Introduction
Grapes
Grapes are a type of fruit that grows in bunches on vines. They vary in colour and can be purple, red, white, green and black. They are a popular fruit used in diet, medicine, and industry.
Definition of grape compounds
Grapes are a rich source of bioactive molecules such as phenolic acids, flavonoids and lipids.1 These are compounds that provide health benefits. Red grapes are considered to have a higher level of antioxidants compared to the others.
Significance of wound healing
The process of wound healing follows tissue injury. The body's ability to recover from injury by repairing and regenerating damaged tissue can prevent infections and further complications, and we are less vulnerable to pathogens and fluid loss.
The connection between grape compounds and wound healing
Naturally derived ingredients are becoming more common in healthcare due to patients' and consumers' concerns about chemical side effects. Grapes contain various compounds that contribute to health benefits, such as those useful in wound healing. This article will explain how grape compounds are linked to wound healing.
Grape compounds
Overview of key grape compounds
1. Resveratrol
Resveratrol is a chemical found in red grapes and products from red grapes, such as wine and juice.2 This can help to reduce symptoms of hay fever and weight loss. It can have helpful effects, such as expanding blood vessels and reducing blood clotting.
2. Quercetin
Quercetin is a chemical compound with antioxidant and anti-inflammatory effects that can help reduce swelling, kill cancer cells and prevent heart disease.3
3. Anthocyanins
Anthocyanins are the blue-red pigments found in plants and fruits such as grapes.4 They are a type of flavonoid, a nutrient source. These also have health benefits in lowering blood pressure, slowing cancer growth and reducing the risk of heart disease.
Sources of grape compounds
Grape compounds, particularly polyphenols and other bioactive molecules can be found in various forms:
- Grapes
- Grape skin
- Grape seed
- Grape juice
- Wine
- Grape supplements
Wound healing process
Phases of wound healing
1. Haemostasis
Haemostasis is the mechanism that leads to the cessation of bleeding from a blood vessel.5 There are many stages in this stage, which will be explained below.
- Vascular spasms: A vascular spasm is the narrowing of the arteries caused by a persistent contraction of the blood vessels, known as vasoconstriction. This narrowing can reduce blood flow
- Forming a platelet plug: In this step, exposed collagen from the damaged surface will encourage platelets to adhere, activate and aggregate to form a platelet plug, sealing off the injured area6
- Coagulation: Coagulation is when the formation of a blood clot occurs. In this stage, fibrinogen is converted to fibrin, forming a mesh that traps more platelets and erythrocytes to produce the clot7 In coagulation, plasma proteins called clotting factors prompt reactions that activate further coagulation factors. This is broken into two pathways:
- The extrinsic pathway is triggered when clotting factors come into contact with substances outside the blood vessel. This pathway is quicker and more direct and begins when damage occurs to the surrounding tissue
- The intrinsic pathway is triggered when clotting factors come into contact with substances inside the blood vessel. This pathway occurs due to damage to the tissue from internal factors such as arterial disease
- These two pathways form a third pathway, called the common pathway
- Clot retraction: Clot retraction is the process where activated platelets transduce contractile forces onto the fibrin network of a thrombus, which, over time, increases clot density and decreases clot size. This is necessary for promoting clot stability and maintaining blood vessel patency
- Clot dissolution: Once the injury has healed, the body will naturally dissolve the blood clot
2. Inflammation
Inflammation is part of the body's defence mechanism. In this process, the immune system recognises and removes harmful stimuli such as damaged cells and pathogens and begins the healing process.8 This helps to control bleeding and prevents infection. The common signs of inflammation are erythema – skin redness, heat and pain. The inflammation stage commonly occurs within the first 24 hours after injury and can last for up to 2 weeks in normal wounds, but this can be longer in chronic non-healing wounds.
3. Proliferation
In the proliferation step, the wound is rebuilt with new granulation tissue made of collagen and extracellular matrix. A new network of blood vessels is developed, known as angiogenesis.9 The appearance of the new granulation tissue will be pink or red and have an uneven texture, but if this is dark in colour, it may indicate an infection.
4. Remodelling
The final step of the wound-healing process is maturation, which occurs when the wound has closed. The collagen is remodelled from type III to type I in this stage. The cellular activity is reduced, and the number of blood vessels in the wounded area decreases.
Factors influencing wound healing
Wound healing can be delayed due to factors of a wound such as desiccation – wounds heal faster in a moist environment than in a dry environment, infection, pressure or trauma.10
Wound healing may also be affected in different ways based on certain characteristics that the person has, such as:11
- Age and gender
- Stress
- Diseases: e.g., diabetes
- Obesity
- Medications: steroids, non-steroid anti-inflammatory drugs, chemotherapy
Grape compounds and their effects on wound healing
Anti-inflammatory properties
Inflammation is a natural response to tissue injury, but chronic or excessive inflammation can slow healing. Grape compounds can help regulate the inflammatory response, reduce excessive inflammation at the wound and promote a controlled healing environment.
Antioxidant effects
Grapes are rich in antioxidants, including various polyphenols, which can help reduce oxidative stress when an imbalance between harmful free radicals and the body's antioxidant defences.12 Grape compounds can protect cells from damage and repair the tissue for wound healing by reducing oxidative stress.
Promotion of collagen production
Collagen is an important protein for wound healing, providing structural support to the healing tissue. Some grape compounds, such as proanthocyanidins found in grape seeds, promote collagen production, accelerating the formation of new tissue and the wound healing process.13
Regulation of cell migration
Cell migration is an essential aspect of wound healing, as it involves the movement of various cell types, such as fibroblasts and immune cells, to the wound site for tissue repair. Some grape compounds may regulate and promote cell migration, ensuring that the necessary cells reach the wound area to assist in the healing process.
Applications and therapeutic potential
Wound dressings and topical treatments
Grape seed extract can release endothelial growth factors, and its topical application can help in the contraction and closure of skin wounds due to its antioxidant and antibacterial properties. This study researched the effect of grape seed extract 2% cream on human skin lesions and found that it showed repair of wounds for the treatment group.14
Dietary intake and supplementation
Grape seed compounds can be taken as a supplement through liquids or tablets. Supplements commonly contain between 50 and 100 milligrams (mg) of the extract.
Safety and considerations
Potential side effects or allergies
Some people may have allergic reactions to grapes and grape products, although this is not very common. Grape lipid transfer protein, an endochitinase and a thaumatin-like protein are possible grape allergens.15 Some people may experience side effects such as stomach pain, indigestion, nausea, or sore throat.
This is usually from eating many grapes, as tannins, a polyphenol found in the skin and seeds of grapes, can cause an upset stomach or nausea. If you notice any side effects from taking grape compounds, you should seek advice from your GP or a healthcare professional.
Interaction with medications
Medications that slow blood clotting, such as anticoagulants and antiplatelet drugs, interact with grapes, as the grape extract may slow blood clotting. Therefore, taking any grape extracts alongside medications that slow down blood clotting can increase the risk of bruising and bleeding. If you have any doubts, it is important to consult and seek medical advice from a GP or healthcare professional before taking grape compounds.
Dosage and recommendations
In some studies, participants could tolerate 300-800g daily from 8-16 weeks. Grape compounds should not be taken by children or pregnant women as there is not enough research to show their use and safety in these groups.
Summary
Grape compounds can come in many forms and have shown their potential to provide various health benefits, including wound healing, due to their antioxidant and anti-inflammatory properties.
In wound healing and wound care, many therapies have associated challenges in inflammation and oxidation. There is potential for using grape compounds in wound care, as clinical research has shown effective results. However, many of these studies are done in laboratory settings, so more research needs to be conducted on the safety of human use of grape compounds in wound healing, so they should be used under medical supervision.
References
- Hornedo-Ortega R, Reyes González-Centeno M, Chira K, Jourdes M, Teissedre PL. Phenolic Compounds of Grapes and Wines: Key Compounds and Implications in Sensory Perception. Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging. 2021 Feb 10;
- Singh AP, Singh R, Verma SS, Rai V, Kaschula CH, Maiti P, et al. Health benefits of resveratrol: Evidence from clinical studies. Medicinal Research Reviews. 2019 Feb 11;39(5):1851–91.
- Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, et al. Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health. ACS Omega. 2020 May 14;5(20):11849–72.
- Khoo HE, Azlan A, Tang ST, Lim SM. Anthocyanidins and anthocyanins: Colored Pigments as food, Pharmaceutical ingredients, and the Potential Health Benefits. Food & Nutrition Research. 2017 Aug 13;61(1):1361779.
- Gale AJ. Current Understanding of Hemostasis. Toxicologic Pathology [Internet]. 2010 Nov 30;39(1):273–80. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126677/
- Storti F, van Kempen THS, van de Vosse FN. A continuum model for platelet plug formation and growth. International Journal for Numerical Methods in Biomedical Engineering. 2014 Jan 13;30(6):634–58.
- Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian Journal of Anaesthesia [Internet]. 2014;58(5):515. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260295/
- Margetic S. Inflammation and haemostasis. Biochemia Medica [Internet]. 2012 Feb 15;22(1):49–62. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062321/
- Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cellular and Molecular Life Sciences. 2016 May 14;73(20):3861–85.
- Thomas Hess C. Checklist for Factors Affecting Wound Healing. Advances in Skin & Wound Care [Internet]. 2011 Apr;24(4):192. Available from: https://journals.lww.com/aswcjournal/fulltext/2011/04000/Checklist_for_Factors_Affecting_Wound_Healing.10.aspx
- Guo S, DiPietro LA. Factors Affecting Wound Healing. Journal of Dental Research [Internet]. 2010 Feb 5;89(3):219–29. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903966/
- Rudrapal M, Khairnar SJ, Khan J, Dukhyil AB, Ansari MA, Alomary MN, et al. Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action. Frontiers in Pharmacology. 2022 Feb 14;13.
- Green B, Yao X, Ganguly A, Xu C, Dusevich V, Walker MP, et al. Grape seed proanthocyanidins increase collagen biodegradation resistance in the dentin/adhesive interface when included in an adhesive. Journal of Dentistry [Internet]. 2010 Nov 1 [cited 2022 Oct 14];38(11):908–15. Available from: https://www.sciencedirect.com/science/article/abs/pii/S030057121000206X
- Hemmati AA, Foroozan M, Houshmand G, Moosavi ZB, Bahadoram M, Maram NS. The topical effect of grape seed extract 2% cream on surgery wound healing. Global Journal of Health Science [Internet]. 2014 Oct 29;7(3):52–8. Available from: https://pubmed.ncbi.nlm.nih.gov/25948437/
- Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome. International Archives of Allergy and Immunology [Internet]. 2007;143(2):92–102. Available from: https://pubmed.ncbi.nlm.nih.gov/17228170/