Review on Clinical Trials of Black Seed Nigella sativa and Its Active Constituent, Thymoquinone PMC
Application of TQ-loaded ethosomes gel formulation (THQ–EGF) has been shown to decline the number and size of sebaceous glands in rats suggesting TQ as an effective treatment option for acne vulgaris [225]. In another randomized controlled trial with NAFLD patients, black cumin treatment (1 g twice a day for three months) caused a decline in BMI, ALT, AST, and overall fatty liver grading on ultrasound following 12 weeks of treatment compared to the placebo group (Hosseini et al., 2018). Together, all these compelling evidences suggest that black cumin preparations and its main active масло от семена на черен кимион compound TQ are likely to be attractive as a promising therapeutic option against a wide range of liver diseases, including NASH. Sativa to mice for six weeks led to death of one mouse after 2 weeks of treatment with 6.4 g/kg of AqE.
Black cumin: Ancient superseed with modern health benefits
We anticipate that information from this critical review would be capitalized for the future development of black cumin-based potential therapeutic agents to be applied for various diseases and the formulation of popular functional foods in order to promote optimum health and reduce the risk of chronic disease. In many cases, TQ has often been credited for the pharmacological effects of black cumin, regardless of the research focused on its health benefits. However, some studies have presented important findings on the significant health benefits caused by other phytochemicals, such as thymohydroquinone [339], thymol [340], and carvacrol [341], suggesting that compounds beyond TQ also deserve attention. Apart from the aforementioned mechanism, there still remain other (albeit not less significant) signaling systems that are targeted by black cumin and TQ, such as unfolded protein response (UPR). Triggering of endoplasmic reticulum (ER) stress is a common phenomenon in several pathological conditions such as hypoxia/reoxygenation and oxidative stress. ER homeostasis is crucial for proteostasis and its disruption results in the buildup of unfolded and misfolded proteins in the ER lumen.
High-Value Bioactive Compounds (Phytochemicals) in the Seed of Nigella sativa
It’s been used in Ayurvedic medicine for treatments related to colds, throat infections, and even hyperglycemia. The seed oil fatty acid composition (32-40%) has been reported by various authors to contain mainly, linoleic, linolenic, oleic, palmitoleic, palmitic acids together with arachidonic, eicosadienoic, stearic, and myristic acid [15, 16, 19]. A new dienoate and two known monoesters along with novel lipids have been isolated from the unsaponified extract of the seed, namely methylnonadeca-15,17-dienoate, pentyl hexadec-12-enoate, and pentyl pentadec-11-enoate [20].
- Nigella sativa has been broadly studied in the last few decades and studies have reported that it possesses a number of medicinal properties and pharmacological actions.
- Infertility is the incapability of a copulate to attain offspring after 12 months of intercourse without contraception.
- The Skin Deep® scoring system was designed to help the public understand whether a product is safe to use or whether it contains ingredients of concern.
- Protection against neuroinflammation by TQ in LPS-activated BV-2 microglia involved autophagy induction through activation and nuclear accumulation of SIRT1 [50].
- Diabetic rats that received NSO exhibited substantial improvements in lipid profile and expressive increment of pancreatic and hepatic antioxidant enzymes also augmented the histological image and glycogen contents other than improvements of average pancreatic islet extent than the diabetic groups [50].
Cancer
Jrah Harzallah et al. reported that TQ at 80 mg/kg, but not ≤40 mg/kg, markedly caused chromosomal aberrations and DNA damage in the liver and kidney of BALB/c mice, indicating its genotoxic risk at high doses [331]. Thus, nanocarrier-based TQ delivery may minimize toxicity although it was not clear why more bioavailable TQ caused relatively less toxicity. As a master upstream kinase, LKB1 phosphorylates and activates AMPK and many other kinases that play a fundamental role in the regulation of cell growth and metabolism [301]. The LKB1–AMPK pathway acts as a cell metabolic checkpoint, arresting cell growth under low intracellular ATP conditions, such as in nutrient-deficient states [301]. Energy overload may suppress LKB1–AMPK signaling, leading to increased cancer risk in patients with obesity or diabetes.
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Another study isolated methicillin-resistant Staphylococcus aureus (MRSA), a strain of bacteria that is difficult to treat and resistant to antibiotics, from the wounds of diabetic patients. Summary Test-tube studies have shown that kalonji and its components may exhibit anti-cancer effects. Kalonji is high in antioxidants, which help neutralize harmful free radicals that may contribute to the development of diseases like cancer.
Molecular Mechanisms Underlying the Pharmacological Effects across Health and Disease Conditions
Hand eczema is a pruritic papulovesicular dermatitis severely influencing the patient’s quality of life. Yousefi et al compared the effects of NS ointment, betamethasone, and eucerin on the severity of hand eczema and the patients’ quality of life [87]. In that study, for new cases of hand eczema in patients between 18 and 60 years of age the mentioned drugs were applied twice daily for 4 weeks. Through particular measures, the authors concluded that NS may be as effective as betamethasone in enhancing quality of life and alleviating the severity of eczema and that both were more effective than eucerin.
Qidwai et al reported that the administration of NS seeds (2 g/day for 6 weeks) did not affect the serum alanine aminotransferase (ALT) or the serum creatinine (Cr) levels in adults [34]. Furthermore, NS at doses of 1, 2 and 3 g/day for 3 months did not adversely affect either the renal or the hepatic functions of diabetic patients [35]. Another study revealed that NS seed powder intake for 40 days caused no significant change in total leukocyte and platelet count [36]. Comprehensive molecular mechanism of black cumin and TQ-mediated pharmacological actions.
15. Nephroprotective Effects
Additionally, the high levels of sterols in Nigella sativa suggest its potential use in preventing cardiovascular diseases (CVDs). Nigella sativa is also effective against diabetes, inflammatory conditions, and menopause. Metabolic syndrome is a cluster of cardio-metabolic conditions that include obesity, insulin resistance, atherogenic dyslipidemia, and high blood pressure (BP) [54] and is a major contributor to the development of diabetes [55]. A RCT done on 60 patients with metabolic syndrome showed that NS oil (5 mL/day) used in combination with atorvastatin and metformin could decrease fasting blood sugar (FBS), LDL, and TC significantly after six weeks of use, but had no significant effect on body mass index (BMI) or waist circumference (WC) [56]. Nigella sativa (black seed or black cumin), which belongs to the Ranunculacea family, is an annual herb with many pharmacological properties.
Safety Evaluation of Black Cumin-Based Therapeutics
In addition to its potentials on activating cellular antioxidant defense system, black cumin can directly scavenge free radicals, as demonstrated in several in vitro chemical assays like DPPH assay [35,292,293,294]. However, by virtue, TQ has a relatively poor capacity to quench free radicals because of its oxidized form [295]. This observation strengthens the idea that TQ can exert its antioxidant capacity by activating the Nrf2-dependent antioxidant defense system.
How long does black seed take to work?
On the other hand, in weight loss and reducing blood sugar levels, studies have shown higher doses of 2–3 grams of black seed oil per day for 8–12 weeks to be most effective (19, 21 , 23 , 24 ).