Thymoquinone (TQ) is a quinone derived from the black seed Nigella sativa and has been extensively studied in pharmaceutical and nutraceutical research due to its therapeutic potential and pharmacological properties. Although the chemopreventive and potential anticancer effects of TQ have been reported, its limited solubility and poor delivery remain the major limitations. In this study, we aimed to characterize the inclusion complexes of TQ with Sulfobutylether-β-cyclodextrin (SBE-β-CD) at four different temperatures (293–318 K). Additionally, we compared the antiproliferative activity of TQ alone to TQ complexed with SBE-β-CD on six different cancer cell lines, including colon, breast, and liver cancer cells (HCT-116, HT-29, MDA-MB-231, MCF-7, SK-BR-3, and HepG2), using an MTT assay. We calculated the thermodynamic parameters (ΔH, ΔS, and ΔG) using the van’t Holf equation. The inclusion complexes were characterized by X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), and molecular dynamics using the PM6 model. Our findings revealed that the solubility of TQ was improved by ≥60 folds, allowing TQ to penetrate completely into the cavity of SBE-β-CD. The IC₅₀ values of TQ/SBE-β-CD ranged from 0.1 ± 0.01 µg/mL against SK-BR-3 human breast cancer cells to 1.2 ± 0.16 µg/mL against HCT-116 human colorectal cancer cells, depending on the cell line. In comparison, the IC₅₀ values of TQ alone ranged from 0.2 ± 0.01 µg/mL to 4.7 ± 0.21 µg/mL. Overall, our results suggest that SBE-β-CD can enhance the anticancer effect of TQ by increasing its solubility and bioavailability and cellular uptake. However, further studies are necessary to fully understand the underlying mechanisms and potential side effects of using SBE-β-CD as a drug delivery system for TQ.

Background: Disruption of the gut microbiota, an essential ecosystem of microorganisms inhabiting the gastrointestinal tract (GIT), has been linked to the development and progression of various gastrointestinal disorders. Probiotics have received considerable attention for their role in gastrointestinal diseases. However, there is a need to synthesise existing evidence to determine the optimal probiotic approach for managing complications of GIT disorders. By conducting a systematic review of randomised controlled trials (RCTs) comparing the effects of probiotic bacteria and yeast in patients with gastrointestinal diseases, we aim to provide a comprehensive and evidence-based analysis of the benefits and limitations of these interventions, which could inform clinical decision-making and improve patient outcomes in this population. Methods: Different databases, including PubMed, Web of Science, and Scopus will be searched to identify randomized controlled trials (RCTs). The titles and abstracts will be screened using Rayyan, and data will be extracted from eligible studies using Microsoft Excel. Critical appraisal and quality assessment will be performed using the ROB 2 tool, while GradePro will be used to assess the certainty of outcomes. All steps will be independently performed by two reviewers. This study will assess the effectiveness of yeast and bacterial probiotics in treating GIT disorders by evaluating inflammation markers, diarrhoeal score and disease severity, stool frequency, length of hospital stay, and adverse effects. By comparing the efficacy of probiotic bacteria and yeast, this review will identify the most effective type of probiotics for different gastrointestinal disorders, potentially enhancing treatment outcomes and reducing healthcare costs. Systematic review registration: PROSPERO (CRD42023384070).