Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Abstract

Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 lg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1b, IL-6, IL-8 and TNF-a evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-jB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-jB and JNK pathways. HIGHLIGHTS 1. Geniposide prevents LPS-induced injury in PC12 cells; 2. Geniposide up-regulates miR-145-5p; 3. Geniposide protects PC12 cells via up-regulation of miR-145-5p; 4. Geniposide inhibits NF-jB and JNK pathways via up-regulation of miR-145-5p.

Retracted: Baicalin relieves TNF‐α‐evoked injury in human aortic endothelial cells by up‐regulation of miR‐145

“…In addition, miR‐145 was also reported to participate in the regulation of various diseases through regulating JNK and p38MAPK pathways. For instance, Ma et al clarified that geniposide suppressed JNK and nuclear factor kappa‐B pathways through increasing miR‐145‐5p expression in LPS‐evoked PC12 cells (Ma et al, ). Moreover, similar results were also achieved in our research demonstrating that BAI pretreatment inhibited JNK and p38MAPK pathways and miR‐145 in activated JNK and p38MAPK pathways.…”

Protective Activity of Aβ on Cell Cultures (PC12 and THP-1 after Differentiation) Preincubated with Lipopolysaccharide (LPS)

“…Therefore, this particular bacterial cell outer membrane compound is widely used to induce inflammation in neuronal cells in in vitro models of spinal cord injury (SCI) or various neurodegenerative diseases, including AD [16,17]. It has been proved in many experiments that PC12 cells treated with LPS showed increased production of proinflammatory cytokines such as Il-1β, Il-6, and TNF-α, as confirmed by mRNA expression measurements [18][19][20][21][22]. It is generally recognized that the amount of microglia and amyloid is dependent on each other based on feedback.…”

PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research

“…Scientists quite often use undifferentiated PC12 cells to test neurotoxicity or antiinflammatory or neuroprotective properties of new pharmacotherapeutics, searching for effective treatment for neurodegenerative and neuroinflammatory diseases like AD. LPS and Aβ are often used to induce a state of inflammation and simulate conditions found in the AD-affected brain [27][28][29][30][31]. Unfortunately, as we prove in our study, undifferentiated PC12 cells show altered response to Aβ 25-35 and LPS compared to NGF-treated cultures induced to differentiation.…”

“…In our opinion, the time of differentiation should be at least 72 h [15]. Therefore, the time of 72 h was chosen in this study, examining the effect of differentiation on sensitivity to harmful factors (LPS and Aβ [25][26][27][28][29][30][31][32][33][34][35].…”