Abstract Recurrent Aphthous Stomatitis (RAS) is a common oral mucosal condition that adversely affects patients’ quality of life. Although its exact etiology remains unclear, current management primarily focuses on symptomatic relief and promotion of ulcer healing. This randomized, double-blind, controlled trial aimed to compare the clinical efficacy of HATAKABB^® Anti-Cough Mouth Spray (HTK) with 0.1% Triamcinolone Acetonide Mouth Spray (TA) in patients with RAS. A total of 64 participants were randomly assigned to receive either HTK or TA three times daily for 7 days. Outcome measures included ulcer size, pain intensity assessed using a visual analog scale (VAS), healing time, and salivary tumor necrosis factor-alpha (TNF-α) levels, evaluated at baseline and after treatment. Baseline characteristics did not differ significantly between groups (P > 0.05). Both treatments resulted in significant reductions in ulcer size after 7 days (P < 0.001). Between-group comparison showed a greater reduction in ulcer size in the HTK group, and non-inferiority analysis confirmed that HTK was not inferior to TA in reducing ulcer size. No significant differences were observed between groups in healing time or VAS scores. Salivary TNF-α levels were significantly reduced in TA after treatment (P < 0.001), and the reduction in TNF-α (ΔTNF-α) was significantly greater in TA than HTK (P = 0.013), consistent with the known anti-inflammatory mechanism of corticosteroids. In conclusion, HTK may represent an effective non-steroidal topical alternative for reducing ulcer size in patients with RAS, particularly for individuals seeking options other than corticosteroid therapy.

Keywords: Recurrent aphthous stomatitis, Triamcinolone acetonide, HATAKABB, TNF-α, Herbal

Funding: This study was supported by the Faculty of Dentistry, Chiang Mai University and HATAKABB (Sim Tien Hor) Co., Ltd.

Citation: Permpoontanalap, M., Pongsiriwet, S., Powcharoen, W., Laosuwan, K., and Ittichaicharoen, J. 2026. Comparison of HATAKABB^® anti-cough mouth spray and 0.1% triamcinolone acetonide mouth spray in treatment of recurrent aphthous stomatitis. Natural and Life Sciences Communications. 25(4): e2026083.

Graphical Abstract:

INTRODUCTION

Recurrent aphthous stomatitis (RAS) is the most common ulcerative condition affecting the oral mucosa, with a reported prevalence of approximately 20% in the general population (Lau and Smith, 2022). The condition is characterized by painful, recurrent ulcers that significantly impair oral function and quality of life. RAS occurs most frequently in adolescents and young adults (Riera Matute and Riera Alonso, 2011), with a slightly higher prevalence in females (Akintoye and Greenberg, 2014).  Clinically, RAS is classified into minor, major, and herpetiform types, of which minor aphthous ulcers account for approximately 70–80% of cases (Edgar et al., 2017) and typically present as small ulcers on nonkeratinized oral mucosa (Reddy et al., 2023).

The pathogenesis of RAS remains incompletely understood (Sanchez-Bernal et al., 2020). Multiple triggering factors have been proposed, including genetic predisposition, psychological stress (Peter et al., 2014), nutritional deficiencies such as vitamin B12 or iron deficiency (Adwar et al., 2024), hormonal alterations, and systemic diseases in which oral ulceration represents a clinical manifestation (Scully et al., 2003). However, accumulating evidence suggests that immune dysregulation plays a central role through T cell–mediated immune responses (Lau and Smith, 2022; Milia et al., 2022) and increased expression of pro-inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-α) (Preeti et al., 2011; Surboyo et al., 2022), contribute to epithelial cell destruction and ulcer formation. Other cytokines, including Interleukins (IL-2, IL-10, IL-1β, and IL-6) (Xiao et al., 2023; Teng and Jin, 2024) have also been implicated in disease activity. Saliva has emerged as a useful, non-invasive medium for evaluating inflammatory biomarkers in RAS (Al Shaar et al., 2024), including TNF-α (Chaudhuri et al., 2018), C-reactive protein (CRP) (Slebioda et al., 2014), reactive oxygen species (ROS) and antioxidant levels (Babaee et al., 2016), and IL-6 (Teng and Jin, 2024), and has been increasingly used for disease monitoring (Zhou and Liu, 2023).

The primary goals of RAS management are pain relief, promotion of ulcer healing, and prevention of recurrence (Challacombe et al., 2015). Topical corticosteroids, particularly 0.1% triamcinolone acetonide (TA) (Belenguer-Guallar et al., 2014), are commonly prescribed and are effective in reducing inflammation and pain (Stoopler et al., 2024). Nevertheless, their use may be associated with adverse reactions that vary according to the duration of therapy, potency, formulation, and site of application. Commonly reported adverse effects include burning sensation, itching, irritation, dryness, allergic contact dermatitis, mucosal atrophy, striae, perioral dermatitis, and oral candidiasis (Kragballe, 1989; Gabros et al., 2025). Moreover, prolonged or repeated use of topical corticosteroids may adversely affect the oral mucosa and may contribute to systemic complications in susceptible patients (Dhar et al., 2014). In addition, some individuals may have contraindications to corticosteroid therapy or may prefer non-steroidal and herbal-based alternatives. These limitations have prompted increasing interest in alternative therapeutic approaches that may provide comparable clinical efficacy while minimizing concerns associated with long-term corticosteroid exposure. Consequently, various natural products have been investigated as alternative treatment options for oral mucosal lesions.

HATAKABB^® Anti-Cough Mouth Spray (HTK) is a traditional multi-herbal formulation indicated primarily for respiratory conditions. It contains extracts from several medicinal plants, including Rhus Chinensis Mill., Glycyrrhiza glabra Linn., Drynaria fortunei, Ophiopogon japonicus, and Polygonatum odoratum. These herbs possess anti-inflammatory (Zaidi et al., 2015), antioxidant (Pastorino et al., 2018), analgesic (Anuja et al., 2010), and immunomodulatory properties (Bi et al., 2023), thereby enhancing the host’s resistance to infection (Chen et al., 2016; Chansiw et al., 2019). Chantarasakha et al. (2022) investigated the anti-inflammatory potential, mechanisms of action, and bioactive constituents of the HTK herbal product. Their findings demonstrated that this formulation significantly reduced the levels of several pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2 (COX-2), and identified pyrogallol—a natural compound with potent anti-inflammatory activity—as one of its principal bioactive components in the cough-relief herbal preparation (Chantarasakha et al., 2022).

A review of the existing literature indicates that no clinical studies have yet evaluated the efficacy of HTK in the management of RAS. Therefore, the present study was designed to compare the therapeutic effectiveness of HTK with that of TA mouth spray in the treatment of RAS.

MATERIAL AND METHODS

Study design and ethical approval

This double-blind randomized controlled trial was approved by the Human Experimentation Committee, Faculty of Dentistry, Chiang Mai University (approval no. 28/2; 12 July 2024). The trial was registered in the Thai Clinical Trials Registry (TCTR20251229020). The study was conducted at the Oral Medicine Clinic, Faculty of Dentistry, Chiang Mai University, Thailand, between October 2024 and June 2025.

Participants

This study included participants over 18 years of age with clinically diagnosed RAS and an ulcer size ≤10 mm. Participants presenting with either single or multiple RAS lesions were eligible for inclusion. In cases with multiple ulcers, the largest lesion was selected as the representative target lesion for clinical measurement and follow-up throughout the study. Exclusion criteria were hypersensitivity to HTK, pregnancy or lactation, RAS associated with systemic conditions e.g., Behçet’s disease, Reiter’s syndrome, Inflammatory Bowel Disease, Cyclic neutropenia, AIDS, Pernicious anemia, or nutritional deficiencies, infectious ulcers, use of corticosteroids or analgesics/NSAIDs within the preceding 2 weeks, and traumatic ulcers. All participants were informed about the study procedures and provided written informed consent prior to enrollment.

Sample size calculation

The sample size was calculated based on the study by Molania et al. (2022) using the online tool Sealed Envelope (https://www.sealedenvelope.com) (Sealed Envelope Ltd, 2012). A total of 72 participants were required for this non-inferiority trial. The non-inferiority margin was set at 0.5 mm, corresponding to 50% of the minimum clinically significant difference of 1 mm in RAS ulcer size, which was considered the smallest detectable change with clinical relevance in ulcer size assessment (Salehi et al., 2024). This margin was selected as a conservative threshold to ensure that HTK would preserve an acceptable clinical effect compared with TA. The calculation was performed using a standard deviation of 0.735, with 80% power and a one-sided significance level of 0.025. The estimated sample size also included a 5% drop-out rate.

Randomization and blinding

Participants were randomly assigned to HTK or TA in a 1:1 ratio using block randomization with variable block sizes of 4 and 8. The allocation sequence was generated by an independent researcher and concealed using sequentially numbered, opaque, sealed envelopes. Both participants and clinical assessors were blinded, and the study sprays were packaged in visually identical bottles.

Study procedures

At baseline, participants underwent medical history taking, vital sign assessment, and oral examination, with documentation of ulcer characteristics. Baseline pain intensity was assessed using a 100-mm Visual Analog Scale (VAS), and unstimulated saliva samples were collected for TNF-α analysis. Participants were randomly assigned to either TA or HTK and instructed to apply the spray directly to the lesion from approximately 1 inch, three times daily after meals, and to avoid eating or drinking for 30 minutes after application. Participants were followed for 7 days, during which pain intensity was recorded daily using the VAS. On day 7, ulcer characteristics, healing time, and salivary TNF-α levels were reassessed after treatment.

Sample preparation

For laboratory processing, 1 mL of saliva was transferred into a clean, dry microcentrifuge tube (Eppendorf). To prevent protein degradation, 10 µL of protease inhibitor cocktail (Protease Inhibitor Cocktail, HMD-ML051-1ML, HiMedia Laboratories, India) was immediately added to each sample. The samples were centrifuged at 10,000 rpm for 10 minutes at 15°C to separate the supernatant from the pellet. After centrifugation, 100 µL of the supernatant was carefully transferred into a new, clean microcentrifuge tube without disturbing the pellet. All samples were sealed with Parafilm and stored at −20°C until laboratory analysis.

Laboratory analysis

Salivary TNF-α levels were quantified using a magnetic bead–based multiplex immunoassay (MILLIPLEX^® Human Cytokine/Chemokine/Growth Factor Panel A, MilliporeSigma, USA) according to the manufacturer’s instructions. All samples were analyzed in batches under controlled laboratory conditions to minimize inter-assay variability, and TNF-α concentrations were determined from standard curves generated for each assay run.

Outcome measurements

The primary outcome was ulcer size reduction after 7 days of treatment. Ulcer size was measured at baseline and on day 7 by the same oral medicine specialist using a calibrated periodontal probe. The maximum diameter of the ulcer was recorded in millimeters. Secondary outcomes included healing time, pain intensity and salivary TNF-α levels. Pain intensity was assessed using a 100-mm visual analog scale (VAS). Baseline and follow-up pain assessments were performed at the clinic. In addition, participants self-recorded their pain intensity once daily after breakfast at approximately the same time each day throughout the study period. Healing time was defined as the number of days until complete ulcer resolution as self-reported by participants. Participants were instructed to define complete healing as the absence of visible ulceration in the oral cavity. Healing time was further categorized as ≤7 days or >7 days to reflect ulcer resolution within the study follow-up period and to facilitate clinically relevant comparison between treatment groups. Salivary TNF-α levels were measured before and after treatment using a magnetic bead–based multiplex immunoassay.

Safety assessment and adverse events

Safety was monitored throughout the study. Participants were instructed to report any adverse events, particularly symptoms of hypersensitivity or allergic reactions following application of the study spray, and the oral mucosa was clinically examined at baseline and follow-up visits. Any suspected allergic reactions or intolerable adverse effects led to discontinuation of the intervention, and all adverse events were recorded descriptively.

Statistical analysis

Data was analyzed using SPSS version 23.0 (IBM Corp., USA). Data distribution was assessed using the Shapiro–Wilk test. Quantitative variables were presented as mean ± standard deviation (SD). Categorical variables at baseline were compared using the chi-square test or Fisher’s exact test, as appropriate. Within-group comparisons were performed using the paired t-test or Wilcoxon signed-rank test, depending on data distribution. Between-group comparisons were conducted using the independent t-test or Mann–Whitney U test, as appropriate. A P-value of less than 0.05 was considered statistically significant. For the primary outcome, non-inferiority was assessed by comparing the 95% confidence interval of the mean difference in ulcer size with the prespecified margin of 0.5 mm.

RESULTS

Participant baseline characteristics

A total of 72 patients were enrolled and randomized equally into two groups (n = 36 per group). Eight participants were lost to follow-up due to relocation or incomplete follow-up. Finally, 64 patients (n = 32 per group) were included in the analysis (Figure 1).

Figure 1. CONSORT flow diagram of the study.

Baseline demographic and clinical characteristics were comparable between TA and HTK (Table 1). Mean age was 26.31 ± 7.03 years in TA and 25.06 ± 5.36 years in HTK, while mean ulcer duration before treatment was 3.00 ± 1.77 and 2.63 ± 1.48 days, respectively. Female participants accounted for 59.37% in TA and 78.13% in HTK, with no significant differences between groups (P > 0.05).

Table 1. Demographic characteristics of the study participants.

Note: P-values < 0.05 vs TA

Comparison of treatment

Ulcer size

Ulcer size decreased significantly after 7 days of treatment in both groups (Table 2). Mean ulcer size decreased from 3.57 ± 1.85 mm to 0.55 ± 1.07 mm in TA and from 3.16 ± 1.63 mm to 0.03 ± 0.18 mm in HTK (P < 0.001 for both). HTK demonstrated significantly greater ulcer size reduction than TA on day 7 (P < 0.001) (Figure 2A).

Non-inferiority analysis demonstrated a mean difference (HTK − TA) of -0.52 mm (95% CI, −0.91 to −0.13). The 95% confidence interval was completely within the prespecified non-inferiority margin (+0.5 mm), indicating that HTK was not inferior to TA (Figure 2B).

Figure 2. Clinical photographs and non-inferiority analysis of ulcer size. Representative clinical photographs of RAS at baseline and after treatment (A); Non-inferiority plot visualizing the mean difference of ulcer size between the HTK and TA at day 7 (B).

Table 2. Comparison of clinical outcomes between TA and HTK.

Note: Δ values indicate changes from baseline to day 7. *P-values < 0.05 vs baseline, **P-values < 0.05 vs TA

Healing time

Healing time was categorized as ulcer resolution within or beyond 7 days. Most participants in both groups required more than 7 days for complete ulcer healing, with no statistically significant difference between groups (P > 0.777) (Table 2).

Pain intensity (VAS Score)

Baseline pain intensity was comparable between TA and HTK (Table 2). Mean VAS scores decreased from 38.81 ± 23.10 mm to 0.17 ± 0.68 mm in TA and from 31.36 ± 19.57 mm to 0 mm in HTK (P < 0.001 for both). Although HTK showed a trend toward faster pain reduction during the first 3 days of treatment, no statistically significant differences in VAS scores were observed between groups at any time point (P > 0.05) (Figure 3).

Figure 3. Mean daily pain intensity assessed by the visual analog scale (VAS) from baseline to day 7.

Salivary TNF-α levels

Salivary TNF-α levels decreased after treatment in both groups (Figure 4A). In TA, salivary TNF-α levels significantly decreased from 67.42 ± 40.08 pg/mL to 34.74 ± 41.11 pg/mL (P < 0.001). In HTK, salivary TNF-α levels decreased from 60.00 ± 63.36 pg/mL to 42.01 ± 36.42 pg/mL; however, this reduction did not reach statistical significance (P = 0.061). Between-group comparison demonstrated that the reduction in salivary TNF-α (ΔTNF-α) was significantly greater in TA than HTK (32.67 ± 56.55 pg/mL vs 17.99 ± 58.97 pg/mL, P = 0.013) (Figure 4B) (Table 2).

Figure 4. Salivary TNF-α levels before and after treatment. Salivary TNF-α levels at baseline and day 7 in TA and HTK (A). ΔTNF-α from baseline to day 7 in both groups (B). *P < 0.05 indicates between-group comparisons; ** P < 0.001 indicates within-group comparisons (TA only). Error bars represent standard deviation. 

Safety and adverse events

No adverse events or treatment-related adverse reactions were reported in either group during the study period.

DISCUSSION

RAS is the most common ulcerative condition of the oral mucosa and can significantly impair quality of life. Although its etiology remains unclear (Porter et al., 2000), increasing evidence indicates that immune dysregulation and elevated inflammatory cytokines, particularly TNF-α, play central roles in its pathogenesis (Hegde et al., 2018). Current management is primarily symptomatic (Altenburg and Zouboulis, 2008), with topical triamcinolone acetonide widely used as the standard treatment (Al-Zaghruri et al., 2025). However, concerns regarding adverse effects and contraindications associated with prolonged corticosteroid use (Satpathi et al., 2024) have prompted growing interest in alternative therapies, including natural compounds and herbal formulations, for the management of RAS (Salehi et al., 2019).

Research on herbal-based therapies for RAS remains limited. Accordingly, this study aimed to compare the therapeutic efficacy of HTK and TA in spray formulations for the management of RAS, using both clinical and biochemical outcomes to evaluate the potential of HTK as an alternative treatment. Previous work by Chantarasakha et al. (2022) demonstrated that HTK suppresses inflammatory mediators, including TNF-α, IL-6, and COX-2, and identified pyrogallol as a key bioactive compound responsible for its anti-inflammatory activity (Chantarasakha et al., 2022). These findings support the pivotal role of TNF-α in the inflammatory pathways underlying RAS (Al Shaar et al., 2024). However, to date, no clinical studies have specifically examined the effect of HTK on salivary TNF-α levels in patients with RAS.

The demographic and baseline characteristics of participants, including sex, age, and ulcer duration, were comparable between the two groups, with no statistically significant differences observed (P > 0.05), supporting the internal validity of the study. The demographic profile of the study population was consistent with previous reports on RAS, particularly the predominance of young to middle-aged adults (Elias et al., 2022) and a slightly higher prevalence among females (Collado Perez et al., 2023).

Clinically, both groups showed a significant reduction in ulcer size after 7 days of treatment; however, the between-group comparison demonstrated a significantly greater reduction in HTK compared with TA (P < 0.001). This finding is noteworthy given that TA is considered the standard topical therapy for RAS. The observed difference may be related to the anti-inflammatory and antioxidant properties previously reported in HTK and its bioactive compounds, particularly pyrogallol. (Chantarasakha et al., 2022).

Other herbal components in HTK may further contribute synergistically to its clinical effects. Flavonoids and polyphenols from Rhus chinensis (Li et al., 2022), cinnamaldehyde from Cinnamomum cassia (Muhammad et al., 2015), and glycyrrhizin from Glycyrrhiza glabra (Dorsareh et al., 2023) have been reported to exert anti-inflammatory and antioxidant effects, including suppression of reactive oxygen and nitrogen species as well as inhibition of NF-κB and COX-2 activity. Additionally, saponins and polysaccharides derived from Polygonatum odoratum possess immunomodulatory properties (Bi et al., 2023) that attenuate excessive inflammatory responses without impairing tissue repair, thereby reducing epithelial damage.

Non-inferiority analysis supported that HTK was not inferior to TA in reducing ulcer size within 7 days. Although the mean difference favored HTK, this finding should be interpreted cautiously, as the study was not designed to assess superiority. Nevertheless, the results suggest that HTK may represent a viable alternative to corticosteroid therapy, providing comparable clinical benefits. Further studies with larger and more diverse populations are warranted to confirm these findings and to evaluate the long-term effectiveness of HTK.

Pain intensity assessed using the VAS decreased progressively over the 7-day period in both groups, consistent with the natural course RAS, in which pain is most pronounced during the first 24–48 hours and gradually subsides as mucosal repair occurs. Although HTK showed a trend toward faster pain reduction during days 1–3, no statistically significant differences in daily VAS scores were observed between groups (P > 0.05), indicating comparable analgesic effects of HTK and TA. This pattern may be explained by the anti-inflammatory effects of TA, which suppress the production of inflammatory mediators and result in relatively rapid pain relief. In contrast, although HTK is not a steroid, it contains peppermint oil, whose principal component, menthol, reduces ulcer irritation and exerts analgesic effects through mechanisms such as vasodilation and calcium channel blockade (Zhao et al., 2022). In addition, HTK contains Prunus armeniaca; a study by Yang et al. (2007) demonstrated that amygdalin, a compound derived from Prunus armeniaca, inhibits COX-2 activity, leading to reduced prostaglandin E2 (PGE2) production, a key mediator of pain sensitization. Early pain reduction is clinically important, as RAS lesions often interfere with eating, speech, and daily activities (Yang et al., 2007).

Healing time did not differ significantly between HTK and TA (P = 0.777), with most participants in both groups requiring more than 7 days for complete ulcer resolution. This finding is consistent with the natural course of minor RAS, which typically resolves spontaneously within 7–14 days, regardless of treatment. Previous literature supports this observation. A systematic review by Quijano et al. (2008) reported that topical corticosteroids are effective in reducing pain and inflammation and may modestly accelerate ulcer resolution; however, they do not appear to promote faster epithelialization compared with alternative therapies (Quijano and Rodriguez, 2008). Similarly, randomized trials and systematic reviews evaluating herbal treatments for RAS have suggested a potential trend toward reduced healing time. However, further well-designed, high-quality randomized controlled trials are still needed to confirm these findings (Li et al., 2016).

The study demonstrated a significant reduction in salivary TNF-α levels in TA (P < 0.001), whereas HTK showed a decreasing trend that did not reach statistical significance (P = 0.061). In addition, comparison of the change in TNF-α levels (ΔTNF-α) between groups revealed a significantly greater reduction in TA (P = 0.013). These findings are consistent with the known mechanism of corticosteroids, which suppress the transcription of pro-inflammatory cytokine genes, including TNF-α, through inhibition of NF-κB activity (Yasir et al., 2023). Several herbal components in HTK have been reported to reduce oxidative stress and promote epithelial regeneration; however, their cytokine-suppressive effects may not be as pronounced as those of TA. Nevertheless, HTK was still able to effectively reduce ulcer size and provide clinical outcomes comparable to or better than TA, despite not producing a statistically significant reduction in TNF-α levels. Interestingly, although HTK demonstrated greater ulcer size reduction, the decrease in salivary TNF-α was less pronounced than that observed in TA. This finding suggests that clinical improvement in RAS may not correlate directly with salivary TNF-α reduction alone. Additional mechanisms related to tissue repair, epithelial regeneration, local anti-inflammatory activity, or patient-related factors may contribute to ulcer healing. Therefore, further studies are needed to clarify the relationship between clinical outcomes and inflammatory biomarkers in RAS.

An interesting observation of the present study is that although healing time did not differ significantly between groups, the greater reduction in ulcer size and the trend toward early pain reduction observed with HTK may confirm clinical benefits in terms of patients’ quality of life, as they may alleviate symptom severity before complete ulcer resolution. In addition, HTK does not carry the potential risks associated with corticosteroid use, such as oral candidiasis or mucosal thinning, which represents a safety advantage.

No serious adverse events were observed in this study, and no participants discontinued treatment due to symptoms suggestive of drug hypersensitivity or allergic reactions following the use of the study sprays. These findings suggest that HTK demonstrated a favorable short-term safety profile during the study period, which is clinically important. However, because the treatment and follow-up duration were limited to 7 days, the present findings support only the short-term safety of HTK. Therefore, longer-term studies are warranted to further evaluate mucosal tolerance, sensitization risk, and potential allergic reactions associated with prolonged or repeated exposure to herbal formulations.

The limitations of this study should be acknowledged. Although pain intensity was assessed daily, clinical follow-up visits were limited to baseline and day 7. More frequent in-clinic follow-up assessments may have provided a more detailed evaluation of ulcer progression and healing dynamics over time. In addition, healing time was self-reported by participants and may therefore be subject to recall bias or subjective interpretation, despite standardized instructions regarding complete ulcer healing being provided.

Despite this limitation, the present study provides clinically relevant evidence supporting the potential role of HTK as a non-steroidal topical option for the management of RAS.

CONCLUSION

This study demonstrates that HTK effectively reduces ulcer size in patients with RAS, with clinical outcomes comparable to those of TA. Although the reduction in salivary TNF-α was less pronounced in HTK, the overall findings suggest that HTK may represent a potentially safe and effective short-term non-steroidal alternative or adjunctive therapy for patients who have contraindications to corticosteroid use.

Further studies with larger sample sizes and extended follow-up periods are warranted to confirm these findings and to evaluate long-term healing, recurrence patterns, and additional biomarkers related to RAS, including pain-related biomarkers. Comparative investigations with other therapeutic modalities and alternative delivery systems, such as an orabase formulation of HTK, as well as comparisons with other herbal formulations, may further clarify its clinical applicability. Studies exploring the potential role of HTK in other inflammatory oral lesions are also recommended.

ACKNOWLEDGEMENTS

The authors would like to sincerely thank all study participants for their time and cooperation. We also gratefully acknowledge the staff of the Faculty of Dentistry, Chiang Mai University, for their valuable assistance with data collection and laboratory procedures. In addition, we would like to thank HATAKABB (Sim Tien Hor) Co., Ltd. for providing the study materials used in this research.

AUTHOR CONTRIBUTIONS

Marisa Permpoontanalap: Conceptualization (Lead), Investigation (Lead), Resources (Lead), Data Curation (Lead);, Formal Analysis (Lead), Writing – Original Draft (Lead), Visualization (Lead); Surawut Pongsiriwet: Conceptualization (Equal), Data Curation (Supporting), Methodology (Lead), Validation (Supporting), Writing – Review & Editing (Equal), Funding Acquisition (Lead); Warit Powcharoen: Methodology (Lead), Data Curation (Supporting), Validation (Supporting), Formal Analysis (Equal), Writing – Review & Editing (Equal); Kittipong Laosuwan: Validation (Supporting), Resources (Supporting), Writing – Review & Editing (Equal); Jitjiroj Ittichaicharoen: Conceptualization (Lead), Methodology (Lead), Validation (Lead), Resources (Lead), Writing – Review & Editing (Lead), Supervision (Lead), Project Administration (Lead), Funding Acquisition (Lead).

CONFLICT OF INTEREST

The authors declared that this study received material and financial support from HATAKABB (Sim Tien Hor) Co., Ltd. The sponsor had no role in the study design, data collection, data analysis, interpretation of the results, or manuscript preparation.

DECLARATION OF GENERATIVE AI USE

This manuscript was prepared with assistance from generative AI tools (ChatGPT, OpenAI) solely for language refinement and organizational clarity. All AI-generated content was reviewed, verified, and edited by the authors, who take full responsibility for the final content.

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