Icariin and Icariside II Reciprocally Stimulate Osteogenesis and Inhibit Adipogenesis of Multipotential Stromal Cells through ERK Signaling

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases. Icariin and icariside II, the main chemical constituents, have attracted great attention from scientists for their potential as antiosteoporosis agents. Our study aimed to evaluate their effects on the lineage commitment of multipotential stromal cells (MSCs). The osteogenesis and adipogenesis of MSCs were assessed by ALP activity, calcium deposition, and adipocyte formation. The expression profiles and levels of osteogenic and adipogenic specific genes were evaluated by cDNA microarray and quantitative real-time PCR. The involvement of extracellular signal-regulated kinase (ERK) signaling was studied by enzyme-linked immunosorbent assay. Icariin and icariside II significantly increased ALP activity and mineralization during osteogenic differentiation of MSCs. Runx2, Col1, and Bmp2 were upregulated in the presence of icariin and icariside II. Meanwhile, they downregulated Pparg, Adipsin, and Cebpb expression during adipogenic differentiation. cDNA microarray revealed 57 differentially expressed genes during lineage commitment of MSCs. In addition, icariin and icariside II enhanced the phosphorylation of ERK, and the above biological effects were blocked by ERK inhibitor U0126. Icariin and icariside II may drive the final lineage commitment of MSCs towards osteogenesis and inhibit adipogenesis through the ERK signaling pathway. Both of them exert multiple osteoprotective effects and deserve more attention for their medicinal and healthcare prospects.

Skimmed Bovine Milk-Derived Extracellular Vesicles Isolated via “Salting-Out”: Characterizations and Potential Functions as Nanocarriers

Bovine milk-derived extracellular vesicles (BM-EVs) are recognized as promising nanoscale delivery vectors owing to their large availability. However, few isolation methods can achieve high purity and yield simultaneously. Therefore, we developed a novel and cost-effective procedure to separate BM-EVs via “salting-out.” First, BM-EVs were isolated from skimmed milk using ammonium sulfate. The majority of BM-EVs were precipitated between 30 and 40% saturation and 34% had a relatively augmented purity. The separated BM-EVs showed a spherical shape with a diameter of 60–150 nm and expressed the marker proteins CD63, TSG101, and Hsp70. The purity and yield were comparable to the BM-EVs isolated via ultracentrifugation while ExoQuick failed to separate a relatively pure fraction of BM-EVs. The uptake of BM-EVs into endothelial cells was dose- and time-dependent without significant cytotoxicity. The levels of endothelial nitric oxide syntheses were regulated by BM-EVs loaded with icariside II and miRNA-155-5p, suggesting their functions as delivery vehicles. These findings have demonstrated that it is an efficient procedure to isolate BM-EVs via “salting-out,” holding great promise toward therapeutic applications.

Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

Icariside II, an active flavonoid, is extracted from the traditional Chinese medicinal herb Epimedii. It possesses multiple biological and pharmacological properties, including anti-inflammatory, anticancer, and anti-osteoporotic properties. In recent years, apoptosis has become the hot spot in anticancer therapies. Icariside II exerts positive effects on inducing apoptosis and inhibiting proliferation in various cancers. The antitumorigenic activity of Icariside II was also proven through cell cycle arrest, triggering autophagy, reducing cellular metabolism, and inhibiting cancer metastasis and tumor-associated angiogenesis. Additionally, Icariside II, as a natural product, contributed to a synergistic effect alongside chemotherapeutic drugs. Due to its poor aqueous solubility and permeability, more strategies were developed to improve its therapeutic effects. This review aimed to summarize the chemopreventive properties of Icariside II in solid tumors and reveal its underlying molecular mechanisms.

Icariside II regulates TLR4/NF-κB signaling pathway to improve septic lung injury

Sepsis is caused by the inadequate response to infection and may eventually lead to fatal organ dysfunction and a high mortality rate. Acute lung injury (ALI) caused by sepsis is an important cause of its high mortality, so effective treatment drugs are urgently needed. Icariside II (ICA II) is derived from Epimedii, a ubiquitous biological flavonoid compound. ICA II has shown multiple biological activities. ICA II alleviates LPS-induced neuroinflammation by inhibiting the TLR4 / MyD88 /NF-κB pathway, however, the possible role of icaridinin II in sepsis induced acute lung injury remains unclear. Herein, we developed a sepsis-related ALI mice model induced by LPS treatment, and found Icariside II ameliorated sepsis-related acute lung injury of mice induced by LPS. Our data further confirmed that Icariside II inhibited the inflammatory response in sepsis-related ALI mice, and ameliorated oxidative stress injury. We further revealed Icariside II inhibited the apoptosis of lung cells via TLR4-NF-κB axis. Our data therefore provided a promising therapeutic drug for the treatment of sepsis-induced ALI.