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Published on: September 4, 2013
Scutellarin Acts via MAPKs Pathway to Promote M2 Polarization of Microglial Cells
Hao-Lun Chen1,2, Li Yang1,2, Xiao-Li-Na Zhang1,2,3
1Department of Anatomy and Histology/Embryology, School of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, People's Republic of China.
Abstract:
Scutellarin, an herbal agent, is known to possess anti-oxidant and anti-inflammatory properties. In activated microglia, it has been reported that this is achieved through acting on the MAPKs, a key pathway that regulates microglia activation. This study sought to determine if scutellarin would affect the commonly described microglia phenotypes, namely, M1 and M2, thought to contribute to pro- and anti-inflammatory roles, respectively. This is in consideration of its potential effect on the polarization of microglia phenotypes that are featured prominently in cerebral ischemia. For this purpose, we have used an experimentally induced cerebral ischemia rat model and LPS-stimulated BV-2 cell model. Thus, by Western blot and immunofluorescence, we show here a noticeable increase in expression of M2 microglia markers, namely, CD206, Arg1, YM1/2, IL-4 and IL-10 in activated microglia both in vivo and in vitro. Besides, we have confirmed that Scutellarin upregulated expression of Arg1, IL-10 and IL-4 in medium supernatants of BV-2 microglia. Remarkably, scutellarin treatment markedly augmented the increased expression of the respective markers in activated microglia. It is therefore suggested scutellarin can exert the polarization of activated microglia from M1 to M2 phenotype. Because M1 microglia are commonly known to be proinflammatory, while M2 microglia are anti-inflammatory and neuroprotective effect, it stands to reason therefore that with the increase of M2 microglia which became predominant by scutellarin, the local inflammatory response is ameliorated. More importantly, we have found that scutellarin promotes the M2 polarization through inhibiting the JNK and p38 signaling pathways, and concomitantly augmenting the ERK1/2 signaling pathway. This lends its strong support from observations in LPS activated BV-2 microglia treated with p38 and JNK inhibitors in which expression of M2 markers was increased; on the other hand, in cells subjected to ERK1/2 inhibitor treatment, the expression was suppressed. In light of the above, MAPKs pathway is deemed to be a potential therapeutic target of scutellarin in mitigating microglia mediated neuroinflammation in activated microglia.
Insights
Scutellarin promotes anti-inflammatory M2 microglia polarization by modulating the MAPKs pathway, reducing neuroinflammation in models of cerebral ischemia. This herbal agent shifts microglia from a pro-inflammatory M1 to a protective M2 phenotype.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Microglia play critical roles in neuroinflammation, with M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes influencing outcomes in neurological conditions.
- Scutellarin, a known antioxidant and anti-inflammatory herbal agent, has been implicated in modulating the Mitogen-Activated Protein Kinase (MAPK) pathway, which regulates microglia activation.
- Understanding scutellarin's effect on microglia polarization is crucial for developing therapeutic strategies for neuroinflammatory diseases like cerebral ischemia.
Purpose of the Study:
- To investigate the effect of scutellarin on the polarization of microglia into M1 and M2 phenotypes.
- To determine if scutellarin influences microglia polarization in the context of cerebral ischemia.
- To elucidate the underlying signaling pathways, specifically MAPKs, involved in scutellarin-mediated microglia polarization.
Main Methods:
- Utilized an in vivo rat model of experimentally induced cerebral ischemia and an in vitro LPS-stimulated BV-2 cell model.
- Employed Western blot and immunofluorescence techniques to assess the expression of M1 and M2 microglia markers.
- Investigated the role of specific MAPK signaling pathways (JNK, p38, ERK1/2) using inhibitors in LPS-activated BV-2 cells.
Main Results:
- Scutellarin treatment significantly increased the expression of M2 microglia markers (CD206, Arg1, YM1/2, IL-4, IL-10) in both in vivo and in vitro models.
- Scutellarin upregulated Arg1, IL-10, and IL-4 in the supernatant of BV-2 microglia, confirming enhanced M2 polarization.
- Scutellarin promoted M2 polarization by inhibiting JNK and p38 pathways while augmenting the ERK1/2 pathway, indicating MAPK pathway modulation.
Conclusions:
- Scutellarin effectively induces the polarization of activated microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory and neuroprotective M2 phenotype.
- The MAPK signaling pathway, particularly the interplay between JNK, p38, and ERK1/2, is a key mechanism through which scutellarin exerts its effects on microglia polarization.
- Scutellarin demonstrates therapeutic potential for mitigating neuroinflammation in conditions like cerebral ischemia by modulating microglia phenotypes via the MAPK pathway.
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