RESUMO
The aim of this study was to determine the effects of ginsenoside Rg1 on the migration of olfactory ensheathing cells (OECs) in vitro, and its influence on the therapeutic efficacy of OECs transplanted in vivo for the treatment of spinal cord injury (SCI). Primary cultured and purified OECs (prepared from rats) were treated with ginsenoside Rg1. The wound healing test indicated that ginsenoside Rg1 promoted the migration of OECs. Real-time RT-PCR demonstrated that ginsenoside Rg1 upregulated the expression of migration-related factors of OECs, including matrix metalloproteinases-2 (MMP-2), MMP-9, and neural cell adhesion molecule 1 (NCAM1). Moreover, Western blot analysis indicated that ginsenoside Rg1 significantly promoted the migration of OECs via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An SCI rat model was induced in vivo using a revised Allen's method. The Basso, Beattie, and Bresnahan (BBB) scores and histological analysis demonstrated that OECs, which were treated with ginsenoside Rg1, exhibited significant improvement in SCI compared with both the control group and the OEC group. Thus, ginsenoside Rg1 may represent a novel treatment target for SCI.
Assuntos
Ginsenosídeos/farmacologia , Neuroglia/efeitos dos fármacos , Neuroglia/transplante , Traumatismos da Medula Espinal/terapia , Animais , Antígeno CD56/genética , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neuroglia/fisiologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Cicatrização/efeitos dos fármacosRESUMO
The objective of this study was to evaluate the immunomodulatory effects of cinobufagin (CBG) isolated from Chan Su (Venenum Bufonis) in vitro. In this paper, our results show that CBG significantly stimulated cell proliferation of splenocytes and peritoneal macrophages (PMΦ) and markedly enhanced the phagocytic activation of PMΦ. CBG also significantly increased CD4(+)CD8(+) double-positive T-cell populations and the percentage of S-phase cells of splenic lymphocytes. The levels of several Th1 cytokines, including interferon-γ and tumor necrosis factor-α, are significantly increased after CBG treatment, whereas the levels of the Th2 cytokine interleukin-4 and interleukin-10 are significantly decreased. As a result, the ratio of Th1/Th2 also increased. Taken together, these results indicated that CBG had potential immune system regulatory effects and suggested that this compound could be developed as a novel immunotherapeutic agent to treat immune-mediated diseases such as cancer.
Assuntos
Venenos de Anfíbios/farmacologia , Bufanolídeos/química , Bufanolídeos/farmacologia , Citocinas/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Venenos de Anfíbios/química , Venenos de Anfíbios/imunologia , Venenos de Anfíbios/isolamento & purificação , Animais , Bufanolídeos/imunologia , Bufanolídeos/isolamento & purificação , Citocinas/metabolismo , Fatores Imunológicos/química , Fatores Imunológicos/imunologia , Fatores Imunológicos/isolamento & purificação , Interferon gama/análise , Interleucina-10/análise , Interleucina-4/análise , Estrutura Molecular , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Fator de Necrose Tumoral alfa/análiseRESUMO
AIMS: To determine whether ginsenoside Rg1 is involved in scratch wound healing through altered expression of related molecules in astrocytes and improved functional recovery after spinal cord injury (SCI). MATERIALS AND METHODS: Astrocytes were isolated from rats, followed by Rg1 treatment. The wound healing test was performed to observe the scratch wound healing in different groups. The expression of nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF), and components of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were detected by western blot. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the altered expression of laminin (LN) and fibronectin (FN). A revised Allen's method for the SCI model was performed, followed by Rg1 treatment. Then, functional scoring was conducted to evaluate the functional recovery. Hematoxylin-eosin (HE) staining showed changes in the void area. Finally, western blot assessed the expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). KEY FINDINGS: Rg1 mediated scratch wound healing through inducing an increased release of LN, FN, NGF, GDNF, and bFGF in vitro. Additionally, Rg1 activated the PI3K/Akt signaling pathway and promoted the functional recovery of hindlimb movement in rats. Furthermore, Rg1 significantly reduced the void area and downregulated the expression of GFAP and CSPGs. SIGNIFICANCE: Rg1 not only enhanced the scratch wound repair in vitro through the release of astroglial neurotrophic factors, adhesion factors, and inhibitory factors, but it also improved the functional recovery in vivo following SCI.
Assuntos
Astrócitos/efeitos dos fármacos , Ginsenosídeos/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Astrócitos/metabolismo , Feminino , Masculino , Fatores de Crescimento Neural/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Five novel homochiral coordination polymers (HCPs) [Cu2(ODBALa)2(bpa)2H2O]·7H2O (1), [M(ODBALa)H2O]·H2O (M = Mn for 2; Co for 3), [Cu(ODBPRo)(bpe)]·7H2O (4) and [Cd2.5(ODBPRo)(HODBPRo)3(bpe)2.5]·13H2O (5) have been successfully synthesized by using designed chiral 4,4'-oxybisbenzoyl alanine/proline derivatives in the absence/presence of N-donor ancillary ligands, where H2ODBALa = 4,4'-oxybisbenzoyl-bis(l-alanine), H2ODBPRo = 4,4'-oxybisbenzoyl-bis(l-proline), bpa = 1,2-bis(4-pyridyl)ethane, and bpe = 1,2-bis(4-pyridyl)ethene. Interestingly, the combination of the chiral derivatives and metal ions gives various chiral metal-organic fragments, which are connected by N-donor ancillary ligands to construct the intriguing homochiral structures. In 1, 40-membered [Cu2(ODBALa)2] metallacycles as beads are strung by bpa ligands, yielding a one-dimension (1D) tortuous chain. Compounds 2 and 3 are isomorphous and possess a 3D metal-organic framework, embedding the unique (µ2-COO)(µ2-Ocarboxylate)(µ2-H2O) triple-bridges and twisted (-Mn4(ODBALa)4-)n left-handed helical chains. In 4, the [Cu(ODBPRo)]n left-handed helical chains are linked by bpe ligands to constitute a high undulated 2D layer. In 5, the crab-like [(Cd1)2(Cd2)(Cd3)2(HODBPRo)6(ODBPRo)2] fragments are joined together to form a 1D left-handed helical chain, which is further connected by bpe ligands to build a remarkable layered network. Magnetic susceptibility measurements of 2 and 3 indicate typical antiferromagnetic behaviour between the triple-bridging Mn(ii) ions in 2, whereas ferromagnetic coupling between the triple-bridging Co(ii) ions exists in 3. Moreover, the photoluminescent spectrum of 5 exhibits a strong solid-state emission at 414 nm.