Rosehip extract and wound healing: A review

Each year, over 100 million patients are afflicted with new scars from medical procedures worldwide. Natural compounds have shown promise in the treatment of scars and skin disorders. Rosehip oil (RO), produced from the pressed fruit of the rosehip (Rosa canina L.) plant, is used in the pharmaceutical, cosmetic, and food industries. The use of this plant in the treatment of scars has yet to be reviewed.


| INTRODUC TI ON
Every year, over 100 million patients are estimated to develop new scars, 1 leading to growing aesthetic concerns. 2The anti-scarring drug market in the United States is valued at around $12 billion USD annually, 1 with the total annual spending on scar management and treatments estimated at over $20 billion annually. 3Not only do scars have a financial burden on patients and healthcare organizations, but for many patients, scars can take a heavy psychological toll. 4,5ck et al. 4 found strong evidence of a severe decrease in quality of life in patients with hypertrophic and keloid scars.Patients report feelings of anxiety and self-consciousness with even minor facial scars, 5 highlighting the importance of effective therapies for scar management.
Scar formation is thought to arise due to an abnormal architecture of collagen resulting from the remodeling phase of wound healing. 5Despite the high public interest in finding effective treatments for scars, the current treatment options have significant limitations, 1 which result from the complexity of wound healing and the multitude of factors that influence it, including age, race, gender, nutrition, and stress. 6tural compounds have shown promise in the treatment of scars and skin disorders. 7Rosehip oil (RO) is used in the pharmaceutical, cosmetic, and food industries.It is produced from the pressed fruit of the rosehip (Rosa canina L.) plant, and the primary constituents of the oil are linolenic acid, linoleic acid, and oleic acid. 7Despite its widespread use in cosmetics, few scientific investigations have been conducted on RO's effect on human wound healing.Therefore, this review aims to evaluate the current body of knowledge regarding the effects of RO on wound healing and its potential mechanism of action in human skin.

| Selection criteria
Studies were considered for inclusion if they examined RO's effect on postsurgical scars (1), focused on any sex and age (2), used a study design of randomized controlled trials, cohort studies, case-control studies, or cross-sectional studies, and employed reliable and valid methods to assess RO's effect on wound healing (3).Only full-text, peer-reviewed studies published in English were included (4).
Exclusion criteria were as follows: Studies not published in English (1), those not focusing on wound healing (2), and studies that do not provide original data, such as reviews, editorials, or opinion pieces (3).Studies were also excluded where full text was not available (4).

| Data analysis and extraction
Once articles meeting the inclusion criteria were identified, the lead author independently extracted information from each article.First, the titles and abstracts of each article were screened for relevance.
Then, full articles were reviewed and data were extracted.The main data points extracted from each article were study design, study population, and primary findings.The screening tool, Rayyan.ai, was employed to organize and screen studies.

| RE SULTS
Initial database searches identified 20 unique articles; 4 articles were selected for detailed review (Figure 1).Two articles were included in the final review (Table 1).

| Characteristics of included studies
The first trial 9 concentrated on the treatment of postsurgical scars.
The study comprised 108 elderly participants who underwent surgical procedures to remove skin tumors over 3 months.The patients were divided into two groups: a treatment group that applied rosehip seed oil twice daily for 6 weeks and a control group that did not receive any additional treatment.The treatment period began following surgical suture removal, and patients were closely monitored for any side effects.The primary outcomes measured were erythema, dyschromia, atrophy, and hypertrophy through evaluation by the same dermatologist.Patient satisfaction was also evaluated.
Outcomes were measured at 6 and 12 weeks.The treatment group showed significantly lower rates of erythema, dyschromia, and atrophy compared to control.
There was no significant difference in hypertrophy.RO was well tolerated with no adverse effects reported.The rosehip group demonstrated significantly increased wound healing rates compared to the silver sulfadiazine control.
compound was applied onto the wound every 6 h until it was deemed "healthy" by the emergency medicine physician.Wound healing time, complications, and patient satisfaction were the primary outcomes measured in this study.

| Efficacy
In the study by Valerón-Almazán et al. 9 the treatment group had significantly lower rates of erythema after both 6 and 12 weeks (73% of treated patients did not present with erythema at 12 weeks vs. 50% of control patients).The rosehip group also showed lower rates of dyschromia, with differences observed at 6 and 12 weeks; only the differences at 12 weeks were significant (63% of treated patients without discoloration vs. 21% control).The atrophy measurement also showed differences between treatment and control at 6 and 12 weeks, with only the second measurement being significant (85% vs. 62% of patients without atrophy found at 12 weeks).Finally, hypertrophy analysis showed increased improvement in RO versus control; the differences were not significant.The rosehip seed oil was well tolerated, with no side effects reported, and none of the participants discontinued the treatment due to adverse effects. In

| DISCUSS ION
The physiological response to a wound in humans is a multifaceted process characterized by a cascade of events leading to the formation of a scar.This process is typically divided into three distinct phases: inflammation, proliferation, and remodeling. 11Aberration of these processes leads to pathological scarring, such as hypertrophic and keloid scars. 12These scars can lead to increased anxiety, decreased self-esteem, and an overall decrease in an individual's quality of life. 4The studies included in this systematic review focused on exploring the potential of RO in treating wounds and reducing scar formation, both common issues in clinical practice.
RO (Rosa canina L.) is native to various regions worldwide and has been traditionally used for its purported health benefits. 13Both analyzed trials suggest its beneficial impact on wound healing.The wound healing effects may be due to the compound's antioxidant and antimicrobial properties attributed to its chemical composition, including fatty acids, polyphenols, vitamins B, C, and E, and carotenoids. 6,14However, the composition of RO can differ based on environmental factors influencing the plant's growth and the process through which the oil is extracted and processed. 7RO products are typically manufactured through the process of cold pressing the oil from the seed or fruit.Another method used is ethanol extraction which has demonstrated efficacy in extracting higher rates of antioxidant compounds. 15The concentration of RO in the medication varies depending on the proprietary formulation the rosehip extract used. 16r example, the FDA found that the maximum use of Rosa canina fruit extract in eye-area skin products was 0.2%, whereas Rosa canina seed extract was used up to 1.5% in lipstick (this is the highest reported concentration).A manufacturer reported that their trademark mixture consists of Rosa canina fruit extract (maximum percentages: 0.45%-0.65%),butylene glycol (maximum percentages: 76.50%-93.50%),and water (maximum percentages: 5.85%-23.05%).
Valerón-Almazán et al. 9 found lower rates of erythema, dyschromia, and atrophy in postsurgical scars amongst the RO group compared to the control group.In Ala et al.'s trial, 10 the rosehip extract treatment showed significantly faster wound healing rates in second-degree burns compared to silver sulfadiazine, a standard burn treatment.These findings demonstrate the potential healing effect of RO.A significant benefit of RO in the studies reviewed was its safety profile.No adverse effects were reported in either of the two trials.The safety of RO, as indicated in these studies, and the fact that it is generally well tolerated make it a promising candidate for further research into optimal dosage and timing of treatment.
The underlying mechanism through which RO influences healing is theorized to involve the promotion of the transition from M1 to M2 macrophages. 6The M1 phenotype is associated with promoting inflammation, whereas M2 macrophages aid in the regeneration of the extracellular matrix and resolution of inflammation. 17sruptions in this transition process can lead to non-healing or chronic wounds. 18Lei et al. 6 observed that RO influenced an increase in the concentration of type III collagen in mice, promoting healthier tissue healing in a "basket weave" style, typical of unscarred skin, in contrast to the traditional parallel lines observed in scar formation.Hypertrophic and keloid scars, the most common forms of pathological scarring, are associated with high concentrations of TGFβ1 and TGFβ2 and a higher collagen I/III ratio. 19An overexpression of TGFβ1 and TGFβ2 and a decreased expression of TGFβ3 are theorized to contribute to the formation of keloids. 19 this context, the findings from the studies included in this review may be due to RO's antagonistic effect on TGFβ1, 6 promoting healthier tissue healing and decreasing scar size.Moreover, RO demonstrated anti-inflammatory and anti-scarring effects, as indicated by its inhibitory effects on inflammatory mediators such as IL-1R and IL-1. 6,20,21 This review's primary limitation lies in the heterogeneity of the selected randomized controlled trials.One trial focused on burn wounds, while the other reviewed postsurgical wounds.
While both types of injuries involve the skin, the nature and severity of these wounds vary significantly, which could affect the results.Moreover, while both studies had control groups, neither employed double-blinding with a placebo.This could potentially introduce bias into the results, despite attempts to standardize procedures.The lack of double-blinding may decrease internal validity, affecting the results' reliability and potentially overestimating the treatment effect.

| CON CLUS ION
In conclusion, RO appears to have a plausible potential mechanism of action for improving scars, appears to be safe, and has been shown to improve scars in two clinical trials.While the existing data provide some promising insights into the potential use of RO for the reduction of postoperative scars in human skin, more rigorously designed studies are needed further to explore the therapeutic use of RO in topical preparations.
Furthermore, it is critical to recognize that while RO may provide a host of benefits for various skin conditions, it does not operate in isolation.It forms part of a broader ecosystem of factors contributing to wound healing and scar reduction.These factors include the individual's age, health status, lifestyle factors such as smoking and diet, and the nature of the wound or scar itself.These elements need to be considered in future research on RO's potential therapeutic uses.At present, while promising, there are insufficient data to confirm its efficacy and optimal dosage.Therefore, we cannot recommend the use of RO for the treatment of wounds.

AUTH O R CO NTR I B UTI O N S
Design, identification of studies, literature analysis, writing, and editing and revision of the manuscript were performed my Malachy Belkhelladi.Conception, identification of studies, editing and revision of the manuscript were performed by Amina Bougrine.

CO N FLI C T O F I NTE R E S T S TATE M E NT
The authors have no conflicts of interest to disclose.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

E TH I C S S TATEM ENT
This literature review was conducted in accordance with the ethical standards of academic research.The authors ensured that all cited studies were published in peer-reviewed journals and obtained through reputable databases.

R E FE R E N C E S
PubMed and MEDLINE databases were searched for articles published in print or electronically prior to December 2022.Additional records were identified through Google Scholar.The search strategy included the terms: Rosehip, Rosa canina, Rosehip oil, Wound, Healing, Scar, and Skin.The preferred reporting items for systematic reviews and metaanalyses 8 flow diagram of the search results is shown in Figure 1.F I G U R E 1 Preferred reporting items for systematic reviews and meta-analyses flow diagram of search results.
Ala et al.'s study10 consisted of 60 patients presenting to the emergency department with second-degree burns of 1%-10% in size, aged between 18 and 65 years, with a mean age of 33.7 years.The study employed a randomized controlled trial, with 30 patients in each group.One group was treated with Adibderm®, an herbal ointment containing rosehip extract, and the other with silver sulfadiazine, a standard treatment for burns.The rosehip-containing TA B L E 1 Study characteristics., dyschromia, atrophy, and hypertrophy