Phytopharmacy Research in the Context of Saudi Arabian Healthcare – the Example of Nigella sativa L. Efficacy on Asthma Inflammation and Outcomes

BACKGROUND: Clinical research using herbal medicines requires specific considerations such as production method, which leads to chemical and pharmacological variability. Asthma is a leading chronic respiratory disease, remains sub-optimally controlled despite conventional costly treatments. Nigella sativa L. (NS) is a traditional herbal treatment for asthma, but lacking well-established scientific evidence. Objectives To develop an integrated research strategy incorporating preclinical and clinical research focusing on NS use in asthma by employing a chemically and pharmacologically well-characterised NS preparation in a well-designed clinical trial. METHODS: Distinct NS preparations were chemically characterised for thymoquinone (main active compound) concentration by High Performance Liquid Chromatography. Human T-lymphocyte, monocyte and A549 epithelial cells were utilised to assess the in-vitro anti-inflammation/immunomodulatory activity of NS preparations. The most potent and suitable NS preparation was clinically evaluated for efficacy as add-on treatment for asthmatics in a phase-II randomised double-blind placebo-controlled clinical trial (RDBPCT). Asthma Control Test (ACT) was the primary outcome. Pulmonary function, blood eosinophils and serum inflammatory markers were secondary outcomes. RESULTS AND DISCUSSION: Ten different NS preparations were obtained, showing variability in thymoquinone concentration and in-vitro anti-inflammatory/immunomodulatory activities. Two thymoquinone-rich oily preparations (a super critical fluid extract and a commercial product registered in Saudi Arabia) showed the best in-vitro activity via inhibiting inflammatory cytokines in human cellular models. In the RDBPCT including 80 asthmatics, the commercial product capsules showed significant improvements in ACT, eosinophilia and some serum cytokines without serious side effects. CONCLUSION: This project addressed important requirements to optimise clinical research using herbal medicines particularly for NS in asthma. Preclinical research on the chemistry and activity of the investigational NS product were the basis for the clinical trial. The RDBPCT revealed a higher level of evidence for the add-on NS treatment in asthma within the Saudi healthcare. This strategy is suggested for future clinical phytotherapeutic research

Comparative Immunomodulatory Activity of Nigella sativa L. Preparations on Proinflammatory Mediators: A Focus on Asthma

Introduction: A range of traditional and commercial preparations of NS is frequently used in the treatment of several inflammatory diseases. Often, these preparations have poor preclinical characterization that may lead to variable pharmacological effects.Objective: To assess the in vitro effects of different chemically defined preparations of NS on some asthma-related mediators of inflammation.Methods: Different NS preparations were obtained by either seed extraction with a spectrum of solvents ranging from lipophilic to hydrophilic, or commercial products were collected. The TQ concentration of NS was analyzed by HPLC. Immunomodulatory activity was assessed by the release of mediators (IL-2, IL-6, PGE2) in primary human T-lymphocytes, monocytes, and A549 human lung epithelial cells.Results: Ten distinct NS preparations showed variability in TQ concentration, being highest in the oily preparations extract-7 (2.4% w/w), followed by extract-10 (0.7%w/w). Similarly, the release of mediators was varied, being greatest in extract-7 and 10 via significantly (<0.05) suppressing IL-2, IL-6, and PGE2 in T-lymphocytes as well as IL-6 and PGE2 in monocytes. Also, PGE2 release in A549 cells was significantly enhanced by both extracts.Conclusion: The TQ concentration and in vitro activity were variable among the different NS preparations. TQ-rich oily NS preparations produced potent favorable immunomodulation in asthma inflammation and can be used in future studies

Anti-Proliferative, Cytotoxic and Antioxidant Properties of the Methanolic Extracts of Five Saudi Arabian Flora with Folkloric Medicinal Use: Aizoon canariense, Citrullus colocynthis, Maerua crassifolia, Rhazya stricta and Tribulus macropterus

Saudi Arabian flora have a history of use as folklore remedies, although such properties have yet to be explored rigorously, and the safety of such remedies should be assessed. This study determined the anti-proliferative, cytotoxic, and antioxidant properties of extracts of the following five plants indigenous to Saudi Arabia: Aizoon canariense, Citrullus colocynthis, Maerua crassifolia, Rhazya stricta, and Tribulus macropterus. The aerial parts of the five plants were collected from various locations of the western and northern regions of Saudi Arabia and used to prepare methanolic extracts. Three approaches were used to determine the proliferation and cytotoxicity effects using HaCaT cells: MTT, FACS, and confocal microscopy. Meanwhile, two approaches were used to study the antioxidant potential: DPPH (acellular) and RosGlo (cellular, using HaCaT cells). C. colocynthis possessed anti-proliferative activity against HaCaT cells, showing a significant decrease in cell proliferation from 24 h onwards, while R. stricta showed significant inhibition of cell growth at 120 and 168 h. The IC50 values were determined for both plant extracts for C. colocynthis, with 17.32 and 16.91 µg/mL after five and seven days of treatment, respectively, and for R. stricta, with 175 and 105.3 µg/mL after five and seven days of treatment. R. stricta and M. crassifolia exhibited the highest capacities for scavenging the DPPH radical with IC50 values of 335 and 448 µg/mL, respectively. The subsequent ROS-Glo H2O2 assay confirmed these findings. The R. stricta and M. crassifolia extracts showed potent antioxidant activity in both acellular and cellular models. The C. colocynthis extract also demonstrated significant anti-proliferation and cytotoxic activity, as did the R. stricta extract. These properties support their usage in folk medicine and also indicate a further potential for development for holistic medicinal use or as sources of new active compounds

Medicinal benefits of Nigella sativa in bronchial asthma: A literature review

Nigella sativa L. (NS) seeds, known as black seed, is a spice and a traditional herbal medicine used in various diseases including bronchial asthma. This review aimed to assess the studies supporting the medicinal use of NS in asthma and to highlight future research priorities. Various medical databases were searched for the effects of NS and its active secondary metabolites in asthma inflammation and outcomes. There were fourteen preclinical studies describing multiple effects of NS in animal or cellular models of asthma including bronchodilation, anti-histaminic, anti-inflammatory, anti-leukotrienes and immunomodulatory effects. Furthermore, seven clinical studies showed improvements in different asthma outcomes including symptoms, pulmonary function and laboratory parameters. However, often these studies are small and used ill-defined preparations. In conclusion, NS could be therapeutically beneficial in alleviating airway inflammation and the control of asthma symptoms, but the evidence remains scanty and is often based on poorly characterised preparations. Accordingly, well-designed large clinical studies using chemically well characterised NS preparation are required. Keywords: Nigella sativa, Black seed, Asthma, Traditional medicine, Clinical studie

Nigella sativa supplementation to treat symptomatic mild COVID-19: A structured summary of a protocol for a randomised, controlled, clinical trial

To investigate the potential efficacy of Nigella sativa (NS) oil supplementation on the outcomes of patients with mild Coronavirus Disease 2019 (COVID-19)

Nigella Sativa Supplementation Accelerates Recovery from Mild COVID-19: First Randomized Controlled Clinical Trial (RCT)

Background Effective treatment for patients with the novel Coronavirus Disease (COVID-19) is desperately needed and is under rigorous research. Nigella sativa oil (NSO), a herbal medicine, that has a documented wide antiviral and immunomodulatory activities offering a therapeutic potential for COVID-19. Methods Adult symptomatic patients with mild COVID-19 were recruited between May and August 2020 from King Abdulaziz University Hospital in Jeddah, Saudi Arabia. They were randomly assigned to receive supplementation with oral capsules of NSO (MARNYS® Cuminmar 500 mg twice daily for 10 days) plus standard of care or standard of care medications alone. The primary endpoint was the proportion of patients recovered (free of symptoms for 3 days) within 14 days after randomization. This trial was registered with clinicaltrials.gov, NCT04401202. Findings A total of 94 patients were enrolled. Their mean age was 35 (SD=11) years old and 57% of them were male. There were 47 patients in the treatment group (NSO) and 47 patients in the control group. The proportion of patients recovered in the treatment group was significantly higher than the control group, 37 (79%) versus 21 (45%) (p=0.001). Additionally, there was a significant difference in the average recovery time among both groups, 9 (SD=3) versus 11 (SD=3) days (p=0.003). Furthermore, 2 patients from the control group required hospitalization within the study period versus none in the treatment group. Adverse events were reported in 3 patients of NSO recipients as gastrointestinal symptoms. Conclusions In this RCT of adult patients with mild COVID-19, NSO was associated with a significant increase in the likelihood of recovery and a decrease in the likelihood of hospitalization. To our knowledge, this is the first RCT that shows potential therapeutic benefits of NSO in patients with COVID-19 which requires further confirmation with larger double-blinded RCTs