on acetyl-CoA carboxylase which is essential for fatty acid biosynthesis in vitro  and antiobesity effects at high doses in rats . Caffeine is the most effective as antiobesity component in oolong tea . It was shown that caffeine decreased food intake  and increased thermogenesis and that the thermogenic effect induced the body weight reduction . Moreover, it was clarified that the thermogenesis by caffeine was synergistically enhanced with catechins in rat adipose tissues . Theanine (Á-glutamylethylamide) is a main amino acid peculiar to green tea and has physiological effects such as relaxation activity , activation of dopamine metabolism, and release in the brain . Moreover, it was reported that theanine suppressed excitation by caffeine . Therefore, they supposed that the physiological effects of catechins, caffeine, and theanine might be concerned with the antiobesity effect of green tea.
Bitter orange, also called Seville orange, bitter orange flower, bitter orange peel, green orange, kijitsu, neroli oil, shangzhouzhiqiao, sour orange, bigarade, neroli flowers, laranja-amarga, laranja-azeda, is known botanically as Citrus x aurantium, L. of the family Rutaceae and sometimes by its taxonomic synonyms, C. aurantiumL. subsp. Aurantiumand C. aurantium subsp. Amara (L.) Engler. Bitter orange is known by many local common names in countries around the world where it is used for food, fragrance, and medicinal purposes . Bitter orange peel contains synephrine; it is p-synephrine (para-synephrine), not M-synephrine (meta-synephrine), and is also called phenylephrine (aka neosynephrine) . A comprehensive review of the presence and distribution of synephrine and chemically similar compounds (tyrmaine, n-methyltyramine, hordenine, and octopamine) in higher plants. Synephrine is considered a non-selective beta-3 agonist. It is a generally accepted theory of pharmacology that beta-3 agonists affect body weight and fat mass , activating lipolysis, and the breaking down of fats .
Therapeutic Benefits of Bitter Orange
Bitter orange is known for its benefits of curing many illnesses and diseases. For example, the peel of bitter orange can cure nasal congestion and dyspepsia, an indigestion problem . The oil and flower of bitter orange can be used to treat duodenal ulcers and constipation. Surprisingly, many severe diseases such as diabetes and high blood pressure can also be cured effectively by the extraction from the oil and flower of bitter orange . Pharmacological actions for C. aurantium include the following: antispasmodic, sedative, tranquilizer, cholagogue, demulcent, eupeptic, tonic, and vascular stimulant; as an antiinflammatory, antibacterial, and antifungal agent and for reducing cholesterol . Bitter orange contains alkaloids synephrine increase energy expenditure and decreased food intake through activation of alpha- and beta-adrenergic receptors. Synephrine alkaloids may also decrease food intake by reducing gastric motility and act as an agent used in weight-loss diet supplement that is claimed to cause strokes and heart attacks [86, 87]. A limited number of studies have been conducted with p-synephrine and bitter orange extracts without the addition of various other ingredients and herbal products. The issue of safety and efficacy is further clouded and complicated by the structural similarity of p-synephrine to ephedrine and other biogenic amines. In spite of the fact that the pharmacokinetics of these compounds and their receptor binding specificities are vastly different due to significant structural and stereochemical differences .
White kidney bean extract is derived from the beans of the genus Phaseolus vulgaris. Anecdotal evidence suggests that extract derived from the beans of this genus is capable of causing reduction in body fat and body weight. However, white kidney bean extract is most efficient as an antiobesity, antidiabetic, and anticardiovascular diseases . Kidney beans are a very good source of cholesterol-lowering fiber, as most other beans. In addition to lowering cholesterol, kidney beans’ high fiber content prevents blood sugar levels from rising too rapidly after a meal, making these beans an especially good choice for individuals with diabetes, insulin resistance, or hypoglycemia . Kidney beans are an excellent source of the trace mineral, molybdenum, an integral component of the enzyme sulfite oxidase, which is responsible for detoxifying sulfites .
Therapeutic Benefits of Kidney Beans
Glycoproteins obtained from kidney beans are however thought to be the most efficient in blocking enzymes responsible for breakdown of carbohydrates. These kidney bean glycoproteins are the ones that have been most extensively researched, especially the proprietary product. So white kidney bean extract helps fight obesity and other metabolic diseases . Kidney bean contribution to heart health lies not just in their fiber but in the significant amounts of folate and magnesium these beans supply. Folate helps lower levels of homocysteine, an amino acid that is an intermediate product in an important metabolic process called the methylation cycle . Elevated blood levels of homocysteine are an independent risk factor for heart attack, stroke, or peripheral vascular disease . Kidney beans’ good supply of magnesium puts yet another plus in the column of its beneficial cardiovascular effects. Magnesium is nature’s own calcium channel blocker. When there is enough magnesium around, veins and arteries breathe a sigh of relief and relax, which lessens resistance and improves the flow of blood, oxygen, and nutrients throughout the body . Kidney bean has beneficial effects on the digestive system, and the heart and soluble fiber help stabilize blood sugar levels. If one has insulin resistance, hypoglycemia, or diabetes, kidney beans can really help to balance blood sugar levels while providing steady, slow-burning energy. Studies of high-fiber diets and blood sugar levels have shown the dramatic benefits provided by these high-fiber foods .
Oats (Avena sativa L.) Family
Gramineaeis grow as hardy annual grasses able to withstand poor soil conditions in which other crops are unable to thrive and are best adapted to areas with a cool, moist climate . Oats are a good source of soluble and insoluble fiber, manganese, selenium, phosphorous, tryptophan, thiamine, and vitamin E (mainly as alpha-tocopherol). The protein content is 15 to 20 % higher than that of other cereal grains, with approximately 10 % consisting of storage proteins known as avenins . These proteins belong to the prolamin group and are related to the gluten found in wheat . Oat bran contains the soluble dietary fiber beta-glucan, a highly viscous soluble polysaccharide with a linear, unbranched structure composed of 4-O- and 3-O-linked beta-D-glucopyranosyl units. Other polysaccharides in oat include starch, araban, and xylan gums. Lipid content is high, especially in unsaturated triglycerides. Lipase, lipoxygenase, and superoxide dismutase are enzymes present in oats .
Therapeutic Benefits of Oats
Meals high in soluble fiber have been shown to reduce the rise in postprandial blood glucose and insulin concentration, attributed in part to an increase in the viscosity of the contents of the stomach and small intestine, with a subsequent reduction in the rate of absorption of digested nutrients. The results of studies of oats in diabetic patients are conflicting . Oat fiber produces modest reductions in cholesterol levels and may exert a small positive effect on the risk of coronary artery disease, but the mechanism is unclear. Although evidence suggests that some soluble fibers bind with bile acids or cholesterol, resulting in an increased clearance of low-density lipoprotein (LDL) cholesterol , this action may be insufficient to account for the observed cholesterol reductions. Other proposed mechanisms include inhibition of hepatic fatty acid synthesis, changes in intestinal motility, and reduction in absorption of macronutrients resulting in increased insulin sensitivity and satiety with a consequent overall reduction in total energy intake [99, 100, 101]. Other factors to be considered when interpreting trial data include the solubility and molecular weight of beta-glucan, unfavorable changes during commercial preparation, storage conditions, and cooking processes .
Goldenberries (Physalisperuviana L.) were harvested at four different maturity stages: immature green, mature green, yellow, and orange, also called cape gooseberry, a perennial plant native to tropical South America and extensively used as part of folk remedies for various diseases. The extracts from different parts of the plant show antihepatotoxic  and anti-inflammatory  activity as well as antiproliferative effects on hepatoma cells . The edible fruits are bearing a complex volatile profile  and containing high levels of vitamins A, B, C, β-carotene, phosphorus, and iron . The juice is rich in fat-soluble bioactive compounds (tocopherols and phytosterols) and could be a novel source of functional drinks .
Therapeutic Benefits of Goldenberry
The medicinal properties of goldenberry have been attributed to the cape gooseberry, including antiasthmatic, diuretic, antiseptic, strengthener for the optic nerve, treatment of throat affections, and elimination of intestinal parasites, amoebas, as well as albumin from kidneys [109, 110]. Goldenberries contain some medicinal compounds, have strong antioxidant property, and prevent peroxidative damage to liver microsomes and hepatocytes . Goldenberry extracts are also reported for its anticancer effects  . The fruit has been widely used as an excellent source of provitamin A, minerals, vitamin C, and some of the vitamin B complex . The fruit of goldenberry contains about 15 % soluble solids (mainly sugars), and its high level of fructose makes it valuable for diabetics. Its high content of dietary fiber is of importance, wherein fruit pectin acts as an intestinal regulator and a detoxifying agent. It has an antiulcer activity, and it is effective in reducing cholesterol level [113, 110]. Goldenberries act as a hypolipidemic, hypocholesterolemic, and atherosclero protective agent. This is probably due to the wealth of phytosterols. Numerous studies have noted that phytosterols induce a decrease in lipoprotein cholesterol levels in total plasma . It has been hypothesized that these compounds provoke a decrease in cholesterol solubility and their absorption across the intestinal barrier, inducing consequently low plasma cholesterol levels . It has been demonstrated that these compounds prevent or delay the development of atherosclerotic lesions. The fatty acid profile of fruit pomace which is rich in essential fatty acids as well as PUFA may also play an important role for pomace health-promoting properties. Other bioactive compounds, such as tocopherols, are present in fruit pomace and could prevent the structural alteration of lipoproteins [113, 110]. The beneficial effects could be also related to minor components, especially flavonoids, which are proposed to exert their action by inhibiting LDL oxidation and platelet aggregation and caroteinoides, which are thought to act mainly as antioxidants .
Anthocyanins are particularly high in cherries and highly concentrated in the skin of the fruit, accumulating during the ripening process . Cherries consist of more than 100 different species, of which the “sweet” and “sour” (tart) cherry species are perhaps the most recognized . Sweet and tart cherries are a good source of many vitamins, minerals, and phytochemicals, but tart cherries contain considerably more total phenolics, which have been partially attributed to the higher content of anthocyanins in tart cherries . One of the most frequently encountered anthocyanins in cherries is cyanidin-3-glucoside, and the quantity of anthocyanins in cherries produced by various cultivars has been measured at 30–79 mg of cyanidin-3-glucoside equivalents (CGE)/100 g in sweet cherries and 45–109 mg CGE/100 g in tart cherries .
Therapeutic Benefits of Cherries
Several pharmaceutical drugs are fairly effective in combating inflammation and reducing blood lipid levels, but these are frequently associated with many devastating and undesirable side effects, creating a demand for safe and natural anti-inflammatory and lipid-lowering agents. In recent years, tart cherries have been cited as a functional food that may have the capacity to reduce the oxidative damage, inflammation, and dyslipidemia associated with the pathogenesis of chronic disease. Several studies have documented the antioxidant properties of tart cherries both in vitro and in vivo, but there are much fewer studies exploring the effects of tart cherries on inflammation and dyslipidemia . Tart cherry diet was associated with significantly increased abdominal fat proliferator-α activated receptors-α mRNA expression; this reduced liver neutral lipid fat content, enhanced hepaticacyl-coenzyme A oxidase activity, and reduced fatty acid synthase activity.Recent study reported that the consuming 100 % tart cherry juice daily on blood lipids including total cholesterol, low-density lipoprotein cholesterol (LDL-C), calculated very low density lipoprotein cholesterol (VLDLC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and the CVD risk ratios as well as the inflammatory biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and erythrocyte sedimentation rate (ESR) . Of the few studies that have analyzed the effects of tart cherry juice on inflammation and serum lipid values in humans, the results have been contradictory, and the characteristics and size of the subject sample have varied. There is a need for further studies in this area, especially among non-diabetic, overweight, and obese individuals that may have a higher probability of suffering from inflammation and dyslipidemia. Therefore, it would be advantageous for further research to explore the responsiveness of large sample size of such participants to a tart cherry juice intervention.
Saffron threads (red stigmas) used to prepare the satiereal extract were mainly of Iranian origin. Stigmas were harvested from mature flowers (C. sativus L; Iridaceae) . Pharmacological studies on saffron demonstrated numerous health properties such as anticancer and antitoxic , antioxidant , antinociceptive and anti-inflammatory , antiatherosclerosis , antidiabetic and insulin resistance , hypotensive , hypolipidemic , hypoglycemic , and antidepressant and mood improving . It is a source of plant polyphenols and carotenoids.
Therapeutic Benefits of Saffron
Saffron would improve mood, hence reducing snacking and the desire to eat. Modulating abnormal frequent snacking might subsequently contribute to a better control of body weight; and by having a positive effect on stress and mood, saffron could be an adjuvant supplement for people who are involved in weight loss programs . Saffron is able to reduce levels of glucose, triglycerides and LDL cholesterol in blood, increase energy expenditure and fat oxidation, as well as lower body weight and adiposity [130, 131]. Research results have shown that they are also capable of inhibiting enzymes related to fat metabolism, including pancreatic lipase, lipoprotein lipase, and glycerophosphate dehydrogenase . Although research about the connection between saffron compounds and body weight is not definitive yet, there are several theories that saffron has a potential to combat against overweight/obesity and related metabolic disorders owing to its high antioxidant activity and different biological properties .
Ginger (Zingiber officinale Roscoe, Zingiberacae family) is one of the most commonly used spices around the world, especially in the Southeast-Eastern Asian countries . It has long been used in traditional medicine as a cure for some diseases including inflammatory disease and demonstrated to have various pharmacological activities such as antiemetic, antiulcer anti-inflammatory, antioxidant, antiplatelet, glucose and lipid lowering, and cardiovascular and anticancer activities . Ginger contains volatile oils mainly sesquiterpene hydrocarbons, predominantly zingeberene (35 %), curcumene (18 %) and farnesene (10 %), and nonvolatile pungent compounds: This species contains biologically active constituents such as gingerol, paradol, and shogoal that have many properties and zingerone that produce a hot sensation in the mouth .
Therapeutic Benefits of Ginger
Ginger is considered as a safe herbal medicine and extract of ginger that contains high content of gingerols and shogoals . Dried rhizomes of ginger produced a significant reduction in elevated lipid levels, body weight, hyperglycemia, and hyperinsulinemia. It is well known that both dried and fresh are considered as medicinal products in some countries. On the other hand, dehydration process keeps the physical and chemical properties of ginger active compounds . The effect of ginger in reducing body weight is highly significant; this may most likely be due to the inhibitory action of ginger on absorption of dietary fats by inhibiting its hydrolysis and as a result may decrease the adipose tissue weight . Ginger acts as a hypolipidemic agent in cholesterol fed rabbits. Also, feeding ginger to rats significantly elevated the activity of hepatic cholesterol-7-hydroxylase, the rate limiting enzyme in bile acid synthesis, thereby stimulating cholesterol conversion to bile acids, resulting in elimination of cholesterol from the body. In addition, pure constituent from ginger [E-8 beta, 17 epoxylabol-12-ene 15,16- dial (ZT)] was shown to inhibit cholesterol biosynthesis in homogenated rat liver .
Fenugreek (Trigonella foenumgraecum) is one of the oldest medicinal plants originating in India and North Africa regions . The use of fenugreek dates back to ancient Egyptians, Greeks and Romans . Fenugreek seeds are commonly used as condiment and seasoning in food preparation and are assumed to possess nutritive properties . In addition, seeds were used as tonic and as a lactation stimulant  as well as for treatment of weakness and edema of legs . Several workers indicated the hypoglycemic and hypolipidemic properties of fenugreek seeds  suggesting that fenugreek may help to control diabetes .
Therapeutic Benefits of Fenugreek
Fenugreek seeds also contain the amino acid 4-hydroxyisoleucine which is known to stimulate insulin secretion from pancreatic islet cells . Besides, they contain other amino acids, such as arginine and tryptophan having hypoglycemic and antidiabetic effects . Fenugreek can inhibit carbohydrate metabolic enzymes such as G-6-Pase . Also, the hypoglycemic action may be related to the high amounts of dietary fibers, as the seeds contain around 50 % pectin that forms a colloid suspension when hydrated, and this can decrease rate of gastric emptying and slow glucose absorption from small intestine . Additionally, fenugreek seeds have shown to lower serum and tissue lipids (TL, TG, TC, and PLs). Fenugreek hypolipidemic action may be an outcome of the achievement of normal glucose level which may reduce degradation of already accumulated lipids and inhibit lipolysis. Besides, fenugreek contains the steroidal saponins that are transformed in the gastrointestinal tract to sapogenins which increase biliary cholesterol excretion, leading to lowered cholesterol levels .
Garlic (Allium sativum L.) has been used as a medicinal plant in many countries for a long time. The main components of garlic are water, carbohydrates, protein, fat and dietary fiber and it contains essential amino acids, vitamins and minerals. In addition, extracts of garlic contains various biologically active compounds such as alliin, allicin, ally methanethiosulfinate, ajoene, diallyl disulfide, diallyltrisulfide, and S-allylycysteine . It is widely known that garlic produces various biological benefits, which include hypocholesterolemic , hypoglycemic , antihypertensive , anticancer  and antioxidant effects .
Therapeutic Benefits of Garlic
The beneficial effects of garlic can be attributed to diverse organosulfur compounds, including allicin and its derivatives . Allicin is a volatile compound and is highly unstable; it breaks down into a series of compounds, such as sulfides, ajoene, vinyldithinins and many others . Ajoene has been shown to induce apoptosis and decrease lipid accumulation in 3 T3-L1 adipocytes . In addition, treatment with ajoene significantly reduced the rate of body weight gain of mice without any change in the amount of food intake , which implies that it has an effect on the process of energy expenditure. Moreover, 1,2-vinyldithiin has been reported to inhibit the differentiation of human preadipocytes . These antiadipogenic actions of organosulfur compounds that are derived from garlic might significantly contribute to the antiobesity effect of garlic . Also, the level of plasma lipid, triglyceride and total cholesterol were lower in garlic extract may be due to decreases of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol 7α-hydroxylase, pentose-phosphate pathway activities , cholesteryl ester transfer protein activity , microsomal triglyceride transfer protein , increased bile acid excretion and inhibition of hepatic fatty acid synthesis .
Purslane (Portulaca oleracea) is considered as one of the richest sources of antioxidants. It is an edible wild plant that belongs to family Portulaceae. The leaves of purslane are commonly used as food staff, since they contain high ratio of ascorbic acid . Purslane extract in the form of ethanolic formulation is rich in polyphenols, flavonoids and anthocyanin, ω-3 fatty acids, and melatonin. It contained large quantities of ω-3-polyunsaturated fatty acids. Moreover, glutathione was also detected in the leaves of purslane. Purslane was used for infant dietary preparations since its leaves have high moisture content, calcium, sodium, potassium, fibre, and alkaloids. It has many medical uses specially hypolipidemic and anti obesity.
Therapeutic Benefits of Purslane
The medical uses of purslane have been reported in several publications. In Mediterranean, central European and Asian countries, purslane is being used in the treatment of burns and trauma, headaches, stomach, intestinal and liver ailments, cough, shortness of breath, and arthritis . Also, this plant has been employed as a purgative, cardiac tonic, emollient, muscle relaxant and as antihelminitic, antifungal, anti-inflammatory, and diuretic treatment . It showed effects indicative of potential antiobesity and antidiabetic actions in rats fed with a high fat obesity-induced diet . The melatonin concentration in purslane was found to exceed that reported in a number of other fruits and vegetables . Melatonin has a variety of important functions including direct free radical scavenging and anti-inflammatory properties also; melatonin in purslane extract may play a role in the observed antiobesity . It was evidenced that purslane appeared to reduce the development of age-related changes . High content of flavonoids, phenolic compounds, melatonin, and ω-3 fatty acids found in ethanolic extract may be responsible for these effects. Furthermore, there are other plants act as natural antioxidant that are reported to management the obesity and reduce the risks associated such as Pistachio, Psylliumfibre, black Chinese tea, sea buckthorn and bilberries. The effect of purslane seeds intake in reducing body weight might be due to insulin resistance . Some documents have also attributed the lipolytic effect of purslane to its content of nor-adrenaline . Antihyperglycemic effect of purslane could be attributed to its effect on increased insulin secretion through closing the K+/ATP channels, influencing membrane depolarization and Ca2+ entry . Another study showed that purslane seeds intake could significantly increase glucagon-like peptide-1 levels in persons with type 2 diabetes . Purslane seeds contain high amounts of flavonoids . The flavonoids have beneficial effects of regulation serum lipid profiles . The effect of purslane intake on lowering serum triglyceride levels might be explained by its high content of omega-3 fatty acids and fiber . Also, purslaneseed mixture rich in polyunsaturated fatty acids had a strong hypolipidemic, hypotriglyceridemic and hypocholesterolemic effects in plasma and liver of rats with a reduction of plasma LDL-C levels and an increase in HDL-C levels .Moreover, the dietary fiber could be promoting the elimination of bile, the lack of bile in body could be reproduced from dietary cholesterol and then the level of serum cholesterol could be decrease .
As mentioned above, it was concluded that obesity is becoming one of the most prevalent health concerns among all populations and age groups worldwide, resulting in a significant increase in mortality and morbidity related to coronary heart diseases, diabetes type 2, metabolic syndrome, stroke, and cancers. Disappointing results after cessation the lifestyle modification or pharmacotherapy compelled the researchers and physicians to rethink to find a new, safe, and striking therapeutic alternative for this global health concern. Many natural products act as antiobesity through various mechanisms to reduce body weight and its complications. Furthermore, there have been some reports on antioxidative stress effects of natural products including curcumin, green tea, bitter orange, oats berry, cherries, ginger, fenugreek, and purslane which may be important in the management of the different diseases accompanying with obesity like cardiovascular diseases and diabetes. Although various studies suggested the pharmaceutical management of obesity and common related diseases; however, further experimental and clinical designed trials are still needed to focus on both safety and efficacy of these herbal medicines to identify their specific compounds and find a mixture of those components with higher efficacy and studying the direct biological effects of these contents on the expression level of the endogenous antioxidants to overcome the health problems associated with obesity.
Conflict of Interest
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