Baicalin Ameliorates Cognitive Impairment and Protects Microglia from LPS-Induced Neuroinflammation via the SIRT1/HMGB1 Pathway

Systemic inflammation often induces neuroinflammation and disrupts neural functions, ultimately causing cognitive impairment. Furthermore, neuronal inflammation is the key cause of many neurological conditions. It is particularly important to develop effective neuroprotectants to prevent and control inflammatory brain diseases. Baicalin (BAI) has a wide variety of potent neuroprotective and cognitive enhancement properties in various models of neuronal injury through antioxidation, anti-inflammation, anti-apoptosis, and stimulating neurogenesis. Nevertheless, it remains unclear whether BAI can resolve neuroinflammation and cognitive decline triggered by systemic or distant inflammatory processes. In the present study, intraperitoneal lipopolysaccharide (LPS) administration was used to establish neuroinflammation to evaluate the potential neuroprotective and anti-inflammatory effects of BAI. Here, we report that BAI activated silent information regulator 1 (SIRT1) to deacetylate high-mobility group box 1 (HMGB1) protein in response to acute LPS-induced neuroinflammation and cognitive deficits. Furthermore, we demonstrated the anti-inflammatory and cognitive enhancement effects and the underlying molecular mechanisms of BAI in modulating microglial activation and systemic cytokine production, including tumor necrosis factor- (TNF-) α and interleukin- (IL-) 1β, after LPS exposure in mice and in the microglial cell line, BV2. In the hippocampus, BAI not only reduced reactive microglia and inflammatory cytokine production but also modulated SIRT1/HMGB1 signaling in microglia. Interestingly, pretreatment with SIRT1 inhibitor EX-527 abolished the beneficial effects of BAI against LPS exposure. Specifically, BAI treatment inhibited HMGB1 release via the SIRT1/HMGB1 pathway and reduced the nuclear translocation of HMGB1 in LPS-induced BV2 cells. These effects were reversed in BV2 cells by silencing endogenous SIRT1. Taken together, these findings indicated that BAI reduced microglia-associated neuroinflammation and improved acute neurocognitive deficits in LPS-induced mice via SIRT1-dependent downregulation of HMGB1, suggesting a possible novel protection against acute neurobehavioral deficits, such as delayed neurocognitive recovery after anesthesia and surgery challenges.

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Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

10.21203/rs.2.17969/v2 ◽

2020 ◽

Author(s):

Shao-Peng Lin ◽

Jue-Xian Wei ◽

Shan Ye ◽

Jiasong Hu ◽

Jingyi Bu ◽

...

Keyword(s):

Cognitive Impairment ◽

Inflammatory Cytokines ◽

Nuclear Translocation ◽

Neuronal Damage ◽

Protective Mechanism ◽

Protective Effects ◽

Neurocognitive Deficits ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

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Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3476212 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Hsin-Ling Yang ◽

Ting-Yu Yang ◽

Yugandhar Vudhya Gowrisankar ◽

Chun-Huei Liao ◽

Jiunn-Wang Liao ◽

...

Keyword(s):

Proinflammatory Cytokine ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Ex Vivo ◽

Root Extract ◽

Piper Methysticum ◽

Serum Lipase ◽

Antioxidant Genes ◽

Anti Inflammatory

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

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GBE50 Attenuates Inflammatory Response by Inhibiting the p38 MAPK and NF-κB Pathways in LPS-Stimulated Microglial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/368598 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Gai-ying He ◽

Chong-gang Yuan ◽

Li Hao ◽

Ying Xu ◽

Zhi-xiong Zhang

Keyword(s):

Signal Transduction ◽

P38 Mapk ◽

Molecular Mechanisms ◽

Morphological Changes ◽

Interleukin 1 ◽

Bv2 Cells ◽

Proinflammatory Responses ◽

Bv2 Microglia ◽

The Central Nervous System ◽

Anti Inflammatory

Overactivated microglia contribute to a variety of pathological conditions in the central nervous system. The major goal of the present study is to evaluate the potential suppressing effects of a new type of Ginko biloba extract, GBE50, on activated microglia which causes proinflammatory responses and to explore the underlying molecular mechanisms. Murine BV2 microglia cells, with or without pretreatmentof GBE50 at various concentrations, were activated by incubation with lipopolysaccharide (LPS). A series of biochemical and microscopic assays were performed to measure cell viability, cell morphology, release of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), and signal transduction via the p38 MAPK and nuclear factor-kappa B (NF-κB) p65 pathways. We found that GBE50 pretreatment suppressed LPS-induced morphological changes in BV2 cells. Moreover, GBE50 treatment significantly reduced the release of proinflammatory cytokines, TNF-αand IL-1β, and inhibited the associated signal transduction through the p38 MAPK and NF-κB p65 pathways. These results demonstrated the anti-inflammatory effect of GBE50 on LPS-activated BV2 microglia cells, and indicated that GBE50 reduced the LPS-induced proinflammatory TNF-αand IL-1βrelease by inhibiting signal transduction through the NF-κB p65 and p38 MAPK pathways. Our findings reveal, at least in part, the molecular basis underlying the anti-inflammatory effects of GBE50.

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Antioxidant and Anti-Inflammatory Effects of Bischofia javanica (Blume) Leaf Methanol Extracts through the Regulation of Nrf2 and TAK1

Antioxidants ◽

10.3390/antiox10081295 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1295

Author(s):

Sewoong Lee ◽

Jain Ha ◽

Jiyoung Park ◽

Eunjeong Kang ◽

Sung-Hyun Jeon ◽

...

Keyword(s):

Molecular Mechanisms ◽

Nuclear Translocation ◽

The Philippines ◽

No Production ◽

Related Factor ◽

Nuclear Factor ◽

Antioxidant Genes ◽

Methanol Extracts ◽

Anti Inflammatory ◽

Bischofia Javanica

Bischofia javanica (Blume) has been traditionally used to treat inflammatory diseases such as tonsillitis and ulcers throughout Asia, including China, Indonesia, and the Philippines: however, the molecular mechanisms by which B. javanica exerts its antioxidant and anti-inflammatory properties remain largely unknown. In this study, we analyzed the antioxidant and anti-inflammatory mechanisms of methanol extracts of B. javanica leaves (MBJ) in vitro and in vivo. MBJ decreased nitric oxide (NO) production and the expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The observed suppression of inflammatory responses by MBJ was correlated with an inhibition of the nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathways. Additionally, MBJ induced nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that upregulates the expression of anti-inflammatory and antioxidant genes. Furthermore, MBJ exhibited antioxidant and anti-inflammatory effects in an acute hepatitis mouse model. In conclusion, our results confirm the medicinal properties of B. javanica, and therefore MBJ could be applied to improve inflammatory and redox imbalances in different types of pathologies.

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A Novel Factor in Olfactory Ensheathing Cell-Astrocyte Crosstalk: Anti-Inflammatory Protein α-Crystallin B

10.1101/2020.08.28.273003 ◽

2020 ◽

Author(s):

Aybike Saglam ◽

Anne L. Calof ◽

Susan Wray

Keyword(s):

Nuclear Factor Kappa B ◽

Nuclear Translocation ◽

Inflammatory Factors ◽

List Type ◽

Olfactory Ensheathing Cell ◽

Reactive Microglia ◽

Secreted Factors ◽

Inflammatory Protein ◽

Growth Inhibitory ◽

Anti Inflammatory

AbstractAstrocytes are key players in CNS neuroinflammation and neuroregeneration that may help or hinder recovery, depending on the context of the injury. Although pro-inflammatory factors that promote astrocyte-mediated neurotoxicity have been shown to be secreted by reactive microglia, anti-inflammatory factors that suppress astrocyte activation are not well-characterized. Olfactory ensheathing cells (OECs), glial cells that wrap axons of olfactory sensory neurons, have been shown to moderate astrocyte reactivity, creating an environment conducive to regeneration. Similarly, astrocytes cultured in medium conditioned by cultured OECs (OEC-CM) show reduced nuclear translocation of Nuclear Factor kappa-B (NFκB), a pro-inflammatory protein that induces neurotoxic reactivity in astrocytes. In this study, we screened primary and immortalized OEC lines to identify these factors and discovered that Alpha B-crystallin (CryAB), an antiinflammatory protein, is secreted by OECs via exosomes, coordinating an intercellular immune response. Our results showed: 1) OEC exosomes block nuclear NFκB translocation in astrocytes while exosomes from CryAB-null OECs could not; 2) OEC exosomes could be taken up by astrocytes and 3) CryAB treatment suppressed multiple neurotoxicity-associated astrocyte transcripts. Our results indicate that OEC-secreted factors are potential agents that can ameliorate, or even reverse, the growth-inhibitory environment created by neurotoxic reactive astrocytes following CNS injuries.Main PointsAstrocytes uptake OEC-secreted exosomes.WT OEC-exosomes, but not CryAB-null OEC-exosomes, block nuclear NFκB translocation in astrocytes.CryAB, and other factors secreted by OECs, suppresses multiple neurotoxicity-associated astrocyte transcripts.

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Hericium erinaceusInhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/8257238 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Hebron C. Chang ◽

Hsin-Ling Yang ◽

Jih-Hao Pan ◽

Mallikarjuna Korivi ◽

Jian-You Pan ◽

...

Keyword(s):

Endothelial Cells ◽

Transcriptional Activation ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Intercellular Adhesion Molecule ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Antioxidant Genes ◽

Anti Inflammatory

Hericium erinaceus(HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50–200 μg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1),γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities ofH. erinaceusmay contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

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Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells

Scientific Reports ◽

10.1038/s41598-019-51614-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 10

Author(s):

Shan Han ◽

Hongwei Gao ◽

Shaoru Chen ◽

Qinqin Wang ◽

Xinxing Li ◽

...

Keyword(s):

Inflammatory Response ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Inflammatory Diseases ◽

Raw264.7 Cells ◽

Tnf Α ◽

Intracellular Ros ◽

Anti Inflammatory ◽

Cellular Thermal Shift Assay

Abstract Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

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Taraxacum officinale Wigg. Attenuates Inflammatory Responses in Murine Microglia through the Nrf2/HO-1 and NF-κB Signaling Pathways

The American Journal of Chinese Medicine ◽

10.1142/s0192415x20500238 ◽

2020 ◽

Vol 48 (02) ◽

pp. 445-462

Author(s):

Linsha Dong ◽

Zhuoma Dongzhi ◽

Yonglong Jin ◽

Youn-Chul Kim ◽

Dong-Sung Lee ◽

...

Keyword(s):

Nuclear Translocation ◽

Inflammatory Responses ◽

Taraxacum Officinale ◽

Related Factor ◽

Nuclear Factor ◽

Proinflammatory Mediators ◽

Bv2 Cells ◽

Murine Microglia ◽

Anti Inflammatory ◽

Ethanol Extracts

As a long-established medicinal and edible homologous plant, Taraxacum officinale Wigg. is widely distributed in Asia, Europe, and other parts of the world. T. officinale is reported to exert a variety of biological and pharmacological activities, including anticancer, hepatoprotective, and anti-obesity effects. In this study, we evaluated the anti-inflammatory effects of ethanol extracts of T. officinale (A-TOW) by examining the suppression of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus. Furthermore, A-TOW also inhibited the nuclear translocation of nuclear factor [Formula: see text]B p65 caused by stimulation with LPS. In addition, A-TOW regulates heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 cells. The effects of A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that the potent anti-inflammatory activity of T. officinale, possibly through the regulation of Nrf2/HO-1 and NF-[Formula: see text]B signaling pathway.

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2019IL-33 and its decoy sST2 in patients with Alzheimer’s Disease and Mild Cognitive Impairment

10.21203/rs.2.17538/v1 ◽

2019 ◽

Author(s):

Marina Saresella ◽

Ivana Marventano ◽

Federica Piancone ◽

Francesca La Rosa ◽

Daniela Galimberti ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Nuclear Translocation ◽

In Vitro System ◽

Interleukin 33 ◽

Anti Inflammatory

Abstract Background: Interleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer’s disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Method: IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1ß and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 in an in vitro system of Aß42-stimulated monocytes was examined. Results: As compared to HC: 1) IL-33 was significantly decreased in serum and CSF of AD and MCI; 2) sST2 was increased in serum of AD and MCI but was undetectable in CSF; 3) serum and CSF IL-1ß concentration was significantly increased and that of IL-10 was reduced in AD and MCI whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aß 42-stimulated monocytes down regulated IL-1b generation in AD, MCI and HC and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aß42-stimulated monocytes of HC alone. Conclusions: These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

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Artocarpus lakoocha Extract Inhibits LPS-Induced Inflammatory Response in RAW 264.7 Macrophage Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21041355 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1355 ◽

Cited By ~ 3

Author(s):

Phateep Hankittichai ◽

Pensiri Buacheen ◽

Pornsiri Pitchakarn ◽

Mingkwan Na Takuathung ◽

Nitwara Wikan ◽

...

Keyword(s):

Molecular Mechanisms ◽

Nuclear Translocation ◽

Ethanolic Extract ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 ◽

Rapid Action ◽

Mitogen Activated Protein ◽

Alternative Agent ◽

Raw 264.7 Macrophage Cells ◽

Anti Inflammatory

Artocarpus lakoocha Roxb. (AL) has been known for its high content of stilbenoids, especially oxyresveratrol. AL has been used in Thai traditional medicine for centuries. However, the role of AL in regulating inflammation has not been elucidated. Here we investigated the molecular mechanisms underlying the anti-inflammation of AL ethanolic extract in RAW 264.7 murine macrophage cell line. The HPLC results revealed that this plant was rich in oxyresveratrol, and AL ethanolic extract exhibited anti-inflammatory properties. In particular, AL extract decreased lipopolysaccharide (LPS)-mediated production and secretion of cytokines and chemokine, including IL-6, TNF-α, and MCP-1. Consistently, the extract inhibited the production of nitric oxide (NO) in the supernatants of LPS-stimulated cells. Data from the immunofluorescence study showed that AL extract suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. Results from Western blot analysis further confirmed that AL extract strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB. The protein expression of iNOS and COX-2 in response to LPS stimulation was significantly decreased with the presence of AL extract. AL extract was found to play an anti-inflammatory role, in part through inhibiting LPS-induced activation of Akt. The extract had negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Specifically, incubation of cells with the extract for only 3 h demonstrated the rapid action of AL extract on inhibiting the phosphorylation of Akt, but not ERK1/2. Longer exposure (24 h) to AL extract was required to mildly reduce the phosphorylation of ERK1/2, p38, and JNK MAPKs. These results indicate that AL extract manipulates its anti-inflammatory effects mainly through blocking the PI3K/Akt and NF-κB signal transduction pathways. Collectively, we believe that AL could be a potential alternative agent for alleviating excessive inflammation in many inflammation-associated diseases.

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