linarin and Inflammation

Cadmium (Cd) contamination in the environment is a major public health concern since it has been linked to osteoporosis and other bone deformities. Linarin is a flavonoid glycoside, and it can promote osteoblastogenesis. This research aimed to investigate the potential role of linarin against Cd-exposed bone deformations in mice model. In our research, male mice were randomly allocated into four groups: control, Cd-exposed, and Cd + linarin (20 and 40mg/kg/bw, respectively). Linarin prevented body weight loss, increased serum calcium (Ca) and phosphorus (P), and bone alkaline phosphatase (BAP) levels in Cd-exposed groups. Furthermore, linarin treatment at 20 and 40mg/kg/bw significantly decreased RANK and OPG, resulting in an increase in RANKL mRNA levels and protein distribution in the bone of Cd-exposed mice. In addition, the bone of Cd-exposed mice administered with linarin showed higher TRAP, NFATc1, MMP9, and RUNX2 mRNA levels and protein distribution. Linarin significantly decreased oxidative stress in Cd-exposed mice bone by decreasing MDA, a lipid peroxidation product. Moreover, linarin protects Cd-exposed mice antioxidant enzymes by increasing bone SOD, CAT, and GPx levels. Besides, linarin suppresses alterations in the inflammatory system, i.e., NF-κB p65/IKKβ, by reducing NF-κB p65, IKKβ, IL-6, and TNF-α in the bone of Cd-exposed animals. This study concluded that linarin has potential to cure osteoporosis in Cd-exposed mice by reducing oxidative stress and inflammation and modulating the RANK/RANKL/OPG pathway.

Topics: Animals; Cadmium; Glycosides; I-kappa B Kinase; Inflammation; Male; Mice; NF-kappa B; Osteoporosis; Osteoprotegerin; Oxidative Stress; RANK Ligand; RNA, Messenger; Signal Transduction

Acute lung injury (ALI) is an important cause of morbidity and mortality for critically ill patients, and linarin (LR) may be a potential treatment for ALI as it reportedly has antioxidant, anti‑inflammatory and apoptotic‑regulating activity. In the present study, the authors report that saline and LR (12.5, 25 and 50 mg/kg) were applied to male C57BL/6 mice via gavage. Then, mice were intratracheally injected with either saline or lipopolysaccharide (LPS). LR‑pretreatment attenuated LPS‑induced ALI and platelet activation and reduced CD41 expression levels and neutrophil platelet aggregates. Additionally, LPS‑triggered pulmonary myeloperoxidase activity and neutrophil infiltration in lung tissues, and this was eliminated by LR dose‑dependently. Furthermore, LPS‑induced oxidative stress and pro‑inflammatory cytokine release were downregulated by LR by inhibiting thioredoxin‑interacting protein and nuclear factor‑κB signaling pathways, including their downstream and upstream signals, such as xanthine oxidase, NLR family WHAT, pyrin domain‑containing 3 (NLRP3), apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain (ASC), caspase‑1, IκB kinase‑α (IKK‑α) and IκBα. Moreover, in LPS‑induced mice, the mitogen‑activated protein kinase pathway was inactivated by LR. In vitro, LR reduced LPS‑induced inflammation and oxidative stress, which was linked to reduction of ROS. In conclusion, LR pretreatment may be protective against LPS‑induced ALI.

Topics: Acute Lung Injury; Animals; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Carrier Proteins; Cytokines; Glycosides; Inflammation; Inflammation Mediators; Lipopolysaccharides; Lung; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Platelet Activation; Reactive Oxygen Species; Signal Transduction; Thioredoxins