Thesis (PhD) - Cyprus International University. Institute of Graduate Studies and Research Pharmaceutıcal Sciences

A wound is formed due to the disruption of living cells’ integrity and brings pain and
inflammation. Due to the adverse effects of currently available topical formulations,
there is a need for a new formulation for wound healing, pain relief and inflammation
with fewer side effects. Salvia veneris is endemic to Cyprus and used for pain relief
and infectious diseases. This study aims to evaluate analgesic and anti-inflammatory
activities of Salvia veneris and to develop a topical formulation from the ethanol
extract of Salvia veneris for wound healing with anti-inflammatory and analgesic
activities as a new treatment strategy for the wounds. In vitro and in vivo studies were
performed to evaluate the biological activities of Salvia veneris extract. One-way
ANOVA was used at the P< 0.05 confidence level for data analysis. In LC–MS/MS
analysis, 21 phenolic compounds were detected in Salvia veneris ethanol extract.
Caffeic acid, Salicylic acid and Protocatechuic Acid are the most abundant
compounds. The total phenolic contents in the extract was calculated as 144.6 mg
GAE/g of dry extract by using Folin–Ciocalteu method. The ethanol extract of Salvia
veneris showed dose-dependent antioxidant activity against DPPH free radicals with
an IC50 value of 4.6 x 10-2 mg/mL. The oral LD50 of the ethanol extract in rats was
determined as greater than 5000 mg/kg. Salvia veneris showed significant (P= 0.008)
analgesic activity in the acetic acid-induced writhing test in mice and significant (P <
0.01) dose-dependent analgesic activity in both phases of the formalin test, similar to
piroxicam. The ethanol extract of Salvia veneris was able to inhibit hypotonicity and
heat-induced erythrocytes membrane haemolysis in a concentration-dependent manner
(P= 0.002). 5 mg/ml of Salvia veneris ethanol extract showed 57% haemolysis
inhibition. In the formalin-induced paw oedema test, 50 and 200 mg/kg of extract
significantly (P < 0.05) suppressed inflammation. Five topical formulations (F1-F5)
were prepared by varying the concentrations of ingredients and evaluated. The topical
formulation of Salvia veneris showed great wound healing activity on wound excision
model. It significantly increased wound contraction rate compared with silver
sulfadiazine (P < 0.01) and negative control (P < 0.01). The present study demonstrates
that the ethanol extract of Salvia veneris has analgesic and anti-inflammatory activities
and the prepared topical formulation is effective on wound healing. Therefore, the
topical formulation can be used as a novel treatment strategy for wound healing,
localized pain, and inflammation.