Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

Bulugonda, Ramakrishna K; Kumar, Kotha Anil; Dharmapuri, Gangappa; Beeda, Harshavardhan; Philip, Gundala Harold; Rao, Dowlathabad Muralidhara; Faisal, Syed M.

doi:10.1038/srep42683

Cited by 65 publications

(27 citation statements)

References 52 publications

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“…There are several known causes of inflammation, and the NF-κB/COX-2/iNOS pathway is a known important mechanism 6,7 . Notably, NF-κB controls various stages of inflammation and immune modulation via the regulation of several molecules, including cytokines (e.g., IL-1β, TNF-α), iNOS, and chemokines 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways

Lee

Cho

et al. 2020

Sci Rep

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Although inflammation is a host defense mechanism, chronic inflammation mediates several diseases, including cancer, allergy, asthma, and autoimmune diseases, and reportedly, it is associated with a 60% mortality rate. There are several reports on the anti-inflammatory effects of Curcuma longa and Allium hookeri. However, although they can be used as culinary materials and have biological effects, they are not effective anti-inflammatory agents. In this study, we evaluated the synergic effect of C. longa and A. hookeri in order to confirm the possibility of a new anti-inflammatory agent. Based on cell viability and cytokine analyses, the appropriate ratio of C. longa and A. hookeri was confirmed using an air pouch animal model. Then, the anti-inflammatory effect of C. longa and A. hookeri co-treatment was evaluated by measuring the immune cell count and cytokines in the exudate and by comparing the morphological changes and cytokines in inflamed skin samples. Additionally, we evaluated the NF-κB/ COX-2 pathway and iNOS levels. The active constituents detected in C. longa were demethoxycurcumin and bisdemethoxycurcumin, and that detected in A. hookeri was methylsulfonylmethane. An in vitro assessment determined the appropriate drug ratio as 3:7. In a carrageenan-induced inflammatory model, co-treatment effectively suppressed inflammatory cytokines, including IFN-γ, IL-1β, IL-6, IL-13, and IL-17, and recovered inflammation-related morphological changes in the skin. The antiinflammatory effect of the co-treatment was mediated through the NF-κB/COX-2 pathway and iNOS inhibition. We concluded that co-treatment with C. longa and A. hookeri synergistically inhibited inflammation via the NF-κB/COX-2/iNOS pathway. Inflammation is a biological, homeostatic defense mechanism against foreign bodies. However, chronic inflammation can cause additional damage in cases of cancer, allergy, asthma, autoimmune diseases, glomerulonephritis, hepatitis, inflammatory bowel disease, rheumatoid arthritis, and other disorders 1. Moreover, chronic inflammation can result in death. Reportedly, chronic inflammatory diseases 2 are associated with a 60% worldwide mortality. Steroidal hormones are the most potent anti-inflammatory drugs owing to their ability to block all inflammatory pathways; however, tolerance against such drugs is easily developed. Hence, non-steroidal anti-inflammatory drugs (NSAIDs) are broadly used. However, NSAIDs have severe adverse effects as they damage the upper gastrointestinal tract by inhibiting prostaglandin synthesis 3. Several cytokines influence the occurrence or inhibition of inflammation. Pro-inflammatory cytokines that promote inflammation include interleukin-1β (IL-1β), IL-6, IL-13, and tumor necrosis factor-alpha (TNF-α) 4. Conversely, anti-inflammatory cytokines that can inhibit inflammation include IL-1Rα, IL-4, IL-10, IL-11, and TGF-β1 5. Furthermore, the nuclear factor kappa B (NF-κB)/cyclooxygenase 2 (COX-2)/inducible nitric oxide synthase (iNOS) pathway is important in the pathogenesis of inflammat...

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways

Lee

Cho

et al. 2020

Sci Rep

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“…MF displays anti-diabetic, anti-cancer, and anti-infection effects by regulating inflammation, apoptosis, and cell proliferation as well as mediating immunomodulation 16 – 19 . In addition, it has been reported to influence the activation or expression of several signal cascades, such as NF-κB, Nrf2/HO-1, mitochondria-dependent pathways, and the NLRP3 inflammasome, and to target multiple cytokines and antioxidant enzymes, such as interleukin (IL)-6, tumor necrosis factor (TNF), superoxide dismutase (SOD), and catalase (CAT) 10 – 12 , 17 , 19 – 21 . In terms of the central nervous system, Yang et al .…”

Section: Introductionmentioning

confidence: 99%

Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation

Wang

Guo

Wang

et al. 2017

Sci Rep

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Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.

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“…Previous investigations elucidated that MF markedly suppressed the productions of IL-6, IL-1b, and TNF-a in LPS-triggered primary hepatocytes, BALB/c mice mammary gland, and peritoneal macrophages (Jeong et al, 2014;Pan et al, 2016;Qu et al, 2017a). Furthermore, an earlier research revealed that PT-MF remarkably decreased the expression of Cox-2, iNOS and TNF-a, and the generation of ROS in LPS-evoked RAW 264.7 cells (Bulugonda et al, 2017). In this investigation, we firstly explored the influences of MF treatment alone on the ATDC5 cells.…”

Section: Discussionmentioning

confidence: 95%

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells

Liu

et al. 2020

Front. Pharmacol.

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Background: Mangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis.Methods: ATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20 mM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 mg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship between miR-181a and PTEN. The underlying mechanism was determined by employing western blot.Results: High doses of MF treatment (15 and 20 mM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-kB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-kB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells.Conclusion: MF attenuated LPS-induced inflammatory damage through miR-181a/ PTEN axis and thereby inhibiting NF-kB pathway and activating PI3K/AKT pathway.

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Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome

Cited by 65 publications

References 52 publications

Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways

Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways

Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells

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