Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling
BackgroundZanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti...
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00359/full |
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| author | Fenfen Qin Fenfen Qin Han Zhang Han Zhang Anlong Liu Anlong Liu Qisheng Wang Qisheng Wang Qinmei Sun Qinmei Sun Shengfeng Lu Qian Li Hongwei Guo Xing Liu Zhigang Lu |
| author_facet | Fenfen Qin Fenfen Qin Han Zhang Han Zhang Anlong Liu Anlong Liu Qisheng Wang Qisheng Wang Qinmei Sun Qinmei Sun Shengfeng Lu Qian Li Hongwei Guo Xing Liu Zhigang Lu |
| author_sort | Fenfen Qin |
| collection | DOAJ |
| description | BackgroundZanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia.MethodsThe inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.ResultsThe extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.ConclusionThe present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level. |
| first_indexed | 2024-04-13T15:18:18Z |
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| last_indexed | 2024-04-13T15:18:18Z |
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| spelling | doaj.art-0dc21f0998fa452bb248d411f60e76fd2022-12-22T02:41:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-04-011010.3389/fphar.2019.00359438536Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB SignalingFenfen Qin0Fenfen Qin1Han Zhang2Han Zhang3Anlong Liu4Anlong Liu5Qisheng Wang6Qisheng Wang7Qinmei Sun8Qinmei Sun9Shengfeng Lu10Qian Li11Hongwei Guo12Xing Liu13Zhigang Lu14College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaFirst Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, ChinaCollege of Pharmacy, Guangxi Medical University, Nanning, ChinaCollege of Pharmacy, Shanxi University of Chinese Medicine, Taiyuan, ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia, Nanjing University of Chinese Medicine, Nanjing, ChinaBackgroundZanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia.MethodsThe inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.ResultsThe extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.ConclusionThe present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level.https://www.frontiersin.org/article/10.3389/fphar.2019.00359/fullZanthoxylum nitidumLiang Mianzheninflammatory painpro-inflammatory cytokinesNF-κBp65p-ERK1/2 |
| spellingShingle | Fenfen Qin Fenfen Qin Han Zhang Han Zhang Anlong Liu Anlong Liu Qisheng Wang Qisheng Wang Qinmei Sun Qinmei Sun Shengfeng Lu Qian Li Hongwei Guo Xing Liu Zhigang Lu Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling Frontiers in Pharmacology Zanthoxylum nitidum Liang Mianzhen inflammatory pain pro-inflammatory cytokines NF-κBp65 p-ERK1/2 |
| title | Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling |
| title_full | Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling |
| title_fullStr | Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling |
| title_full_unstemmed | Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling |
| title_short | Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling |
| title_sort | analgesic effect of zanthoxylum nitidum extract in inflammatory pain models through targeting of erk and nf κb signaling |
| topic | Zanthoxylum nitidum Liang Mianzhen inflammatory pain pro-inflammatory cytokines NF-κBp65 p-ERK1/2 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00359/full |
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