Yi-Hong Zou1, Liang Zhao1, You-Kai Xu2, Jing-Mei Bao1, Xin Liu1, Jun-Sheng Zhang1, Wei Li1, Abrar Ahmed1, Sheng Yin1, Gui-Hua Tang3. 1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. 2. Key Laboratory of Tropical Plant Resource and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Yunnan 666303, China. 3. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: tanggh5@mail.sysu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history. AIM OF THE STUDY: The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases. MATERIAL AND METHODS: The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay. RESULTS: Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2. CONCLUSIONS: Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history. AIM OF THE STUDY: The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases. MATERIAL AND METHODS: The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay. RESULTS: Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2. CONCLUSIONS: Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.
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