Effect of  Nigella sativa  and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

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Abstract

Background

Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT.

Methods

A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT.

Results

A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone.

Conclusion

Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.

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Most cited references 43

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Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

Christopher Dunnill, Thomas Patton, James Brennan … (2017)

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

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Diabetes and Wound Angiogenesis

Uzoagu Okonkwo, Luisa A. DiPietro (2017)

Diabetes Mellitus Type II (DM2) is a growing international health concern with no end in sight. Complications of DM2 involve a myriad of comorbidities including the serious complications of poor wound healing, chronic ulceration, and resultant limb amputation. In skin wound healing, which has definite, orderly phases, diabetes leads to improper function at all stages. While the etiology of chronic, non-healing diabetic wounds is multi-faceted, the progression to a non-healing phenotype is closely linked to poor vascular networks. This review focuses on diabetic wound healing, paying special attention to the aberrations that have been described in the proliferative, remodeling, and maturation phases of wound angiogenesis. Additionally, this review considers therapeutics that may offer promise to better wound healing outcomes.

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A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.

Theresa Vincent, Etienne Neve, Jill Johnson … (2009)

Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.

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Author and article information

Contributors

Abid Nordin: m.abid.nordin@gmail.com

Haziq Kamal: kamalntee1@gmail.com

Muhammad Dain Yazid: dain@ppukm.ukm.edu.my

Aminuddin Saim: aminuddin_saim@yahoo.com

Ruszymah Idrus: ruszyidrus@gmail.com

Journal

Journal ID (nlm-ta): BMC Complement Altern Med

Journal ID (iso-abbrev): BMC Complement Altern Med

Title: BMC Complementary and Alternative Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6882

Publication date (Electronic): 30 October 2019

Publication date PMC-release: 30 October 2019

Publication date Collection: 2019

Volume: 19

Electronic Location Identifier: 290

Affiliations

[1 ]ISNI 0000 0004 1937 1557, GRID grid.412113.4, Department of Physiology, Faculty of Medicine, , Universiti Kebangsaan Malaysia, ; 56000 Cheras, Kuala Lumpur Malaysia

[2 ]Nordin Kamil Consulting, 30-2, Jalan Dwitasik, Dataran Dwitasik, 56000 Cheras, Kuala Lumpur Malaysia

[3 ]ISNI 0000 0004 1937 1557, GRID grid.412113.4, Tissue Engineering Centre, Faculty of Medicine, , Universiti Kebangsaan Malaysia, ; 56000 Cheras, Kuala Lumpur Malaysia

[4 ]Ear, Nose & Throat Consultant Clinic, Ampang Puteri Specialist Hospital, 68000 Ampang, Selangor Malaysia

Article

Publisher ID: 2706

DOI: 10.1186/s12906-019-2706-2

PMC ID: 6821016

PubMed ID: 31666058

SO-VID: 0611a6d7-b7f1-49ad-ab8c-fe02a296b23c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 26 March 2019

Date accepted : 9 October 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004515, Universiti Kebangsaan Malaysia;

Award ID: FF-2017-020

Funded by: AMRUS Medik Sdn Bhd

Award ID: FF-2017-020

Custom metadata

ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: nigella sativa,thymoquinone,epithelial,mesenchymal,wound healing,fibrosis

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: nigella sativa, thymoquinone, epithelial, mesenchymal, wound healing, fibrosis

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review

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Abstract

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The International Journal of Person Centered Medicine

Most cited references 43

Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

Diabetes and Wound Angiogenesis

A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.

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