In Vitro and In Vivo Anti-Inflammatory and Antidepressant-like Effects of L. Extracts.

L. has been widely used by humans for centuries for various purposes, such as industrial, ceremonial, medicinal, and food. The bioactive components of L. can be classified into two main groups: cannabinoids and terpenes. These bioactive components of L. leaf and inflorescence extracts were analyzed. Mice were systemically administered 30 mg/kg of L. leaf extract 1 h before lipopolysaccharide (LPS) administration, and behavioral tests were performed. We conducted an investigation into the oxygen saturation, oxygen tension, and degranulation of mast cells (MCs) in the deep cervical lymph nodes (DCLNs). To evaluate the anti-inflammatory effect of L. extracts in BV2 microglial cells, we assessed nitrite production and the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The main bioactive components of the L. extracts were THCA (a cannabinoid) and β-caryophyllene (a terpene). L. leaf extract reduced the immobility time in the forced swimming test and increased sucrose preference in the LPS model, without affecting the total distance and time in the center in the open field test. Additionally, L. leaf extract improved oxygen levels and inhibited the degranulation of MCs in DCLNs. The L. extracts inhibited IL-1β, IL-6, TNF-α, nitrite, iNOS, and COX-2 expression in BV2 microglia cells. The efficacy of L. extracts was suggested to be due to the entourage effect of various bioactive phytochemicals. Our findings indicate that these extracts have the potential to be used as effective treatments for a variety of diseases associated with acute inflammatory responses.