Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder by inducing neutrophil apoptosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.

Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells.

Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herb Salvia miltiorrhiza Bunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease. In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4+ T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naïve CD4+ T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factor ß1 (TGF-ß1) upregulation and by directly targeting naïve CD4+ T cells in vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-ß1-polarized Treg Cells in vitro and in vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.

[Correlation analysis between foliar endophytic fungi of Salvia miltiorrhiza and effective components].

The aim of this study was to comprehensively investigate the correlations between foliar fungal endophyte communities and effective components accumulations in Salvia miltiorrhiza. Foliar samples of S. miltiorrhiza were collected in 5 different areas. Their fungal endophyte communities and effective component contents were determined by denaturing gradient gel electrophoresis (DGGE) and high performance liquid chromatography (HPLC), respectively. The results showed that, for characteristics of foliar fungal endophyte communities and effective component contents, there were both similarities and differences among the five samples. Correlation analysis of DGGEs' band and 24 effective components revealed a significant correlations (P < 0.01). For examples, 4 bands (15, 18, 23 and 26) were all significantly correlated with the accumulations of caffeic acid, salvianolic acid B, salvianolic acid C and dihydrotanshinone I.

[Genetic diversity and volatile components of Asarum sieboldii in Qin-ba region].

OBJECTIVE: To analyze the genetic diversity and the volatile components of Asarum sieboldii from seven habitats in Qin-ba region. METHODS: The genetic diversity of the herb was analyzed by ISSR (inter simple sequence repeat) markers; The relative content volatile components of the herb were dectected by head space solid-phase microextraction gas chromatogrphy-mass spectrometry (HS-SPME-GC-MS). The contents of the 3 main components were analyzed by steam distillation gas chromatography-mass spectrometry (GC-MS). RESULTS: 57 bands were amplified from 7 populations by 6 reliable primers, 51 of which were polymorphic (89.47% of the total). The cluster analysis presented that these resources were divided into two main groups. There were differences in the chemical components and the contents of Asarum sieboldii from the 6 wild habitats. Except for some same components, many unique components were identified in them respectively. In addition, some components could be detected only in some populations which had smaller genetic distance. CONCLUSION: Cluster analysis shows no direct correlation between genetic distance and geographic distance of Asarum sieboldii in Qin-ba region. The accumulations of some volatile components of Asarum sieboldii are possibly related to genetic diversity.

[The volatile components of three radix et rhizoma asari].

OBJECTIVE: To analyze and compare the volatile components of Asarum sieboldii Miq, Asarum himalaicum Hook. F. et Thoms and Asarum. debile Franch in the same area. METHODS: The volatile components were extracted from three Radix et Rhizoma Asari by solid-phrase microextraction and their contents were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: 59, 99 and 85 volatile components were identified from Asarum sieboldii Miq, Asarum himalaicum Hook. F. et Thoms and Asarum debile Franch, representing the ralative content of 82.75% - 99.43% of the volatile oil. 16 of same components were identified in the three Radix et Rhizoma Asari, and the contents of the same components were different among them. In addition, some unique components were identified in them respectively. CONCLUSION: There were differences among the chemical components and the contents of the volatile oil of the three Radix et Rhizoma Asari. The results could give certain reference value for the medicine whether Asarum himalaicum Hook. F. et Thoms and Asarum debile Franch can replace Asarum sieboldii Miq.