Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats - PubMed (original) (raw)

Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats

Shahid Karim et al. Front Pharmacol. 2021.

Abstract

Introduction: Current study was designed to evaluate the wound healing activity of a Saudi pomegranate peel extract on excision wound healing in experimentally induced diabetes in rats. Methodology: Animals were divided into three groups: diabetic excision wound with no treatment, diabetic excision wound with gel alone and diabetic excision wound with Saudi pomegranate peel extract in gel. Animals were monitored for clinical signs, weekly body weight, morbidity and mortality during entire study period. The efficacy parameters evaluated were percent wound contraction, Hydroxyproline content, estimation of Transforming Growth Factor ß1 (TGF-ß1), Vascular Endothelial Growth Factor (VEGF), and Epidermal Growth Factor (EGF) in wound lysates by ELISA, mRNA expression of TGF-ß1, VEGF, and EGF in wound lysates by qPCR, Estimation of nitric oxide (NO) and NO synthase (NOS) in Wound Lysates and histopathology of skin for reepithelization, neovascularization, and inflammation. Results: The Saudi pomegranate peel extract in gel (5.0 g extract per 100 g gel) showed significant wound healing activity when compared to the vehicle control [p < 0.05] following 21 days of treatment. Animals in the control and treatment groups were apparently normal through the study with no significant differences in body weights between groups. Expression of mRNA of TGFβ1, EGF and VEGF in wounds was the highest on day 14 post treatment 4.3, 3.5 and 0.9 fold higher respectively in the treatment group when compared to vehicle control, and on day 21, the values were 0.12, 0.3 and 0.83, respectively. No statistically significant differences were observed in TGF-ß1 levels in wounds on days 4, 7, 14 and 21 post treatment when compared to the vehicle control (_p_ > 0.05). Significantly higher levels of VEGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Significantly higher levels of EGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Mean hydroxyproline levels were higher in treatment group on days 4 and 7 when compared to vehicle control. NO levels in treatment group were significantly lower on days 7, 14 and 21 when compared to vehicle control (p < 0.05). NOS activity in treatment group were significantly lower on days 4 and 7 when compared to vehicle control (p < 0.05). Histopathological changes in skin wound in the treatment group were consistent with wound healing when compared to the vehicle group. Conclusion: This study's findings suggest that topical application of SPPE gel effectively enhanced wound healing in experimentally induced diabetic conditions.

Keywords: EGF; TGF beta 1; VEGF; diabetes; nitric oxide; pomegranate peel extract; topical gel; wound healing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1

(A) Calibration curve of standard gallic acid for determination of total phenolic content in SPPE. (B) Calibration curve of standard quercetin for determination of total flavonoid content in SPPE.

FIGURE 2

Effect of SPPE gel on wound contraction in diabetic rats. (A) The percentage wound contraction was measured at 4, 7, 14, and 21 days after wound creation. Data expressed as mean ± SEM (n = 6). (B) Representative pictures of wound contraction at 4, 7, 14, and 21 days after wound creation.

FIGURE 3

Effect of treatments with Diabetic control (G1), Vehicle (G2), and SPPE gel (G3) on hydroxyproline contents in wound tissues of rats at day 4, 7, 14 and 21 post wounding. Values are represented as mean ± SEM (n = 6).

FIGURE 4

Effect of SPPE gel on expression of TGF-β1 (A), VEGF (B), and EGF (C) in wound tissues of rats at day 4, 7, 14, and 21 post treatment Diabetic control (G1), Vehicle (G2), SPPE gel (G3). Values are represented as mean ± SEM (n = 6).

FIGURE 5

Nitric Oxide (NO) levels (A) and Nitric Oxide synthase (NOS) activity (B) in skin homogenate following treatments with diabetic control (G1), Vehicle (G2), SPPE gel (G3) Values are represented as mean ± SEM (n = 6).

FIGURE 6

(A) G1, Day 0; Skin with normal epidermis (EP) and dermis (H&E X 100×). (B) G1, day 4: Skin with inflammatory cells (IN), collagen formation (C), neovascularization (arrowhead) and ulceration (U) (H&E X 100×). (C) G2, Day 4: Skin with inflammatory cells (IN) and collagen formation (C) (H&E X 100×) (D) G3, Day 4: Skin with inflammatory cells (IN), collagen formation (C) and fibroblast proliferation (F) and neovascularization (arrowhead) (H&E X 100×). (E) G1, Day 7: Skin with inflammatory cells (IN), collagen formation (C), fibroblast proliferation (F) and neovascularization (arrowhead) (H&E X 100×). (F) G2, day 7: Skin with inflammatory cells (IN), granulation tissue (G), fibroblast proliferation (arrow), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (G) G3, Day 7: Skin with inflammatory cells (IN), collagen formation (C), granulation tissue (G), fibroblast proliferation (arrow), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (H) G1, Day 14: Skin with inflammatory cells (IN), collagen formation (C), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (I) G2, Day 14: Skin with inflammatory cells (IN) and collagen formation (C) (H&E X 100×). (J) G3, Day 14: Skin with inflammatory cells (IN), collagen formation (C), granulation tissue (G), fibroblast proliferation (arrow), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (K) G1, Day 21: Skin with inflammatory cells (IN), collagen formation (C), granulation tissue (G), fibroblast proliferation (arrow), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (L) G2_,_ Day 21: Skin with inflammatory cells (IN), collagen formation (C), granulation tissue (G), fibroblast proliferation (arrow), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×). (M) G3, Day 21: Skin with inflammatory cells (IN), granulation tissue (G), neovascularization (arrowhead) and immature epidermis (IE) (H&E X 100×).

FIGURE 7

Box plots of histopathology scores for skin parameters through treatment. Horizontal lines in boxes represent median and error bars represent minimum and maximum. *Significantly different from G2 [p < 0.05, Kruskal-Wallis test]. 0 = None, 1 = Rare or Minimal, 2 = Moderate, 3 = Abundant, and 4 = Severe or Marked.

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Effects of Methanolic Extract Based-Gel From Saudi Pomegranate Peels With Enhanced Healing Potential on Excision Wounds in Diabetic Rats - PubMed (original) (raw)