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Background. Herpes simplex virus type 2 (HSV-2) infestation was the most widespread STD (sexually transmitted diseases) among humans and was the leading cause of infectious recurrent genital herpes. Existing therapies against HSV-2 did incompletely restrain the comeback of activated HSV-2 infestation. Geranium wilfordii Maxim had long been used as traditional Chinese medicine for treating the diseases owing to its anti-inflammatory and antiviral effects. Herein, the study was designed to investigate the antiviral activity of G.wilfordii and its potential effect in regulating the host's immune response. Methods. To identify the stage of infection at which the compounds inhibited HSV-2, we performed virucidal, therapeutic, and prophylactic assays. The antiviral efficacy was evaluated by the analysis of viral components HSV-2 gD and VP16. The antiviral activities of these compounds were also evaluated by phenotypic analysis, such as cell proliferation and apoptosis. Molecular docking studies on candidate compounds were done to indicate binding interactions between the compounds and adopted compound targets. Results. Quercetin, corilagin, and geraniin inhibited the replication of HSV-2, with geraniin showing greater TI. The obtained IC50 value of quercetin was 204.7 μM and TI (IC50/EC50) was 5.1, whereas the obtained IC50 value of corilagin was 118.0 μg/ml and TI was 4.05. Geraniin exhibited prominent antiviral activity with an IC50 of 212.4 μM and an EC50 of 18.37 μM, resulting in a therapeutic index (TI) of 11.56. Geraniin showed important in vitro virucidal activity through blocking viral attachment. Compared with the virus group, the apoptosis rates in quercetin-, corilagin-, and geraniin-treated groups were significantly decreased (p < 0.001).The expressions at the transcription genes of virus own replication key factors (including HSV-2 gD and VP16) and cytokines (including TBK1) of infected cells treated with quercetin, corilagin, and geraniin were inhibited. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin, corilagin, and the activity site of HSV-2 gD. Molecular docking studies demonstrated the effects of corilagin by targeting TBK1. Conclusions. Together, these results highlighted the importance of G.wilfordii treatment in HSV-2 infection and underscored its therapeutic potential. However, additional in vitro and in vivo research was required to validate our findings. [ABSTRACT FROM AUTHOR]

Stem cell therapy with neural precursor cells (NPCs) has the potential to improve neuroregeneration after spinal cord injury (SCI). Unfortunately, survival and differentiation of transplanted NPCs in the injured spinal cord remains low. Growth factors have been successfully used to improve NPC transplantation in animal models, but their extensive application is associated with a relevant financial burden and might hinder translation of findings into the clinical practice. In our current study, we assessed the potential of a reduced number of growth factors in different combinations and concentrations to increase proliferation and differentiation of NPCs in vitro. After identifying a "cocktail" (EGF, bFGF, and PDGF-AA) that directed cell fate towards the oligodendroglial and neuronal lineage while reducing astrocytic differentiation, we translated our findings into an in vivo model of cervical clip contusion/compression SCI at the C6 level in immunosuppressed Wistar rats, combining NPC transplantation and intrathecal administration of the growth factors 10 days after injury. Eight weeks after SCI, we could observe surviving NPCs in the injured animals that had mostly differentiated into oligodendrocytes and oligodendrocytic precursors. Moreover, "Stride length" and "Average Speed" in the CatWalk gait analysis were significantly improved 8 weeks after SCI, representing beneficial effects on the functional recovery with NPC transplantation and the administration of the three growth factors. Nevertheless, no effects on the BBB scores could be observed over the course of the experiment and regeneration of descending tracts as well as posttraumatic myelination remained unchanged. However, reactive astrogliosis, as well as posttraumatic inflammation and apoptosis was significantly reduced after NPC transplantation and GF administration. Our data suggest that NPC transplantation is feasible with the use of only EGF, bFGF, and PDGF-AA as supporting growth factors. [ABSTRACT FROM AUTHOR]

Stem cell therapy with neural precursor cells (NPCs) has the potential to improve neuroregeneration after spinal cord injury (SCI). Unfortunately, survival and differentiation of transplanted NPCs in the injured spinal cord remains low. Growth factors have been successfully used to improve NPC transplantation in animal models, but their extensive application is associated with a relevant financial burden and might hinder translation of findings into the clinical practice. In our current study, we assessed the potential of a reduced number of growth factors in different combinations and concentrations to increase proliferation and differentiation of NPCs in vitro. After identifying a "cocktail" (EGF, bFGF, and PDGF-AA) that directed cell fate towards the oligodendroglial and neuronal lineage while reducing astrocytic differentiation, we translated our findings into an in vivo model of cervical clip contusion/compression SCI at the C6 level in immunosuppressed Wistar rats, combining NPC transplantation and intrathecal administration of the growth factors 10 days after injury. Eight weeks after SCI, we could observe surviving NPCs in the injured animals that had mostly differentiated into oligodendrocytes and oligodendrocytic precursors. Moreover, "Stride length" and "Average Speed" in the CatWalk gait analysis were significantly improved 8 weeks after SCI, representing beneficial effects on the functional recovery with NPC transplantation and the administration of the three growth factors. Nevertheless, no effects on the BBB scores could be observed over the course of the experiment and regeneration of descending tracts as well as posttraumatic myelination remained unchanged. However, reactive astrogliosis, as well as posttraumatic inflammation and apoptosis was significantly reduced after NPC transplantation and GF administration. Our data suggest that NPC transplantation is feasible with the use of only EGF, bFGF, and PDGF-AA as supporting growth factors. [ABSTRACT FROM AUTHOR]