Effects of Nigella sativa on Obesity: History
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Contributor:
Siti Hajar Adam
,
Izuddin Fahmy Abu
,
Datu Agasi Mohd Kamal
,
Ami Febriza
,
Mohd Izhar Ariff Mohd Kashim
,
Mohd Helmy Mokhtar

Obesity has become a worldwide epidemic and its prevalence continues to increase at an alarming rate. It is considered a major risk factor for the development of several comorbidities, including type 2 diabetes, stroke, other cardiovascular diseases and even cancer. Conventional treatments for obesity, such as dietary interventions, exercise and pharmacotherapy, have proven to have limited effectiveness and are often associated with undesirable side effects. Therefore, there is a growing interest in exploring alternative therapeutic approaches. Nigella sativa (NS), a medicinal plant with multiple pharmacological properties, has gained attention due to its potential role in the treatment of obesity and its associated complications. 

  • thymoquinone
  • antioxidants
  • anti-obesity
  • body weight

1. Chemical Composition of Nigella sativa

Numerous chemical compounds have been identified in Nigella sativa (NS). The compounds may vary depending on the area of cultivation, degree of ripeness, processing methods and isolation techniques. Different extraction methods or solvents, such as in oil samples extracted with a cold press, hexane, tetrahydrofuran, ethanol, dichloromethane and methanol, yielded different amounts of chemical compounds as the methods used affected the oil quality [1]. NS consisted of significant amounts of iron, copper, zinc, phosphorus, calcium, thiamine, niacin, pyridoxine, and folic acid [2][3][4]. In addition, it had maximum nutritional value with a significant amount of 20–85% vegetable protein, 7–94% fibre, 38.02% fat and 31.94% carbohydrate [5]. Apart from these, NS also contains bioactive phytochemicals such as terpenes and terpenoids, phytosterols, alkaloids, tocols and polyphenols [6]. Table 1 lists the chemical composition of NS.
The main constituent of NS, which is considered to have to medicinal value, is thymoquinone (TQ) [7]. TQ (2-isopropyl-5-methylbenzo-1, 4-quinone) is the main constituent of the volatile oil of the NS seeds [8]. TQ can be found in tautomeric forms, such as the enol form, the keto form, and in combination. The pharmacological properties of this compound are due to the keto form, which constitutes the major part (about 90%) of the compound [8]. TQ is a promising compound for modern pharmacology because it has been shown to act as a modulator in several pharmacological pathways involving inflammatory responses, oxidative markers, apoptosis, peroxisome proliferator-activated receptors (PPARs) and transcription factors [9].
The bioactive compounds in NS, especially TQ and polyphenols such as gallic acid, p-coumaric acid, naringenin and quercetin, are thought to play a role in the inhibitory effect of NS on the digestive enzyme α-amylase and glucose uptake in the intestine, which could explain its properties as an anti-obesity agent [10][11]. Further studies could focus on the chemical compounds in NS that mediate the anti-obesity effect, with a view to possibly extracting them and using them as an anti-obesity agent.
Table 1. Lists of the chemical composition of NS.
Component Composition References
Fatty acid Linoleic acid, oleic acid, lauric acid, stearic acid, linolenic acid [12][13]
Vitamin Ascorbic acid, tiamin, riboflavin, pyridoxine, niacin [13][14]
Mineral Calcium, magnesium, potassium, phosphorus and iron [15]
Alkaloids Nigellidine, nigeglanine, nigelanoid, 17-O-(β-d-glucopyranosyl)-4-O-methylnigellidine, 4-O-methylnigeglanine [16]
Terpenes and Terpenoids Thymoquinone, thymohydroquinone, dithymoquinone, p-cymene, sesquiterpene longifolene [6][12]
Polyphenols Apigenin, naringenin, gallic acid, rutin, quercetin, kaempferol [17]
Phytosterols Campesterol, stigmasterol, β-sitosterol [18]
Tocols β-tocotrienol, γ-tocopherol isomer, β-sitosterol [12]
Saponin Alpha-hederin (α-HN),
3-O-(β-d-xylopyranosyl-(1-3)-α-l-rhamnopyrnaosyl-(1-2)-α-l-arabinopyranosyl]-28-O-(α-l-rhamno-pyranosyl-(1-4)-β-d-glucopyranosyl-(1-6)-β-d-glucopyranosyl] hederagenin,
3-O-[α-L-rhamnopyranosyl-(1-2)-α-L-arabinopyranosyl]-28-O-[α-L-rhamnopyranosyl-(1-4)-β-D-glucopyranosyl-(1-6)-\β-D-glucopyranosyl]-hederagenin
and 3-O-[β-D-xylopyranosyl-(1-3)-α-L-rhamnopyranosyl-(1-2)-α-L-arabinopyranosyl]-hederagenin		 [19][20][21]

2. Clinical Studies

Body weight (BW) and waist circumference are the ideal anthropometric predictors of abdominal obesity that can be used to predict cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome and other chronic diseases. In a clinical trial of obese women who followed a low-calorie diet and received 3 g/day NS oil, BW, TG and very low-density lipoprotein (VLDL) levels and waist circumference (WC) decreased significantly at the end of the 8-week study period compared to the placebo group [22]. It is possible that NS produces these effects due to its high unsaturated fatty acid content, antioxidant and anti-inflammatory components. Previously, it was shown that the hypotriglyceridaemic effect of NS could be due to the presence of unsaturated fatty acids [23]. Unsaturated fatty acids may modulate the levels of TG and VLDL by affecting the synthesis and degradation of TG-rich lipoproteins. Moreover, NS antioxidants such as TQ and ter-butylhydroquinone (TBHQ) could prevent lipid peroxidation and improve enzyme function in lipid metabolism [24][25]. Meanwhile, a follow-up study showed that the intake of NS oil (3 g/day) in obese women led to a reduction in body fat mass (BFM) and insulin levels, while adiponectin levels increased compared to the placebo group. Adiponectin is an adipokine that is mainly secreted by adipose tissue and has anti-inflammatory and insulin-sensitising properties. However, no significant changes were observed in body mass index (BMI), insulin sensitivity and nuclear receptor PPAR-γ [26]. Liver enzymes also did not change significantly after the intervention, and none of the participants experienced severe side effects, demonstrating the safety of NS. The findings of this research show that taking NS oil in combination with a low-calorie diet can influence hormone secretion and body composition in obese women.
As shown in animal studies, the potential mechanisms of NS against obesity could include the reduction in appetite and food intake, as well as the active components of NS, such as TQ and thymol, which can influence fat metabolism and insulin secretion [27]. In addition, phytochemicals have been shown to have the ability to manifest their anti-obesity properties through many pathways, including inhibiting the activity of digestive enzymes such as pancreatic lipase and amylase, thereby modulating appetite and reducing white adipose tissue production [28].
Previous research has shown that central obesity is a risk factor that increases the likelihood of cardiovascular events and is associated with metabolic syndrome, insulin resistance and other metabolic disorders. According to a study of centrally obese men, a daily intake of 3000 mg NS resulted in significant reductions in BW, WC and systolic BP. Although not statistically different from the control group, several biochemical measures, including serum free testosterone, diastolic BP, fasting blood glucose (FBG), TG and HDL cholesterol, uric acid and hs-CRP were reduced [29]. To achieve better results, it has been suggested that the dose should be increased and the duration of the treatment should be prolonged. Meanwhile, in a study on obesity, diabetes and dyslipidaemia, patients treated with 6 weeks of standard treatment (atorvastatin 10 mg/day, metformin 500 mg/twice daily in tablet form) were compared with an experimental group receiving the same treatment with NS oil 2.5 mL/twice daily for the same period. In this research, the experimental group showed significantly better results in total cholesterol, low-density lipoproteins (LDL) and FBG levels. In addition, the NS group also showed a decrease in BW, BMI and abdominal circumference, although the difference was not significant [23]. In a comparative study between obese prediabetics taking NS oil soft gelatine capsules 450 mg twice daily and those receiving metformin 500 mg tablets twice daily, anthropometric (BW, BMI), glycaemic, lipid and inflammatory markers were assessed before and six months after the interventions. It was found that both groups showed equivalent improvements in anthropometric (BW, BMI) and glycaemic indicators. In particular, NS improved the lipid panel and showed a significant reduction in TNF-α levels, in contrast to the metformin group [30]. To determine the exact effect of NS on obesity, further studies should be conducted with more participants, longer treatment periods and different NS doses in both sexes [31].
A recent study showed that anthropometric and body composition indices, including BW, BMI, WC, body fat percentage (BFP), BFM and visceral fat area, as well as appetite and satiety were improved in obese and overweight women through the daily consumption of 2000 mg of NS oil for two periods of eight weeks [31]. The anti-obesity effects of NS have been shown to be due to its bioactive constituents, including TQ, thymol, the lipase enzyme, and various unsaturated fatty acids, such as linolenic acid, linoleic acid, oleic acid, arachidonic acid, and eicosadienoic acid [32][33]. Meanwhile, numerous studies have shown that supplementation of NS can improve insulin sensitivity and metabolic status, leading to an improvement in metabolic profile and a significant reduction in BW [34][35][36]. Thus, the findings may suggest that the consumption of NS is a safe adjuvant therapy for the treatment of obesity in adult women.
In obese people, the level of reactive oxygen species (ROS) is increased and at the same time antioxidant defence mechanisms are reduced. Obesity is associated with increased oxidative stress, which can lead to the initiation and progression of inflammatory processes [37]. It should also be noted that the hormone leptin, which is produced by fat cells, also contributes to the triggering of oxidative stress [38]. Weight loss has been shown to strengthen antioxidant defences [39][40]. A study by Namazi et al. (2015) showed that an eight-week low-calorie diet supplemented with 3 g/day NS oil resulted in a significant reduction in BW and an increase in antioxidant superoxidase dismutase (SOD) in red blood cells in obese women compared to the placebo group [41]. This could be due to the fact that NS has a protective effect against free radical attacks [41]. A previous study showed that treatment of rats with hepatotoxicity-induced lipid peroxidation with 10 mg/kg TQ orally for 5 weeks decreased lipid peroxidation and increased SOD activity in liver tissue [42]. There is also evidence that the synergistic action of the antioxidant components in NS may protect tissues from lipid peroxidation and oxidative stress. The regulation and expression of antioxidant enzyme genes to defend against free radical attack has been proposed as another possible mechanism for the antioxidant effects of NS. In rats suffering from lipid peroxidation caused by hepatotoxicity, Wahab et al. found that TQ (10 mg/kg orally for 5 weeks) increased SOD activity in liver tissue and decreased lipid peroxidation. It has been postulated that TQ has the ability to maintain cell membrane integrity and attenuate the enhanced process of lipid peroxidation [42].
Another study found that consuming NS supplements helps obese people prevent cardiovascular diseases (CVD). Healthy overweight and obese women showed an overall improvement in their cardiovascular disease risk variables after consuming 2000 mg/day of NS for 8 weeks. Specifically, supplementation of NS also lowered the following parameters: systolic blood pressure (BP), TC/HDL-C ratio, serum glutamic-oxaloacetic transaminase, low-density lipoprotein cholesterol and elevated serum high-density lipoprotein cholesterol [43]. The overall improvement in cardiovascular disease risk factors showed that NS supplements may help prevent possible cardiovascular disease in adults with obesity. A more recent study with a similar subject group and intervention demonstrated that supplementation with NS oil had a positive effect on BW and improved important parameters of adipogenesis and obesity, such as the reduction in transcription levels and blood levels of TNF-α; the significant increase in AdipoR1 expression, serum adiponectin, gene expression and serum levels of PPAR-γ [44]; the increase in serum total antioxidant capacity (TAC) and the significant decrease in serum malondialdehyde (MDA) levels [45]. Table 2 shows a summary of clinical studies of NS against obesity and its complications. Meanwhile, Figure 1 summarises the effects of NS against obesity and its complications in animal and clinical studies.
Plants 12 03210 g001
Figure 1. Effects of N. sativa in obesity. Solid black lines indicate a mechanism associated with development of obesity, including oxidative stress, systemic inflammation and insulin resistance. The green arrows indicate increased effects and red arrows indicate decreased effects following NS administration. Malondialdehyde (MDA); superoxide dismutase (SOD); glutathione peroxidase (GPx; interleukin (IL); tumour necrosis factor-alpha (TNF-⍺); high density lipoprotein (HDL); low density lipoprotein (LDL).
Table 2. Summary of clinical studies of NS against obesity and its complications.
Type of Study Treatment Dosage Duration of Study Outcomes of the Study Reference
Double-blind, randomized placebo-controlled clinical trial; 90 obese women. 3 g/day NS oil intervention 8 weeks ↓ BW, WC, TG and VLDL. [22]
Prospective study, 60 patients with obesity, diabetes and dyslipidaemia. Atorvastatin 10 mg/day, tablet Metformin 500 mg/twice a day and NS oil 2.5 mL/twice daily 6 weeks ↓ total cholesterol, VLDL and FBG. [23]
Double-blind, randomized placebo-controlled clinical trial; 50 obese women. 3 g/day NS oil intervention 8 weeks ↓ BFM and insulin levels.
↑ Adiponectin levels.
No serious side effects.
No altered liver enzyme levels.		 [26]
Double blind test with placebo control, pre-test and post-test design; intervention among 39 central obesity men. 3000 mg of NS 3 months ↓ BW, WC, and systolic BP. [29]
Open-label, randomized, prospective,
comparative study; 70 obese prediabetic subjects.		 NS oil soft gelatine capsules 450 mg twice daily 6 months Improved anthropometric and glycaemic parameters and lipid panel.
↓ TNF-α,		 [30]
Crossover, double-blind, placebo-controlled RCT; 39 obese and overweight women. 2000 mg/d NS Two 8-week periods of intervention and a 4-week wash-out period ↓ BMI, BW, WC, BFP, BFM, visceral fat area and feeling of appetite. [31]
Double-blind, randomized placebo-controlled clinical trial; 49 obese women. 3 g/day NS oil intervention 8 weeks ↓ BW.
↑ SOD levels.		 [41]
Crossover, randomised-controlled trial; 39 obese and overweight healthy women. 2000 mg/day of NS oil 8 weeks separated by a 4-week washout period ↑ serum HDL.
↓ LDL, TC/HDL-C ratio, serum glutamic-oxaloacetic transaminase and systolic BP.		 [43]
Secondary analysis of a crossover, double-blind, randomized clinical trial; 39 obese and overweight healthy women. 2000 mg/day of NS supplement 8 week intervention separated by a 4-week washout period ↑ serum TAC.
↓ serum MDA.		 [45]
A crossover, randomised-controlled trial, overweight/obese women. 2000 mg/d) of NS Oil Two periods of intervention (8 weeks in each) were cross-changed by a 4-week washout period ↓ BW, transcription levels and blood concentrations of TNF-α.
↑ AdipoR1 expression and serum adiponectin and gene expression and serum levels of PPAR-γ.		 [44]
 

This entry is adapted from the peer-reviewed paper 10.3390/plants12183210

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