Wound healing potential of mouth gel containing isopimarane diterpene from Kaempferia galanga rhizomes for treatment of oral stomatitis

Abstract

Background: Oral ulcers have an impact on 25% of the global population including patients who are suffering from chemotherapy and radiotherapy treatments. Kaempferia galanga L. has been traditionally used for treatment of mouth sores and tongue blisters. However, the wound healing study of isopimarane diterpenes isolated from K. galanga is still limited.

Objective: This study aims to evaluate the wound healing potential of 6β-acetoxysandaracopimaradiene-1α,9α-diol (KG6), a compound isolated from Kaempferia galanga, by examining its biological activities. Additionally, we investigate the physicochemical and biological properties of (KG6) in formulated mouth gels.

Methods: The KG6 mouth gels at 0.10%, 0.25% and 0.50% w/w were formulated using sodium carboxymethylcellulose as a gelling agent, and their physicochemical and biological stabilities were assessed through a heating-cooling acceleration test. The quantification of KG6 contents in KG6 mouth gels was determined using gas chromatography. Both KG6 and KG6 mouth gels were evaluated for their wound healing properties including cell proliferation, cell migration, and antioxidant activity (H₂O₂-induced oxidative stress) in human gingival fibroblast (HGF-1-ATCC CRL-2014) (HGF-1). In addition, the anti-inflammatory activity against nitric oxide (NO) production was investigated in macrophage cells (RAW 264.7).

Results: After KG6 mouth gels were incubated under heating-cooling acceleration condition, the physicochemical properties of the KG6 mouth gels remain stable across various parameters, including appearance, color, smell, texture, pH, viscosity, separation, and KG6 content. The biological studies indicated that the KG6 compound possessed good wound healing potential. The 0.50% KG6 mouth gel exhibited marked anti-inflammatory effect by inhibiting NO production with an IC₅₀ of 557.7 µg/ml, comparable to that of Khaolaor mouth gel, a positive control. The 0.25% KG6 mouth gel increased HGF-1 cell proliferation to 101.7-103.5%, whereas all formulations of KG6 mouth gel enhanced HGF-1 cell migration to 94.7-98.9%, higher than Khaolaor mouth gel (73.5%). Moreover, 0.50% KG6 mouth gel also showed a good antioxidant effect under H₂O₂-induced oxidative stress.

Conclusion: This study substantiates the significant biological activities related to the wound healing property of 0.50% KG6 mouth gel for treatment of aphthous ulcers and oral stomatitis from chemotherapy and radiotherapy treatments.

Keywords: KG6; Kaempferia galanga; Mouth gel; Wound healing.

Figure 1. GC chromatograms.

Gel base before heating-cooling (A), gel base after heatingcooling (B), 0.10% KG6 mouth gel before heating-cooling (C), 0.10% KG6 mouth gel after heating-cooling (D), 0.25% KG6 mouth gel before heating-cooling (E), 0.25% KG6 mouth gel after heating-cooling (F), 0.50% KG6 mouth gel before heating-cooling (G), 0.50% KG6 mouth gel after heating-cooling (H), and KG6 compound (I).

Figure 2. Chemical structure of 6β-acetoxysandaracopimaradiene-1α,9α-diol (KG6).

Figure 3. The migration behavior of HGF-1 cells under the influence of the KG6 treatment.

Figure 4. The migration behavior of HGF-1 cells was examined in response to the before and after heating-cooling test of gel base and KG6 mouth gel treatment.

Figure 5. The migration behavior of HGF-1 cells was examined in response to treatment with the positive controls (TA oral paste and Khaolaor mouth gel).