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Cited by 50Bee Products Chemical AnalysisWound Healing and TreatmentsHealthcare and Venom Research

Anti-Inflammatory and Histological Analysis of Skin Wound Healing through Topical Application of Mexican Propolis

Open access
Balderas-Cordero, Daniela, Canales-Alvarez, Octavio, Sánchez-Sánchez, Roberto, Cabrera-Wrooman, Alejandro, Canales-Martinez, Maria Margarita, Rodriguez-Monroy, Marco Aurelio·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241411831PMC PMC10380968
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Abstract

Skin wound healing is a complex biochemical process of tissue repair and remodeling in response to injury. Currently, the drugs used to improve the healing process are inaccessible to the population, are costly, and have side effects, making the search for new treatment alternatives necessary. Propolis is a natural product produced by bees that is widely recognized and used in folk medicine for its multiple biomedical activities. However, therapeutic information regarding Mexican propolis is limited. This study aimed to evaluate the wound-healing effect of the Chihuahua ethanolic extract of propolis (ChEEP). Macroscopic and histological analyses were performed using a mouse wound-healing model. The topic acute toxicity assay showed that propolis at 10% w/v had no toxic effects. ChEEP has antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Moreover, it exhibited good anti-inflammatory activity evaluated through mouse ear edema induced by 12-O-tetradeca-noylphorbol-13-acetate (TPA). A full-thickness incision lesion was created in mice and treated topically with 10% ChEEP. At Day 14 post-treatment, it was observed that propolis increased wound contraction and reduced healing time and wound length; furthermore, propolis increased the tensile strength of the wound, as determined with the tensiometric method, and promoted the formation of type I collagen at the site of injury, as evaluated with Herovici stain. These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process. It should be noted this is the first time that the wound-healing activity of a Mexican propolis has been evaluated.

AI snapshot

Written from the paper’s full text.

TL;DR

Topical 10% Chihuahua ethanolic extract of propolis (ChEEP) was non-toxic, antibacterial against Gram-positive wound bacteria, strongly anti-inflammatory, and improved incisional wound healing in mice. The paper reports increased wound contraction, reduced wound length, higher tensile strength, and earlier type I collagen formation at Day 14.

Key findings

  • Acute dermal toxicity: 10% ChEEP produced no macroscopic irritation and skin histology similar to healthy control; 50% ChEEP caused erythema/edema by Day 4, excoriation/ulceration by Day 8, inflammatory infiltrate, loss of normal skin architecture, decreased skin/muscle thickness, and loss of stratum corneum.
  • Antibacterial activity: ChEEP inhibited *Staphylococcus aureus* and *Staphylococcus epidermidis* at 6, 12, or 18 mg with no statistically significant differences among concentrations; it produced minimal inhibition of *Pseudomonas aeruginosa* only at 6 mg and no inhibition of *Escherichia coli*; Gram-positive vs Gram-negative inhibition differed significantly.
  • Anti-inflammatory activity: in the TPA ear edema model, 10% ChEEP reduced ear thickness by 91.6%, significantly different from TPA and diclofenac groups; diclofenac reduced thickness by 27.3%.
  • Wound healing: at Day 14, ChEEP significantly increased wound contraction and reduced wound length vs negative control and recoveron; tensile strength increased by 40.4% vs healthy skin reference, compared with 18.4% for negative control and 28.9% for recoveron; Herovici staining showed type I collagen predominated in ChEEP-treated wounds at Day 14, while type III persisted in negative control and a mixture was seen in recoveron.

Methods

  • ChEEP was prepared from Mexican propolis collected in Chihuahua, extracted with ethanol, and formulated in UltraSonic conductive gel at 10% or 50% w/v.
  • Seven-week-old male CD-1 mice were used, randomly assigned to groups of five (n = 5). Assays included OECD acute dermal toxicity, Kirby-Bauer antibacterial testing against *S. aureus*, *S. epidermidis*, *P. aeruginosa*, and *E. coli*, TPA-induced ear edema, and a 1 cm full-thickness dorsal incision wound model with topical treatment twice daily and sacrifice at Days 3, 7, or 14.
  • Outcomes included macroscopic wound contraction, wound length via ImageJ, H&E and Herovici histology, and tensiometric tensile strength. Data were expressed as means ± SD and analyzed by one-way ANOVA or unpaired t test, with p < 0.05 considered significant.

Limitations

  • The paper states that extrapolating from mice to humans is limited by differences in skin physiology, immune response, and pharmacokinetics, and that further studies are needed, including clinical trials, mechanism-of-action work, immunohistochemical analyses, direct wound-model anti-inflammatory/antioxidant evaluation, pharmacokinetic studies, and safety/effective-dose/long-term adverse-effect assessments.
  • Evident from the text: all experiments used male CD-1 mice with n = 5 per group, a single ChEEP source from Chihuahua, and no human data; antibacterial testing found no statistically significant differences among the three ChEEP concentrations against Gram-positive bacteria.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms241411831

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

19 of 34 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    ChEEP has a high proportion of phenolic compounds.

    “Accordingly, ChEEP was reported to have a high proportion of phenolic compounds [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] 2018, Hypoglycaemic and antioxidant effects of propolis of Chihuahua in a model of experimental diabetes, Evid.-Based Complement. Altern. Med. source
  • Premisecitation

    Flavonoids identified in ChEEP include pinocembrin, kaempferol, chrysin, naringin, naringenin, quercetin, acacetin, and luteolin.

    “Flavonoids such as pinocembrin, kaempferol, chrysin, naringin, naringenin, quercetin, acacetin, and luteolin were identified in ChEEP by HPLC-DAD and HPLC-MS [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] 2018, Hypoglycaemic and antioxidant effects of propolis of Chihuahua in a model of experimental diabetes, Evid.-Based Complement. Altern. Med. source
  • Interpretationcitation

    Differences in metabolism, bioavailability, and clearance rates between mice and humans can influence the concentration and duration of propolis components in the skin.

    “Differences in metabolism, bioavailability, and clearance rates between mice and humans can influence the concentration and duration of propolis components in the skin.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] Florian, 2020, Translational drug discovery and development with the use of tissue-relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy, Exp. Dermatol. source

      Section 3.3 (page unavailable) describes species-specific differences between rodents and humans, and section 3.4 says dermal drug concentration and bioavailability matter. The paper does not address propolis components or say that mouse–human differences in metabolism and clearance alter their concentration or duration in skin. (LLM, conf=0.79)

      Experimental — accuracy not yet measured
  • Premisecitation

    Substances' absorption, distribution, metabolism, and excretion can vary across species.

    “Furthermore, substances’ absorption, distribution, metabolism, and excretion can vary across species.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] Florian, 2020, Translational drug discovery and development with the use of tissue-relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy, Exp. Dermatol. source

      Section 3.3 describes species-specific differences in human and rodent skin and immune systems, while sections 3.2 and 3.4 discuss drug PK/PD. None of the retrieved passages says that absorption, distribution, metabolism, or excretion varies across species; searches for those terms and for species-specific pharmacokinetics did not establish the claim. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Premisecitation

    The same antibacterial behavior (better against Gram-positive than Gram-negative) has been reported for propolis from Brazil, Canada, Africa, and Mexico (Sonora).

    “The same behavior has already been reported with propolis from Brazil, Canada, Africa and Mexico (Sonora) [38,39,40,41,42].”
    Quote in the paperNot a substantial claim2 of 5 sources checked
    • cites [38] Berretta, 2012, Propolis standardized extract (EPP-AF®), an innovative chemically and biologically reproducible pharmaceutical compound for treating wounds, Int. J. Biol. Sci. source
    • cites [39] Rahman, 2010, Antibacterial activity of propolis and honey against Staphylococcus aureus and Escherichia coli, Afr. J. Microbiol. Res. source
    • cites [40] Nedji, 2014, Antimicrobial activity of Algerian propolis in foodborne pathogens and its quantitative chemical composition, Asian Pac. J. Trop. Dis. source
    • cites [41] Velazquez, 2007, Antibacterial and free-radical scavenging activities of Sonoran propolis, J. Appl. Microbiol. source
    • cites [42] Silva-Beltrán, N.P., Umsza-Guez, M.A., Ramos Rodrigues, D.M., Gálvez-Ruiz, J.C., de Paula Castro, T.L., and Balderrama-Carmona, A.P. (2021). Comparison of the biological potential and chemical composition of Brazilian and Mexican propolis. Appl. Sci., 11. source

      Section 3.5 (Antibacterial Activity; page unavailable) reports higher activity against Gram-positive than Gram-negative strains for Brazilian and Mexican propolis extracts. The paper does not establish that pattern for Canada or Africa, and the passage does not identify the Mexican samples as specifically from Sonora. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 14
  • The quote only partly states this claim. 2

  • May combine two claims.

    Premisecitation

    Propolis has been shown to reduce scar formation, shorten healing time, increase wound contraction, enhance epithelialization, and accelerate tissue repair.

    “Propolis has been shown to reduce scar formation, shorten healing time, increase wound contraction, enhance epithelialization, and accelerate tissue repair [24,36,54].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [24] Yang, 2022, Research progress on therapeutic effect and mechanism of propolis on wound healing, Evid.-Based Complement. Altern. Med. source
    • cites [36] Oryan, 2018, Potential role of propolis in wound healing: Biological properties and therapeutic activities, Biomed. Pharmacother. source
    • cites [54] Conceição, M., Gushiken, L.F.S., Aldana-Mejía, J.A., Tanimoto, M.H., Ferreira, M.V.d.S., Alves, A.C.M., Miyashita, M.N., Bastos, J.K., Beserra, F.P., and Pellizzon, C.H. (2022). Histological, Immunohistochemical and Antioxidant Analysis of Skin Wound Healing Influenced by the Topical Application of Brazilian Red Propolis. Antioxidants, 11. source

      The Results (section 3.1; page unavailable) report better epithelialization with one Brazilian red propolis formulation, supporting that part of the claim. They also report no significant difference in wound contraction versus untreated wounds. The Discussion (section 4; page unavailable) describes reduced scarring only as a possibility requiring confirmation, and the paper does not establish a shorter healing time. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    ChEEP contains 31.4% phenolic compounds and 6.2% flavonoids, exceeding the minimum parameters of NOM-003-SAG/GAN-2017.

    “31.4% (314 mg equivalent of gallic acid/g) of the total ChEEP extract are phenolic compounds and 6.2% (6.25 mg equivalent of quercetin/g) are flavonoids [27]”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [27] 2018, Hypoglycaemic and antioxidant effects of propolis of Chihuahua in a model of experimental diabetes, Evid.-Based Complement. Altern. Med. source

      Results §3.5 reports 314 mg gallic acid equivalents/g of extract and 6.25 mg quercetin equivalents/g, supporting the cited measurements. It does not report that these values exceed NOM-003-SAG/GAN-2017; moreover, 6.25 mg/g is 0.625%, not 6.2%. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [74] (2017). Propóleos, Producción y Especificaciones Para su Procesamiento (Standard No. NORMA Oficial Mexicana NOM-003-SAG/GAN).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ChEEP has very strong antioxidant activity with an SA50 of 15.75 μg/mL.

    “the antioxidant capacity (SA50) of ChEEP was determined, and the extract showed an SA50 = 15.75 μg/mL [27], in agreement with the antioxidant activity index is considered a very strong antioxidant activity [73].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [27] 2018, Hypoglycaemic and antioxidant effects of propolis of Chihuahua in a model of experimental diabetes, Evid.-Based Complement. Altern. Med. source
    • cites [73] Scherer, 2009, Antioxidant activity index (AAI) by the 2,2-diphenyl-1-picrylhydrazyl method, Food Chem. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The chemical composition of ChEEP was previously analyzed, and eight compounds were identified.

    “In a previous study carried out by the work team, the chemical composition of the ChEEP was analyzed by High-Performance Liquid Chromatography–Diode Array Detection (HPLC-DAD) and Liquid Chromatography–Mass Spectrometry (HPLC-MS) [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] 2018, Hypoglycaemic and antioxidant effects of propolis of Chihuahua in a model of experimental diabetes, Evid.-Based Complement. Altern. Med. source

  • May combine two claims.

    Premisecitation

    Gram-negative bacteria have a more chemically complex cell wall with negatively charged lipopolysaccharides that act as a barrier, providing greater resistance.

    “Gram-negative bacteria have a more chemically complex wall, with the presence of the negatively charged lipopolysaccharides, which act as a barrier, providing greater resistance [45].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [45] Rufatto, 2018, Brazilian red propolis: Chemical composition and antibacterial activity determined using bioguided fractionation, Microbiol. Res. source

      The Discussion (page unavailable) says Gram-negative bacteria have a more chemically complex cell wall that provides greater resistance. It does not mention negatively charged lipopolysaccharides or identify them as the barrier responsible. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Mice may exhibit a more robust or different immune response compared to humans, so the effects of propolis on immune modulation and inflammation observed in mice may not directly translate to humans.

    “Mice may exhibit a more robust or different immune response compared to humans, meaning that the effects of propolis on immune modulation and inflammation observed in mice may not directly translate to humans [91,92].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [91] Agarwal, 2020, Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells, Sci. Rep. source

      The Introduction and Discussion (page numbers not supplied) describe differences between human and rodent immune systems and warn that findings from traditional rodent models may not translate to humans. The paper does not address propolis or establish that mice have a more robust immune response, so those parts of the claim are unsupported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [92] Ho, 2019, T cells and the skin: From protective immunity to inflammatory skin disorders, Nat. Rev. Immunol. source

  • May combine two claims.

    Premisecitation

    The antibacterial activity of propolis is attributed to the synergism of phenolic acids and flavonoids, which inhibit nucleic acid synthesis and depolarize the cytoplasmic membrane, leading to bacterial death.

    “The antibacterial activity of propolis has been attributed to the synergism of the phenolic acids and flavonoids in its chemical composition; these molecules inhibit the nucleic acid synthesis and depolarize the cytoplasmic membrane, which leads to bacterial death [18,40,43,44].”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [18] Martinotti, 2015, Propolis: A new frontier for wound healing?, Burn. Trauma source

      The Review’s “Biological effects of propolis compounds” section says antibacterial effects may result from synergy among propolis compounds, while “Wound healing properties of propolis” attributes antimicrobial activity chiefly to flavonoids and also names coumaric and caffeic acid esters. Neither section states that these compounds inhibit bacterial nucleic acid synthesis or depolarize the cytoplasmic membrane, so the claimed mechanism of bacterial death is unsupported by this copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [40] Nedji, 2014, Antimicrobial activity of Algerian propolis in foodborne pathogens and its quantitative chemical composition, Asian Pac. J. Trop. Dis. source
    • cites [43] 2014, Mecanismos involucrados en la actividad antioxidante y antibacteriana del propóleos, Biotecnia source

      The Conclusions (p. 6) attribute propolis’s antimicrobial activity to flavonoids and phenolic acids, but describe their interaction as possibly individual or synergistic. The mechanisms section (p. 5) reports inhibition of DNA or RNA synthesis and dissipation of bacterial membrane potential. The claim overstates these findings by presenting synergy and the full sequence leading to bacterial death as an established, general mechanism. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [44] Ramos, 2007, Propolis: A review of its anti-inflammatory and healing actions, J. Venom. Anim. Toxins Incl. Trop. Dis. source

      The passage labeled Abstract reports that propolis has in vitro antibacterial activity arising from synergy among its compounds, mainly the flavonoids pinocembrin and galangin. It does not identify phenolic acids as partners in that antibacterial synergy or say that the compounds inhibit bacterial nucleic acid synthesis or depolarize the cytoplasmic membrane. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Pharmacokinetic differences are crucial when extrapolating dosages used in animal studies to potential clinical applications.

    “Considering these pharmacokinetic differences is crucial when extrapolating dosages used in animal studies to potential clinical applications [93].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [93] Florian, 2020, Translational drug discovery and development with the use of tissue-relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy, Exp. Dermatol. source

      Section 3.2 says that assessing target-organ PK and PD is important when moving from preclinical tests to clinical effects. The Conclusions also caution that animal data poorly predict clinical efficacy. Neither passage specifically discusses pharmacokinetic differences between animals and humans or extrapolating animal-study dosages to clinical use. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Propolis induces faster replacement of type III to type I collagen, better fiber organization, reepithelization, and an increase in myofibroblasts on Day 14, suggesting enhanced fibroblastic activity and collagen synthesis.

    “It has been reported that propolis induces a faster replacement of type III to I collagen, better fiber organization, reepithelization of the damaged area and an increase in the amount of myofibroblasts on Day 14, suggesting that propolis enhances fibroblastic activity, as well as collagen synthesis and deposition [63,64,65].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [63] Olczyk, 2013, Propolis modifies collagen types I and III accumulation in the matrix of burnt tissue, Evid.-Based Complement. Altern. Med. source

      The Results and Discussion report increased extractability of collagens I and III in propolis-treated pig burns, and the Discussion cites a suggestion that propolis enhances reepithelization. They do not establish faster replacement of type III by type I collagen, better fiber organization, or an increase in myofibroblasts on Day 14. The paper discusses myofibroblasts generally but does not report that day-specific finding; page numbers were not supplied. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [64] Cardoso, 2013, The incorporation of Brazilian propolis into collagen-based dressing films improves dermal burn healing, J. Ethnopharmacol. source
    • cites [65] Barreto, 2009, Effect of bovine type-I collagen-based films containing red propolis on dermal wound healing in rodent model, Int. J. Morphol.

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    ChEEP reduces TPA-induced ear edema in mice, decreasing ear thickness by 91.6%, significantly different from the TPA and diclofenac groups.

    “Propolis reduced the inflammation caused by TPA, decreasing ear thickness by 91.6%, which was significantly different from the TPA and diclofenac groups (Figure 4E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mean tensile strength of wounds in negative control and recoveron groups increased by approximately 18.4% and 28.9% compared to healthy skin, while the ChEEP group increased by 40.4%; all groups showed significant differences.

    “The mean tensile strength in the negative control and recoveron groups tended to increase by approximately 18.4% and 28.9%, respectively, compared to that of the reference group (healthy skin), while that of the ChEEP group increased further by 40.4%. All groups presented significant differences in mean tensile strength (Figure 8).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ChEEP produces minimal inhibition of Pseudomonas aeruginosa at 6 mg and no inhibition of Escherichia coli at any tested concentration.

    “The results contrasted with Gram-negative bacteria, where minimal inhibition of Pseudomonas aeruginosa was found at the lowest concentration tested (6 mg), whereas with Escherichia coli, no trace of inhibition was observed at any of the concentrations tested”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Topical application of ChEEP at 50% caused mild skin irritation in mice, including erythema, edema, excoriation, ulceration, inflammatory infiltrate, loss of normal skin architecture, decreased skin thickness, and loss of the stratum corneum.

    “The ones treated with 50% ChEEP, the highest concentration, showed erythema and edema on the fourth day post-treatment; on day eight, excoriation and ulceration; on the 12th, the appearance of hair; and on the 14th, a slight shine was observed in the area where the extract was applied”
    • Also stated in: § 2.1. Acute Dermal Toxicity of ChEEP · plain
      “Histological analysis of the skin on the 14th day revealed the presence of abundant inflammatory infiltrate, loss of the normal architecture of the skin, decreased thickness of the skin and muscle, and a greater number of blood vessels and sebaceous glands compared to that of the control group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ChEEP inhibits the growth of Staphylococcus aureus and Staphylococcus epidermidis at concentrations of 6, 12, and 18 mg, with no statistically significant differences among these concentrations.

    “Propolis showed to inhibit the growth of the two Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis at the three concentrations tested, 6, 12 or 18 mg of ChEEP (Figure 3A,B); however, there were no statistically significant differences between them.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Recoveron and 10% ChEEP groups did not differ from the control on Days 3 and 7, but both treatments significantly increased wound contraction on Day 14.

    “Statistical analysis showed that the recoveron and 10% ChEEP groups did not differ from the control on Days 3 and 7; however, both treatments significantly increased wound contraction on Day 14 (Figure 5B–D).”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Topical application of ChEEP at 10% w/v produced no toxic effects in mice, with no signs of irritation, inflammation, ulceration, or change in skin coloration, and skin architecture similar to healthy controls.

    “The topic acute toxicity assay showed that propolis at 10% w/v had no toxic effects.”
    • Also stated in: § 2.1. Acute Dermal Toxicity of ChEEP · plain
      “the mice treated with 10% ChEEP did not show any signs of irritation, inflammation, ulceration or change in skin coloration at the macroscopic level”
    • Also stated in: § 2.1. Acute Dermal Toxicity of ChEEP · plain
      “Since ChEEP at 10% did not have a toxic effect on the skin of the experimental organisms, it was decided to use this concentration in the following tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ChEEP stimulates and accelerates the replacement of type III to type I collagen, explaining the significant increase in tensile strength.

    “suggesting that ChEEP will stimulate and accelerate the replacement of type III to I collagen, explaining the significant increase in the tensile strength of the skin (40.4%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process.

    “These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The mouse wound-healing model is predictive of wound healing in humans.

  • May combine two claims.

    Premisecitation

    Propolis is effective in treating skin wounds, including difficult-to-heal ulcers in diabetic patients, promoting a higher healing percentage than classical interventions.

    “Recently, a systematic review and meta-analysis of more than 40 published studies found strong evidence that propolis is effective in the treatment of skin wounds, including difficult-to-heal ulcers found in patients with diabetes; in fact, propolis was shown to promote a higher percentage of healing than the interventions classically employed [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Albuquerque, 2023, Use of propolis for skin wound healing: Systematic review and meta-analysis, Arch. Dermatol. Res.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Variances in the presence and distribution of skin components, such as sebaceous and sweat glands, may affect the efficacy and safety of propolis.

    “Variances in the presence and distribution of skin components, such as sebaceous and sweat glands, may also affect the efficacy and safety of propolis.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The structure and function of the skin can differ between species, with mice having a thinner epidermis and higher hair follicle density than humans, potentially impacting the penetration and absorption of topical treatments.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Caution should be exercised when applying results from animal studies, such as the mouse model used in this research, to clinical settings.

    “Given these factors, caution should be exercised when applying results from animal studies, such as the mouse model used in this research, to clinical settings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The experimental animals in the acute dermal toxicity assay were randomly assigned into three groups.

    “The experimental animals were randomly assigned into three groups: one control group, without treatment; two experimental groups, treated with 10% and 50% ChEEP, which received two daily doses of 50 mg over the shaved area for 14 days.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The study protocols were approved by the Institutional Ethics Committee of UNAM, FESI, according to NOM-062-ZOO-1999.

    “The present study protocols were approved by the Institutional Ethics Committee of the Universidad Nacional Autónoma de México (UNAM), Facultad de Estudios Superiores Iztacala (FESI), according to the guidelines of the Federal Regulations for Animal Experimentation and Care (NOM-062-ZOO-1999, Ministry of Agriculture, Mexico City).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites NOM-062-ZOO-1999

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The acute dermal toxicity trial was conducted in accordance with OECD guidelines.

    “The trial was conducted in accordance with OECD guidelines [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] OECD (2017). OECD Guidelines for the Testing of Chemicals, Section 4, OECD.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    These effects are related to the high polyphenolic composition of ChEEP.

    “These effects are related to the high polyphenolic composition of ChEEP.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    These results constitute the first in vivo study of the effects of Mexican propolis on the wound-healing process.

    “These results constitute the first in vivo study of the effects of Mexican propolis on the wound-healing process.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The antibacterial activity tests were performed in triplicate.

    “Five-millimeter diameter disks were coated with 6, 12 or 18 mg of ChEEP, disks with 25 μg chloramphenicol (Sigma-Aldrich, Saint Louis, MO, USA) were used as a positive control, and the tests were performed in triplicate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The experimental animals were randomly assigned in groups of five animals each (n = 5).

    “The experimental animals were randomly assigned in groups of five animals each (n = 5) and received treatments according to the objective of each trial.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The experimental animals in the topical anti-inflammatory assay were randomly assigned into three groups.

    “The experimental animals were randomly assigned into three groups: TPA (only positive control), TPA plus diclofenac (Novartis, Mexico City) (nonsteroidal anti-inflammatory drug, negative control) and TPA plus ChEEP.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Animals in the wound incision assay were randomly distributed into four experimental groups.

    “Animals were randomly distributed, and four experimental groups were established: negative control without treatment; positive control treated with recoveron NC® (Armstrong Laboratorios, Mexico City), a commercial wound-healing drug; propolis group treated with 10% ChEEP formulation; and a reference group with healthy skin without any treatment.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The left ears of the mice were not treated and were the control in each organism.

    “The left ears of the mice were not treated and were the control in each organism.”
    Quote in the paperSubstantial claim
31 of 31

  • The paper relies on this without support.

    The wound-healing activity of a Mexican propolis has not been evaluated before this study.

    “It should be noted this is the first time that the wound-healing activity of a Mexican propolis has been evaluated.”

  • The paper relies on this without support.

    The mouse wound-healing model is predictive of wound healing in humans.

    “These findings suggest that the topical administration of ChEEP can improve skin wound healing, probably due to the synergistic effect of its components, mainly polyphenols, in different steps of the wound-healing process.”

  • The paper relies on this without support.

    The structure and function of the skin can differ between species, with mice having a thinner epidermis and higher hair follicle density than humans, potentially impacting the penetration and absorption of topical treatments.

    “The structure and function of the skin can differ between species, with mice having a thinner epidermis and higher hair follicle density than humans, potentially impacting the penetration and absorption of topical treatments.”

  • The paper relies on this without support.

    Propolis is a mixture of biochemical compounds that act in synergy, influencing different targets and different biomedical activities.

    “Propolis is a mixture of biochemical compounds that act in synergy, influencing different targets and, therefore, different biomedical activities, such as those evaluated in this study.”

  • The paper relies on this without support.

    The solvent did not interfere with the assay.

    “TPA was dissolved in ethanol (2.5 µg/20 mL), and the solvent did not interfere with the assay.”

  • The paper relies on this without support.

    The extract was free of the solvent.

    “Once the dissolved extract was obtained, it was taken to a solvent evaporation process through distillation at reduced pressure in a rotary evaporator. The extract was free of the solvent.”

  • The paper relies on this without support.

    Ethanolic extract was selected because it is the way available for the population.

    “Ethanolic extract was selected because it is the way available for the population.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Flavonoid percentage does not match the reported amount per gram

    Minor

    The reported 6.25 mg per gram corresponds to 0.625%, not 6.2%. The paper's phenolic-compound figure uses the expected conversion: 314 mg per gram corresponds to 31.4%.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Grillo, 2012, Comparative study of topical green and red propolis in the repair of wounds induced in rats, Rev. Col. Bras. Cir., 39, 515
  2. Gábor, M. (2003). Inflammation Protocols, Springer.
  3. Alberti, 2019, Effect of propolis nanoparticles on early-stage wound healing in a diabetic noncontractile wound model, Nanotechnol. Adv. Mater. Sci., 2, 1
  4. Khorasani, 2016, Combined effect of Iranian propolis and honey on healing of induced incisional wound in rat, IIOAB J., 7, 184
  5. Alexandru, 2015, Phenolic content, antioxidant activity and effect on collagen synthesis of a traditional wound healing polyherbal formula, Stud. Univ. Vasile Goldis Arad. Ser. Stiintele Vietii (Life Sci. Ser.), 25, 41

Cited by

Sorted by citations

Related

Authors
Balderas-Cordero, D., Canales-Alvarez, O., Sánchez-Sánchez, R., Cabrera-Wrooman, A., Canales-Martinez, M. M., & Rodriguez-Monroy, M. A.
Affiliations
  • Universidad Nacional Autónoma de México, Facultad de Estudios Superiores Iztacala (MX)
  • Laboratorio de Investigación Biomédica en Productos Naturales, Carrera de Medicina, UNAM, FES-Iztacala, Avenida de los Barrios Número 1, Tlalnepantla 54090, Estado de México, Mexico
  • Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Ciudad de México 14389, Mexico
  • Laboratorio de Tejido Conjuntivo, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Ciudad de México 14389, Mexico
  • Laboratorio de Farmacognosia, UBIPRO, UNAM, FES-Iztacala, Avenida de los Barrios Número 1, Colonia Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-07-23
Volume
24
Issue
14
Pages
11831
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241411831
PMC
PMC10380968
OpenAlex
W4385202633
Cited by
49
References
88
Citations by year
2026: 14 · 2025: 21 · 2024: 13 · 2023: 1
FWCI
9.71
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
DGAPA-PAPIIT-UNAM (IN204821, IN205020)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Insect Science › Bee Products Chemical Analysis
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Pharmacology › Healthcare and Venom Research
Keywords
skin wound healing, topical application, anti-inflammatory activity, antibacterial activity, Staphylococcus aureus, Staphylococcus epidermidis, ear edema, wound tensile strength, type I collagen, polyphenols, ethanolic propolis extract, topical toxicity
MeSH terms
Ethanol, Animals, Anti-Inflammatory Agents, Anti-Bacterial Agents, Disease Models, Animal, Propolis, Wound Healing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-31.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-31.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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