Berberine (BBR) is one of the major alkaloids and has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the mechanisms of BBR protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with BBR significantly reduced 6-OHDAinduced generation of reactive oxygen species (ROS), caspase-3 activation, and subsequent cell death. BBR also upregulated heme oxygenase-1 (HO-1) expression, which conferred protection against 6-OHDA-induced dopaminergic neuron injury and besides, effect of BBR on HO-1 was reversed by siRNA-Nrf2. Furthermore, BBR induced PI3K/Akt and p38 activation, which are involved in the induction of Nrf2 expression and neuroprotection. These results suggest that BBR may be useful as a therapeutic agent for the treatment of dopaminergic neuronal diseases.

Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)–induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)–generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to coelenterazine-h as a substrate for luciferase without external light irradiation, Luc-RGP fused with a small lead peptide–induced breast cancer cell death through the generation of BL-sensitive ROS in the plasma membrane. Even with extremely low light energy, BLiP-PDT exhibited targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BLiP-PDT is immediately useful as a promising theranostic approach against various cancers.

Naringin, a flavanone glycoside extracted from various plants, has a wide range of pharmacological effects. In the present study, we investigated naringin’s mechanism of action and its inhibitory effect on lipopolysaccharide-induced tumor necrosis factor-alpha and high-mobility group box 1 expression in macrophages, and on death in a cecal ligation and puncture induced mouse model of sepsis. Naringin increased heme oxygenase 1 expression in peritoneal macrophage cells through the activation of adenosine monophosphate-activated protein kinase, p38, and NF-E2-related factor 2. Inhibition of heme oxygenase 1 abrogated the naringin’s inhibitory effect on high-mobility group box 1 expression and NF-kB activation in lipopolysaccharide-stimulated macrophages. Moreover, mice pretreated with naringin (200 mg/kg) exhibited decreased sepsis-induced mortality and lung injury, and alleviated lung pathological changes. However, the naringin’s protective effects on sepsis-induced lung injury were eliminated by zinc protoporphyrin, a heme oxygenase 1 competitive inhibitor. These results revealed the mechanism underlying naringin’s protective effect in inflammation and may be beneficial for the treatment of sepsis.