PMID: 

Environ Sci Pollut Res Int. 2019 Dec 31. Epub 2019 Dec 31. PMID: 31889292

Abstract Title: 

Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats.

Abstract: 

Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy; however, its effect against MTX hepatotoxicity remains unexplored. This study investigated the role of FA in modulating oxidative stress, inflammation, Nrf2/HO-1 signaling, and PPARγ in MTX-administered rats. Following oral FA supplementation for 15 days, rats received a single dose of MTX at day 16 and samples were collected at day 19. MTX provoked multiple histological manifestations, including degenerative changes, steatosis, inflammatory cells infiltration and hemorrhage, and altered serum transaminases, bilirubin, and albumin. Reactive oxygen species, lipid peroxidation, and nitric oxide were increased in the liver of rats that received MTX. FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats. FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3, whereas increased Bcl-2, Nrf2, NQO1, HO-1, and PPARγ. In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.

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PMID: 

Am J Transl Res. 2019 ;11(11):7074-7083. Epub 2019 Nov 15. PMID: 31814910

Abstract Title: 

Astragaloside II alleviates the symptoms of experimental ulcerative colitisand.

Abstract: 

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory intestinal disease, and its morbidity is rising worldwide. Previous study indicated that astragaloside II (AS II), a monomeric compound, was used to treat bowel disease. However, the effects of AS II on UC remains unclear. Thus, this study aimed to investigate the therapeutic effects of AS II on experimental UCand.METHODS: CCD-18Co cells were stimulated by 1μg/mL LPS to mimic UC. In addition, dextran sulfate sodium (DSS)-induced UC mouse model was established. CCK-8 assay was used to detect cell proliferation. Moreover, the concentrations of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in CCD-18Co cells and colon tissues were determined by ELISA, respectively. Meanwhile, the expressions of hypoxia-inducible factor 1α (HIF-α), phospho-inhibitor of NF-κB (p-IκB) and phospho-NF-κB p65 (p-p65) were detected by western blottingand, respectively.RESULTS: In this study, the levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 were significantly increased in lipopolysaccharide (LPS)-stimulated CCD-18Co cells. However, LPS-induced inflammatory response was markedly alleviated by AS II. In addition, LPS-induced HIF-α, p-IκB and p-p65 proteins increases were markedly ameliorated by AS II treatment. Moreover, AS II reduced disease activity index (DAI) scores and increased the colon lengths in DSS-treated mice. Meanwhile, AS II decreased the levels of IL-6, TNF-α, IL-1β, NO, MPO and MDA, and increased the level of SOD in colon of DSS-treated mice. Furthermore, AS II downregulated the expressions of HIF-α, p-IκB and p-p65 in DSS-induced UC in mice.CONCLUSION: Our findings indicated that AS II could alleviate inflammatory response in LPS-induced CCD-18Co cells and in DSS-induced UC in mice. In conclusion, AS II may serve as a potential agent for the treatment of UC.

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PMID: 

Dig Dis Sci. 2020 Jan 3. Epub 2020 Jan 3. PMID: 31900718

Abstract Title: 

Astragaloside IV Synergizes with Ferulic Acid to Alleviate Hepatic Fibrosis in Bile Duct-Ligated Cirrhotic Rats.

Abstract: 

BACKGROUND: Due to the multi-factorial etiology of hepatic fibrosis, multi-target therapeutics based on combinatory drugs is known to be a promising strategy for the disease.AIMS: The present study attempted to test the hypothesis that astragaloside IV combined with ferulic acid synergistically inhibits activation of hepatic stellate cells in vivo.METHODS: Bile duct-ligated rats were treated with astragaloside IV or/and ferulic acid for 28 days. Liver fibrosis was measured by histological examination. The oxidative stress-related biomarkers were measured with spectrophotometry. Expressions of mRNA and protein were measured by real-time PCR and Western blotting.RESULTS: Bile duct-ligated rat treatment with astragaloside IV and ferulic acid in combination resulted in synergistic alleviation of hepatic fibrosis. Simultaneously, activation of hepatic stellate cells was significantly inhibited by the combination therapy when compared with astragaloside IV or ferulic acid alone. Interestingly, astragaloside IV, but not ferulic acid, induced accumulation of Nrf2 in the nucleus, synthesized antioxidant enzymes through negative regulation of glycogen synthase kinase-3β, scavenged reactive oxygen species, and, in turn, suppressed hepatic stellate cells activation in bile duct-ligated rats. Conversely, ferulic acid, but not astragaloside IV, suppressed TGF-β1 and its receptors expression, which resulted in downregulation of Smad3 and Smad4.CONCLUSIONS: These findings suggest that the combination of astragaloside IV and ferulic acid synergistically induces deactivation of hepatic stellate cells through inhibition of the TGF-β pathway and activation of the Nrf2 pathway, and suggest that combination of astragaloside IV and ferulic acid is a promising candidate for the treatment of hepatic fibrosis.

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PMID: 

Pharm Biol. 2020 Dec ;58(1):89-97. PMID: 31906765

Abstract Title: 

Astragaloside IV protects ATDC5 cells from lipopolysaccharide-caused damage through regulating miR-203/MyD88.

Abstract: 

Osteoarthritis (OA) is a degenerative arthrosis sickness. Astragaloside IV (AS-IV) functions by relieving inflammatory damage.We aimed to investigate the mechanism by which AS-IV protects ATD cells from lipopolysaccharide (LPS)-induced damage.ATDC5 cells were transfected with miR-203 inhibitor and NC inhibitor (150 nM) or pEX-MyD88 and sh-MyD88 (50 nM) for 48 h, pre-treated by 15 μg/mL AS-IV for 24 h, then treated by 5 μg/mL LPS for 12 h. Dual-luciferase activity testing was used to determine whether miR-203 could bind to MyD88. CCK-8 and flow cytometry were used to detect cell activity and apoptosis, respectively, and qRT-PCR, western blots, and ELISA were performed to detect expression levels of miR-203 and inflammatory cytokines.Based on the 50% inhibiting concentration (IC), there was no significant difference of AS-IV (0 to 15 μg/mL) on cell viability. Fifteen μg/mL was the optimal concentration of AS-IV in treating LPS-induced inflammatory damage in subsequent experiments since this was a semi-lethal concentration. AS-IV significantly reduces LPS-induced viability, apoptosis and the release of TNF-α, IL-6 and iNOS mainly through up-regulating miR-203. Further, MyD88 was a target gene of miR-203 and negatively regulated by miR-203. Knockdown of MyD88 inhibited LPS-induced inflammatory damage by inhibiting the NF-κB signal pathway.AS-IV protects ATDC5 cells against LPS-induced damage mainly via regulating miR-203/MyD88. Our results support a theoretical basis for in-depth study of the function of AS-IV and the clinical cure of OA.

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PMID: 

Sleep Breath. 2020 Jan 6. Epub 2020 Jan 6. PMID: 31907823

Abstract Title: 

Astragaloside IV ameliorates intermittent hypoxia-induced inflammatory dysfunction by suppressing MAPK/NF-κB signalling pathways in Beas-2B cells.

Abstract: 

PURPOSE: Intermittent hypoxia is a characteristic pathological change in obstructive sleep apnoea (OSA) that can initiate oxidative stress reaction and pro-inflammatory cytokine release. The purpose of this study was to assess the effect and protective mechanism of Astragaloside IV (AS-IV) in intermittent hypoxia-induced human lung epithelial Beas-2B cells.METHODS: Human lung epithelial Beas-2B cells were exposed to intermittent hypoxia or normoxia in the absence or presence of AS-IV. MTT assay was performed to determine the cell viability. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. The levels of cytokines interleukin (IL)-8, IL-1β, and IL-6 were evaluated by enzyme-linked immunosorbent assay and real-time PCR. The expression of Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear transcription factor-kappa B (NF-κB) signalling pathways was analysed by western blot.RESULTS: The results showed that AS-IV significantly reduced the levels of ROS, LDH, MDA, IL-8, IL-1β, and IL-6, and increased the level of SOD in intermittent hypoxia-induced Beas-2B cells. It also suppressed the phosphorylation of MAPKs, including P38, c-Jun N-terminal kinase and extracellular signal-regulated kinase, and inhibited the activation of the NF-κB signalling pathway by reducing thephosphorylation of IκBα and p65.CONCLUSIONS: AS-IV attenuates inflammation and oxidative stress by inhibiting TLR4-mediated MAPK/NF-κB signalling pathways in intermittent hypoxia-induced Beas-2B cells.

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PMID: 

Med Sci Monit. 2019 Dec 19 ;25:9737-9751. Epub 2019 Dec 19. PMID: 31856143

Abstract Title: 

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

Abstract: 

BACKGROUND This study aimed to prepare doxorubicin- and tetrahydrocurcumin-loaded and transferrin-modified PEG-PLGA nanoparticles (Tf-NPs-DOX-THC) for enhanced and synergistic chemoradiotherapy. MATERIAL AND METHODS Tf-NPs-DOX-THC were prepared via the double-emulsion method. The morphologies and particle sizes of the prepared nanoparticles were examined by TEM and DLS, respectively. The in vitro MTT, apoptosis, and clone formation assays were performed to detect the proliferation and radiosensitivity of cells with various treatments. Cellular uptake assay was also conducted. The tissue distribution of Tf-NPs was investigated by ex vivo DOX fluorescence imaging. The in vivo tumor growth inhibition efficiency of various treatments was evaluated in orthotopic C6 mouse models and C6 subcutaneously grafted mouse models. RESULTS Tf-NPs-DOX-THC exhibited high drug-loading efficiency (6.56±0.32%) and desirable particle size (under 250 nm). MTT, apoptosis, and clone formation assays revealed the enhanced anti-cancer activity and favorable radiosensitizing effect of Tf-NPs-DOX-THC. Strong fluorescence was observed in the brains of mice treated with Tf-NPs-DOX. The in vitro release ofdrug from nanoparticles was in a pH-sensitive manner. Tf-NPs-DOX-THC in combination with radiation also achieved favorable anti-tumor efficacy in vivo. CONCLUSIONS All results suggest that a combination of Tf-NPs-DOX-THC and radiation is a promising strategy for synergistic and sensitizing chemoradiotherapy of glioma.

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If you have symptoms of pelvic floor disorders such as urinary incontinence, pelvic organ prolapse, painful sexual intercourse or pelvic pain, learning how to do pelvic floor exercises in the comfort of your home could help you avoid surgery, relieve symptoms and regain your quality of life.

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PMID: 

Cancers (Basel). 2019 Dec 30 ;12(1). Epub 2019 Dec 30. PMID: 31905887

Abstract Title: 

Protein Kinase B Inactivation Is Associated with Magnolol-Enhanced Therapeutic Efficacy of Sorafenib in Hepatocellular Carcinoma In Vitro and In Vivo.

Abstract: 

Although sorafenib, an oral multikinase inhibitor, was approved as a treatment drug of advance hepatocellular carcinoma (HCC), treatment efficacy still requires improvement. Searching for the adjuvant reagent for enhancing sorafenib efficacy remains as a critical issue. Sorafenib has been proved to suppress extracellular signal-regulated kinases (ERK) in HCC; however, protein kinase B (AKT) was not affected by it. Targeting AKT in combination with sorafenib could be an important breakthrough point of HCC treatment. Many herbal compounds and composite formulas have been shown to enhance anti-HCC activity of sorafenib. Magnolol is a bioactive compound extracted from the bark of theand has been shown to induce apoptosis and inhibit cell invasion in HCC in vitro. However, whether magnolol sensitizes HCC to sorafenib is ambiguous. In this study, we indicated that magnolol significantly enhanced sorafenib-diminished tumor cell growth, expression of anti-apoptotic proteins, and migration/invasion ability compared to sorafenib alone. Magnolol significantly boosted sorafenib-induced extrinsic/intrinsic dependent apoptosis pathways in HCC. Notably sorafenib could not reduce protein level of AKT (Ser473), but expression of AKT (Ser473) was significantly decreased by magnolol or magnolol combined with sorafenib. LY294002 as specific AKT inhibitor was used to confirm that AKT inactivation may promote anticancer effect of sorafenib. Taken together, AKT inhibition is associated with magnolol-enhanced the therapeutic effect of sorafenib in HCC. We suggested magnolol as the potential adjuvant which may enhance therapeutic benefits of sorafenib in patients with HCC.

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PMID: 

J Interferon Cytokine Res. 2020 Jan 9. Epub 2020 Jan 9. PMID: 31916911

Abstract Title: 

Magnolol Alleviates IL-1β-Induced Dysfunction of Chondrocytes Through Repression of SIRT1/AMPK/PGC-1α Signaling Pathway.

Abstract: 

Osteoarthritis is a common chronic joint disease related with mitochondrial dysfunction, damage, and synthetic defects in chondrocytes. Magnolol is a lignin extracted fromwith antioxidant and anti-inflammation functions. This study aims to investigate the function of magnolol on mitochondrial dysfunction, oxidative stress, and inflammation in human primary chondrocytes. Chondrocytes were stimulated with IL-1β to mimic the pathogenesis of osteoarthritis. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA was employed to examine the concentration of inflammatory cytokine IL-8. Protein expression of SIRT1/pAMPK/PGC-1α, metabolism-related proteinsand Cox2 were examined by Western blot. Mitochondrial function, reactive oxygen species concentration, superoxide dismutase activity, and NF-κB activity were analyzed using commercial kit, respectively. We demonstrated that magnolol increased SIRT1/AMPK/PGC-1α expression in human chondrocytes. Magnolol could alleviate IL-1β-induced mitochondrial dysfunction and oxidative stress through SIRT1/AMPK/PGC-1α signaling pathway in human chondrocytes. In addition, magnolol maintained the anabolism and catabolism of extracellular matrix balance by SIRT1/AMPK/PGC-1α signaling pathway. Furthermore,magnolol alleviated IL-1β-induced inflammation in human chondrocytes. Magnolol alleviates IL-1β-induced dysfunction of chondrocytes through repressing SIRT1/AMPK/PGC-1α signaling pathway, which provides a potential new therapeutic strategy for human osteoarthritis.

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PMID: 

Front Pharmacol. 2019 ;10:1459. Epub 2019 Dec 5. PMID: 31920652

Abstract Title: 

Magnolol Prevents Acute Alcoholic Liver Damage by Activating PI3K/Nrf2/PPARγ and Inhibiting NLRP3 Signaling Pathway.

Abstract: 

Alcoholic liver damage (ALD) is a toxic liver damage caused by excessive drinking. Oxidative stress is one of the most crucial pathogenic factors leading to ALD. Magnolol is one of the main active constituents of traditional Chinese medicine, which has been reported to possess many pharmacological effects including anti-inflammatory, anti-oxidant, and anti-tumor. However, the effects of magnolol on ALD remain unclear. In this study, we firstly evaluated the protective effects of magnolol on ALD, and then tried to clarify the mechanism underlying the pharmacological activities. AST, ALT, GSH-Px, and SOD were detected by respective kits. Histopathological changes of liver tissue were analyzed by H&E staining. The activities of PI3K, Nrf2, and NLRP3 signaling pathways activation were detected by western blotting analysis. It was showed that alcohol-induced ALT and AST levels were significantly reduced by magnolol, but the antioxidant enzymes of GSH-Px and SOD levels were significantly increased. Magnolol attenuated alcohol-induced pathologic damage such as decreasing hepatic cord swelling, hepatocyte necrosis, and inflammatory cell infiltration. Furthermore, it was found that magnolol inhibited oxidative stress through up-regulating the activities of HO-1, Nrf2, and PPARγ and the phosphorylation of PI3K and AKT. And magnolol also decreased inflammatory response by inhibiting the activation of NLRP3inflammasome, caspase-1, and caspase-3 signaling pathway. Above results showed that magnolol could prevent alcoholic liver damage, and the underlying mechanism was through activating PI3K/Nrf2/PPARγ signaling pathways as well as inhibiting NLRP3 inflammasome, which also suggested magnolol might be used as a potential drug for ALD.

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