Protective effects of isorhynchophylline against silicon-dioxide-induced lung injury in mice

Abstract

Inhalation of silicon dioxide (SD) results in pulmonary inflammatory responses and fibrosis. Isorhynchophylline (Isorhy) is the main alkaloid in the traditional Chinese herb Tripterygium wilfordii, which is reported to have anti-inflammatory activities in the nervous system. However, the effects of Isorhy on SD-induced pulmonary inflammation and fibrosis in mice are unknown. Male mice were exposed to a single dose of SD (2.5 mg/kg, intranasal inoculation) to induce pulmonary fibrosis (PF). The mice were woken up and immediately treated with Isorhy (20 mg/kg, intraperitoneal injection) for 14 or 42 days. The effects of Isorhy on inflammatory responses and lung fibrosis induced by SD were then investigated. After the 14-day treatment, there was a significant reduction in inflammatory cell infiltration in the lungs of mice, with reduced recruitment of inflammatory cells to the lungs. The concentration of pro-inflammatory factors in the bronchoalveolar lavage fluid was reduced, which alleviated inflammatory injury in the lung tissue. After the 42-day treatment, Isorhy alleviated inflammation and inhibited the release of fibrogenic factors in mice with PF. Isorhy also significantly reduced collagen deposition in the lung tissues of mice. Isorhy has the ability to reduce inflammatory responses and fibrosis associated with SD-induced acute lung injury.

Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin‐induced pulmonary fibrosis in mice

“…Alveolar counts, areas, area percentages and circumferences were evaluated using Image‐Pro Plus 6.0. Moreover, double‐blind scoring was performed for the evaluation of tissue inflammation and tissue fibrosis based on the following scale: Tissue inflammation 24 : 0 = the absence of tissue inflammation; 1 = random distribution of inflammatory cells; 2 = inflammatory cells surrounding most of the bronchi and veins by a thin layer (thickness of one to five cells); 3 = inflammatory cells surrounding most of the bronchi and veins by a thick layer (a thickness of >5 cells); and 4 = complete pulmonary inflammation around all veins and bronchi. Tissue fibrosis 25 : 0 = normal pulmonary tissue; 1 = minimal thickness in alveoli and bronchial walls; 2–3 = medium thickness in alveoli and bronchial walls without significant damage to the lung structure; 4–5 = increase in fibrosis with significant damage to the lung structure and formation of small clumps of fibrotic tissue; 6–7 = severe destruction of the structure, large areas of fibrosis and presence of “honeycomb lung”; and 8 = total pulmonary fibrosis. …”

Indole-Based Small Molecules as Potential Therapeutic Agents for the Treatment of Fibrosis

“…Mice treated with isorhy showed alleviation in body weight loss induced by SD. In addition, isorhy treatment substantially assuaged inflammatory cell infiltration and fibroblast excessive proliferation ( Qiu et al, 2020 ).…”

Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway

“…The etiology of ALI is complex, with unclear exact pathogenesis [ 3 ]. However, it is currently believed that the excessive activation and recruitment of inflammatory cells in the lung tissue and the uncontrolled release of inflammatory factors are the root cause of ALI, independent of its specific etiology [ 4 ]. A variety of infla mmatory cytokines are involved in the occurrence and development of ALI.…”

“…A variety of infla mmatory cytokines are involved in the occurrence and development of ALI. Among them, IL-1β and TNF-α are the two key cytokines [ 4 ]. Because they can further trigger the secretion of other pro-inflammatory cytokines, they are also called “early responsive cytokines” [ 4 ].…”