Aloperine

Onco Targets Ther. 2018 May 11;11:2735-2743.

Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in prostate cancer in vitro and in vivo.[Pubmed: 29785122]

Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that Aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated.
METHODS AND RESULTS:
PCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells. ALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells.
CONCLUSIONS:
Based on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa.

Sci Rep. 2018 Apr 19;8(1):6265.

Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation.[Pubmed: 29674691]

Aloperine is a quinolizidine alkaloid extracted from Sophora alopecuroides. It has been proven to alleviate oxidative stress and effectively promote tumor cell apoptosis in mice. Herein, we investigated whether Aloperine could also mediate its protective effects on bleomycin (BLM)-induced pulmonary fibrosis. Pathological staining, western blot, RT-PCR and flow cytometry were used to evaluate the impact of Aloperine on the development of pulmonary fibrosis. The effect of Aloperine on fibroblast proliferation, differentiation and related signaling pathways were next investigated to demonstrate the underlying mechanisms.
METHODS AND RESULTS:
In the present report, we showed that Aloperine provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuated lung injury and reduced fibrosis along with alleviated fibroblast proliferation and differentiation. Additionally, we provided in vitro evidence revealing that Aloperine inhibited cellular proliferation in PDGF-BB-stimulated mouse lung fibroblasts by repressed PI3K/AKT/mTOR signaling and fibroblast to myofibroblast differentiation by repressed TGF-β/Smad signaling.
CONCLUSIONS:
Overall, our data showed that Aloperine could protect the mice against BLM-induced pulmonary fibrosis by attenuated fibroblast proliferation and differentiation, which indicated that Aloperine may be therapeutically beneficial for IPF patients.

Exp Ther Med. 2017 Jan;13(1):315-320.

Aloperine attenuates hydrogen peroxide-induced injury via anti-apoptotic activity and suppression of the nuclear factor-κB signaling pathway.[Pubmed: 28123508 ]

Aloperine is an alkaloid that exerts significant inhibitive effects on acute inflammation and Type III and IV hypersensitivity caused by a variety of inflammatory agents. The aims of the present study were to investigate whether the protective effect of Aloperine attenuates hydrogen peroxide (H2O2)-induced injury, and to identify the underlying mechanisms involved.
METHODS AND RESULTS:
Nucleus pulposus cells were extracted from adult male Sprague-Dawley rats, and incubated with fresh medium containing 200 μM H2O2 for 24 h. In the study, treatment with Aloperine significantly increased cell viability and suppressed apoptosis in H2O2-treated nucleus pulposus cells in a dose-dependent manner. In addition, 10 and 100 nM Aloperine significantly inhibited H2O2-induced tumor necrosis factor-α and interleukin-6 activities, and significantly increased the H2O2-reduced superoxide dismutase and glutathione peroxidase activities in nucleus pulposus cells (all P<0.01). However, Aloperine treatment (10 and 100 nM) significantly reduced the H2O2-induced caspase-9 activity in nucleus pulposus cells. Furthermore, addition of 10 and 100 nM Aloperine significantly suppressed nuclear factor-κB (NF-κB) and phosphorylated-protein kinase B expression levels in H2O2-treated nucleus pulposus cells.
CONCLUSIONS:
In conclusion, the protective effect of Aloperine attenuated H2O2-induced injury via hyperproliferation, its anti-apoptotic activity and suppression of the NF-κB signaling pathway.

Exp Ther Med. 2018 Apr;15(4):3847-3855.

Aloperine activates the Nrf2-ARE pathway when ameliorating early brain injury in a subarachnoid hemorrhage model.[Pubmed: 29563984]

Aloperine (ALO) exhibits neuroprotective effects against oxidative stress in vitro; however, its protective effect in early brain injury (EBI) following experimental subarachnoid hemorrhage (SAH) remains to be elucidated. The aim of the current study was to evaluate the antioxidant activity of ALO in EBI, and its association with nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) survival pathway.
METHODS AND RESULTS:
In the present study, an experimental SAH model was induced in rats following a prechiasmatic cistern injection. All rats were randomly divided into five groups: Sham, SAH, SAH+ vehicle, and an SAH+ ALO group (including low and high doses). ALO was administrated intraperitoneally at 2 and 24 h following induction of the SAH model. Brain samples were collected from each group at 48 h after SAH induction. Subsequently, western blotting, immunohistochemistry and cell apoptosis assays were performed, along with assessments for brain edema, neurological deficit, and the activity of oxidant/antioxidant factors. It was observed that the expression of Nrf2-ARE pathway-associated agents, including Nrf2, and heme oxygenase-1, were markedly increased in the high concentration ALO group compared with that of the SAH group. In addition, the level of oxidative damage was reduced. Furthermore, early brain damage, including brain edema, neurological deficit and cellular apoptosis were significantly ameliorated.
CONCLUSIONS:
In conclusion, the results of the present study indicate that ALO can ameliorate oxidative damage against EBI following SAH, most likely via the Nrf2-ARE survival pathway.