## 4 Discussion
MMP-9 and TIMP-1 are also involved in the pathophysiology of COPD, as they degrade the extracellular matrix (ECM) [35]. MMP-9, which is secreted by macrophages originating from neutrophils and from circulating monocytes, is in charge of tissue remodeling and healing through the destruction of basement membrane collagen-IV [36]. Increased MMP-9 activity may be essential in the development of airway fibrosis and emphysema by encouraging the breakdown of alveolar wall basement membranes [37]. TIMP-1 binds to the precursors and active form of MMP-9 to reduce its activity [38]. In COPD patients, higher levels of MMP-9 with higher enzymatic activity are produced as a result of elevated MMP-9 and TIMP-1 expression as well as increased alveolar macrophages. Asymmetry in the levels of MMP-9 and TIMP-1 may cause COPD by generating abnormal ECM breakdown or an accumulation of ECM proteins in the pulmonary alveoli and small airway walls [39]. According to histopathological evidence, CS- and LPS-induced inflammation and fibrosis were alleviated by CBD treatment. Taken together, these findings imply that CBD may be sufficient to stop the structural changes that are typical of COPD, such as pulmonary emphysema and widespread lung inflammation. Inflammation is controlled at the molecular level by intracellular signaling pathways, such as MAPK and NF-\(\kappa\)B [40]. Activation of MAPK and/or NF-\(\kappa\)B was found to correlate with the production of proinflammatory mediators. As demonstrated here, mice exposed to CS and LPS had significantly higher levels of IL-1\(\beta\), IL-6, and TNF-\(\alpha\) in their BALF and lung tissue, and this increase in cytokines appears to depend on the NF-\(\kappa\)B pathway. Both IL-1B and TNF-\(\alpha\) promoted the NF-\(\kappa\)B-DNA binding complex, and the combined action of the two cytokines on human pulmonary microvascular endothelial cells increased the magnitude of this effect [41]. The MAPK is also a pathway through which various proinflammatory cytokines, such as IL-1B and TNF-\(\alpha\), serve as key effectors in numerous cellular responses [42; 43]. To identify the molecular mechanisms responsible for CBD-induced suppression of inflammatory responses, the ability of CBD to alter MAPK phosphorylation and NF-\(\kappa\)B activation in COPD-induced mice was tested. Treatment with CS and LPS markedly increased phosphorylation levels of ERK and p38 MAPK, with both being suppressed by CBD. In addition, CBD reduced nuclear expression of NF-\(\kappa\)B and blocked its phosphorylation in the lung tissue of mice exposed to CS and LPS, indicating the crucial roles of MAPKs and NF-\(\kappa\)B pathways in CBD-induced anti-inflammatory activity. CBD contains approximately 15 herbs. The ratios of the components required to create CBD are described very differently in each study in the literature. Rehmania, the main herb in the blend, makes up between 8% and 32% of the total weight [44]. Iridoids, triterpene glycosides (saponins), and steroid glycosides are the three types of terpene series glycosides found in most herbs. Although distinct terpene glycosides have different properties, the general effects are sedative, antipyretic, and anti-inflammatory [45]. The anti-inflammatory action of the CBD formula is thought to have a significant impact on improving conditions induced by CS and LPS.