Citrus clementine Peel Essential Oil Ameliorates Potassium Dichromate-Induced Lung Injury: Insights into the PI3K/AKT Pathway

Abstract

Acute Lung Injury (ALI) is a life-threatening syndrome that has been identified as a potential complication of COVID-19. There is a critical need to shed light on the underlying mechanistic pathways and explore novel therapeutic strategies. This study aimed to examine the potential therapeutic effects of Citrus clementine essential oil (CCEO) in treating potassium dichromate (PDC)-induced ALI. The chemical profile of CCEO was created through GC–MS analysis. An in vivo study in rats was conducted to evaluate the effect of CCEO administrated via two different delivery systems (oral/inhalation) in mitigating acute lung injury (ALI) induced by intranasal instillation of PDC. Eight volatile compounds were identified, with monoterpene hydrocarbons accounting for 97.03% of the identified constituents, including 88.84% of D-limonene. CCEO at doses of 100 and 200 mg/kg bw exhibited antioxidant and anti-inflammatory properties. These significant antioxidant properties were revealed through the reduction of malondialdehyde (MDA) and the restoration of reduced glutathione (GSH). In addition, inflammation reduction was observed by decreasing levels of cytokines tumor necrosis factor-α and tumor growth factor-β (TNF-α and TGF-β), along with an increase in phosphatidylinositide-3-kinase (PI3K) and Akt overexpression in lung tissue homogenate, in both oral and inhalation routes, compared to the PDC-induced group. These results were supported by histopathological studies and immunohistochemical assessment of TGF-β levels in lung tissues. These findings revealed that CCEO plays an integral role in relieving ALI induced by intranasal PDC and suggests it as a promising remedy.

The Pharmacological Effects and Potential Applications of Limonene From Citrus Plants: A Review

“…7 The phosphoinositide 3-kinase (PI3 K)/Akt signaling pathway is linked to the formation of pulmonary fibrosis induced by novel coronavirus pneumonia, and d-limonene can reduce PI3K/protein kinase B (Akt)/IκB kinase-α (IKK-α)/nuclear factor kappa-B (NF-κB) p65 signaling pathway expression and phosphorylation. 8,9 Chi et al 10 found that limonene (20, 50, and 75 mg/kg) had a strong antiinflammatory effect and could significantly improve lung function in mice with lipopolysaccharide-induced acute lung damage, with the mechanism being related to the inhibition of extracellular signal-regulated kinase (ERK), p38 Mitogen-activated protein kinase (MAPK), NF-κB, and C-Jun N-terminal kinase signal pathways. D'Alessio et al 11 found that limonene (10 mg/kg) lowered TNF-α levels and inflammation in colitis model rats.…”