<i>Glycyrrhiza uralensis</i> and Semilicoisoflavone B Reduce Aβ Secretion by Increasing PPARγ Expression and Inhibiting STAT3 Phosphorylation to Inhibit BACE1 Expression

Gu, Ming-Yao; Chun, Yoon S.; Zhao, Dong; Ryu, Shi Yong; Yang, Hyun Ok

doi:10.1002/mnfr.201700633

Cited by 13 publications

(13 citation statements)

References 44 publications

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“…STAT proteins play a central role in regulating cytokinedependent inflammation [38][39][40]. 7 STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) are identified and STAT3 is highly associated with inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Scrodentoids H and I, a Pair of Natural Epimerides from Scrophularia dentata, Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells

Mao

Sun

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Scrophularia dentata is an important medicinal plant and used for the treatment of exanthema and fever in Traditional Tibetan Medicine. Scrodentoids H and I (SHI), a pair of epimerides of C19-norditerpenoids isolated from Scrophularia dentata, could transfer to each other in room temperature and were firstly reported in our previous work. Here, we first reported the anti-inflammatory effects of SHI on LPS-induced inflammation. Purpose. To evaluate the anti-inflammatory property of SHI, we investigated the effects of SHI on LPS-activated THP-1 cells. Methods. THP-1 human macrophages were pretreated with SHI and stimulated with LPS. Proinflammatory cytokines IL-1β and IL-6 were measured by RT-PCR and enzyme-linked immunosorbent assays (ELISA). The mechanism of action involving phosphorylation of ERK, JNK, P38, and STAT3 was measured by western Blot. The NF-κB promoter activity was evaluated by Dual-Luciferase Reporter Assay System in TNF-α stimulated 293T cells. Results. SHI dose-dependently reduced the production of proinflammatory cytokines IL-1β and IL-6. The ability of SHI to reduce production of cytokines is associated with phosphorylation depress of JNK and STAT3 rather than p38, ERK, and NF-κB promoter. Conclusions. Our experimental results indicated that anti-inflammatory effects of SHI exhibit attenuation of LPS-induced inflammation and inhibit activation through JNK/STAT3 pathway in macrophages. These results suggest that SHI might have a potential in treating inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

Scrodentoids H and I, a Pair of Natural Epimerides from Scrophularia dentata, Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells

Mao

Sun

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Western blotting experiment was performed according to our previously described method . Briefly, APPsw‐transfected HeLa cells and SH‐SY5Y cells were harvested after treatment with samples for the indicated times.…”

Section: Methodsmentioning

confidence: 99%

“…RT‐PCR was performed according to the previously described method . Briefly, TRIzol reagent (Invitrogen) was used to extract total RNA, and Superscript‐III kit (Invitrogen, A10752030) was used to synthesize cDNA according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

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Licoflavonol Reduces Aβ Secretion by Increasing BACE1 Phosphorylation to Facilitate BACE1 Degradation

Chun

Yong

et al. 2019

Molecular Nutrition Food Res

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Scope In the previous study, Glycyrrhiza uralensis Fisch extract (GUE) inhibited Aβ secretion by inhibiting β‐site APP‐cleaving enzyme 1 (BACE1) transcription, and the active compounds semilicoisoflavone B (SB) and licoflavonol (LF) inhibited Aβ secretion. SB corresponds to the same mechanism as GUE, but LF has a different mechanism. In this study, the mechanism underlying inhibition of Aβ by LF is investigated. Methods and results The effects of LF on Aβ, sAPPα, and sAPPβ secretion are evaluated by ELISA, and the effect of LF on BACE1 expression is detected by western blotting. It is found that the effect of LF on Aβ secretion is due to promotion of BACE1 protein degradation, and that the effect of LF on Aβ and BACE1 expression is attenuated after cotreatment with the lysosome inhibitor chloroquine. In a subsequent mechanistic study, it is found that LF increases BACE1 phosphorylation to increase its interactions with ADP ribosylation factor‐binding proteins 1 and 3 (GGA1 and GGA3, respectively) and eventually facilitate BACE1 delivery to lysosomes for degradation. Conclusion This study is the first to demonstrate that the BACE1 phosphorylation inducer LF can modulate BACE1 trafficking and lead to facilitating degradation of BACE1, eventually decreasing Aβ secretion.

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“…STAT proteins play a central role in regulating cytokine-dependent inflammation and immunity [47][48][49]. 7 STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) are identified and STAT3 is highly associated with inflammatory response.…”

Section: Stat3 Inhibition Blocked the Anti-inflammatory Effect Of Mirmentioning

confidence: 99%

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

Zhang

Liu

Shang

et al. 2018

Cell Physiol Biochem

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Background/Aims: miR-135a is reduced in several cancers and has been suggested to mediate immune and inflammatory responses. However, the effect of miR-135a on inflammatory bowel diseases was obscure. This study firstly attempted to investigate the hypothesis that miR-135a alleviates dextran sodium sulfate (DSS)-induced inflammation in colonic cells and potential mechanisms are also studied. Methods: Caco-2 and HT-29 cells in this study were treated with DSS, miR-135a mimic, and S3I-201, and then CKK-8 assay was used to test cell viability. Expressions of miR-135a, cytokines, and signal transducers and activators of transcription factors (STATs) were determined by RT-PCR. Also, cytokine productions were further tested by using ELISA kits. Activation or inactivation of STAT3 signal was validated by western blotting analysis. Results: The results showed that DSS markedly downregulated miR-135a expression (P< 0.05) and induced inflammatory response in Caco-2 and HT-29 cells evidenced by the up regulations and productions of interleukin-1β (IL-1β) and tumor necrosis factor-ɑ (TNF-ɑ) (P< 0.05). Transfection with miR-135a mimic significantly alleviated DSS-induced upregulation and productions of IL-1β and TNF-ɑ in Caco-2 and HT-29 cells (P< 0.05). STATs were analyzed and miR-135a mimic treatment reversed STAT3 downregulation in DSS-challenged Caco-2 and HT-29 cells compared with the mimic control (P< 0.05). Also, STAT3 phosphorylation was inhibited in DSS-challenged Caco-2 cells and miR-135a mimic activated STAT3 signal (P< 0.05). S3I-201, an inhibitor of STAT3 signal, further used to inactivate STAT3 signal and the results showed that S3I-201 blocked the anti-inflammatory effect of miR-135a mimic on Caco-2 and HT-29 cells evidenced by the lowered expressions and productions of proinflammatory cytokines ((IL-1β and TNF-ɑ) (P< 0.05). Conclusion: Our results indicated that miR-135a alleviated DSS-induced inflammation and activated STAT3 signal in colonic cells. Inhibition of STAT3 reversed the anti-inflammatory function of miR-135a by regulating proinflammatory cytokines. Thus, STAT3 signal might serve, at least in part, as the potential mechanism of miR-135a-mediated anti-inflammatory effect in colonic cells.

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Glycyrrhiza uralensis and Semilicoisoflavone B Reduce Aβ Secretion by Increasing PPARγ Expression and Inhibiting STAT3 Phosphorylation to Inhibit BACE1 Expression

Abstract: These findings indicate that GUE and SB may function as PPARγ agonists, thereby inhibiting BACE1 expression and ultimately reducing the secretion of Aβ.

Cited by 13 publications

References 44 publications

Scrodentoids H and I, a Pair of Natural Epimerides from Scrophularia dentata, Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells

Scrodentoids H and I, a Pair of Natural Epimerides from Scrophularia dentata, Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells

Licoflavonol Reduces Aβ Secretion by Increasing BACE1 Phosphorylation to Facilitate BACE1 Degradation

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

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