Topical Application of Propolis Enhances Cutaneous Wound Healing by Promoting TGF-Beta/Smad-Mediated Collagen Production in a Streptozotocin-Induced Type I Diabetic Mouse Model

Hozzein, Wael N.; Badr, Gamal; Ghamdi, Ahmad Al; Sayed, Ayat A.; Al-Waili, Noori S.; Garraud, Olivier

doi:10.1159/000430221

Cited by 122 publications

(113 citation statements)

References 56 publications

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“…In this context, we previously demonstrated the beneficial effects of TQ in the induction of growth arrest of multiple myeloma cancer cells and its protective anti-diabetic effects [36][37][38][39]. Moreover, we provided clear evidence for the effects of other natural antioxidants (camel whey protein and bee propolis) as immune-modulators in accelerating the healing process of diabetic wounds in experimental animal models [40][41][42][43][44][45][46]. Most interesting, we demonstrated that natural antioxidants isolated from snake and ant venoms enhanced normal lymphocyte functions and exerted antitumor effects in different human and animal cancer cells [47][48][49][50][51][52][53].…”

Section: Discussionmentioning

confidence: 78%

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Guida

El-Aal

Kafafy

et al. 2016

Cell Physiol Biochem

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Background/Aims: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation-induced T cell imbalance, and on immune dysfunction induced by gamma-rays. Methods: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro-apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4⁺ and CD8⁺ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. Results: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-α and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro-inflammatory cytokine (TNF-α and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. Conclusions: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity.

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Section: Discussionmentioning

confidence: 78%

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Guida

El-Aal

Kafafy

et al. 2016

Cell Physiol Biochem

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“…The transforming growth factor (TGF)-β/Smad signaling pathway plays an important role in a variety of processes including cell growth, proliferation, differentiation and apoptosis, and TGF-β is involved in many fibrotic diseases including keloids through its role in promoting extracellular matrix (ECM) production and tissue fibrosis [17,18]. TGF-β is a member of a family of secreted cytokines that binds to and induces the dimerization of TGF-β type II receptors and the subsequent phosphorylation of TGF-β type I receptors, which phosphorylate Smad2/3 leading to the translocation of Smad4 to the nucleus and the activation of the expression of target genes [19].…”

Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway

Jiang

Yu²,

Xia³

et al. 2016

Cell Physiol Biochem

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Background: Keloids are fibroproliferative scars that develop as a result of a dysregulated wound healing process; however, the molecular mechanisms of keloid pathogenesis remain unclear. Keloids are characterized by the ability to spread beyond the original boundary of the wound, and they represent a significant clinical challenge. Previous work from our group suggested that growth differentiation factor (GDF)-9 plays a role in the invasive behavior of keloids. Here, we examined the involvement of GDF-9 in keloid formation and spread and elucidated a potential underlying mechanism. Methods: The expression of GDF-9, cyclooxygenase (COX)-2, vascular epidermal growth factor (VEGF)-C, matrix metalloprotease (MMP)-2, MMP-9, transforming growth factor (TGF)-β1, and the related signaling pathway components in human keloid tissues or keloid fibroblasts (kFBs) was monitored by qRT-PCR and western blot. A series of overexpression and silencing experiments in normal and keloid fibroblasts were used to modify the expression of GDF-9. The effects of GDF-9 on kFB proliferation and migration were assessed using the CCK-8, cell cycle and scratch wound healing assays. Results: GDF-9 promotes fibroblast proliferation and migration. GDF-9 silencing in kFBs decreased cell proliferation, blocked cell cycle progression, downregulated the angiogenic markers COX-2 and VEGF-C, and downregulated MMP-2 and MMP-9 expression, whereas it had no effect on the levels of TGF-β1. GDF-9 silencing significantly inhibited Smad2 and Smad3 phosphorylation in kFBs. Conclusions: GDF-9 promotes the proliferation and migration of kFBs via a mechanism involving the Smad2/3 pathway.

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“…Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-β/Smad2, 3 signalling axis in wounded tissues (Hozzein et al, 2015).…”

Section: Propolismentioning

confidence: 96%

“…Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad 2 and Smad 3 as well as a marked reduction in collagen production (Hozzein et al, 2015). Smads are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus.…”

Section: Diabetic Ulcersmentioning

confidence: 99%

Propolis and bee venom in diabetic wounds; a potential approach that warrants clinical investigation

Al-Waili¹,

Hozzein²,

Badr³

et al. 2015

Afr. J. Trad. Compl. Alt. Med.

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Background: Wound healing in diabetes mellitus is a complex multi-stage process that requires the proper function of multiple systems. The mechanisms of impaired wound healing of diabetic wounds are still poorly understood. Therefore, various interventions are being used for wound management without great success. Bee products have various properties that make them an important addition to the diabetic wound management. Methods: This review summarized previous and recently published papers of the effects of two bee products, propolis and bee venom, on the wound healing. The main results were obtained from preclinical experimentation. Results: Diabetes mellitus compromises immune system, increases infections, impairs wound healing, and affects cells and factors involved in the wound healing. There is an increasing interest in natural products in modern medicine as part of disease management. Bee products are natural substances that others and we have explored some of their biological activities and applications in the treatment of various diseases. Some of these products are bee venom and propolis. These products have analgesic, antioxidant, antimicrobial, and anti-inflammatory properties. In addition, both propolis and bee venom contain considerable amounts of antioxidants that have a great role in accelerating wound healing. Conclusion: There is sound rationality and scientific data for using propolis and bee venom in diabetic wound healing. We believe that topical application of propolis in addition to bee venom might have a place in repairing damaged tissues and accelerating the healing of diabetic wounds.

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Topical Application of Propolis Enhances Cutaneous Wound Healing by Promoting TGF-Beta/Smad-Mediated Collagen Production in a Streptozotocin-Induced Type I Diabetic Mouse Model

Cited by 122 publications

References 56 publications

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl-2 Signaling

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway

Propolis and bee venom in diabetic wounds; a potential approach that warrants clinical investigation

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