We use cookies to ensure our website works properly and to personalise your experience. Cookies policy
12Krishak College of Pharmacy, Rajgarh, Mirzapur, Uttar Pradesh, India.
3,4Om Sai Vindhya College of Pharmacy, Marihan, Mirzapur, Uttar Pradesh, India.
5Pharmacist, National Mobile Medical Unit, National Health Mission Uttar Pradesh, India.
Wound healing is a coordinated biological process involving hemostasis, inflammation, proliferation, and tissue remodelling. Delayed repair can be associated with infection, persistent inflammation, oxidative stress, impaired perfusion, metabolic disease, and other patient- and wound-related factors. Medicinal plants contain chemically diverse constituents—including flavonoids, phenolic acids, tannins, terpenoids, saponins, and polysaccharides—that have been investigated for possible effects on processes involved in tissue repair. However, the value of a botanical ingredient depends not only on preliminary biological activity but also on reliable botanical identification, chemical characterization, formulation performance, stability, local safety, and the quality of supporting evidence. This critical review connects phytochemical considerations with topical dosage-form design and evidence-based evaluation. Conventional gels, creams, ointments, emulgels, films, hydrogels, and selected nano-enabled systems are compared in terms of potential advantages, limitations, and development needs. Analytical and biological methods—including marker-based standardization, chromatographic fingerprinting, release testing, antimicrobial assays, cell-based models, preclinical wound models, and clinical outcomes—are discussed with attention to what each method can and cannot establish. Clinical reviews suggest that several botanical interventions merit further investigation, but heterogeneity in products, indications, controls, and study quality limits broad conclusions. The review proposes a botanical-to-clinical evidence framework that links identity and chemical quality to formulation performance, biological plausibility, safety, and clinically meaningful outcomes.
The skin is a protective barrier against physical, chemical, and microbial insults. When tissue integrity is disrupted, the body initiates a coordinated repair response involving haemostasis, inflammatory cells, keratinocytes, fibroblasts, endothelial cells, extracellular matrix, and signalling mediators. The conventional phases of wound healing—haemostasis, inflammation, proliferation, and remodelling—overlap and depend on appropriate timing and coordination [1,2]. Infection, impaired oxygenation, diabetes, nutritional deficiencies, smoking, age, medication exposure, and other factors may delay or disrupt repair [1]. Wound repair and regeneration have also been described in foundational work [18].
Plant-derived materials have a long history of topical use for cuts, burns, ulcers, and skin irritation. Contemporary research has examined botanical extracts and isolated phytochemicals for antioxidant, antimicrobial, anti-inflammatory, and tissue-modulating properties [3–6]. Examples frequently discussed in the literature include Aloe vera, Centella asiatica, Curcuma longa, Calendula officinalis, and other species. Yet evidence for a plant species cannot automatically be transferred to every extract, concentration, plant part, or finished formulation.
A recurring translational problem is the separation of phytochemistry, formulation development, and biological evaluation into disconnected activities. A crude extract may show activity in a chemical assay but have inadequate stability or availability in the intended vehicle. Conversely, a novel delivery system may improve release or physical characteristics without demonstrating better wound outcomes. This review therefore focuses on the relationship between botanical quality, dosage-form performance, experimental evidence, and clinical relevance.
2. Review approach and scope
This manuscript is a critical narrative review, not a completed systematic review. It synthesizes established wound-healing biology, botanical research, topical formulation science, and published evidence reviews. Relevant literature can be located through PubMed/MEDLINE, Scopus, Web of Science, publisher platforms, and reference lists using combinations of terms such as “herbal topical formulation,” “wound healing,” “phytoconstituents,” “botanical standardization,” “hydrogel,” “clinical trial,” and “wound dressing.” A final journal submission should document the actual search dates, full database-specific strategies, eligibility criteria, and selection process if these are undertaken. No new search counts or PRISMA flow numbers are claimed in this narrative draft. PRISMA 2020 is relevant if the work is converted into a systematic review, but it is not a substitute for conducting a systematic search [7].
3. Biological basis of wound repair
3.1 Haemostasis and inflammation
Haemostasis limits blood loss and produces a provisional matrix that supports subsequent cellular activity. Inflammation follows, with neutrophils and macrophages contributing to microbial control, removal of damaged material, and signalling for repair. Inflammation is necessary, but its persistence or dysregulation may contribute to chronic wounds [1,2]. Plant constituents proposed to influence inflammatory or redox pathways should therefore be assessed for dose-dependent effects and possible interference with normal host defence. “Anti-inflammatory” activity is not intrinsically beneficial in every wound context.
3.2 Proliferation and remodelling
The proliferative phase includes re-epithelialization, fibroblast activity, granulation tissue formation, angiogenesis, and extracellular-matrix deposition. During remodelling, collagen and other matrix components are reorganized. Early wound closure does not necessarily predict scar quality, tensile strength, recurrence, or durable healing. The chosen endpoints must match the intended product claim and wound indication [1,2].
4. Phytoconstituents and their potential relevance
Botanical extracts contain mixtures whose composition can vary with species, plant part, growing conditions, harvesting, processing, solvent, and storage. Mechanistic hypotheses should be linked to characterized materials and appropriate controls rather than inferred from a plant name alone [3,8].
Table 1: Selected Phytoconstituent Classes and Evidence Considerations. the Table Summarizes Research Hypotheses, Not a Ranking of Clinically Proven Agents.
| Constituent class | Examples | Potential relevance investigated | Critical consideration |
|---|---|---|---|
| Flavonoids | Quercetin, kaempferol | Redox and inflammatory signalling; possible effects on cell responses | Compound, dose, and model matter; assay activity is not clinical efficacy. |
| Phenolic acids and polyphenols | Caffeic acid, gallic acid; curcuminoids are a distinct polyphenol group | Antioxidant and inflammation-related effects; selected antimicrobial activity | Solubility, oxidation, and analytical interference may influence results. |
| Tannins | Hydrolysable and condensed tannins | Protein interactions and astringent properties; selected antimicrobial hypotheses | High concentrations can impair cell compatibility; composition needs characterization. |
| Terpenoids/triterpenes | Asiatic acid, madecassic acid and related compounds | Investigated for tissue repair and inflammation-related pathways | Evidence for isolated compounds cannot be assumed for unstandardized extracts. |
| Saponins | Asiaticoside, madecassoside | Investigated in relation to collagen and repair-associated responses | Marker content and dose in the finished product should be reported. |
| Polysaccharides | Aloe-derived polysaccharides; plant gums | Potential biological effects and/or roles in hydration, viscosity, and matrix formation | Distinguish active ingredient from excipient function. |
| Volatile constituents | Selected essential-oil terpenes | In vitro antimicrobial activity and possible topical applications | Volatility, oxidation, irritation, sensitization, and cytotoxicity require assessment. |
4.1 Representative botanical materials
Aloe vera has been examined in several wound-related indications, but results should be interpreted by wound type, product preparation, comparator, and study design. A Cochrane review found insufficient evidence to establish a broad conclusion for aloe in acute and chronic wounds, while a later clinical-trial review identified a wider but heterogeneous literature [9,10]. These findings illustrate why an apparent positive signal should not be generalized to all aloe products.
Centella asiatica contains triterpenoid constituents, including asiaticoside, madecassoside, asiatic acid, and madecassic acid. These have been investigated in relation to collagen-associated processes and tissue repair. Clinical and formulation evidence remains product-specific; standardized extracts and isolated compounds should not be treated as interchangeable [3,11].
Curcuma longa and its constituent curcumin provide a useful formulation case study. Curcumin has been studied in topical systems, but limited aqueous solubility and formulation-dependent stability can constrain delivery. Claims that a carrier improves therapeutic activity require direct comparison at an equivalent dose, with appropriate vehicle controls [8,12].
Calendula officinalis and other botanicals have also been studied in wound-related contexts. A literature review of medicinal plants reports broad preclinical interest, while clinical reviews emphasize variation in preparations and outcomes [3,4]. A botanical’s traditional use can justify research but does not replace rigorous assessment of safety, efficacy, and product quality.
5. Topical dosage forms and formulation strategies
The appropriate dosage form depends on the extract’s physicochemical properties, the wound’s exudate level and location, required residence time, stability, patient acceptability, and intended clinical use. Conventional dosage forms may be sufficient for some products; advanced delivery systems should be justified by demonstrable advantages. General wound dressing and drug-delivery principles provide a useful basis for these comparisons [19,20].
Table 2: Critical Comparison of Topical Dosage Forms. Characteristics Depend on the Specific Product and Are Not Universal Performance Rankings.
| Dosage form | Potential advantages | Limitations / development questions | Useful evaluation |
|---|---|---|---|
| Gel | Convenient spreading; often non-greasy; compatible with selected aqueous extracts | Drying, preservative needs, poor accommodation of some lipophilic materials | pH, viscosity, homogeneity, release, microbial quality, stability |
| Cream / emulgel | Can accommodate selected hydrophilic and lipophilic ingredients | Emulsion instability, excipient incompatibility, complex release behaviour | Phase stability, droplet characteristics, rheology, marker assay, release |
| Ointment | Occlusion and prolonged surface contact may be useful | Greasy feel; may be unsuitable for highly exuding wounds | Consistency, content uniformity, release, tolerability, stability |
| Hydrogel dressing | Hydrated network; potential moisture management and active-ingredient incorporation | Maceration risk, dehydration, mechanical or adhesion limitations | Swelling, fluid handling, mechanics, moisture transmission, release, biocompatibility |
| Film / sheet | Defined geometry; potential sustained contact | Flexibility, removal, adhesion, and moisture balance need optimization | Thickness, tensile properties, adhesion, moisture transmission, release |
| Nano-enabled carrier | May improve solubility, protect selected constituents, or alter delivery | Scale-up, characterization, safety, cost, and regulatory complexity | Size distribution, loading, release, stability, local toxicity, reproducibility |
5.1 Conventional semisolids
Gels, creams, emulgels, and ointments are familiar topical systems with established manufacturing approaches. Formulation design should account for extract polarity, marker stability, compatibility with excipients, spreadability, residence time, and the wound environment. The complete formulation—not only the isolated extract—must be characterized. A product with acceptable appearance and viscosity may still have poor marker uniformity, inadequate release, or insufficient microbial protection.
5.2 Hydrogels and wound-contact materials
Hydrogels and polymeric wound dressings have attracted attention because their hydrated structures can help manage the local wound environment and incorporate selected active ingredients. Reviews of polysaccharide-based hydrogels describe the interplay between polymer structure, extract composition, and final material properties [13]. Yet a hydrogel’s water content or novelty does not itself establish superior healing. Swelling, mechanical integrity, exudate handling, extract stability, release, biocompatibility, and usability should be evaluated for the intended wound.
5.3 Nano-enabled delivery
Nanocarriers may be investigated where they solve a defined problem such as poor solubility, oxidation, or inadequate delivery. The development rationale should identify the limitation of the conventional system and test whether the new carrier addresses it. Controls should separate the effects of the carrier, botanical active, and complete formulation. Greater complexity is justified only if it yields meaningful gains in product performance, safety, or clinical utility.
6. Botanical authentication and standardization
Botanical quality begins with correct identity. Manuscripts should report the accepted scientific name, plant family, plant part, authentication procedure, collection details when relevant, and voucher specimen information. Extraction methods should include solvent composition, plant-to-solvent ratio, time, temperature, concentration or drying procedure, and extract yield. These details are necessary to reproduce a preparation.
Preliminary phytochemical screening can guide investigation but is not sufficient for standardization. Chromatographic fingerprinting and quantitative assays for justified markers are more informative. Marker selection should distinguish identity markers, manufacturing consistency markers, and constituents with a demonstrated pharmacological rationale. The presence of a marker does not automatically prove that it causes the claimed effect. Ethnopharmacological and in vitro wound-healing investigations also stress the need to align experimental models with the biological claim [21].
Quality assessment may also need to consider microbial contamination, pesticides, heavy metals, residual solvents, adulterants, and degradation products. The finished formulation should be tested because a matrix can change assay performance, stability, and marker recovery. Botanical standardization should therefore extend from the raw material through the extract to the final product [3,14].
7. Evidence-based evaluation
Table 3: Evidence Levels and Interpretation Limits.
| Stage | Methods / outcomes | What it can establish | What it cannot establish alone |
|---|---|---|---|
| Identity and chemical quality | Authentication, voucher specimen, chromatographic fingerprint, marker assay | Identity and compositional consistency | Clinical effectiveness |
| Physicochemical quality | pH, viscosity, homogeneity, spreadability, content uniformity | Product consistency and suitability for intended use | Biological activity or healing |
| Stability / microbiology | Marker retention, appearance, phase behaviour, microbial limits, preservative effectiveness as appropriate | Quality during defined storage/use conditions | Efficacy in patients |
| Release / permeation | In vitro release and suitable barrier models | Release behaviour under specified test conditions | Clinical absorption or improved healing without further evidence |
| Antioxidant / antimicrobial assays | Validated chemical assays and microbial tests with controls | Activity in the specific assay and test conditions | Wound closure or infection control in patients |
| Cell-based assays | Viability, migration, proliferation, mechanistic endpoints | Cell responses under model conditions | Whole-tissue healing |
| Preclinical studies | Appropriate wound models, histology, wound area, tensile strength where relevant | Effects in the selected model | Direct clinical effectiveness |
| Clinical studies | Complete closure, time to healing, adverse events, pain, recurrence, patient-relevant outcomes | Effectiveness and safety in the studied population | Universal efficacy for other formulations or wound types |
7.1 Physicochemical and stability testing
pH, viscosity, spreadability, homogeneity, and content uniformity should be selected and interpreted in relation to the dosage form and product specification. Stability studies should evaluate relevant physical, chemical, and microbiological attributes under justified conditions and in the intended packaging. For water-containing products, preservative performance and microbial quality can be particularly important. “Natural” does not mean sterile or self-preserving.
7.2 Release, permeation, and biological assays
In vitro release testing describes how a constituent leaves a formulation under specified conditions; permeation testing evaluates movement through a selected barrier model. These are distinct questions. Increased release is not synonymous with increased wound healing, and skin permeation may not be the desired endpoint for a product intended to act locally on a wound surface.
Antioxidant assays can indicate chemical reactivity or selected redox-related properties but may be affected by extract colour, turbidity, solvent, and matrix interference. Antimicrobial assays should include appropriate positive, negative, vehicle, and interference controls. A zone of inhibition does not establish clinical infection control. Cell migration or scratch assays should be paired with viability measurements and interpreted cautiously because closure of an artificial gap is not equivalent to healing of a complex wound [15].
7.3 Preclinical and clinical evidence
Animal models can examine wound contraction, re-epithelialization, granulation tissue, inflammatory changes, collagen-related outcomes, and local tolerability. Study design should include suitable comparators, prespecified endpoints, appropriate sample-size reasoning, transparent reporting, and ethical approval. Results should be reported for the specific model and should not be extrapolated automatically to human wounds.
Clinical assessment should specify wound type, severity, intervention, comparator, standard care, treatment duration, follow-up, primary outcome, and adverse-event monitoring. Time to complete healing and the proportion of wounds completely healed are generally more clinically meaningful than an isolated laboratory marker. Reviews of clinical herbal wound studies report promising signals but also highlight heterogeneity and the need for larger, better-designed trials [4,5,16]. A 2026 systematic review and meta-analysis of traditional polyherbal formulations reported a non-significant pooled trend toward shorter healing time and emphasized limitations related to heterogeneity and study quality [17]. This is an important counterweight to overly broad claims of efficacy.
8. Critical synthesis and research gaps
Table 4: Priority Gaps and Proposed Improvements.
| Research gap | Why it matters | Recommended improvement |
|---|---|---|
| Incomplete botanical identification | Different species and plant parts may differ chemically | Report authentication and voucher specimen details |
| Uncharacterized extract | Results cannot be reproduced or compared | Document extraction and quantify justified markers |
| Weak vehicle controls | Carrier effects may be misattributed to the extract | Compare vehicle, active material, and complete formulation |
| Single-assay efficacy claims | Chemical activity may not predict tissue repair | Use complementary, biologically relevant endpoints |
| Limited cytotoxicity assessment | Apparent migration or antimicrobial effects may reflect toxicity | Pair activity testing with suitable viability and tolerability tests |
| Inadequate stability data | Chemical composition may change during storage | Use stability-indicating methods and appropriate packaging |
| Heterogeneous clinical outcomes | Results across studies may not be comparable | Use standardized outcomes and clear wound definitions |
| Overgeneralization | Evidence for one extract cannot validate all products from a species | Restrict conclusions to the tested preparation and indication |
9. Proposed botanical-to-clinical evidence framework
The main synthesis proposed in this review is a five-stage framework: (1) botanical identity and chemical quality; (2) formulation development and reproducibility; (3) analytical, release, and biological characterization; (4) preclinical validation with appropriate controls; and (5) clinical validation using meaningful patient outcomes. Progression should depend on evidence quality and the intended product claim rather than on the number of tests performed.
This framework is a proposed organizing model for research and is not presented as a validated regulatory pathway. Its purpose is to make gaps visible: an unidentified extract cannot be standardized; an unstable formulation cannot provide reliable exposure; a positive in vitro assay cannot establish whole-wound healing; and preclinical activity cannot replace clinical validation.
10. Safety and translational considerations
Potential concerns include contamination, pesticides, heavy metals, residual solvents, undeclared ingredients, degradation products, local irritation, allergic contact reactions, and formulation-related cytotoxicity. Essential oils and concentrated extracts require particular attention because composition and tolerability can vary. Safety findings for intact skin may not apply to damaged tissue. Traditional use can inform hypotheses but does not establish the safety of a concentrated extract or a new delivery system.
Translation also requires reproducible manufacturing, packaging compatibility, shelf-life evidence, user acceptability, and feasible cost. Complex nano-enabled systems may be scientifically interesting but can introduce manufacturing and regulatory challenges. Development decisions should consider whether added complexity produces a measurable and clinically relevant benefit.
11. Future directions
REFERENCES
Chandresh Maurya, Pooja Kumari, Pratik Kumar Vishwkarma, Rohit Singh, Vinod Kumar Maurya, Herbal Topical Formulations for Wound Healing: Phytoconstituents, Formulation Strategies and Evidence-Based Evaluation, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 10, 4634-4641. https://doi.org/10.5281/zenodo.23762085
10.5281/zenodo.23762085