Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice

Abstract

Inhalation of crystalline silica particles leads to pulmonary fibrosis, eventually resulting in respiratory failure and death. There are few effective drugs that can delay the progression of this disease; thus, patients with silicosis are usually only offered supportive care. Dioscin, a steroidal saponin, exhibits many biological activities and health benefits including its protective effects against hepatic fibrosis. However, the effect of dioscin on silicosis is unknown.Methods: We employed experimental mouse mode of silicosis. Different doses of dioscin were gavaged to the animals 1 day after crystalline silica instillation to see the effect of dioscin on crystalline silica induced pulmonary fibrosis. Also, we used RAW264.7 and NIH-3T3 cell lines to explore dioscin effects on macrophages and fibroblasts. Dioscin was also oral treatment but 10 days after crystalline silica instillation to see its effect on established pulmonary fibrosis.Results: Dioscin treatment reduced pro-inflammation and pro-fibrotic cytokine secretion by modulating innate and adaptive immune responses. It also reduced the recruitment of fibrocytes, protected epithelial cells from crystalline silica injury, inhibited transforming growth factor beta/Smad3 signaling and fibroblast activation. Together, these effects delayed the progression of crystalline silica-induced pulmonary fibrosis. The mechanism by which dioscin treatment alleviated CS-induced inflammation appeared to be via the reduction of macrophage, B lymphocyte, and T lymphocte infiltration into lung. Dioscin inhibits macrophages and fibroblasts from secreting pro-inflammatory cytokines and may also function as a modulator of T helper cells responses, concurrent with attenuated phosphorylation of the apoptosis signal-regulating kinase 1-p38/c-Jun N-terminal kinase pathway. Also, dioscin could block the phosphorylation of Smad3 in fibroblast. Oral treatment of dioscin could also effectively postpone the progression of established silicosis.Conclusion: Oral treatment dioscin delays crystalline silica-induced pulmonary fibrosis and exerts pulmonary protective effects in mice. Dioscin may be a novel and potent candidate for protection against crystalline silica-induced pulmonary fibrosis.

Clinical efficacy of acetylcysteine combined with tetrandrine tablets on patients with silicosis and its effect on exercise tolerance and pulmonary function

“…Zhang et al (23) showed that acetylcysteine reduced the reactive oxygen species in rats exposed to silica, and also inhibited the mitochondrial apoptotic pathway, thereby reducing the severity of pulmonary fibrosis. Tetrandrine is a calcium antagonist that blocks the calcium channel of fiber cells and inhibits their proliferation (24). Moreover, it can inhibit collagen synthesis in silicosis tissue and act on cell microtubules to make collagen form fibrous structure only outside the cells, and reduce collagen protein in silicosis tissue and loosen or even degrade the tubercle of patients with silicotic nodules.…”

Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages

“…CS particulates (Min-U-Sil 5 ground silica with size distribution of 97% < 5 µm diameter, 80% < 3 µm diameter, and median diameter 1.4 µm) were purchased form the U.S. Silica Company (Frederick, MD, USA). The pretreatment of CS and the establishment of silicosis animal models were performed as previously described [25,26]. The schematic representation for the in vivo treatment schedule is presented in Figure S1.…”

Studies on the Constituents of the <i>Dioscorea tokoro</i> Rhizome

“…Protoyononin and protocompound x were new compounds isolated from natural sources. Among the compounds isolated from Dioscorea tokoro, dioscin, protodioscin, gracillin and protogracillin are distributed in many plants and many aspects of their biological activity have already been reported [15][16][17][18] . However, there are no reports on the bioactivities of yononin, protoyononin, protoyonogenin, tokoronin, prototokoronin, tokorogenin, compound x and protocompound x, whose distributions are limited.…”