Objective: Oxidative stress plays an important role in the pathogenesis of Hashimoto's thyroiditis. Because of the major anti-oxidant properties of black cumin, the current study aimed to evaluate the effect of powdered Nigella sativa seeds on markers of oxidative stress, endothelial dysfunction and serum lipids in patients with Hashimoto's thyroiditis.

Methods: Forty patients with Hashimoto's thyroiditis, aged between 22 and 50 years old, participated in the trial and were randomly allocated into two groups of intervention and control receiving powdered N. sativa or placebo daily for 8 weeks. Changes in markers of oxidative stress, including total anti-oxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and biomarkers of endothelial dysfunction including Intracellular Adhesion Molecule (ICAM)-1, Vascular Cell Adhesion Molecule (VCAM)-1 and serum lipids were also evaluated.

Results: Treatment with N. sativa, significantly increased serum TAC, SOD and reduced MDA concentrations with no significant change in GPX (P < 0.05). A significant reduction in VCAM-1 (P = 0.0012), body mass index (P = 0.002), serum concentrations of low density lipoprotein cholesterol (P = 0.002) and triglyceride (P = 0.02) were also reported in N. sativa-treated group after 8 weeks; while serum high density lipoprotein cholesterol (HDL) also significantly increased (P < 0.05). No change in other parameters were reported.

Conclusions: Giving attention to the potent beneficial effects of powdered black cumin seeds in improving oxidative stress, endothelial dysfunction, serum lipids and anthropometric features in patients with Hashimoto's thyroiditis, this medicinal plant can be considered as a therapeutic agent in management of Hashimoto-related metabolic abnormalities.

Trial registration number: Iranian registry of clinical trials (registration number IRCT2015021719082N4).

Ethnopharmacological relevance: Nigella sativa (N. sativa) L. (Ranunculaceae), well known as black cumin, has been used as a herbal medicine that has a rich historical background. It has been traditionally and clinically used in the treatment of several diseases. Many reviews have investigated this valuable plant, but none of them focused on its clinical effects. Therefore, the aim of the present review is to provide a comprehensive report of clinical studies on N. sativa and some of its constituents.

Materials and methods: Studies on the clinical effects of N. sativa and its main constituent, thymoquinone, which were published between 1979 and 2015, were searched using various databases.

Results and discussion: During the last three decades, several in vivo and in vitro animal studies revealed the pharmacological properties of the plant, including its antioxidant, antibacterial, antiproliferative, proapoptotic, anti-inflammatory, and antiepileptic properties, and its effect on improvement in atherogenesis, endothelial dysfunction, glucose metabolism, lipid profile dysfunction, and prevention of hippocampus pyramidal cell loss. In clinical studies, antimicrobial, antioxidant, anti-inflammatory, antitumor, and antidiabetic properties as well as therapeutic effects on metabolic syndrome, and gastrointestinal, neuronal, cardiovascular, respiratory, urinary, and reproductive disorders were found in N. sativa and its constituents.

Conclusion: Extensive basic and clinical studies on N. sativa seed powder, oil, extracts (aqueous, ethanolic, and methanolic), and thymoquinone showed valuable therapeutic effects on different disorders with a wide range of safe doses. However, there were some confounding factors in the reviewed clinical trials, and a few of them presented data about the phytochemical composition of the plant. Therefore, a more standard clinical trial with N. sativa supplementation is needed for the plant to be used as an inexpensive potential biological adjuvant therapy.

Ethnopharmacological relevance: Endothelial dysfunction is involved in lesion generation by the promotion of both early and late mechanism(s) of atherosclerosis such as adhesion molecules up-regulation, increased chemokine secretion and leukocyte adherence, increased cell permeability, enhanced low-density lipoprotein oxidation, cytokine elaboration, platelet activation and vascular smooth muscle cell migration, and proliferation. Nigella sativa is from the Ranunculaceae family which is used in some countries for various medicinal purposes. Nigella sativa seed has been widely used in traditional medicine for the treatment of diabetes.

Aim of the review: This review article summarized the therapeutic effects of Nigella sativa on endothelial dysfunction.

Methods: Databases such as PubMed, Web of Science, Google Scholar, Scopus, and Iran Medex were considered. The search terms were " Nigella sativa " or "endothelium" and " Diabetes"," endothelial dysfunction ", " Thymoquinone " and " anti-inflammatory effect ".

Results: The current review shows that Nigella sativa and Thymoquinone have a protective effect on endothelial dysfunction induced by diabetes. This is done by several mechanisms such as reduction of inflammatory and apoptotic markers, improving hyperglycemia, hyperlipidemia and antioxidant function, inhibiting platelet aggregation, and regulating eNOS, VCAM-1 and LOX-1 genes expression that involve in the endothelial dysfunction. Thymoquinone also reduces expression and secretion of some cytokines such as MCP-1, interleukin-1β, TNF-α, NF-κB, and Cox-2 that result in anti-inflammation effect.

Conclusion: Thymoquinone, the main phenolic terpene found in Nigella sativa, has several important properties such as antidiabetic, anti-inflammatory, and antioxidant activity. Therefore, Nigella sativa can improve endothelial dysfunction.

Ethnopharmacological relevance: Nigella sativa L. seed has been widely used in traditional medicine for the treatment of diabetes. The major reason for vascular complications in diabetic patients is endothelial dysfunction. However, the impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear.

Aim of the study: This study was conducted to evaluate the effect of the hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in streptozotocin (STZ)-induced diabetic rat.

Materials and methods: Treated rats received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6 weeks. The fasting blood glucose and lipids were measured and atherogenic index of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity responses of isolated aortic rings were evaluated in the presence of cumulative concentrations of Ach (10^-8-10^-5 M). eNOS, VCAM-1, and LOX-1 genes expression in aortic tissue was assessed by using real time polymerase chain reaction (PCR).

Results: Male diabetic Wistar rats treated with N. sativa seed extract for six weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant responses of aortic rings to Ach were markedly improved. N. sativa seed significantly increased eNOS in mRNA expression level and function, while it decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which assessed only in mRNA level.

Conclusions: The results of this study showed that N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties and improved vasoreactivity, endothelial dysfunction, and vascular inflammation in diabetic rats' aorta.

Objective: The purpose of this up-to-date comprehensive systematic review was to evaluate and summarize all research studies in the field in order to clarify the magnitude of Nigella sativa (N. sativa) effects on the management of Diabetes mellitus (DM) and its complications.

Methods: A systematic review was conducted in a Cochrane style and in accordance PRISMA checklist using the published studies in PubMed/MEDLINE, SCOPUS, and EMBASE databases that were searched up to January 2019. Abstracts that met PICO criteria for qualitative studies underwent dual review for data extraction to evaluate study quality and details.

Results: Dietary supplementation with N. sativa preparations can improve various secondary complications of diabetic patients. N. sativa preparations possess antidiabetic, hypoglycemic, anti-hyperlipidemic, antihypertensive, and anti-obesity effects. Beneficial effects of N. sativa preparations include the restoration of the antioxidant defense systems, the increase in the activity of antioxidant enzymes, the decrease of inflammatory biomarkers, the suppression of the production pro-inflammatory mediators, improvement of endothelial dysfunction, and hepatic, kidney, heart and immune system functions. They have key roles in managing diabetes-induced inflammation and oxidative stress in diabetic patients.

Conclusion: N. sativa preparations have key roles in herbal medicine as an adjuvant in the treatment and management of patients with DM and its complications. Moreover, the beneficial effects of N. sativa preparations were differently based on dosage forms, active ingredients, and duration of intervention. The best dosage to improve glycemic indices and lipid and lipoprotein profiles is 2 g daily powdered N. sativa for at least 12 weeks.

Background: Thymoquinone (TQ) is a bioactive phytoconstituent obtained from Nigella sativa (black seeds). It has promising potential in cancer prevention.

Objective: Previous studies have shown that TQ can modulate signaling pathways responsible for cancer progression, thus enhancing the efficacy and improving the safety profile of clinically used anticancer drugs.

Method: TQ acts on cell cycle and inhibits progression from G1 to S phase by targeting various proteins (cyclin D1, cyclin E, and p27). It also exhibits histone deacetylase (HDAC) inhibitory effects, targets p21 and Maspin, and induces pro-apoptotic gene, Bax and downregulates anti-apoptotic gene Bcl-2. Breast cancer (BC) is reported as one of the most common malignancies in women.

Results: Despite the research and advancement, it remains one of the most common causes of cancer related deaths among women. Recent advancements in molecular screening of BC led to the identification of clinically challenging condition of triple negative breast cancer (TNBC). TNBC is characterized by the absence of targetable receptors viz. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expressions. It is also characterized by reduced or absence of phosphatase and tensin homolog (PTEN) expression, a tumor suppressor gene having diverse functions including regulation of apoptosis, cell cycle, and metastasis.

Conclusion: Since TQ has been reported to up-regulate several growth factors such as vascular endothelial growth factor (VEGF), EGF and PTEN expression, the present review article discusses the targeting potential of TQ for therapeutic intervention against such types of breast cancer.

The endothelium, a highly active structure, regulates vascular homeostasis through the release of numerous vasoactive factors that control vascular tone and vascular smooth cell proliferation. A larger number of medicinal plants and their isolated chemical constituents have been shown to beneficially affect the endothelium. For example, flavonoids in black tea, green tea, and concord grape cause a vasodilation possibly through their antioxidant properties. Allicin, a by-product of the enzyme alliinase, has been proposed to be the main active metabolite and responsible for most of the biological activities of garlic, including a dose-dependent dilation on the isolated coronaries. Thymoquinone, the principal phytochemical compound found in the volatile oil of the black seed, and the hawthorn extract have also been shown to improve aging-related impairment of endothelium-dependent relaxations in animal models. In this review, the effect of some of the natural products, including Camellia sinensis (black tea and green tea), Vitis labrusca (concord grape), Allium sativum (garlic), and Nigella sativa (black seed) and Crataegus ssp (hawthorn extract), is explored. The molecular mechanisms behind these potential therapeutic effects are also discussed.

Objective: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat.

Materials and methods: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations.

Results: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10(-6) - 10(-5) M) compared to diabetic group (p<0.05 to p<0.01). The relaxation response to Ach 10(-8) M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10(-7) - 10(-5) M were significantly higher in all treated groups compared to diabetic group (p<0.05 to p<0.001).

Conclusion: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats.