*3.4. Inflammation*

Tissue injury, cell damage, infections due to pathogens, and alterations in biochemicals lead to a biological response called inflammation. In neurological disorders, the important components involved in inflammatory processes are believed to be mast cells, ependymal cells, microglia, astrocytes, and macrophages [88]. Microglia, a type of neuronal support cell acting as resident macrophages located throughout the brain by changing their morphology, actively respond to inflammation and participate in removing damaged neurons and pathogens. An ethanol extract from *M. koenigii* leaves showed significant analgesic and anti-inflammatory activity when explored using carrageenan-induced hind paw edema in albino rats [89]. Another study also confirmed the anti-inflammatory activity of an *M. koenigii* leaf extract in carrageenan-induced paw edema [90]. Additionally, the study recognized the analgesic activity of curry leaves with several experimental models. *M. koenigii* leaf extracts effectively attenuate the pain which is induced by an intraperitoneal injection of acetic acid and subplantar injection of formalin in mice, and the analgesic effect was elucidated with the writhing responses and pain responses in the late phase. Furthermore, it was reported that higher concentrations (20 and 40 mg/kg, per os (p.o.)) reduced the early-phase inflammatory responses induced by formalin [91].

Khurana et al. evaluated the in vitro and in vivo efficacy of a hydroalcoholic extract of *M. koenigii* curry leaves rich in carbazole alkaloids against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. The activity of inflammatory cytokines interleukin 1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and p65-NFκB was significantly reduced by the hydroalcoholic extract of *M. koenigii*. In addition, the hydroalcoholic extract of *M. koenigii* reduced the expression of nitrotyrosine (NT), myeloperoxidase (MPO), IL-1β, intercellular adhesion molecule 1 (ICAM-1), and cyclooxygenase (COX-2), and increased the expression of Nrf2 [92]. Iman et al. evaluated the anti-inflammatory activity of an extract of *M. koenigii* and its bioactive compound girinimbine against lipopolysaccharide/interferon-gamma-induced RAW 264.7 cells. The girinimbine showed reduced levels of NO overproduction and pro-inflammatory cytokine levels IL-1β and TNF-α in the peritoneal fluid. These findings strongly suggest that girinimbine could act as an anti-inflammatory agent by suppressing inflammation [85]. Another study also confirmed the anti-inflammatory activity of an *M. koenigii* leaf extract. Bioactive compounds like murrayakonine A, O-methylmurrayamine A, and mukolidine were reported for their efficiency in inhibiting TNF-α and IL-6 release in LPS-induced inflammation in human peripheral blood mononuclear cells (PBMCs) [39]. The above studies have shed light on the mechanism of the anti-inflammatory activity of *M. koenigii* leaves and their active compounds, which are comparable to nonsteroidal anti-inflammatory drugs (NSAIDs).
