Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy. Angelica gigas Nakai (AGN) roots have been widely used in oriental medicine to treat blood-related diseases, including cancer. However, the effects of AGN on myelosuppression have not been studied. Here, we investigated the effects of AGN ethanol extract (AGNEX) on cyclophosphamide-induced myelosuppression. AGNEX treatment significantly decreased white blood cell levels while increasing red blood cell and platelet levels in the peripheral blood. It inhibited thymus and spleen atrophy. It also enhanced serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. qRT-PCR results showed that AGNEX decreased the expression of IL-1b and stem cell factor (SCF) in the bone marrow (BM) while increasing the mRNA expression of IL-3 and IL-6 in the spleen. Although AGNEX did not significantly decrease apoptosis and cell cycle arrest in the BM and splenocytes, AGNEX plays a positive role in cyclophosphamide-induced myelosuppression. AGNEX administration increased BM cells in the femur while decreasing apoptotic BM cells. These findings suggest that AGNEX could be used to treat myelosuppression and as a combination therapy in cancer patients.

Loranthus tanakae Franch. & Sav. found in China, Japan, and Korea is traditionally used for managing arthritis and respiratory diseases. In this study, we analyzed the components of L. tanakae 70% ethanol extract (LTE) and investigated the therapeutic effects of LTE on pulmonary inflammation using cells exposed to cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in vitro and in vivo in mice and performed a network analysis between components and genes based on a public database. We detected quercitrin, afzelin, rhamnetin 3-rhamnoside, and rhamnocitrin 3-rhamnoside in LTE, which induced a significant reduction in inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and inflammatory cells in CSC exposed H292 cells and in mice, accompanied by a reduction in inflammatory cell infiltration into lung tissue. In addition, LTE increased translocation into the nuclei of nuclear factor erythroid-2-related factor 2 (Nrf2). By contrast, the activation of nuclear factor (NF)-κB, induced by CSC exposure, decreased after LTE application. These results were consistent with the network pharmacological analysis. In conclusion, LTE effectively attenuated pulmonary inflammation caused by CSC+LPS exposure, which was closely involved in the enhancement of Nrf2 expression and suppression of NF-κB activation. Therefore, LTE may be a potential treatment option for pulmonary inflammatory diseases including chronic obstructive pulmonary disease (COPD).

Copper oxide nanoparticles (CuO NPs) have seen increasing use across various industries, raising significant concerns about their potential toxicity and the exacerbation of pre-existing conditions like asthma. Asthma, a chronic inflammatory condition of the airways, can be triggered or worsened by environmental factors such as allergens, air pollutants, and chemicals, including nanoparticles. This study aimed to investigate the pulmonary toxicity induced by CuO NPs and their impact on asthma, with a particular focus on the role of thioredoxin-interacting protein (TXNIP). Using an ovalbumin (OVA)-induced asthma model, we found that CuO NP exposure led to significant increases in inflammatory cell infiltration, cytokine production, airway hyperresponsiveness, OVA-specific immunoglobulin (Ig)E levels, and mucus production. These pathological changes were closely associated with the upregulation of TXNIP-related signaling pathways, including phosphorylated apoptosis signal-regulating kinase (p-ASK)1, the Bax/Bcl-2 ratio, and cleaved caspase-3 activation. Complementary in vitro experiments using NCI-H292 respiratory epithelial cells showed that CuO NP treatment enhanced TXNIP signaling and increased mRNA expression and the production of inflammatory cytokines. Notably, TXNIP knockdown significantly attenuated these CuO NP-induced effects. In conclusion, our findings suggest that CuO NP exposure not only induces pulmonary toxicity but also exacerbates asthma, primarily through the activation of the TXNIP signaling pathway.

Titanium dioxide nanoparticles (TiO₂NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO₂NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO₂NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO₂NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO₂NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO₂NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO₂NP-induced pulmonary toxicity.

Asian sand dust (ASD), generated from the deserts of China and Mongolia, affects Korea and Japan during spring and autumn, causing harmful effects on various bio-organs, including the respiratory system, due to its irritants such as fine dust, chemicals, and toxic materials. Here, we investigated the therapeutic effects of silibinin against ASD-induced airway inflammation using mouse macrophage-like cell line RAW264.7 and a murine model. ASD was intranasally administered to mice three times a week and silibinin was administered for 6 days by oral gavage. In ASD-stimulated RAW264.7 cells, silibinin treatment decreased tumor necrosis factor-α production and reduced the expression of p-p65NF-κB, p-p38, and cyclooxygenase (COX)-2, while increasing heme oxygenase (HO)-1 expression. In ASD-exposed mice, silibinin administration reduced inflammatory cell count and cytokines in bronchoalveolar lavage fluid and decreased inflammatory cell infiltration in lung tissue. Additionally, silibinin lowered oxidative stress, as evidenced by decreased 8-hydroxy-2’-deoxyguanosin (8-OHdG) expression and increased HO-1 expression. The expression of inflammatory-related proteins, including p-p65NF-κB, COX-2, and p-p38, was markedly reduced by silibinin administration. Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.