Triptolide exhibits anti-inflammatory effects on adipocytes and macrophages by inhibition of AMPK/mTOR pathway

2021 ◽  
Author(s):  
Xue-li Li ◽  
Zhao Liu
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Chinese Herb ◽  
Mtor Signaling ◽  
Low Grade ◽  
Mtor Signaling Pathway ◽  
Raw264.7 Macrophages ◽  
Inflammatory Models ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Obesity is a growing global health problem and chronic over-nutrition disease with lipid accumulation that results in low-grade chronic inflammation in the microenvironment of adipose tissue. Triptolide is a diterpene lactone compound extracted from the roots of the Chinese herb TWHF and possesses a therapeutic potential due to its immunosuppressive and anti-inflammatory properties. In this study, we built obesity-related inflammatory models of adipocytes using LPS, Ma-CM and raw264.7 macrophages, while the obesity-related inflammatory models of macrophages were built using LPS and Ad-CM system. We used these inflammatory models to investigate the anti-inflammatory property of triptolide. Treatment of triptolide (0.005, 0.010, 0.020 and 0.040 μ M) inhibited LPS-induced or macrophages conditioned medium-stimulated activation of AMPK/mTOR signaling pathway (p < 0.05). The results showed that triptolide reduced the release of chemokines MCP-1, RANTES, EOTAXIN and KC in LPS, Ma-CM or RAW264.7 macrophages-stimulated 3T3-L1 adipocytes. Triptolide also diminished MCP-1, RANTES, EOTAXIN, KC and TNF-α in Ad-CM stimulated RAW264.7 macrophages, while expression of MCP-1, RANTES, TNF-α, GM-CSF and IL-6 was decreased in LPS stimulated RAW264.7 macrophages (p < 0.05). These results demonstrate that triptolide is not only effective against inflammatory response of RAW264.7 macrophages or 3T3-L1 adipocytes, but also disrupts the crosstalk between macrophages and adipocytes, particularly by inhibiting secretion of pro-inflammatory mediators through inhibiting the activation of AMPK/mTOR signaling pathway. Triptolide might benefit to ameliorate obesity-induced inflammatory diseases.

scholarly journals The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hajer Tlili ◽  
Anca Macovei ◽  
Daniela Buonocore ◽  
Manuela Lanzafame ◽  
Hanen Najjaa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Plant Extract ◽  
Therapeutic Potential ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Cellular Growth ◽  
Cancer Drug ◽  
Mtor Signaling Pathway ◽  
Epicatechin Gallate ◽  
Saponin Content

Abstract Background Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia. In the present work, the biochemical profile of the main compounds present in the plant leaf extract was determined and the anti-leukemic potential of the plant extracts against acute monocytic leukaemia (AML) THP-1 cells was investigated. Methods After HPLC identification of some phenolic compounds present in the plant extract and the quantification of saponin content, the cytotoxic effect of Rhus tripartita extracts on THP-1 cell culture was evaluated using the colorimetric MTT assay for cell viability. THP-1 cells were incubated with medium containing the relative IC50 concentrations of total plant extract, saponin extract and some standard compounds (rutin (R); kaempferol (K); mixture of catechin, epicatechin, and epicatechin-gallate (CEEG); ellagic acid (EA). Finally, qRT-PCR and western blotting analysis were used to evaluate the effect of some flavonoids present in a crude extract of polyphenols and the total extract of saponins on cell survival and apoptosis. Results Analysis of expression level of some gene (PIK3CA, PTEN, AKT1, mTOR, EIF4E, RPS6KB1, and TSC1) involved in the mTOR pathway and the phosphorylation of S6 and AKT proteins allowed to observe that a total Rhus tripartita extract and some of the compounds found in the extract controls THP-1 cell proliferation and apoptosis via regulation of the PI3K-Akt-mTOR signaling pathway. Conclusion Rhus tripartita-induced inhibition of cell cycle and induction of apoptosis may involve the mTOR pathway. Therefore, Rhus tripartita extract may be a useful candidate as a natural anti-cancer drug to support the treatment of AML.

Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway

2020 ◽  
Vol 152 ◽  
pp. 104626 ◽  
Author(s):  
Ana Sanches-Silva ◽  
Lara Testai ◽  
Seyed Fazel Nabavi ◽  
Maurizio Battino ◽  
Kasi Pandima Devi ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF-α Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K-Akt-mTOR Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Guangtao Han ◽  
Yubiao Zhang ◽  
Haohuan Li
Keyword(s):  
Signaling Pathway ◽  
Combination Treatment ◽  
Inflammatory Cytokine ◽  
Combined Treatment ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Tnf Α

Osteoarthritis (OA) is a chronic joint disease characterized by cholesterol accumulation in chondrocytes, cartilage degeneration, as well as extracellular matrix (ECM) destruction, and joint dysfunction. Curcumin, a chemical that can reduce cholesterol levels in OA patients, also can inhibit the progression of OA. However, a high concentration of curcumin may also trigger apoptosis in normal chondrocytes. Besides curcumin, probucol that is found can also effectively decrease the cholesterol level in OA patients. Considering that high cholesterol is a risk factor of OA, it is speculated that the combination treatment of curcumin and probucol may be effective in the prevention of OA. To investigate the possible effects of such two chemicals on OA pathophysiology, chondrocyte apoptosis and autophagy behavior under inflammatory cytokine stress were studied, and specifically, the PI3K-Akt-mTOR signaling pathway was studied. Methods. Cell proliferation, colony formation, and EdU assay were performed to identify the cytotoxicity of curcumin and probucol on chondrocytes. Transwell assay was conducted to evaluate chondrocyte migration under TNF-α inflammation stress. Immunofluorescence, JC-1, flow cytometry, RT-PCR, and western blot were used to investigate the signal variations related to autophagy and apoptosis in chondrocytes and cartilage. A histological study was carried out on OA cartilage. Glycosaminoglycan (GAG) release was determined to evaluate the ECM degradation under stress. Results. Compared with a single intervention with curcumin or probucol, a combined treatment of these two chemicals is more effective in terms of protecting chondrocytes from stress injury induced by inflammatory cytokines. The promoted protection may be attributed to the inhibition of apoptosis and the blockage of the autophagy-related PI3K/Akt/mTOR pathway. Such results were also verified in vitro by immunofluorescence staining of OA chondrocytes and in vivo by immunohistochemistry staining of cartilage. Besides, in vivo studies also showed that when applied in combination, curcumin and probucol could block the PI3K-AKT-mTOR signaling pathway; promote COL-II expression; suppress P62, MMP-3, and MMP-13 expression; and inhibit TNF-α-stimulated cartilage degradation. Moreover, the combined medication could help reduce the release of ECM GAGs in OA cartilage and alleviate the severity of OA. Conclusion. A combined treatment of curcumin and probucol could be used to protect chondrocytes from inflammatory cytokine stress via inhibition of the autophagy-related PI3K/Akt/mTOR pathway both in vitro and in vivo, which might be of potential pharmaceutical value for OA prevention and therapy.

scholarly journals Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential

Leukemia ◽  
2013 ◽  
Vol 28 (4) ◽  
pp. 739-748 ◽  
Author(s):  
L M Neri ◽  
A Cani ◽  
A M Martelli ◽  
C Simioni ◽  
C Junghanss ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway

2021 ◽  
Author(s):  
Hajer Tlili ◽  
Anca Macovei ◽  
Daniela Buonocore ◽  
Manuela Lanzafame ◽  
Hanen Najjaa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Plant Extract ◽  
Therapeutic Potential ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Cellular Growth ◽  
Cancer Drug ◽  
Mtor Signaling Pathway ◽  
Epicatechin Gallate ◽  
Saponin Content

Abstract Background Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia. In the present work, the biochemical profile of the main compounds present in the plant leaf extract was determined and the anti-leukemic potential of the plant extracts against acute monocytic leukaemia (AML) THP-1 cells was investigated. Methods After HPLC identification of some phenolic compounds present in the plant extract and the quantification of saponin content, the cytotoxic effect of Rhus tripartita extracts on THP-1 cell culture was evaluated using the colorimetric MTT assay for cell viability. THP-1 cells were incubated with medium containing the relative IC50 concentrations of total plant extract, saponin extract and some standard compounds (rutin (R); kaempferol (K); mixture of catechin, epicatechin, and epicatechin-gallate (CEEG); ellagic acid (EA). Finally, qRT-PCR and western blotting analysis were used to evaluate the effect of some flavonoids present in a crude extract of polyphenols and the total extract of saponins on cell survival and apoptosis. Results Analysis of expression level of some gene (PIK3CA, PTEN, AKT1, mTOR, EIF4E, RPS6KB1, and TSC1) involved in the mTOR pathway and the phosphorylation of S6 and AKT proteins allowed to observe that a total Rhus tripartita extract and some of the compounds found in the extract controls THP-1 cell proliferation and apoptosis via regulation of the PI3K-Akt-mTOR signaling pathway. Conclusion Rhus tripartita-induced inhibition of cell cycle and induction of apoptosis may involve the mTOR pathway. Therefore, Rhus tripartita extract may be a useful candidate as a natural anti‑cancer drug to support the treatment of AML.

Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 187-195 ◽  
Author(s):  
Xing Li ◽  
Peigen Xie ◽  
Yu Hou ◽  
Shudong Chen ◽  
Peiheng He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Chinese Herb ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Background/Aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats. Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], ­IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism. Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway. Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

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