The search for new tools against obesity is one of the main challenges of pharmaceutical research in the last decades [1
]. Despite a variety of studies focusing on the management of this disease, its global incidence is raising, resulting in enormous social costs [4
]. Obesity consists of an excessive fat accumulation in adipose tissues.
Beside the weight gain, obesity is a complex public health issue, as this pathological condition is linked to an increased risk of other diseases, including type 2 diabetes, cardiovascular diseases and cancer [6
]. Obesity constitutes a pre-requisite for the so-called “metabolic syndrome,” defined as a combination of risk factors, such as obesity, insulin resistance, dyslipidaemia and hypertension, that together are able to cause serious outcomes, such as type 2 diabetes mellitus and cardiovascular diseases [9
]. Diabetes is one of the greatest health care problems, that has been calculated to affect 387 million people worldwide in 2014 and that could potentially reach pandemic levels by 2030. A number of studies have underlined the close relationship between obesity and diabetes: it has been estimated that about 90% of type 2 diabetes is related to excessive body weight. Because of this strong association, the term “diabesity” has been coined [10
Despite the huge investments for the development of effective anti-obesity agents, only a few drugs have been approved for marketing. Furthermore, several of them have been withdrawn due to their side effects, such as dinitrophenol, sibutramine or rimonabant [11
Orlistat, introduced in 1998, was the first really successful drug against obesity. This molecule is a semisynthetic derivative of the natural lipase inhibitor produced by Streptomyces toxytricini
and it is a potent pancreatic and gastric lipase inhibitor, able to prevent dietary fat absorption by 30%. However, also this drug might not be well tolerated, since some side effects, such as diarrhoea, faecal incontinence, flatulence, bloating and dyspepsia, commonly occur [2
Recently, four other new drugs have been introduced: lorcaserin and phentermine+topiramate ER, approved by FDA in 2012 and successively naltrexone SR/bupropion SR and liraglutide recently approved in both the USA and Europe. Nevertheless, also with these drugs some patients may experience different adverse effects [14
A negative correlation between the consumption of fruits and vegetables and the incidence of several diseases has been confirmed by many epidemiological studies. Plants are an important source of health-promoting compounds, such as vitamins and flavonoids. Because of the recognition of the importance of edible plants also for human health and not only as food, there is a great interest toward plant-derived pharmaceuticals, dietary supplements and functional foods [15
Alongside other new anti-obesity drugs that are currently under investigation [17
], the potential role of plants and their metabolites has been taken into account in most recent studies as an alternative in the treatment of obesity, with the aim to find well-tolerated natural effective drugs. A variety of natural products that includes medicinal plant extracts or isolated pure compounds is currently on the market. Different plants contain bioactive components with anti-obesity effects on body metabolism and for this reason they have been investigated and reported to be useful in treatment of obesity, diabetes and other chronic diseases [18
Different classes of phytochemicals have been proved to modulate obesity through various mechanisms of action, such as polyphenols [19
], terpenes [21
] and saponins [23
The activity of many effective herbal medicines in the management of obesity has been reported [24
Allium cepa L. is one of leading vegetable crops in the world and the phytochemical and biological characteristics of this species have been deeply investigated. The purpose of this review is to present a comprehensive overview of recent and relevant studies related to the beneficial effects of A. cepa L. against obesity and its related comorbidities, such as hyperlipidaemia, hypertension and diabetes. Both in vitro and in vivo effects of onion dietary supplementation are presented and discussed. Moreover, the potential anti-obesity activity of onion bioactive components and their possible mechanisms of action are reported.
2. Allium cepa L.: Botany, Distribution and Phytochemistry
The species Allium cepa
L., commonly known as onion, has been for a long time considered a member of the Liliaceae family [30
] but according to more recent taxonomic schemes the genus Allium
belongs to the family Amaryllidaceae, subfamily Allioideae [32
]. This genus is one of the largest monocot genera as it comprises about 850 species [33
is a biennial plant with adventitious and fibrous roots and 3–8, distichous, glaucous leaves. The bulb is made of concentric, enlarged fleshy leaf bases. The outer leaf base dries and becomes thin and variously coloured, forming the protective coat, while the inner leaf bases thicken when the bulb develops. The mature bulb can be globose, ovoid or elongate and its size varies depending on the cultivar [34
is a bulbous plant widely cultivated in almost every country of the world. According to the last available FAO statistics [35
], in 2016 the top producers of onions were China (23,849,053 tonnes) and India (19,415,425 t), followed by Egypt and USA (about 3,000,000 t), Iran, Turkey, Russian Federation, Pakistan, Bangladesh and Brazil (from 2,345,768 to 1,657,441 t). Onions produced in European countries accounted for 10.9% of the world production, being Asia (65.5%) the most important producer.
Because of its worldwide distribution, a great number of cultivars can be identified: ‘Stardust,’ ‘Snowpack,’ ‘Redlight,’ ‘Hytech’ [36
], ‘Tropea,’ ‘Montoro’ [37
], ‘Festival,’ ‘Castillo’ [38
], ‘Nazik Red’ and ‘Ailsa Craig’ [39
] are just some examples.
At present, approximately 13,000 onion accessions are held in gene banks worldwide. A high genetic variability can be observed regarding the morphological features [36
Onion bulb is used as both vegetable and flavouring. The bulb is eaten raw or cooked. The leaves and the flowers of the plant are also edible and are often used in salads. The seeds of the plant are sprouted and eaten as well [34
]. Onion is used as food and spice in diets of almost all cultural areas. In addition, onions can be processed into various products such as dehydrated powder or juice, which are used for the seasoning and flavouring of food [36
Onion is rich in several phytonutrients that are recognized as important elements of the Mediterranean diet but it has received attention also for its biological properties and potential application in the treatment and prevention of a number of diseases [34
]. A. cepa
is known to contain many vitamins and minerals and is rich in sulphur amino acids. Moreover, a variety of secondary metabolites has been identified in this species, such as flavonoids (particularly flavonols and anthocyanin), phytosterols and saponins [40
]. Many studies focused on the phytochemical composition of onions, which have been already extensively reviewed [41
3. A. cepa Biological Activities
A variety of biological properties has been reported for A. cepa
. A great number of studies focus on its antimicrobial potential, which has been already reviewed in dept by Teshika and colleagues [42
]. However also other properties, such as antioxidant, anti-melanogenesis, antispasmodic and antiproliferative activities, have been attributed to this species.
The antioxidant properties of A. cepa
have been deeply investigated and documented [44
]. These studies are very important as recent findings have demonstrated a link between increased body weight and fat deposition and enhanced oxidative stress. The lower levels of antioxidant might play a role in the development of obesity comorbidities. It has been hypothesized that obesity could be inversely associated with antioxidant intake [46
]. Moreover, antioxidants may be important in the management of the different obesity related diseases such as cardiovascular diseases and diabetes [47
] Benkeblia [48
] reported the radical scavenging and antioxidant properties of the methanolic extracts of different onion cultivars from Algeria: A. cepa
‘Premier’ (green onion), ‘Jaune d’Espagne’ (yellow onion), ‘Amposta’ (red) and ‘Rouge’ (purple).
The radical scavenging and antioxidant activities of extracts from skin and edible part of red onion A. cepa
var. Red baron from Slovenia have been instead investigated by Škerget and colleagues [49
]. The best radical scavenging potential was observed for the onion skin pure acetone extract, while the highest antioxidant activity, measured through the β-carotene bleaching test, was demonstrated for the onion skin extracted with 35% and 60% acetone and 60% ethanol. On the other hand, a low antioxidant activity was observed for onion edible part extracts in these experiments.
Santas and colleagues reported the antioxidant properties of three different Spanish A. cepa
cultivars: white skinned onion ‘Fuentes de Ebro,’ white skinned onion ‘Calçot de Valls’ and yellow skinned onion ‘Grano de Oro’ [50
]. Plant materials were extracted with 75% methanol and obtained extracts were then fractionated. Ethyl acetate subfractions contained the highest amount of flavonoids and the Trolox equivalent antioxidant capacity was reported to be 74.86, 24.59 and 4.55 µmol Trolox/g for ‘Grano de Oro,’ ‘Fuentes de Ebro’ and ‘Calçot de Valls,’ respectively.
A strong antioxidant activity was demonstrated for red onion ‘N-53′ from India [51
]. A good antioxidant potential was also reported for the bulb methanolic extracts of three A. cepa
cultivars: ‘Pusa Red’ (red), ‘Pusa White Round’ (white) and ‘Arka Pitamber’ (yellow) [52
Also Benmalek and co-workers assessed the radical scavenging of A. cepa
. An IC50
value equal to 2.91 × 10−5
mg/mL was reported for the outer layer of red onions [53
The oxygen radical absorbance capacity of A. cepa
has been also reported [54
]. Pulp and skin were extracted with distilled water and 95% ethyl alcohol. The highest ORAC value and total phenolic content were detected for the ethyl alcohol extract of onion skin.
Lee and colleagues [55
] evaluated the antioxidant properties of four different extracts from A. cepa
peels: plant material was extracted with hot ethanol (60°C), hot water (80°C) and by means of subcritical water extraction at 110°C and 165°C. The ethanolic onion peel extract showed a better DPPH radical scavenging activity and a highest antioxidant activities determined by ferric thiocyanate assay compared to the other samples.
Also A. cepa
essential oil showed antioxidant properties [56
]. The essential oil was extracted by supercritical CO2
extraction and biological properties were assayed by means of ABTS assay (IC50
= 0.67 mg/mL), DPPH test (IC50
= 0.63 mg/mL) and metal chelating assay (IC50
= 0.51 mg/mL).
Interestingly, the potential activity of A. cepa
against oxidative stress was verified also in vivo. Campos and co-workers [57
] investigated the effects of the consumption of onion extract in STZ-induced diabetic rats. Onion bulbs were collected from Brazil and extracted with water by infusion (40 g/100 mL). It was demonstrated that onion intake was able to decrease superoxide dismutase activity while no increased lipid hydroperoxide and lipoperoxide concentrations were observed in treated diabetic rats.
The antioxidant potential of the ethanolic extract and fractions of A. cepa
were studied by Baragob and co-workers both in vitro and in vivo [58
]. In vitro activities were verified using DPPH and NO radical scavenging methods, whereas the in vivo effects on antioxidant enzyme were assessed in the erythrocytes and pancreas of normal and STZ-induced diabetic rats. Before treatment, normal groups contained higher enzyme levels of SOD, CAT, GSH and LPO than diabetic groups, while the administration of A. cepa
ethanolic extract and its chloroform fraction in diabetic groups significantly increased the level of SOD, CAT and GSH and decreased LPO level to near normal erythrocytes and pancreas.
Ren and colleagues [59
] assessed the in vitro antioxidant activity of two onion varieties (‘Hyskin’ and ‘Red Baron’) grown in a 6-year field study. The influence of conventional, organic and mixed cultivation practices on phytochemical composition and antioxidant activity was verified as well. Both varieties showed the best effectiveness under fully organic management.
Different onion by-products have also been reported to possess good antioxidant properties that make onion useful as functional food ingredient [60
Moreover, Gawlik-Dziki and colleagues [61
] investigated the antioxidant potential of breads enriched with A. cepa
skin. The food supplement was prepared by drying onions (A. cepa
‘Wolska’) in an oven at 50 °C and by powdering the plant material using a laboratory mill. For the experiments, the flour used in the formula of control bread (wheat bread flour 600 g, type 750) was replaced with onion skin at 1%, 2%, 3%, 4%, 5% levels. Bioaccessibility and bioavailability were determined in vitro by using the human gastrointestinal tract model. Breads were then extracted with 80% methanol and bread extracts were assayed for their antiradical activity, their ability to inhibit lipid peroxidation, the metal chelating activity and the ferric reducing power. The antioxidant potential of onion enriched bread was significantly higher than that observed in the control.
Furthermore, Helen and co-workers [62
] demonstrated that onion oil is an effective antioxidant against the oxidative damage caused by nicotine in rats to a similar extent to vitamin E.
The appropriate processing technologies and storage conditions able to preserve the antioxidant capacity of onions have been also investigated. Siddiq and co-workers [63
] reported that the use of mild-heat treatment for processing fresh-cut onions (50 and 60 °C) did not affect the antioxidant activity (evaluated by means of ABTS and DPPH tests) and the colour of fresh-cut onions. Moreover, a good antioxidant activity has been recently demonstrated for onion polysaccharide fractions [64
Anti-melanogenesis properties have been also reported for A. cepa
. A strong melanin biosynthesis inhibitory activity on B16 melanoma cells was reported for the methanolic extract of the dried skin of A. cepa
from Indonesia [65
]. Quercetin and quercetin 4′-O
-β-glucoside were the most active identified compounds. Obtained results demonstrated that A. cepa
skin extract could likely act as a potent skin-whitening agent by inhibiting the melanin formation in B16 melanoma cells, similarly to arbutin, which was used as a positive control.
Interestingly, the fresh juice of onion bulbs was tested for its androgenic effects on the spermatogenesis cycle in Wistar albino rats [66
]. Administration of 0.5 g/rat and 1 g/rat of freshly prepared onion juice significantly increased sperm motility and viability as compared to the control after 20 days of treatment. Serum total testosterone level was also increased.
Moreover, Naseri and co-workers investigated the antispasmodic activity of onion peel extract [67
]. Onion peel powder was extracted with 70% ethanol trough maceration and the antispasmodic effects were evaluated on Wistar rat ileum contractility. Onion peel extract was able to reduce the KCl and carbachol-induced ileum contractions in a dose dependent manner.
Another potential biological property of A. cepa
was investigated by Sakakibara and co-workers [68
], who verified the antidepressant-like effect in a rat behavioural model of depression. Onions from Japan were peeled and processed to a powder with a freeze dryer. Rats were orally administered with A. cepa
powder dissolved in water or with the synthetic antidepressant imipramine for 14 days of treatment. The immobility time in FST was significantly reduced by the administration of onion at a dosage of 50 mg/kg, similarly to imipramine.
extract exerted also antiproliferative activity. Obesity has been associated with an increased risk of developing some forms of cancer, such as breast [69
], endometrial [70
], prostate [71
] and colorectal cancer [72
]. This relationship may be due to different mechanisms, depending on the cancer site, such as insulin resistance and alterations in circulating levels of steroid hormones [73
Effectiveness on the human breast cancer MDA-MB-231 cells was reported by Wang and colleagues [74
]. The ethyl acetate fraction of onion showed the best inhibition of cell viability, with an IC50
value equal to 52 μg/mL. This fraction, interestingly, was the most effective in inhibiting FAS in vitro, with an IC50
value equal to 2.4 ± 0.3 μg/mL. Western blotting analysis demonstrated that FAS was expressed in high level in MDA-MB-231 cells. The treatment with this fraction at the concentrations of 25 μg/mL and 50 μg/mL for 24 h induced a decrease of the intracellular FAS activities of MDA-MB-231 cells (56.3% and 32.1%) compared to the control. Obtained results seem to suggest that the apoptosis induced by onion ethyl acetate fraction might occur via inhibition of FAS.
The antiproliferative activity of A. cepa
on MDA-MB-231 cells was also assessed by Fredotović and co-workers, who verified the antiproliferative effects of the methanolic extract of the plant on both these breast cancer cells and the human glioblastoma cell line-A1235A [75
Moreover, A. cepa
was also proved to be effective against the murine melanoma cell line B16F10 [76
] and the human colorectal adenocarcinoma Caco-2 cell line [77
]. The effects on human hepatocellular carcinoma cells HepG2 were tested as well [77
Onion is a plant with a long history of traditional medicinal uses. The extensive studies conducted in the last years confirmed that this species is a rich source of putative health-promoting phytochemicals, including flavonoids and organosulfur compounds. A number of works deal with the potential beneficial effects of onion dietary supplement. A. cepa extracts, its fractions and its identified bioactive components can induce their effects troughs different mechanisms of action: pancreatic lipase inhibition, adipogenesis inhibition and energy expenditure increase have been documented. Moreover, a substantial number of studies have proven the efficacy of A. cepa in the treatment of pathological conditions linked to obesity, such as hyperlipidaemia, diabetes, hypertension, cardiovascular diseases and inflammatory state. At the state of the art, quercetin and organosulfur compounds seems to be the compounds responsible for the anti-obesity potential of A. cepa and so the most promising molecules for a therapeutic application.
On the other hand, a very few number of studies contradicted these positive results. However, a comparative analysis of data cannot be easily performed. It has to be taken into account that the studies concerning A. cepa here reviewed were conducted on different plant materials, grown and harvested in different pedo-climatic conditions and whose active principles were extracted through more than one extraction techniques and solvents. Actually, for these reasons, the phytochemical composition of investigated samples might vary even consistently. These differences should be taken into account in further investigations on the potential use of onion in effective formulations intended for weight control and /or the treatment of obesity related comorbidities.
Edible plants have a great potential as functional ingredients able to induce anti-obesity effects. They represent an effective tool in the fight against overweight and obesity. Onion enriched food could be also taken into account for their potential use in obesity treatment and prevention. In the future research, both genetic engineering, for the improvement of the active metabolites synthesis and food industry and its innovative approaches, might play an important role in the development of healthier foods useful against obesity.