Icariin protects against iron overload‐induced bone loss via suppressing oxidative stress

Abstract

Iron overload is common in patients with diseases such as hemoglobinopathies, hereditary hemochromatosis or elderly men and postmenopausal women. This disorder is frequently associated with bone loss and recently has been considered as an independent risk factor for osteoporosis. By excess reactive oxygen species (ROS) production through Fenton reaction, iron could induce osteoblast apoptosis, inhibit osteoblast osteogenic differentiation. Moreover, Iron could also promote osteoclasts differentiation and bone absorption. The goal of the study is to investigate whether icariin could reverse iron overload‐induced bone loss in vitro and in vivo. Icariin is the major active ingredient of Herba Epimedii and has antioxidant, antiosteoporosis functions. In the current study, we demonstrated that oral administration of icariin significantly prevented bone loss in iron overloaded mice. Icariin could protect against iron overload‐induced mitochondrial membrane potential dysfunction and ROS production, promote osteoblast survival and reverse the reduction of Runx2, alkaline phosphatase, and osteopontin expression induced by iron overload. Icariin also inhibited osteoclasts differentiation and function. Moreover, we also found that icariin remarkably reduced iron accumulation in bone marrow, suggesting that icariin has the ability to regulate systemic iron metabolism in vivo. These results indicated that icariin could be a potential natural resource for developing medicines to prevent or treat iron overload‐induced osteoporosis.

ROS-Mediated Necroptosis Is Involved in Iron Overload-Induced Osteoblastic Cell Death

“…However, our data suggested that the characteristics of osteoblastic cell death induced by iron overload seem to be closely related to necrosis, as proved by the higher PI-positive rate of cells and the typical necrotic morphological features obtained by TEM. Similar phenomena have also been found by previous work, which implied that necrosis might be the primary type of cell death for the osteoblastic cells in the iron overload-associated bone diseases [ 7 , 40 ].…”

“…Ferric ammonium citrate (FAC) (Sigma, St. Louis, MO, USA), a source of iron, was utilized to mimic iron overload conditions in vivo and in vitro [ 7 , 9 , 22 ]. To evaluate the cytotoxic effect of iron overload, the MC3T3-E1 osteoblastic cells were exposed to FAC (50, 100, and 200 μ M) for 24, 72, and 120 h, respectively.…”

Astaxanthin protects against osteoarthritis via Nrf2: a guardian of cartilage homeostasis

“…RT-PCR was used to quantify the expression of related genes. The procedure was performed as previously described [47]. Total RNA was isolated from chondrocytes using a total RNA extraction kit (Toyobo, Japan).…”

“…ROS levels were detected using a DCFH-DA assay kit (S0033, Beyotime, China). These experiments were performed following a previously described protocol [47]. Fluorescence was assessed using a fluorescence microscope (Evos fl auto, Life Technologies, United States) and flow cytometer.…”

Improved Pharmacokinetics of Icariin (ICA) within Formulation of PEG-PLLA/PDLA-PNIPAM Polymeric Micelles

“…Epimedii Folium is the dry aerial part of various plants of the genus Epimedium brevicornu Maxim of Berberidaceae. In addition to its pungent nature and sweet flavor, it also possesses the functions of tonifying the kidneys [1], muscle or bone strengthening [2], dispelling rheumatism [3], etc. Clinically, it is commonly applied for the treatment of impotence, seminal emission, weakness of muscles and bones, rheumatic arthralgia, anti-tumor, numbness, and contracture [4,5,6,7,8,9,10].…”