Evaluation of the Anti-Inflammatory, Analgesic and Antioxidant Activities of Achillea millefolium L. and Psidium guajava L. Herbal Gargle Development for Oral Mucositis

Oral mucositis is a painful inflammatory and ulcerative complication of anticancer therapy. Its pathogenesis involves treatment-induced cellular injury, reactive oxygen species, inflammatory signaling, epithelial disruption, ulceration and delayed healing. The present article integrates the in-vivo pharmacological and formulation findings of a work investigating Achillea millefolium L. and Psidium guajava L. for oral mucositis management. Ethanolic extracts were evaluated in carrageenan-induced paw edema and hot-plate models, followed by development of five herbal gargle formulations and evaluation in a methotrexate-induced oral mucositis model. Both extracts demonstrated dose- and time-dependent anti-inflammatory and analgesic responses. At 4 h, EAM 200 mg/kg produced 62.21% inhibition of paw edema, while EPG 200 mg/kg produced 65.21%; indomethacin produced 80.11%. In the hot-plate model, EAM 200 mg/kg increased reaction time to 5.20 s at 90 min and EPG 200 mg/kg to 4.98 s, compared with 7.89 s for pentazocine. Among five gargles, F3 demonstrated pH 6.45, viscosity 9.64 cP, minimal sedimentation, excellent redispersibility, low foam formation, favorable stability and the lowest microbial load. In the oral mucositis model, F3 was associated with recovery of body weight, improved food intake, reduction of mucositis score from 3 in disease control to 1, 0% mortality, improved hematological parameters and restoration of tongue architecture on histopathology. The findings support F3 as a promising preclinical herbal gargle candidate while emphasizing the need for standardized and controlled studies. Keywords: Achillea millefolium; Psidium guajava; herbal gargle; oral mucositis; carrageenan edema; hot plate; methotrexate; histopathology; antioxidant; anti-inflammatory.