Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats

Kandhare, Amit D.; Ghosh, Pranab; Bodhankar, Subhash L.

doi:10.1016/j.cbi.2014.05.012

Cited by 142 publications

(102 citation statements)

References 77 publications

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“…Diabetes is known to cause tissue damage by inducing apoptosis, such as that seen in endothelial cells in DM foot ulcer in rats with an elevated expression of IL-1b observed. 52 However, a causative relation of elevated IL-1b and endothelial cell apoptosis was not established in the study. Our study provided direct in vivo evidence that exogenous IL-1Ra reduced the number of apoptotic cells in the healing epithelial sheet and in the stroma near the leading edge of healing DM corneas.…”

Section: Il-1ra and Diabetic Cornea Wound Healingmentioning

confidence: 82%

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

Yan

Gao

Sun

et al. 2016

The American Journal of Pathology

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fanxq@sh163. net.Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1b and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1b in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1b or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinaseeAkt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1beIL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1b and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients. (Am J Pathol 2016 http://dx

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Section: Il-1ra and Diabetic Cornea Wound Healingmentioning

confidence: 82%

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

Yan

Gao

Sun

et al. 2016

The American Journal of Pathology

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“…Release of this pro-inflammatory cytokines via activation of NF-kB, a transcription factor, resulted in an inflammatory response via recruitment of neutrophils and macrophages to the wound site (Kandhare et al, 2014a). It leads to release of ROS and reactive nitrogen species (RNS) including superoxide, hydrogen peroxide, hydroxyl radical, hypochlorous acid, nitric oxide, and peroxynitrite which contribute to the pathogenesis of wounds.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis reflects a rapid switch to the proliferative phase from the inflammatory phase of healing (Kandhare et al, 2014a). Bcl-2-associated X protein (BAX) is a pathological index of apoptotic changes in the cell under stressful conditions and the expression of Bax has been reported to be elevated with ROS (Kandhare et al, 2014a).…”

Section: Discussionmentioning

confidence: 99%

“…Flavonoids are one of the most copious and prevalent groups of naturally occurring antioxidants and serve as potent inhibitors of lipid peroxidation in the biological membrane of the citrus family (Kandhare et al, , 2014a. They are also well documented to facilitate rapid wound healing as they possess excellent antimicrobial, antioxidant, anti-inflammatory, and astringent properties (Tsuchiya et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…They are also well documented to facilitate rapid wound healing as they possess excellent antimicrobial, antioxidant, anti-inflammatory, and astringent properties (Tsuchiya et al, 1996). Naringin (4 0 ,5,7-trihydroxy flavanone 7-rhamnoglucoside) is a major and active flavanone glycoside which was reported to possess various pharmacological properties including antimicrobial, antimutagenic, antiinflammatory, cholesterol lowering, antioxidant, antiulcer, anticancer, antiatherogenic, hepatoprotective, cardioprotective, renoprotective, and neuroprotective effects Jeon et al, 2001;Kandhare et al, 2012bKandhare et al, , 2014aKumar et al, 2014). It has inhibitory potential against tumor necrosis factor-a (TNF-a) and transforming growth factor-b (TGF-b) which is involved in the pathogenesis of various interstitial diseases (Chen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats

Kandhare

Alam

Patil

et al. 2015

Pharmaceutical Biology

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111

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Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors. Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models. Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters. Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p50.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p50.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p50.05) restored by NOF. Treatment produced a significant increase (p50.05) in tensile strength, hydroxyproline content, and protein content. TNF-a, IL-1b, IL-6, IL-8, NF-jB, smad-7, and Bax mRNA expression were significantly down-regulated (p50.05) by NOF, whereas polymerase gamma (pol-g), smad-3, VEGF and TGF-b, and collagen-1 mRNA expressions were significantly up-regulated (p50.05) by NOF. Histological alterations in wound skin were also restored by NOF. Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-jB, TNF-a, and ILs), apoptotic (pol-g and Bax), and up-regulated growth factor (VEGF and TGF-b) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.

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Photothermal/Photodynamic Synergistic Antibacterial Hydrogel Dressing with pH/Glucose Dual Responsive Pirfenidone Release for Diabetic Foot Ulcers

Pan,

Li,

et al. 2024

Adv Funct Materials

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Diabetic foot ulcers (DFU) are notoriously challenging to heal due to severe infection, excessive inflammation, and difficulty in angiogenesis. In response to these problems, first, a pH/glucose dual‐responsive hydrogel dressing (HPC) is constructed using dual dynamic crosslinking through Schiff base and phenylboronate ester between m‐aminophenylboronic acid and adipic dihydrazide bifunctionalized hyaluronic acid (AHP) and oxidized chondroitin sulfate (OCS). Then, polydopamine‐reduced graphene oxide compounded glycine‐modified fullerene (GPC) with photothermal/photodynamic synergistic antibacterial properties and the drug pirfenidone (PFD) with pro‐angiogenesis and suppress inflammatory are loaded into the above HPC hydrogel. Based on the response of Schiff base/phenylboronate ester to pH/glucose, the HPC/GPC/PFD (HPCG/PFD) hydrogel can accelerate the release of PFD, thereby improving excessive inflammation and angiogenesis in DFU. In addition, dual dynamic crosslinking provided the hydrogel with good on‐demand removal and self‐healing performance, while GPC brought good tissue adhesion, antioxidation, and electrical conductivity to the hydrogel. The rheology, morphology, mechanical properties, swelling, degradation, and biocompatibility of the hydrogel have been well verified. Finally, in the DFU model of rats, this hydrogel can promote wound repair by reducing infection and inflammation, accelerating wound closure, and enhancing epidermal regeneration, collagen deposition, and angiogenesis, showing promoting effect on diabetic wound healing.

show abstract

Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats

Cited by 142 publications

References 77 publications

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas

Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats

Photothermal/Photodynamic Synergistic Antibacterial Hydrogel Dressing with pH/Glucose Dual Responsive Pirfenidone Release for Diabetic Foot Ulcers

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