Calycosin Ameliorates Bleomycin-Induced Pulmonary Fibrosis via Suppressing Oxidative Stress, Apoptosis, and Enhancing Autophagy

Abstract

Calycosin (CA) is a flavonoid extracted from the root of Astragalus membranaceus and has antioxidant, anti-inflammation, and antiapoptosis properties. The objective of this study was to investigate the efficacy of CA in protecting against pulmonary fibrosis. CA (14 mg/kg) and SB216763 (20 mg/kg) were administrated to bleomycin-induced pulmonary fibrosis mice for 3 weeks. The results concluded that CA alleviated the inflammation and collagen deposition in pulmonary fibrosis. In addition, CA reduced MDA level, enhanced SOD and TAC activities, and increased the activity of the Nrf2/HO-1 pathway. CA also regulated the expressions of apoptosis-related proteins. Moreover, CA enhanced autophagy via upregulating LC3, beclin1, PINK1, and reducing p62. CA also increased expression of LAMP1 and TFEB, and inhibited the release of lysosome enzymes from ruptured lysosomes. These results provide new evidence that CA protects against pulmonary fibrosis through inhibiting oxidative stress and apoptosis. In addition, autophagy abnormality and lysosome dysfunction are restored by CA.

Olea europaea L. Leaf Extract Alleviates Fibrosis Progression and Oxidative Stress Induced by Bleomycin on a Murine Model of Lung Fibrosis

“…The results of this study revealed clearly significant oxidative disturbance after the BLM treatment as indicated in MDA, SOD, and CAT levels evaluation which corroborates with those of Liu et al 28 Interestedly, OLE induced significant restoration of these activities. Indeed, treatment with OLE induced a significant increase in CAT activity in lung parenchyma which was dropped after the BLM treatment, and these results corroborate with those of Rouibah et al 29 and Elgebaly et al 30 OLE has been described to protect rats against oxidative stress by inducing a reduction/inhibition of the ROS formation which can improve CAT production.…”

Investigation of Ogikenchuto (TJ‐98) for intestinal fibrosis using a mouse model of dextran sulfate sodium‐induced colitis

“…One previous study showed that TJ‐98 ameliorates organ fibrosis [20]. This study suggests that the inhibition of IL‐1β may be involved in the amelioration of intestinal shortening and fibrosis by TJ‐98.…”

“…Calcineurin inhibitors, including tacrolimus, have short-term, but not long-term, therapeutic effects [20,21]. There have been no reports on the effects of TJ-98 with a calcineurin inhibitors.…”

Natural plant resource flavonoids as potential therapeutic drugs for pulmonary fibrosis

“…A recent study demonstrated that calycosin effectively ameliorated the severity of fibrosis in BLM-induced mouse models by repressing EMT and blocking the AKT/GSK3β/β-catenin pathway [ 92 ]. Additionally, calycosin has demonstrated a highly potent inhibitory effect against inflammation and collagen deposition in BLM-induced mice while simultaneously enhancing the Nrf2/HO-1 pathway and inducing apoptosis [ 93 ]. Notably, calycosin promoted the upregulation of LC3, beclin1, and PINK1 and reduced p62 expression while amplifying the expression of LAMP1 and TFEB; thus, resulting in enhanced autophagy and the inhibition of lysosome enzyme release from ruptured lysosomes [ 93 ].…”

“…Additionally, calycosin has demonstrated a highly potent inhibitory effect against inflammation and collagen deposition in BLM-induced mice while simultaneously enhancing the Nrf2/HO-1 pathway and inducing apoptosis [ 93 ]. Notably, calycosin promoted the upregulation of LC3, beclin1, and PINK1 and reduced p62 expression while amplifying the expression of LAMP1 and TFEB; thus, resulting in enhanced autophagy and the inhibition of lysosome enzyme release from ruptured lysosomes [ 93 ]. Furthermore, calycosin inhibited TGF-β1-induced EMT and alleviated pulmonary fibrosis by regulating the miR-375/YAP1 signaling pathway [ 94 ].…”