New research combining lab experiments and a human trial reveals that black cumin seed not only downregulates the genes that drive fat cell formation but also improves cholesterol levels, highlighting its potential as a natural approach to supporting healthier metabolic outcomes.
Study: Black Cumin Seed (Nigella sativa) Confers Anti-Adipogenic Effects in 3T3-L1 Cellular Model and Lipid-Lowering Properties in Human Subjects. Image credit: Dionisvera/Shutterstock.com
A study in Food Science & Nutrition examines the potential of Nigella sativa (black cumin seed) to address obesity-related conditions. In vitro and human trial findings highlight the anti-adipogenic and lipid-lowering effects of black cumin seed extract.
What is obesity?
Obesity is a chronic disease involving excessive body fat accumulation that is linked to metabolic disorders such as dyslipidemia and insulin resistance, as well as cardiovascular diseases (e.g., heart attack and stroke). Excess fat tissue can lead to inflammation and hormonal imbalances, which can negatively affect blood sugar, blood pressure, and cholesterol levels.
Adipogenesis is the process by which preadipocytes differentiate into mature adipocytes, and it plays a crucial role in the development of obesity and its related complications. Previous research has shown that transcription factors, including CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARγ), regulate adipogenesis and lipid accumulation.
Medicinal values of black cumin seeds
Nigella sativa, also known as black cumin, belongs to the Ranunculaceae family and has been traditionally used medicinally across North Africa, South Asia, and the Mediterranean. Black cumin seed and its oil contain many bioactive compounds, including alkaloids, flavonoids, and essential oils, which contribute to its medicinal properties. Previous studies have identified thymoquinone (TQ) as the key active ingredient responsible for black cumin's therapeutic effects.
Research using cell cultures and animal models has shown that black cumin possesses several beneficial properties, including antimicrobial, antioxidant, anti-inflammatory, antidiabetic, immunomodulatory, antihypertensive, antitumor, and anti-obesity effects.
Cumin seed powder and oil exhibited significant improvement in lipid profiles by lowering low-density lipoprotein (LDL), cholesterol, and triglycerides (TG), while simultaneously increasing high-density lipoprotein cholesterol (HDL-C) levels. Regular consumption between 500 mg and 2 g daily has been associated with favorable cholesterol modulation in past studies.
Although previous research has shown that TQ inhibits adipogenesis through pathways such as AMPK and MAPKs, these studies have not yet fully clarified the molecular mechanisms underlying its anti-adipogenic action.
Testing cumin
The current study used the 3T3-L1 cellular model to evaluate the anti-adipogenic potential of black cumin seed extract (BSE). The seeds were washed in water, dried, and ground into powder using a grinder. The methanolic extraction method with a rotary evaporator was used to obtain BSE.
Phytochemical analyses of BSE were conducted using a standard protocol. Fourier Transform Infrared (FTIR) spectroscopy was used to identify the functional groups present in BSE, while the gas chromatography (GC)-mass spectrometry (MS) technique was used for fatty acid profile analysis.
Cell viability was assessed using the neutral red assay, lipid accumulation was evaluated using Oil Red O staining, and adipogenic gene expression was assessed using real-time PCR.
Additionally, a randomized controlled human trial was conducted to evaluate the lipid-lowering properties of black cumin seed powder by measuring serum cholesterol levels. Participants in the intervention group consumed 5 g/day of black cumin seed powder for 8 weeks.
Effects of black cumin
Phytochemical analysis of BSE revealed the presence of total phenolic content (TPC) of 35.475 mg GAE/g dry weight (DW) and a total flavonoid content (TFC) of 39.51 mg QE/g DW. FTIR spectra identified functional groups associated with TQ, including C=O stretching of the quinone, C–O stretching or C–H bending of the aromatic ring, and aromatic C=C stretching.
GC-MS analysis of black cumin seed oil revealed approximately twenty-three different fatty acids. The extract was dominated by methyl eicosatrienoate (69.29 %), methyl 11,14,17-eicosatrienoate (25.2 %), and methyl linoleate (4.05 %).
The neutral red assay demonstrated that BSE concentrations up to 250 μg/mL did not induce cytotoxicity in 3T3-L1 preadipocytes. Cell viability remained constant across all tested BSE concentrations, indicating the extract's non-toxicity. The current study selected 80 μg/mL and 120 μg/mL of BSE for further experimentation.
Compared with control cells, BSE-treated cells showed reduced lipid accumulation of 10.9 % and 40.63 % at concentrations of 80 μg/mL and 120 μg/mL, respectively. This finding implies that BSE may impede adipocyte differentiation in 3T3-L1 cells. In addition, BSE treatment at 80 μg/mL and 120 μg/mL reduced glycerol-3-phosphate dehydrogenase (GPDH) activity, indicating a decline in triglyceride level. The current study highlights the role of black cumin in adipogenesis by decreasing glycerol production in 3T3-L1 cells.
Quantitative real-time PCR (qRT-PCR) analysis revealed that 3T3-L1 cells treated with BSE for 48 hours showed a significant reduction in mRNA levels of C/EBPα, C/EBPβ, and PPARγ compared to the control group. This finding indicated that BSE inhibits adipogenesis by downregulating the expression of these key transcription factors.
The randomized trial evaluated the impact of 8 weeks of black cumin seed supplementation on appetite and lipid profile in participants. This trial included 42 eligible participants (male: 73 %; female: 27 %), including 22 in the treatment group and 20 in the control group. All participants were aged 18 or older with a body mass index (BMI) exceeding 25.0 kg/m2.
The intervention group showed a significant increase in Council on Nutrition Appetite Questionnaire (CNAQ) scores compared to the control group, suggesting no adverse effect on appetite, rather than indicating a biological appetite-enhancing effect. Black cumin seed supplementation indicated no signs of clinical toxicity or any other adverse effects. Furthermore, the test group showed a significant reduction in total cholesterol, LDL-C, and TG, along with an increase in HDL-C.
The future for cumin
The current study highlighted the potential of black cumin seed supplements in improving serum lipid profiles, which could help manage dyslipidemia and reduce cardiovascular risk. However, the absence of a placebo in the control group should be considered when interpreting the findings.
In the future, long-term research with larger sample sizes is required to validate the findings. The underlying mechanisms of the health benefits of black cumin seed require further investigation.
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Journal reference:
- Ahmed, S. et al. (2025) Black Cumin Seed (Nigella sativa) Confers Anti-Adipogenic Effects in 3T3-L1 Cellular Model and Lipid-Lowering Properties in Human Subjects. Food Science & Nutrition. 13(9), e70888. https://doi.org/10.1002/fsn3.70888. https://onlinelibrary.wiley.com/doi/10.1002/fsn3.70888