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Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)

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ABSTRACT

1–45–1844444: Four novel compounds () as well as fourteen reported compounds () were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti-inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound demonstrated the best anti-inflammatory activity and was chosen for further research. Compound greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-κB was attenuated after treatment with compound in vitro. Compound was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role.

No MeSH data available.


Compound 4 inhibited LPS-stimulated NF-κB activation.(A) Cells were pretreated with compound 4 as aforementioned. The protein expression of p-p65, p-65, and p-IKKα/β was determined by Western blotting. (B) Cells were pretreated with/without compound 4 (10 μM) for 1h and then treated with LPS (1 μg/mL) for another 1 h. The translocation of NF-κB p65 was examined by immunofluorescence. Tan IIA, tanshinone IIA.
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f4: Compound 4 inhibited LPS-stimulated NF-κB activation.(A) Cells were pretreated with compound 4 as aforementioned. The protein expression of p-p65, p-65, and p-IKKα/β was determined by Western blotting. (B) Cells were pretreated with/without compound 4 (10 μM) for 1h and then treated with LPS (1 μg/mL) for another 1 h. The translocation of NF-κB p65 was examined by immunofluorescence. Tan IIA, tanshinone IIA.

Mentions: The transcription factor NF-κB p65 plays pivotal roles in the control of pro-inflammatory genes expression. Dysregulation of NF-κB p65 has been medicated in the progression of many inflammatory diseases, tumors, immune dysfunctions, etc.34. Translocation from cytoplasm to nucleus, NF-κB p65 is indispensable for the activation of inflammatory genes expression and secretion, including COX-2, TNF-α, iNOS, IL-1b, IL-6 and IL-83435. Therefore, we explored the effect of compound 4 on expression and nuclear translocation of NF-κB p65. The expression of p-p65 induced by LPS was dose-dependently inhibited by compound 4 (Fig. 4A). Furthermore, immunofluorescence results showed that nuclear expression of p65 stimulated by LPS was significantly reversed after treatment with compound 4 (Fig. 4B) suggesting that compound 4 was able to disrupt translocation of p65 in LPS-induced RAW264.7 cells. In addition, compound 4 could markedly decrease the expression of the p-IKK-α/β (Fig. 4A). Collectively, these findings suggested that compound 4 suppressed LPS-induced NF-κB p65 activation and translocation.


Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)
Compound 4 inhibited LPS-stimulated NF-κB activation.(A) Cells were pretreated with compound 4 as aforementioned. The protein expression of p-p65, p-65, and p-IKKα/β was determined by Western blotting. (B) Cells were pretreated with/without compound 4 (10 μM) for 1h and then treated with LPS (1 μg/mL) for another 1 h. The translocation of NF-κB p65 was examined by immunofluorescence. Tan IIA, tanshinone IIA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036060&req=5

f4: Compound 4 inhibited LPS-stimulated NF-κB activation.(A) Cells were pretreated with compound 4 as aforementioned. The protein expression of p-p65, p-65, and p-IKKα/β was determined by Western blotting. (B) Cells were pretreated with/without compound 4 (10 μM) for 1h and then treated with LPS (1 μg/mL) for another 1 h. The translocation of NF-κB p65 was examined by immunofluorescence. Tan IIA, tanshinone IIA.
Mentions: The transcription factor NF-κB p65 plays pivotal roles in the control of pro-inflammatory genes expression. Dysregulation of NF-κB p65 has been medicated in the progression of many inflammatory diseases, tumors, immune dysfunctions, etc.34. Translocation from cytoplasm to nucleus, NF-κB p65 is indispensable for the activation of inflammatory genes expression and secretion, including COX-2, TNF-α, iNOS, IL-1b, IL-6 and IL-83435. Therefore, we explored the effect of compound 4 on expression and nuclear translocation of NF-κB p65. The expression of p-p65 induced by LPS was dose-dependently inhibited by compound 4 (Fig. 4A). Furthermore, immunofluorescence results showed that nuclear expression of p65 stimulated by LPS was significantly reversed after treatment with compound 4 (Fig. 4B) suggesting that compound 4 was able to disrupt translocation of p65 in LPS-induced RAW264.7 cells. In addition, compound 4 could markedly decrease the expression of the p-IKK-α/β (Fig. 4A). Collectively, these findings suggested that compound 4 suppressed LPS-induced NF-κB p65 activation and translocation.

View Article: PubMed Central - PubMed

ABSTRACT

1–45–1844444: Four novel compounds () as well as fourteen reported compounds () were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti-inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound demonstrated the best anti-inflammatory activity and was chosen for further research. Compound greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-κB was attenuated after treatment with compound in vitro. Compound was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role.

No MeSH data available.