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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.


MAPKs contributed to the anti-inflammatory activity of compound 4.Cells were pretreated with compound 4 as aforementioned. The protein expression was determined by Western blotting. Tan IIA, tanshinone IIA.
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f5: MAPKs contributed to the anti-inflammatory activity of compound 4.Cells were pretreated with compound 4 as aforementioned. The protein expression was determined by Western blotting. Tan IIA, tanshinone IIA.

Mentions: The activation of MAPKs signaling including JNK1/2, ERK1/2, and p38MAPK was always involved in cellular responses to inflammatory stress36. To explore the role of JNK1/2, ERK1/2, or p38MAPK signaling in compound 4’s anti-inflammatory effect, their protein expression was detected. As shown in Fig. 5, treated with compound 4, the expression of p-JNK1/2 and p-ERK1/2 was dramatically decreased in a dose-dependent manner, while the expression of total JNK1/2 and ERK1/2 showed no changes. However, compound 4 demonstrated no obvious effect on p38MAPK. Collectively, these findings indicated that JNK and ERK might participate in the anti-inflammation process of compound 4 in LPS-stimulated RAW264.7 cells.


Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen)
MAPKs contributed to the anti-inflammatory activity of compound 4.Cells were pretreated with compound 4 as aforementioned. The protein expression was determined by Western blotting. Tan IIA, tanshinone IIA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: MAPKs contributed to the anti-inflammatory activity of compound 4.Cells were pretreated with compound 4 as aforementioned. The protein expression was determined by Western blotting. Tan IIA, tanshinone IIA.
Mentions: The activation of MAPKs signaling including JNK1/2, ERK1/2, and p38MAPK was always involved in cellular responses to inflammatory stress36. To explore the role of JNK1/2, ERK1/2, or p38MAPK signaling in compound 4’s anti-inflammatory effect, their protein expression was detected. As shown in Fig. 5, treated with compound 4, the expression of p-JNK1/2 and p-ERK1/2 was dramatically decreased in a dose-dependent manner, while the expression of total JNK1/2 and ERK1/2 showed no changes. However, compound 4 demonstrated no obvious effect on p38MAPK. Collectively, these findings indicated that JNK and ERK might participate in the anti-inflammation process of compound 4 in LPS-stimulated RAW264.7 cells.

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.