Erratum: An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

[This corrects the article on p. 4189 in vol. 12, PMID: 32913497.].

α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice.

Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese medicine Cyperus rotundus L. In this study, we found that α-Cyperone abolished the IL-1ß-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 µM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition, in vivo studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.

An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

Acute blunt skeletal muscle injury occurs frequently in sports and traffic accidents, and even leads to muscle necrosis and impaired functionality. Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. Tanshinone IIA is extracted from Salvia Miltiorrhizae, which is effective in the treatment of injury repair. But the clinical application of tanshinone IIA is limited due to its low water solubility, low permeability to biofilm and low bioavailability. In this study, tanshinone IIA liposomes were prepared to improve the bioavailability and sustained release of tanshinone IIA. The particle size, dispersion coefficient, zeta potential, encapsulation efficiency (EE) and drug loading (DL) of tanshinone IIA liposomes were 150.67 ± 27.23 nm, 0.20 ± 0.015, -8.73 ± 2.28 mV, 70.32 ± 4.04% and 15.63%, respectively. The results of quantitative real-time polymerase chain reaction (QRT-PCR) showed that tanshinone IIA liposome significantly promoted the expression of vimentin and reduce MHCIIB expression compared with other groups (P < 0.05). Western blotting showed that tanshinone IIA liposome could effectively promote the expression of autophagy-related proteins (VPS34, Beclin 1 and CTSD) and decrease p62 expression levels to treat injured muscle. Through HE, immunohistochemistry, ELISA and serological tests, we found that tanshinone IIA liposome not only effectively promoted the expression of desmin, but also reduced the expression of collagen-I and inhibited the production of pro-inflammatory factors, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (P < 0.05). In addition, tanshinone IIA liposome therapy significantly reduced the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) after muscle injury compared with other groups (P < 0.05). In conclusion, tanshinone IIA liposome possesses an effective therapeutic effect on acute blunt muscle injury in rats by augmenting autophagy and alleviating oxidative stress. The continuous release of tanshinone IIA encapsulated by liposomes for disease treatment provide a new idea for the efficient and safe use of drugs with low lipid solubility and bioavailability for the treatment of acute blunt muscle injury and repair of other injuries.

An injectable liposome for sustained release of icariin to the treatment of acute blunt muscle injury.

OBJECTIVES: Icariin, extracted from Epimedium, is a kind of flavonoid and possesses osteogenesis and antioxidant. This study aimed to evaluate the therapeutic effects of icariin liposome on acute blunt skeletal muscle injury in rats. METHODS: Icariin liposome was prepared by the thin-film dispersion method. After muscle injury, the corresponding treatment measures were given every day for two weeks. Recovery and mechanism of muscle injury were evaluated by QRT-PCR, HE, immunohistochemistry, malondialdehyde, superoxide dismutase and serological tests. KEY FINDINGS: The particle size, polydispersity index, zeta potential, encapsulation efficiency and drug loading of icariin liposomes were 171.37 ± 38.23 nm, 0.27 ± 0.01, -5.59 ± 1.36 mV, 78.15 ± 2.04% and 15.62%, respectively. The QRT-PCR showed that icariin liposome significantly promoted the expression of MHCIIB and vimentin. Through HE, immunohistochemistry, ELISA and serological tests, we found that icariin liposome effectively promoted desmin expression, reduced collagen I expression and inhibited the production of pro-inflammatory factors, including TNF-α and IL-6. Icariin liposome therapy significantly reduced the level of malondialdehyde and increased the activity of superoxide dismutase. CONCLUSIONS: Icariin liposome has excellent therapeutic effects on acute blunt muscle injury in rats by improving immunity, repairing cytoskeleton and cellular integrity, anti-inflammation, anti-fibrosis and antioxidant stress.