Berberine, a plant alkaloid used in Chinese medicine, has broad cell-protective functions in a variety of cell lines. Chondrocyte apoptosis contributes to the pathogenesis of cartilage degeneration in osteoarthritis (OA). However, little is known about the effect and underlying mechanism of berberine on OA chondrocytes. Here, we assessed the effects of berberine on cartilage degeneration in interleukin-1β (IL-1β)-stimulated rat chondrocytes and in a rat model of OA. The results of an MTT assay and western blotting analysis showed that berberine attenuated the inhibitory effect of IL-1β on the cell viability and proliferating cell nuclear antigen expression in rat chondrocytes. Furthermore, berberine activated Akt, which triggered p70S6K/S6 pathway and up-regulated the levels of aggrecan and Col II expression in IL-1β-stimulated rat chondrocytes. In addition, berberine increased the level of proteoglycans in cartilage matrix and the thickness of articular cartilage, with the elevated levels of Col II, p-Akt and p-S6 expression in a rat OA model, as demonstrated by histopathological and immunohistochemistry techniques. The data thus strongly suggest that berberine may ameliorate cartilage degeneration from OA by promoting cell survival and matrix production of chondrocytes, which was partly attributed to the activation of Akt in IL-1β-stimulated articular chondrocytes and in a rat OA model. The resultant chondroprotective effects indicate that berberine merits consideration as a therapeutic agent in OA.
Photodynamic
therapy (PDT) is becoming a promising therapeutic
regimen but is limited by the hypoxic microenvironment in solid tumors
and the undesirable post-treatment phototoxicity side effects on normal
tissues. To overcome these restrictions and enhance the antitumor
therapeutic effect, near-infrared (NIR) light-activated, cancer cell-specific,
hypoxia prodrug-loaded chlorin e6 liposomes were developed for tumor
selective combination therapy guided by multimodal imaging. The photothermal
agent indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine
(TPZ) were coencapsulated into the liposomes, followed by modification
with cRGD and conjugation with GdIII to form ICG/TPZ@Ce6-GdIII theranostic liposomes (ITC-GdIII TLs). In the
ITC-GdIII TLs, both the fluorescence and photodynamic effect
of Ce6 were quenched by ICG via fluorescence resonance energy transfer.
The ITC-GdIII TLs can effectively reach the tumor site
through the enhanced permeability and retention effect as well as
the cRGD-mediated active targeting ability. The fluorescence and photodynamic
effect of Ce6 can be activated by the photothermal effect of ICG under
NIR light. Upon subsequent irradiation with a 660 nm laser, the released
Ce6 could kill cancer cells by generating cytotoxic singlet oxygen.
Furthermore, the PDT process would induce hypoxia, which in turn activated
the antitumor activity of the codelivered hypoxia-activated prodrug
TPZ for a combination antitumor effect. The TLs could be utilized
for multimodal imaging (fluorescence/photoacoustic/magnetic resonance
imaging)-guided cascade-activated tumor inhibition with optimized
therapeutic efficiency and minimized side effects, holding great potential
for constructing intelligent nanotheranostics.
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