Achillea extracts elicit anti-diabetic neuropathic pain by modulating inflammatory cytokines

Abstract

The Eastern-Mediterranean herbal-remedies are utilized for their immunomodulatory-potentials. Achillea species have ethno-pharmacological significance. The current-work aims to perform an in-depth phytochemical-investigation on three Eastern-Mediterranean Achillea species, mainly, Achillea kotschyi Boiss. (AK) , Achillea falcata L. (AF) , and Achillea aleppica DC. (AAL) essential oils (EOs), and to investigate their antidiabetic, and antineuropathic pain, and inflammation, and to have insights into their mechanisms of action. The methods include EO-isolation from three different samples of each of the three species examined, optimization, and validation of GC-MS method, in - vivo antioxidant-technique, HbA1c diabetes-assessment, insulin-level, thermal-hyperalgesia and tactile-allodynia experiments, anti-inflammatory, and inflammatory-markers, TNF-α, IL-6, and 10 level monitoring. The optimized and validated GC-MS method was developed to quantify the major EO components. The highest components detected on AK-EO were thujone (35.84 ± 0.01 %), α -phellandrene (15.99 ± 0.01), and ocimene (12.31 ± 0.01 %), while those of AF were ocimene (65.11 ± 0.01 %), thujone (14.68 ± 0.01 %), and resorcinol (5.00 ± 0.01 %), and the AAL-EO were m -toluamide (49.35 ± 0.01 %), eucalyptol (21.08 ± 0.01 %), and ocimene (13.48 ± 0.01 %). AAL-EO showed superiority in normalizing HbA1c-levels. AAL-EO showed the highest improvement in both thermal-hyperalgesia and tactile-allodynia latencies. The insulin-secretagogue-potential and the improvement of the antioxidant serum-catalase levels might be their mechanism of antinociception. AAL-EO highest-dose (300 mg/kg)showed superiority in the anti-inflammatory-potentials both acutely and chronically, compared to AK and AF-EOs. The decrease in the inflammatory-mediators, TNF-α and IL-6, and the improvement of IL-10 titers proved to be their mechanism of anti-inflammation. In conclusion, AK, AF, and AAL proved to be rich in essential-oil components that can ameliorate chronic-conditions like diabetes, diabetic-neuropathy pain, and inflammation. • Achillea aleppica essential oil was the most potent antidiabetic neuropathy and anti-inflammatory secondary metabolites. • GC-MS validation and optimization. • The mechanism: modulation of inflammatory mediators, and antioxidant effect. • Efficient natural essential oils ameliorated inflammation and diabetic-neuropathy.