Search Results (1,269)

Search Parameters:
Keywords = NLRP3

Order results

Result details

Results per page

Show export options Show export options

Select all

Export citation of selected articles as:

15 pages, 4308 KiB

Open AccessArticle

Therapeutic Effect of Donepezil on Neuroinflammation and Cognitive Impairment after Moderate Traumatic Brain Injury

by Dong Hyuk Youn, Younghyurk Lee, Sung Woo Han, Jong-Tae Kim, Harry Jung, Gui Seung Han, Jung In Yoon, Jae Jun Lee and Jin Pyeong Jeon

Life 2024, 14(7), 839; https://doi.org/10.3390/life14070839 (registering DOI) - 1 Jul 2024

Viewed by 239

Abstract

Background: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil—an acetylcholinesterase (AChE) inhibitor—on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. Methods: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 μM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. Results: In vitro, donepezil was found to lead to increased cell viability and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1β), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. Conclusions: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 2nd Volume)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

17 pages, 4502 KiB

Open AccessArticle

Hydroethanolic Extract of Lepidium apetalum Willdenow Alleviates Dextran Sulfate Sodium-Induced Colitis by Enhancing Intestinal Barrier Integrity and Inhibiting Oxidative Stress and Inflammasome Activation

by Kwang-Youn Kim, Yun-Mi Kang, Ami Lee, Yeon-Ji Kim, Kyung-Ho Kim and Youn-Hwan Hwang

Antioxidants 2024, 13(7), 795; https://doi.org/10.3390/antiox13070795 (registering DOI) - 29 Jun 2024

Viewed by 158

Abstract

The prevalence of ulcerative colitis (UC) has surged in Asian nations recently. The limitations of traditional drug treatments, including biologics, have spurred interest in herbal medicines for managing UC. This study aimed to elucidate the protective mechanisms of hydroethanolic extract from Lepidium apetalum Willdenow (LWE) on intestinal integrity and inflammation in a dextran sodium sulfate (DSS)-induced colitis model of inflammatory bowel disease (IBD). Using UPLC-MS/MS analysis, eleven phytochemicals were identified in LWE, including catechin, vicenin-2, and quercetin. LWE restored transepithelial electrical resistance (TEER) and reduced paracellular permeability in IL-6-stimulated Caco-2 cells, increasing the expression of the tight junction proteins ZO-1 and occludin. LWE treatment alleviated DSS-induced colitis symptoms in mice, reducing body weight loss, disease activity index values, and spleen size, while improving colon length and reducing serum FITC-dextran levels, indicating enhanced intestinal barrier function. LWE suppressed NLRP3 inflammasome activation, reducing protein levels of pro-caspase-1, cleaved-caspase-1, ASC, and NLRP3, as well as mRNA levels of IL-1β, IL-6, and TNF-α. LWE treatment upregulated activity and mRNA levels of the antioxidant enzymes SOD1 and NQO1. Additionally, LWE modulated the Nrf2/Keap1 pathway, increasing p-Nrf2 levels and decreasing Keap1 levels. LWE also restored goblet cell numbers and reduced fibrosis in DSS-induced chronic colitis mice, increasing gene and protein expressions of ZO-1 and occludin. In summary, LWE shows promise as a therapeutic intervention for reducing tissue damage and inflammation by enhancing intestinal barrier function and inhibiting colonic oxidative stress-induced inflammasome activation. Full article

(This article belongs to the Special Issue Significance of Antioxidant Mechanisms in Intestinal Inflammation)

22 pages, 1019 KiB

Open AccessReview

The Novel Role of the NLRP3 Inflammasome in Mycotoxin-Induced Toxicological Mechanisms

by Chengshui Liao, Fengru Xu, Zuhua Yu, Ke Ding and Yanyan Jia

Vet. Sci. 2024, 11(7), 291; https://doi.org/10.3390/vetsci11070291 - 28 Jun 2024

Viewed by 189

Abstract

Mycotoxins are secondary metabolites produced by several fungi and moulds that exert toxicological effects on animals including immunotoxicity, genotoxicity, hepatotoxicity, teratogenicity, and neurotoxicity. However, the toxicological mechanisms of mycotoxins are complex and unclear. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric cytosolic protein complex composed of the NLRP3 sensor, ASC adapter protein, and caspase-1 effector. Activation of the NLRP3 inflammasome plays a crucial role in innate immune defence and homeostatic maintenance. Recent studies have revealed that NLRP3 inflammasome activation is linked to tissue damage and inflammation induced by mycotoxin exposure. Thus, this review summarises the latest advancements in research on the roles of NLRP3 inflammasome activation in the pathogenesis of mycotoxin exposure. The effects of exposure to multiple mycotoxins, including deoxynivalenol, aflatoxin B1, zearalenone, T-2 toxin, ochratoxin A, and fumonisim B1, on pyroptosis-related factors and inflammation-related factors in vitro and in vivo and the pharmacological inhibition of specific and nonspecific NLRP3 inhibitors are summarized and examined. This comprehensive review contributes to a better understanding of the role of the NLRP3 inflammasome in toxicity induced by mycotoxin exposure and provides novel insights for pharmacologically targeting NLRP3 as a novel anti-inflammatory agent against mycotoxin exposure. Full article

(This article belongs to the Special Issue Nutraceuticals to Mitigate the Secret Killers in Animals)

13 pages, 453 KiB

Open AccessArticle

Chronic HIV Infection Increases Monocyte NLRP3 Inflammasome-Dependent IL-1α and IL-1β Release

by Hedda Hoel, Tuva Børresdatter Dahl, Kuan Yang, Linda Gail Skeie, Annika Elisabet Michelsen, Thor Ueland, Jan Kristian Damås, Anne Ma Dyrhol-Riise, Børre Fevang, Arne Yndestad, Pål Aukrust, Marius Trøseid and Øystein Sandanger

Int. J. Mol. Sci. 2024, 25(13), 7141; https://doi.org/10.3390/ijms25137141 (registering DOI) - 28 Jun 2024

Viewed by 182

Abstract

Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to play a role in these inflammatory responses. In particular, preliminary data indicate the involvement of IFI16 and NLRP3 inflammasomes in chronic HIV infection. This study explores inflammasome function in monocytes from people with HIV (PWH); 22 ART-treated with suppressed viremia and 17 untreated PWH were compared to 33 HIV-negative donors. Monocytes were primed with LPS and inflammasomes activated with ATP in vitro. IFI16 and NLRP3 mRNA expression were examined in a subset of donors. IFI16 and NLRP3 expression in unstimulated monocytes correlated negatively with CD4 T cell counts in untreated PWH. For IFI16, there was also a positive correlation with viral load. Monocytes from untreated PWH exhibit increased release of IL-1α, IL-1β, and TNF compared to treated PWH and HIV-negative donors. However, circulating monocytes in PWH are not pre-primed for inflammasome activation in vivo. The findings suggest a link between IFI16, NLRP3, and HIV progression, emphasizing their potential role in comorbidities such as cardiovascular disease. The study provides insights into inflammasome regulation in HIV pathogenesis and its implications for therapeutic interventions. Full article

(This article belongs to the Special Issue Role of NLRP3 Inflammasome in Inflammatory and Immunological Diseases)

26 pages, 2050 KiB

Open AccessReview

Research Progress of Pyroptosis in Diabetic Kidney Disease

by Qingqing Fan, Rongxuan Li, Huiting Wei, Weiyue Xue, Xiang Li, Ziyao Xia, Le Zhao, Ye Qiu and Di Cui

Int. J. Mol. Sci. 2024, 25(13), 7130; https://doi.org/10.3390/ijms25137130 (registering DOI) - 28 Jun 2024

Viewed by 144

Abstract

Pyroptosis, known as one typical mode of programmed cell death, is generally characterized by the cleaved gasdermin family (GSDMs) forming pores in the cell membrane and inducing cell rupture, and the activation of aspartate-specific proteases (caspases) has also been found during this process. Diabetic Kidney Disease (DKD) is caused by the complication of diabetes in the kidney, and the most important kidney’s function, Glomerular Filtration Rate (GFR), happens to drop to less than 90% of its usual and even lead to kidney failure in severe cases. The persistent inflammatory state induced by high blood glucose implies the key pathology of DKD, and growing evidence shows that pyroptosis serves as a significant contributor to this chronic immune-mediated inflammatory disorder. Currently, the expanded discovery of GSDMs, pyroptosis, and its association with innate immunity has been more attractive, and overwhelming research is needed to sort out the implication of pyroptosis in DKD pathology. In this review, we comb both classical studies and newly founds on pyroptosis, prick off the novel awakening of pyroptosis in DKD, and center on the significance of pyroptosis in DKD treatment, aiming to provide new research targets and treatment strategies on DKD. Full article

(This article belongs to the Section Biochemistry)

26 pages, 5983 KiB

Open AccessArticle

Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis

by Islauddin Khan, Sukhmandeep Kaur, Arun K. Rishi, Breana Boire, Mounika Aare and Mandip Singh

Biomedicines 2024, 12(7), 1442; https://doi.org/10.3390/biomedicines12071442 - 28 Jun 2024

Viewed by 188

Abstract

Background: In this study, we investigated in detail the role of cannabidiol (CBD), beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Methods: Briefly, streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague–Dawley rats, and we performed procedures involving Randall Sellito calipers, a Von Frey aesthesiometer, a hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed using a laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, and JC1 and Mitosox staining were performed to determine mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides in vitro. The rats were administered BC (30 mg/kg), CBD (15 mg/kg), or combination via i.p. injections, while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Results: Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides. Furthermore, the BC and CBD combination treatment in vivo could prevent the deterioration of the mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted using Western blotting. Conclusions: the present study demonstrated that STZ and HG-induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that a CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system. Full article

(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids 2.0)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

---

Figure 6

---

Figure 7

---

Figure 8

---

Figure 9

---

Figure 10

---

Figure 11

---

Figure 12

---

Figure 13

14 pages, 2962 KiB

Open AccessArticle

A Synthetic Derivative SH 66 of Homoisoflavonoid from Liliaceae Exhibits Anti-Neuroinflammatory Activity against LPS-Induced Microglial Cells

by Md Samsuzzaman, Lalita Subedi, Seong-Min Hong, Sanha Lee, Bhakta Prasad Gaire, Eun-Ji Ko, Ji-Woong Choi, Seung-Yong Seo and Sun-Yeou Kim

Molecules 2024, 29(13), 3037; https://doi.org/10.3390/molecules29133037 - 26 Jun 2024

Viewed by 387

Abstract

Naturally occurring homoisoflavonoids isolated from some Liliaceae plants have been reported to have diverse biological activities (e.g., antioxidant, anti-inflammatory, and anti-angiogenic effects). The exact mechanism by which homoisoflavonones exert anti-neuroinflammatory effects against activated microglia-induced inflammatory cascades has not been well studied. Here, we aimed to explore the mechanism of homoisoflavonoid SH66 having a potential anti-inflammatory effect in lipopolysaccharide (LPS)-primed BV2 murine microglial cells. Microglia cells were pre-treated with SH66 followed by LPS (100 ng/mL) activation. SH66 treatment attenuated the production of inflammatory mediators, including nitric oxide and proinflammatory cytokines, by down-regulating mitogen-activated protein kinase signaling in LPS-activated microglia. The SH66-mediated inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and the respective inflammatory biomarker-like active interleukin (IL)-1β were noted to be one of the key pathways of the anti-inflammatory effect. In addition, SH66 increased the neurite length in the N2a neuronal cell and the level of nerve growth factor in the C6 astrocyte cell. Our results demonstrated the anti-neuroinflammatory effect of SH66 against LPS-activated microglia-mediated inflammatory events by down-regulating the NLRP3 inflammasome complex, with respect to its neuroprotective effect. SH66 could be an interesting candidate for further research and development regarding prophylactics and therapeutics for inflammation-mediated neurological complications. Full article

(This article belongs to the Collection Bioactive Natural Molecules from Functional Foods)

► Show Figures

Graphical abstract

---

Figure 2

---

Figure 3

---

Figure 4

---

Figure 5

---

Figure 6

---

Figure 7

---

Scheme 1

17 pages, 1295 KiB

Open AccessReview

Future Therapeutics: Targeting the NLRP3 Inflammasome Pathway to Manage Diabetic Retinopathy Development and Progression

by Charisse Y. J. Kuo, Ilva D. Rupenthal, Rinki Murphy and Odunayo O. Mugisho

Int. J. Transl. Med. 2024, 4(3), 402-418; https://doi.org/10.3390/ijtm4030027 - 24 Jun 2024

Viewed by 502

Abstract

While existing local therapies partially restore vision loss from diabetic retinopathy (DR), there is currently no reliable treatment to prevent the onset or stop the progression of the disease. This review seeks to explore the inflammatory molecular mechanisms underpinning DR pathogenesis, which have not been targeted by current interventions. Specifically, this review explores the role of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome in DR onset and progression. Evidence through clinical trials has begun to note that specific drugs (fenofibrate, metformin) appear effective in slowing DR progression independent of lipid or glucose-lowering, respectively, suggesting that other mechanisms are at play. Novel therapeutics that inhibit the activation of the NLRP3 inflammasome pathway may provide a novel treatment for halting DR progression. Full article

► Show Figures

Figure 1

17 pages, 1743 KiB

Open AccessArticle

The Effects of Dietary Pterostilbene on the Immune Response, Antioxidant Function, and Jejunal Structure of Broilers

by Zesheng Yin, Xue Sun, Xuehong Chai, Xin Zhou, Yingjie Wang, Mengru Liu and Xingjun Feng

Animals 2024, 14(13), 1851; https://doi.org/10.3390/ani14131851 - 22 Jun 2024

Viewed by 398

Abstract

This experiment was carried out to investigate the effect of pterostilbene (PTE) supplementation in feed on Arbor Acres broilers in terms of serum biochemical parameters, immune and inflammatory responses, antioxidant status, and intestinal morphological structure. For a duration of 42 days, a total of 480 1-day-old Arbor Acres broilers were randomly divided into four groups. Each group was assigned to receive either the basal diet or the basal diet supplemented with 200, 400, or 600 mg/kg of PTE. Each treatment consisted of eight replicates, with 15 chicks per replicate. In comparison with the control group, three PTE treatments significantly increased the lymphocyte transformation rate in the spleen of broilers. The automated biochemical analysis, enzyme-linked immunosorbent assay, and RT-qPCR analysis kits found that 400 mg/kg of PTE significantly increased the serum levels of complement C3, IL-4, and iNOS; reduced the serum levels of IL-6, TNF-α, and mRNA levels of the genes IL-6, IL-8, TNF-α, NLRP3, and IFN-γ; significantly improved the activities of antioxidant enzymes including CAT, GSH-Px, and T-SOD in the jejunum; and significantly reduced the MDA contents in the serum and jejunum of broilers. Nikon microscope observations and ImagePro Plus 6.0 measure results found that 400 mg/kg of PTE supplementation significantly reduced the relative length and weight of the jejunum and improved the jejunal villi structure, resulting in increased intestinal villi, deepened crypt, and an enhanced ratio of villi height to crypt depth (VH/CD). RT-qPCR and Western blot found that dietary PTE also resulted in increased mRNA levels of the genes Claudin-2, Occludin, ZO-1, and Sirt1, and decreased NF-κB protein levels in the jejunum. The results of this study demonstrated that dietary PTE improved the immune function and intestinal health of broilers by reducing inflammation and increasing the antioxidant capacity of the animals. Full article

(This article belongs to the Collection Sustainable Animal Nutrition and Feeding)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

---

Figure 6

22 pages, 18013 KiB

Open AccessArticle

Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

by Walaa Bayoumie El Gazzar, Heba Bayoumi, Heba S. Youssef, Tayseer A. Ibrahim, Reham M. Abdelfatah, Noha M. Gamil, Mervat K. Iskandar, Amal M. Abdel-Kareim, Shaymaa M. Abdelrahman, Mohammed A. Gebba, Mona Atya Mohamed, Maha M. Mokhtar, Tayseir G. Kharboush, Nervana M. Bayoumy, Hatun A. Alomar and Amina A. Farag

Toxics 2024, 12(7), 445; https://doi.org/10.3390/toxics12070445 - 21 Jun 2024

Viewed by 798

Abstract

Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity. Full article

(This article belongs to the Special Issue Drug and Pesticides-Induced Oxidative Stress and Apoptosis)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

---

Figure 6

---

Figure 7

---

Figure 8

---

Figure 9

---

Figure 10

13 pages, 3256 KiB

Open AccessArticle

Cheungsam Seed Husk Extract Reduces Skin Inflammation through Regulation of Inflammatory Mediator in TNF-α/IFN-γ-Induced HaCaT Cells

by Ji-Ye Han, Yun Jung Lee, Do-Won Lim, Hyun-Ju Jung, EunJeong Kwon, Jongki Hong and Young-Mi Lee

Plants 2024, 13(12), 1704; https://doi.org/10.3390/plants13121704 - 19 Jun 2024

Viewed by 433

Abstract

Cannabis contains numerous natural components and has several effects such as anticancer, anti-inflammatory and antioxidant. Cheungsam is a variety of non-drug-type hemp, developed in Korea and is used for fiber (stem) and oil (seed). The efficacy of Cheungsam on skin is not yet known, and although there are previous studies on Cheungsam seed oil, there are no studies on Cheungsam seed husk. In this study, we investigated the potential of Cheungsam seed husk ethanol extract (CSSH) to alleviate skin inflammation through evaluating the gene and protein expression levels of inflammatory mediators. The results showed that CSSH reduced pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MCP-1 and CXCL10) and atopic dermatitis-related cytokines (IL-4, CCL17, MDC and RANTES) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, ERK, JNK and p38 phosphorylation were decreased and p-p65, p-IκBα, NLRP3, caspase-1, p-JAK1 and p-STAT6 were suppressed after CSSH treatment. CSSH significantly increased the level of the skin barrier factors filaggrin and involucrin. These results suggest that Cheungsam seed husk ethanol extract regulates the mechanism of skin inflammation and can be used as a new treatment for skin inflammatory diseases. Full article

(This article belongs to the Special Issue Phytochemical Characterization and Medicinal Value of Natural Products)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

---

Figure 6

---

Figure 7

13 pages, 3792 KiB

Open AccessArticle

Oxymatrine Attenuates Ulcerative Colitis through Inhibiting Pyroptosis Mediated by the NLRP3 Inflammasome

by Jing Sun, Shuai Wang, Zhengtian Zhao, Jiaqi Lu, Yiming Zhang, Wen An, Wei Li, Li Yang and Xiaowei Tong

Molecules 2024, 29(12), 2897; https://doi.org/10.3390/molecules29122897 - 18 Jun 2024

Viewed by 336

Abstract

Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Sophora flavescens Aiton, which has many effects, such as anti-inflammation, anti-oxidative stress, and immunosuppression. This study aimed to investigate whether OMT could attenuate ulcerative colitis by inhibiting the NOD-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis. In this study, the UC rat models were established by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in vivo, while RAW264.7 cells and peritoneal macrophages were stimulated with Lipopolysaccharides/Adenosine Triphosphate (LPS/ATP) in vitro to simulate pyroptosis models, and Western blotting (WB) and other detection techniques were applied to analyze proteins involved in the NLRP3 inflammasome pathway. Our results showed that OMT alleviated colitis ulcers and pathological damage in the TNBS-induced UC rats and exhibited an inhibitory effect on pyroptosis at the early stage of UC. In the model group, the pyroptosis reached the peak at 24 h after modeling with the contents of active-cysteine-aspartic proteases-1 (caspase-1), Gasdermin D (GSDMD)-N, and cleaved-interleukin-1 beta (IL-1β) to the highest expression level. Meanwhile, we found that OMT (80 mg kg⁻¹) remarkably decreased the expression levels of NLRP3, active-caspase-1, and cleaved-IL-1β at 24 h in the lesion tissue from UC rats. Further experiments on cells demonstrated that OMT at concentrations of 100 and 250 μM significantly inhibited cell death caused by NLRP3 inflammasome activation (p < 0.05), downregulated caspase-1, GSDMD, and decreased the levels of active-caspase-1, GSDMD-N, cleaved-IL-1β in RAW326.7 cells, and peritoneal macrophages. In summary, these results indicated that OMT could attenuate ulcerative colitis through inhibiting pyroptosis mediated by the NLRP3 inflammasome. The inhibition of the NLRP3 inflammasome may be a potential strategy for UC. Full article

(This article belongs to the Special Issue Bioactive Compounds in Plant Extracts: Anti-inflammatory, Antioxidant, and Anticancer Properties and Applications)

► Show Figures

Figure 1

---

Figure 3

---

Figure 4

---

Figure 5

Abstract

Trueperella pyogenes is an important opportunistic pathogenic bacterium widely distributed in the environment. Pyolysin (PLO) is a primary virulence factor of T. pyogenes and capable of lysing many different cells. PLO is a member of the cholesterol-dependent cytolysin (CDC) family of which the primary structure only presents a low level of homology with other members from 31% to 45%. By deeply studying PLO, we can understand the overall pathogenic mechanism of CDC family proteins. This study established a mouse muscle tissue model infected with recombinant PLO (rPLO) and its single-point mutations, rPLO N139K and rPLO F240A, and explored its mechanism of causing inflammatory damage. The inflammatory injury abilities of rPLO N139K and rPLO F240A are significantly reduced compared to rPLO. This study elaborated on the inflammatory mechanism of PLO by examining its unit point mutations in detail. Our data also provide a theoretical basis and practical significance for future research on toxins and bacteria. Full article

Search Results (1,269)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (1,269)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI