Microencapsulation of Nigella sativa seeds oil containing thymoquinone by spray‐drying for functional yogurt production

The present work reports on the microencapsulation of Nigella sativa seeds oil containing thymoquinone (TQ) by spray‐drying, using modified starch (MS) and maltodextrin (MD) mixture as wall materials aimed at producing functional yogurt. First, the impact of different ratios of MS/MD on microencapsulation efficiency (ME) and TQ retention was investigated. The highest ME (90.10%) was found in microcapsules prepared from emulsion with 80/20 ratio of MS/MD; however, the microcapsules prepared with 50/50 ratio was selected for considering TQ stability under storage conditions and functional yogurt production due to an acceptable ME (89.48%) and better TQ retention (61.12%). The results showed that the microcapsules stored at refrigerator temperature had the highest content of TQ after 4 weeks. Moreover, the results of chemical and sensory analysis suggest that N. sativa seeds oil microcapsules can be used for producing functional yogurt due to high stability of TQ and proper chemical and sensory properties.     

Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71?nm. The highest drug loading was observed with SNEDDS-F6 of ～45?mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.     

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.     

Anti-cancer properties and mechanisms of action of thymoquinone,the major active ingredient of Nigella sativa

Over the past two decades, studies have documented the wide-range anti-cancer effects of Nigella sativa, known as black seed or black cumin. Thymoquinone (TQ), its major active ingredient, has also been extensively studied and reported to possess potent anti-cancer properties. Herein, we provide a comprehensive review of the findings related to the anti-cancer activity of TQ. The review focuses on analyzing experimental studies performed using different in vitro and in vivo models to identify the anti-proliferative, pro-apoptotic, anti-oxidant, cytotoxic, anti-metastatic, and NK-dependent cytotoxic effects exerted by TQ. In addition, we pinpoint the molecular mechanisms underlying these effects and the signal transduction pathways implicated by TQ. Our analysis show that p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways are among the most significant pathways through which TQ mediates its anti-cancer activity. Experimental findings and recent advances in the field highlight TQ as an effective therapeutic agent for the suppression of tumor development, growth and metastasis for a wide range of tumors.     

百里醌对阪崎克罗诺肠杆菌的抑制作用

为探究百里醌对阪崎克罗诺肠杆菌的抑制作用及可能的抑制机理,检测了百里醌对阪崎克罗诺肠杆菌的最 小抑菌浓度（minimal inhibitory concentrations,MIC）及对其生长动力学模型的影响,并测定百里醌处理后阪崎肠 杆菌胞内ATP浓度、胞内pH值、膜电位、细胞膜完整性的变化,最后利用场发射扫描电子显微镜观察细胞形态的 改变。结果表明：百里醌对阪崎克罗诺肠杆菌的MIC为0.3～0.6 mg/mL;百里醌使阪崎克罗诺肠杆菌的生长迟滞期 延长,最大生长速率减小;百里醌影响了阪崎克罗诺肠杆菌细胞膜的通透性,表现为：质量浓度为MIC和2×MIC 的百里醌使细胞内ATP浓度由6.52 μmol/L分别降低为0.27 μmol/L和0.17 μmol/L,胞内pH值分别由5.69降低为5.22和 4.99,细胞膜完整菌体比例分别降低至80%和22%,引起细胞膜膜电位超极化;场发射扫描电子显微镜观测表明百 里醌使阪崎克罗诺肠杆菌细胞膜褶皱,菌体干瘪。综上所述,百里醌是通过影响细胞膜通透性和改变细胞形态抑制 阪崎克罗诺肠杆菌。这些结果表明百里醌有潜力作为控制阪崎克罗诺肠杆菌的天然抑菌剂应用于食品中。     

Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review

Despite existing conventional hypoglycemic drugs to manage diabetes, their non-availability and cost in low-income countries coupled with the associated side effects remain a major concern. Consequently, exploring for alternative treatments to manage diabetes has been a continuous priority. Nigella sativa L. (NS) (Family: Ranunculaceae) is regarded as a valuable traditional remedy in diabetes management and extensively studied for its biological properties. This systematic review provides a comprehensive and critical analysis of clinical studies on the efficacy, safety, and mechanism of action of NS and its compound thymoquinone (TQ) in diabetes management. The main scientific databases which were scrutinised were Scopus, PubMed, Google Scholar, and Web of Science. Data search was conducted from inception to January 2022. A total of 17 clinical studies were obtained; 16 studies on Nigella sativa L. and 1 study on its compound TQ. N. sativa was found to be highly potent in terms of its hypoglycemic activity when compared to placebo based on improvement in parameters including fasting blood glucose (FBG), postprandial blood glucose (PPBG), Hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and homeostatic model assessment for assessment of beta-cell functionality (HOMA-β). The compound TQ in combination with a daily dose of metformin demonstrated a greater reduction in the levels of HbA1c and blood glucose compared to metformin alone. The bioavailability of TQ can be enhanced by using nanoparticulate drug delivery systems. Considering the findings of the clinical studies along with negligible adverse effects, NS has strong potential application in bioproduct development for the management of diabetes. Further investigations should explore the detailed mechanism of actions by which TQ exerts its therapeutic antidiabetic effects to provide more insights into its clinical use in the management of diabetes.