## 6 Therapeutic Actions of Madecassoside and Other Major Compounds in _C. asiatica_
### Lung Diseases  
Pulmonary fibrosis (PF) is a chronic, progressive, irreversible and fatal lung disease [184]. As described above, macdecassoside exhibits significant antioxidant and anti-inflammatory activities, which are also implicated in PF. An analogue of macdecassoside, asiaticoside, was shown to suppress septic lung injury induced by cecal ligation and puncture in mice [185], as well as to inhibit collagen expression and TGF-\(\beta\)/Smad signaling pathway activation in keloid fibroblasts [96]. These findings led to an investigation of the effect of macdecassoside on bleomycin (BLM)-induced PF in a mouse model. In this study, macdecassoside improved pathological changes in the lung and decreased collagen deposition. Expression of \(\alpha\)-smooth muscle actin and TGF-\(\beta\)1 were reduced while phosphorylation of Smad2 and Smad3 (major factors in TGF-\(\beta\)1 signaling [96]) in the lung tissues were inhibited. Furthermore, macdecassoside attenuated the oxidative damage and inflammation present at the early stage of PF; this was evidenced by a reduction in total leukocytes in the bronchoalveolar lavage fluid, the reduced myeloperoxidase activity and MDA levels, as well as the increased SOD activity and GSH level in the lung tissues [186]. The anti-PF of macdecassoside in a bleomycin mouse model was suggested to be mediated by activation of PPAR\(\gamma\), leading to subsequent generation of hepatocyte growth factor (HGF) in the colon, from where the upregulated HGF perhaps enters the circulation to reach the lung and impede PF; antagonism of PPAR\(\gamma\) almost completely prevented the macdecassoside-induced HGF production and its ability to reduce PF [187]. Other studies have shown the effectiveness of HGF in attenuating the fibrotic remodeling in both a rat and mouse PF model [188; 189]. On the other hand, asiatic acid was reported to ameliorate lung fibrosis and inflammation in BLM-induced PF in mice via TGF-\(\beta\)1-induced Smad2/3 and ERK 1/2 signaling pathway inhibition and NLRP3 inflammasome inactivation [190].  
Acute lung injury (ALI) is an acute inflammatory disorder that causes disruption of the lung endothelial and epithelial barriers [191]. Asiaticoside exhibited protective effects against LPS-induced ALI by lowering the load of IL-6 and TNF-\(\alpha\) while elevating IL-10 secretion [192]; this protective effect was mediated by inhibiting inflammatory cell infiltration and downregulating the NF-\(\kappa\)B signaling pathway [193]. Similar findings were obtained in a study investigating the effect of asiatic acid on LPS-induced ALI, where the anti-inflammatory mechanism of asiatic acid was associated with the inhibition of the LPS-induced TLR4 signaling pathway [194]. In a model of ALI produced by spinal cord injury, asiatic acid was reported to activate Nrf2 and inhibit the NLRP9 inflammasome pathway [195]. Asiatic acid was also suggested to have the potential to treat chronic obstructive pulmonary disease (COPD), due to its ability to hinder the pulmonary inflammatory response via suppression of inflammatory mediators and induction of HO-1 [196].