Basic Science research on turmeric has mistakenly (?) focused on Curcurmin as the presumed active ingredient of turmeric. That focus was likely to find a commercially lucrative new drug from un-patentable inexpensive Turmeric.
I believe that focus is unfortunate. Less than 5% 0f turmeric is curcumin. Multiple other compounds are present and may represent active contributory ingredients.
The story of vitamin E as the active ingredient in walnuts helping in vascular and heart disease is a case in point. Millions of people for years took vitamin E because of that wrong assumption.
I STRONGLY DISCOURAGE USE OF ORAL CURCURMIN AND CURCURMIN/ PIPERARINE COMBINATIONS DUE TO recent reports from Italy of POSSIBLE HEPATOTOXICITY None of those reports were about whole turmeric powder.
All over this post I have quoted curcumin research because that is primarily what is online everywhere. Some turmeric clinical research is available too.
I only use whole turmeric powder bought online or in the grocery store. NOT CURCURMIN.
A Pub Med search for more information about turmeric and curcumin in wound healing was done by me in August and Sept 2022 and is the basis of this post.
Text here is quoted with minor modifications from this review article by Volllono et al here. Potential of Curcumin in Skin Disorders
Laura Vollono 1, Mattia Falconi 2, Roberta Gaziano 3, Federico Iacovelli 2, Emi Dika 4, Chiara Terracciano 5, Luca Bianchi 1 and Elena Campione 1,*
* Correspondence: campioneelena@hotmail.com
Molecules 2022, 27, 3566. https://doi.org/10.3390/ molecules27113566Stefania Vitale 1 , Sara Colanero 2 , Martina Placidi 1 , Giovanna Di Emidio 1 , Carla Tatone 1 , Fernanda Amicarelli 1 and Anna Maria D’Alessandro 1,*
Both articles quoted below by me have references for you to review the research.
Wound treatment represents a therapeutic challenge with escalating economic impact worldwide. Costs are rising sharply as newer more and more expensive modalities are developed to monetize the large number of wounds as the Coca Cola Pepsi generation ages and develops chronic diseases predisposing to non healing wounds.
The growing burden of chronic noncommunicable diseases such as diabetes, vascular diseases was helped by the
Bush-Era Gag Rule that Prevented Criticism of Soda.
The Bush (W) Administration Blocked States from Using Federal Funds to Discourage Soda Consumption.
"Wound healing is a complex, dynamic process that involves a sequence of cellular and molecular events. It can be divided in a simplified manner into four phases:
(1) hemostasis.
(2) inflammation
(3) proliferation with formation of granulation tissue.
(4) remodeling, with formation of new epithelium and scarring.
SHORT SUMMARY OF Wound-healing process.
(A) Hemostasis: A clot is formed providing a temporary barrier to fluid loss and pathogen entry; acts as a reservoir of bioactive factors and antimicrobials; and initiates tissue repair pathways.
(B) Inflammatory phase: Early step with damage-associated molecular pattern activation, free radicals, and reactive molecular species production to recruit immune cells; release of immune cells; release of antimicrobial species; infiltrating immune cells t that secrete amplifying alarmin signals (endogenous, constitutively expressed, chemotactic, and immune-activating proteins/peptides that are released as a result of degranulation, cell injury or death.
(C) Proliferation phase: Migration and proliferation of keratinocytes, collagen/extracellular matrix synthesis; decreased vessel permeability; new capillary and lymphatic vessel angiogenesis; epithelialization; and de novo formation of granulation tissue.
(D) Remodeling (maturation): Collagen/extracellular matrix reorganization and realignment; extracellular matrix contraction; matrix turnover (synthesis and degradation);endothelia and fibroblast apoptosis; repigmentation. "
DETAILS OF WOUND HEALING PROCESS
"Coagulation and Hemostasis
Immediately after injury coagulation and hemostasis take place to prevent bleeding [18,19]. These processes require multiple interlinked steps to protect the blood vessel and provide a matrix that allows the invasion of cells needed in the later phases of healing [20,21]. The coagulation cascade is activated leading to platelet aggregation and clot formation [19]. In rapid succession, three steps occur during hemostasis. Vascular spasm is the initial response as blood vessels constrict to reduce blood loss. In the second step, within seconds of a blood vessel’s epithelial wall being disrupted, platelets adhere to one another to form a temporary seal over the vessel wall rupture. Collagen, exposed at the site of injury, promotes platelets to adhere to the injury site. The third and final phase is known as blood clotting or coagulation. The coagulation cascade, or secondary hemostasis, is a series of steps in response to bleeding caused by tissue injury, where each step activates the next and ultimately produces a blood clot. Coagulation strengthens the platelet plug with fibrin threads, which function as “molecular glue.” After a few minutes, the fibrinous platelet block is entirely established [19–22]. Platelet-derived growth factors and cytokines also play a role in the wound-healing process by activating and attracting neutrophils, as well as macrophages, endothelial cells, and fibroblasts [17,21].
3.2. Inflammatory Phase
This phase is composed of two separate steps, an early inflammatory phase and a late inflammatory phase [23]. The early inflammatory phase activates the molecular events that lead to the infiltration of the wound site by neutrophils, whose main function is to prevent infection [24]. Later macrophages appear in the wound and continue the process of phagocytosis before progressing to the next phase of healing [23,24,26–31]. Macrophages play an important role in the late stages of the inflammatory response, acting as key regulatory cells and storing a large amount of potent tissue growth factors [17,24,27–33]. The last cells to enter the wound site (in the late inflammatory phase) are lymphocytes, which play an important role in collagenase regulation and are later required for collagen remodeling, the production of extracellular matrix components, and their degradation [23,29,31].
3.3. Proliferative Phase
This phase encompasses the major healing processes and starts on the third day after an acute wound and lasts for approximately 2 weeks (Figure 1C). Following the injury, fibroblasts and myofibroblasts proliferate in the surrounding tissue for the first three days [30] before migrating into the wound, attracted by factors such as Transforming Growth Factor-(TGF-) and Platelet-Derived Growth Factor (PDGF), which are released by inflammatory cells and platelets [34]. Once in the wound, the fibroblasts proliferate profusely and proceed to the deposition of the newly synthesized extracellular matrix by producing matrix proteins such as hyaluronan, fibronectin, proteoglycans, and type 1 and type 3 procollagen. Collagen synthesis represents a crucial event. Indeed, collagen is an important component in all phases of wound healing since it contributes to the integrity and strength of all tissues [35–37]. At a macroscopic level, during this phase of wound healing, an abundant formation of granulation tissue can be observed. Then, within a few days, a microvascular network throughout the granulation tissue is organized. The modeling and establishment of new blood vessels are critical in wound healing and take place concurrently during all phases of the reparative process. Finally, epithelialization occurs. Within a few hours of the injury, epithelial cells start to migrate to the wound site from the wound edges; when the advancing epithelial cells meet, migration stops, and the basement membrane starts to form [29].
3.4. Remodeling Phase
During wound remodeling, scar tissue formation takes place and is com- pleted in approximately one year or even more [18,29,38–40]. As the wound heals, the growth of capillaries stops, the density of fibroblasts and macrophages is reduced by apop- tosis, and the blood flow and metabolic activity decrease [35,37,41]. The final result is a fully matured scar with a decreased number of cells and blood vessels and high tensile strength [23,41]. Although most wounds are the result of simple injuries, systemic and local factors may alter and slow down the course of the finely balanced repair process, leading to the occurrence of wounds that do not heal in a timely and orderly manner and evolve in chronic, non-healing wounds. Therefore, according to the tissue’s ability to completely repair the wound, they are classified generally as acute or chronic wounds.
4. Acute and Chronic Wounds
While acute wounds take only a few weeks to heal, chronic wounds require several months to heal completely. An acute wound is defined as a recent wound that has yet to progress through the sequential stages of wound healing. They can be superficial injuries involving both the epidermis and superficial dermis or full-thickness skin damage in which the subcutaneous layer is compromised. Examples of acute wounds are surgical incisions, thermal wounds, abrasions, and lacerations. They heal through the routine processes of inflammation, tissue formation, and remodeling, which occur in a timely fashion. Acute wound healing is regulated by cytokines and growth factors released proximal to the wound [42].
Chronic wounds are those that fail to progress through the normal stages of healing and are not repaired in an orderly and timely manner [20,43]. The healing process is incomplete and disturbed by various factors, which prolong the phases of homeostasis, inflammation, proliferation, or remodeling by one or more stages. These factors can include infection, tissue hypoxia, necrosis, exudate, and excess levels of inflammatory cytokines [38]. The continuous state of inflammation in the wound creates a cascade of tissue responses that together perpetuate a non-healing state. Since the healing proceeds in an uncoordinated manner and the functional and anatomical outcomes are poor, these wounds frequently relapse [20,39]. Chronic wounds may be related to various causes, including neuropathic diseases, pressure, arterial and venous insufficiency, burns, and/or vasculitis (Figure 2) [44]
CURCURMIN During the inflammatory phase a significant number of neutrophils are recruited at the wounded site, releasing proteases, reactive oxygen species (ROS), and inflammatory mediators such as TNF-α and IL-1. Curcumin is able to reduce inflammation through the inhibition of nuclear factor κB (NF-κB) and the suppression of TNF-α expression, as well as through the impairment of LPS signaling. Moreover, curcumin exerts its anti-inflammatory effects by acting on other signaling pathways, such as peroxisome proliferator-activated receptor-gamma (PPAR-γ) and myeloid differentiation protein 2-TLR 4 co-receptor (TLR4-MD2).
Excessive oxidative stress plays a major role in prolonged inflammation, a significant feature in the pathogenesis of chronic non-healing wound. In fact, while low levels of ROS are formed during the physiologic wound healing process, their excessive production cannot be balanced by the cellular antioxidant system, leading to oxidative stress, lipid peroxidation (LPx), DNA breakage and enzyme inactivation, including free-radical scavenging enzymes, in a self-perpetuating cycle resulting in chronic disease. The reducing potential of its electron-donating groups allows curcumin to restore the redox balance and suppress transcription factors related to oxidation, while sustaining the production and activity of antioxidant enzymes and their constituents, such as glutathione (GSH). Moreover, a protective action of curcumin against hydrogen peroxide has been observed in vitro in human keratinocytes and fibroblasts.
CURCURMIN During the proliferative phase of wound healing, the dermis is invaded by proliferating fibroblasts producing immature ECM proteins (EDA fibronectin and type III collagen) as well as activating growth factors such as TGF-β1, leading to reparation of the wounded dermal layer.
Simultaneously, keratinocytes migrate at the wounded site, where they proliferate and differentiate in order to restore the overlying epithelium. A major role in this process is played by hair follicle stem cells.
Curcumin may exert significant action during the proliferative phase. In fact, it has been demonstrated that curcumin is able to reduce the number of membrane matrix metallo-proteinases (MMPs), increase the hydroxyproline and collagen synthesis, and accelerate the maturation of collagen fibers. In addition, curcumin also promotes the differentiation of fibroblasts into myofibroblasts, which marks the beginning of wound contraction, and reduces the epithelization period in wounds.
CURCURMIN In animal models, daily curcumin topical application accelerated wound healing in irradiated mini-pigs, and the application of chrysin-curcumin-loaded nanofibers reduced the levels of IL-6, MMP-2, TIMP-1, TIMP-2, and iNOS gene expression in male rats, resulting in the acceleration of the healing process of surgical wounds. Transdermally applied curcumin on surgical wounds on rats produced marked inhibition of H2O2-induced damage to keratinocytes and fibroblasts, while application of curcumin-oligochitosan nanoparticle complex or with application of oligochitosan coated curcumin-loaded-liposomes resulted in faster healing of surgical wounds in mice compared with controls [29,30]. In a diabetic rat model, wounds treated with curcumin showed an accelerated reepithelization rate compared with untreated controls [125]. Treatment with curcumin-loaded polymeric bandages resulted in significantly lower expression of PI3K and pAKT, indicative of an inhibition of the PI3K/AKT/NFκB axis, reduced LPx levels, and increase in collagen compared with controls.
Enhancement of wound healing by curcumin in animals
Many new formulations of curcumin have been developed in order to achieve better topical application at the wound site, such as chitosan-alginate sponges, curcumin-loaded polymeric bandages, alginate foams, collagen films, and nano-emulsion and hydrogel. The incorporation into these formulations resulted in increased curcumin bioactivity, although no formulation showed a significant difference in its effect compared to the others.
Alginate-curcumin based systems for wound healing
Acute and chronic wound care is a pressing need, and alginate-based wound dressings provides many benefits over the conventional wound dressings.
To increase the efficacy of alginate dressing, curcumin was used as a potential antibacterial and ani-inflammatory biomaterial for rapid healing of wounds. In combination with alginate and other biopolymers curcumin increases the potency of wound healing of the wound dressing systems. Many alginate-curcumin systems have been used as drug delivery systems, wound dressing materials, tissue regeneration materials, and other applications in recent years. Curcumin’s use in wound healing applications as wound dressing products has been well researched over the last few decades and published in numerous publications [154]. Other than alginate, chitosan was the mostly used biopolymers for preparation of wound care dressing materials. The focused on researches and experiments done with alginate and curcumin and related wound healing dressing systems and summarized here
Alginate- curcumin formulations Composition Investigation level/stage Result Ref. Sponge Chitosan, sodium alginate (CA) and curcumin in-vivo CA-Curcumin sponge can promote the formation of the collagen, thus accelerate the healing process. [120] Foam Sodium alginate and curcumin in-vitro It can be removed easily from the wound site with wound healing effect. [155] Hydrogel N,O carboxymethyl chitosan/oxidised alginate and nano-curcumin in-vivo It enhances the re-epithelialization, collagen deposition and accelerate the process of wound healing. [156] Polymeric bandage Chitosan, Sodium alginate, oleic acid and Curcumin in-vivo It enhances wound healing. [157] Microfibre sodium alginate, gelatine and Curcumin in-vivo The composite has the potential to wound healing platform. [158] Film Bacterial cellulose, alginate, gelatine and curcumin in-vitro It has potency for wound care, periodontitis and oral cancer treatment. [159] Fabric scaffold Curcumin and Gymnemasylvestre, graphene oxide, polyhydroxy butyrate-sodium alginate in-vivo Effective against diabetic wound as well as normal wound. [160] Film Human Elastin-Like Polypeptide (HELP), alginate and curcumin in-vitro Effective for drug delivery, wound healing, and tissue regeneration. [161] Hydrogel Curcumin, β-cyclodextrin
Sodium alginate, Chitosanin-vitro It inhibits the Gram-negative (E. coli) and Gram-positive bacteria (S. aureus) growth to heal the wound. [162] Sponge Curcumin, chitosan–alginate and β-cyclodextrin in-vivo It facilitate cutaneous wound healing. [163] Membrane Alginate membrane, polycaprolactone (PCL) nanoparticles, Curcumin in-vivo It can accelerate wound healing without removal of the membrane. [164] Patch Sodium alginate/PVA-Titanium dioxide (TiO2) and curcumin in-vitro It shows antibacterial and antifungal activities and can be used for wound healing. [165] Curcumin Encapsulated particle Pluronic F127 (PF127), calcium chloride (CaCl2), sodium alginate, chitosan, curcumin in-vitro It has potency of good drug delivery and further research needed to test the efficacy for wound healing. [166]
Curcumin-induced angiogenesis hastens wound healing in diabetic rats
- PMID: 25454972
- DOI: 10.1016/j.jss.2014.10.019
Results: Curcumin application caused markedly fast wound closure with well-formed granulation tissue dominated by fibroblast proliferation, collagen deposition, and complete early regenerated epithelial layer. Immunohistochemistry for CD31 revealed well-formed blood vessels with increased microvessel density on days 3, 7, and 14 in the curcumin-treated group. Expressions of VEGF and TGF-β1 on days 3, 7, and 14, hypoxia-inducible growth factor-1 alpha, stromal cell-derived growth factor-1 alpha, and heme oxygenase-1 on days 3 and 7 were increased in curcumin-treated diabetic rats, as compared with other groups.
Conclusions: Curcumin enhanced the neovasculogenesis and accelerated the wound healing in diabetic rats by increased expressions of various factors
Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen
Affiliations- PMID: 29659146
- PMCID: PMC7950016
- DOI: 10.1111/iwj.12904
CLINICAL STUDIES FOUND ONLINE ON TURMERIC IN WOUNDS
Clinically, patients affected by diabetic wounds treated with curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds reported a significantly faster healing process compared to those treated with patients receiving treatment with placebo scaffold.
As mentioned above, topical application of curcumin seems to have more pronounced effects on wound healing compared to its oral administration in the treatment of wounds, owing to higher accessibility of the drug at the wound site.
Another clinical paper linked below has photographs of wound healing. 60 patients were divided into three groups one of the groups was Turmeric plus Honey. Turmeric alone was not used in this paper. Turmeric Mixed Honey Topical Application Enhances Healing, is Safe and Economical in Chronic Wounds
Additional studies I could not personally review on Pub Med --
One reportedly is from UK. 3 are from India. Details in a direct quote from linked review below Literature related to turmeric for wound healing
Licj et al ,(1993) conducted a comparative randomized study for the total of 20 patients grouped in to 4 units based on wound size. The samples were selected from Medical research unit, U.K with four different interventions. The wounds in group I patients were dressed daily with 0.9% normal saline (controls). Turmeric powder was applied topically in an amount of 0.5gm/cm2 of wound surface to the wounds of group II patients. In group III patients, turmeric powder was applied topically to the wounds and were given 1.5% turmeric aqueous suspension by mouth (via) daily drinking water. Group IV patients were given 1.5% turmeric solution by mouth and their wounds were dressed daily with 0.9% normal saline. At 0,3,6 and 10 the mean area of the wounds was similar in all groups. At days 17 and 25 however, the treatment groups exhibited significantly smaller wounds when compared to control (P<0.05 each group). In addition, all patients in groups 2 and 3 and 75% of the patients in group IV had healed wounds at day 32, compared to only 38% in the control group. Thus, turmeric powder in both oral and topical applications, enhanced wound contraction and healing in this model. The wound status was examined through bates Jensen wound assessment scale. It indicates, that local application and oral intake of turmeric enhances wound contraction when compared to daily cleaning with saline. The effectiveness rate was about 78%and it shows high significance.
Despande, Marks & Begum,(2000) conducted a randomized clinical trial study for 78 patients with diabetic wounds in the foot from National Institute of Health in Pune based on structured questionnaire data collection on wound status and Batson Index, the treatment continued for 2 weeks and the healing effects noted for 81% of patients on continuous application of curcumin with the dose of 1.5gm daily twice. Thus the significance (p=0.05) shows highly reliable.
Shiva & Vandana,(2002) conducted a clinical study to evaluate the potential efficacy of fresh turmeric paste to heal wounds for 18 patients. The samples was selected from government ayurvedic college, Nagercoil. Turmeric paste was applied topically to the wound for 14 days. Wound healing was assessed on treatment0,3,7,14. At the end of 14th day it was observed that the wound healing was significantly faster (p>0.01) in experimental group.
Srivastava & Suvira,(2002) conducted a randomized experiments for 20 samples with leg ulcer from the village of Orissa, India.Curcumin were given in the dose of 0.1 mg / cm2 surface for a period of 3 months to enhance rapid wound healing. Enhancement of collagen synthesis and marked wound healing were demonstrated to a rate of 87% with the reliability of r=+1 and shows highly significance. The residents of Orissa village has shown the greater acceptance of curcumin application over the wound,where it is cost effective and easy for application.
Rajinder Raina & Verma,(2008) conducted a randomized clinical trial of application of turmeric powder with the dose of 0.5-1gm for the period of 3 weeks and to find out the wound status level among diabetic clients in general clinics of West Bengal. Wound measurements was done using Bates-jensen wound assessment scale.At the end of the third week it was found the healing effects was noted for 73% of clients. The significance( p=0.05)
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