Lycopodium Alkaloids from Phlegmariurus carinatus with Cytotoxic and Neuroprotective Effects.

One new fawcettimine-type alkaloid, phlecarinadine A (1), and twelve known ones (2-13) were isolated from the whole plant of Phlegmariurus carinatus. Their chemical structures were unambiguously established by extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) spectroscopic and high resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configuration of 1 was elucidated by the electronic circular dichroism (ECD) technique. These compounds were tested for their cytotoxic and neuroprotective activities. None of these compounds revealed cytotoxic activity against five tumor cells. Phlegmariurine B (2) exhibited potential neuroprotective effects against hemin-induced HT22 cell damage, with a 17.76 % increase in cell survival at 10 µM. In further study, 2 can ameliorate hemin-induced neuronal cell death via an anti-apoptotic pathway. These findings suggest that 2 might be a valuable lead compound with neuroprotective activity.

Abietane diterpenoids with neuroprotective activities from Phlegmariurus carinatus.

Two new abietane diterpenoids, phlecarinatone A (1) and phlecarinatone B (2), along with two known analogues (3 and 4), were isolated from Phlegmariurus carinatus. The structures of 1 - 4 were unambiguously elucidated by comprehensive spectroscopic analyses. Abietane diterpenoids were isolated from the plant for the first time. All isolates were tested for their neuroprotective activities against H2O2-induced SH-SY5Y cells injury, and compound 2 showed moderate effect at the concentrations ranging from 5 ∼ 20 µM in vitro assay.

Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion.

Oxaliplatin (OXA) is the common and extremely potent anti-advanced colorectal cancer chemotherapeutic. Accumulating evidence reveals that OXA evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome and dose-limiting adverse effects is poorly understood. It is well known that cyclooxygenase-2 (COX-2) as well as phosphoinositide 3-kinase (PI3K)/Akt signaling mediate the neuropathic pain. But it is still unclear whether COX-2 or PI3K/Akt signaling participates in the regulation of OXA-induced hypersensitivity, as well as the linkage between COX-2 and PI3K/Akt signaling in mediating OXA-induced hypersensitivity. In this paper, we investigated the anti-nociceptive effect of celecoxib, an inhibitor of COX-2, on the OXA-induced neuropathic pain. We found that OXA increased the expression of cyclooxygenase-2 (COX-2) and Akt2 in the lumbar 4-5 (L4-5) dorsal root ganglion (DRG). And the administration of celecoxib alleviates the OXA-induced hypersensitivity and suppresses the COX-2 and PI3K/Akt2 signaling. Our findings showed that COX-2 and PI3K/Akt2 signaling in DRG contributed to the OXA-induced neuropathic pain. In addition, celecoxib enhanced the OXA-induced mortality of the human colon cancer cell line HCT-116. Thus, celecoxib might play a dual role in colorectal cancer treatment: alleviating OXA-induced neuropathic pain and facilitating the anti-tumor effects of OXA through their synergistic role.