Nutrients

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12 pages, 5738 KiB

Open AccessArticle

Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype

by Bo-Young Kim, Ji Hyeon Ryu, Jisu Park, Byeongjun Ji, Hyun Soo Chun, Min Sun Kim and Yong-Il Shin

Nutrients 2023, 15(12), 2750; https://doi.org/10.3390/nu15122750 - 14 Jun 2023

Cited by 1 | Viewed by 1855

Abstract

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing [...] Read more.

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels—similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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17 pages, 3659 KiB

Open AccessArticle

Antioxidative and Anti-Inflammatory Activities of Rosebud Extracts of Newly Crossbred Roses

by Cuicui Wang, In-Jeong Kim, Hye-Rim Seong, Chan Ho Noh, Sangryong Park, Tae Myoung Kim, Heon Sang Jeong, Ka Young Kim, Seung Tae Kim, Hyun-Gyun Yuk, Sang-Chul Kwon, Ehn-Kyoung Choi and Yun-Bae Kim

Nutrients 2023, 15(10), 2376; https://doi.org/10.3390/nu15102376 - 19 May 2023

Viewed by 1645

Abstract

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury and pain, as well as acute and chronic diseases. Since long-term uses of synthetic steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects [...] Read more.

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury and pain, as well as acute and chronic diseases. Since long-term uses of synthetic steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) was found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. In a subcutaneous air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells, and inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a representative steroid). Notably, PVRE also inhibited PGE₂, similar to dexamethasone and indomethacin (a representative NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS—NO and COX-2—PG pathways, and that PVRE could be a potential candidate as an anti-inflammatory material for diverse tissue injuries. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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19 pages, 13905 KiB

Open AccessArticle

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

by Ke Fu, Yanzhi Li, Shu Dai and Yunxia Li

Nutrients 2023, 15(9), 2065; https://doi.org/10.3390/nu15092065 - 25 Apr 2023

Cited by 4 | Viewed by 1709

Abstract

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through [...] Read more.

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p-NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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19 pages, 3080 KiB

Open AccessArticle

Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation

by Rawan Nehme, Arthur Chervet, Caroline Decombat, Lucie Longechamp, Adrien Rossary, Rebecca Boutin, Amandine Rousset, François Senejoux, Caroline Vachias, Céline Auxenfans, Didier Fraisse, Jean-Baptiste Guyon, Edith Filaire, Jean-Yves Berthon, Mona Diab-Assaf, Laetitia Delort and Florence Caldefie-Chezet

Nutrients 2023, 15(7), 1751; https://doi.org/10.3390/nu15071751 - 3 Apr 2023

Cited by 2 | Viewed by 2606

Abstract

Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis—a plant widely consumed as Rooibos tea—are increasingly being [...] Read more.

Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis—a plant widely consumed as Rooibos tea—are increasingly being investigated for their positive effects on various health issues including inflammation. The aim of our study was to examine the effect of Rooibos extract on obesity and the associated low-grade chronic inflammatory state by testing antioxidant activity, cytokine secretions, macrophage polarization and the differentiation of human adipocytes through the development of adipospheroids. Rooibos extract significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFN-γ, IL-12, IL-2 and IL-17a) in human leukocytes. Additionally, Rooibos extract down-regulated LPS-induced macrophage M1 polarization, shown by a significant decrease in the expression of pro-inflammatory cytokines: TNFα, IL-8, IL-6, IL-1β and CXCL10. In addition, Rooibos inhibited intracellular lipid accumulation and reduced adipogenesis by decreasing the expression of PPARγ, Ap2 and HSL in adipospheroids. A significant decrease in leptin expression was noted and this, more interestingly, was accompanied by a significant increase in adiponectin expression. Using a co-culture system between macrophages and adipocytes, Rooibos extract significantly decreased the expression of all studied pro-inflammatory cytokines and particularly leptin, and increased adiponectin expression. Thus, adding Rooibos tea to the daily diet is likely to prevent the development of obesity associated with chronic low-level inflammation. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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15 pages, 2775 KiB

Open AccessArticle

Rutin, a Flavonoid Compound Derived from Garlic, as a Potential Immunomodulatory and Anti-Inflammatory Agent against Murine Schistosomiasis mansoni

by Rabab S. Hamad

Nutrients 2023, 15(5), 1206; https://doi.org/10.3390/nu15051206 - 28 Feb 2023

Cited by 4 | Viewed by 2200

Abstract

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its [...] Read more.

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its efficacy. The current study investigated the possible immunomodulatory and anti-inflammatory action of rutin, a natural flavonoid compound isolated from garlic, on liver fibrotic markers in mice infected with S. mansoni in comparison to PZQ. Male albino CD1 mice were infected with 100 ± 2 S. mansoni cercariae/mouse and treated with garlic, rutin, or PZQ. At the end of the experiment, the liver and intestines were harvested for parasitological and histological assessment and to analyze the proinflammatory cytokine. Rutin significantly affects the pathological alterations caused by Schistosoma in the liver. This may be partially explained by a decrease in the number of eggs trapped in the tissues of the liver and a modification in the serum levels of certain cytokines, which are implicated in the formation of Schistosoma granuloma. In conclusion, rutin has strong anti-schistosome properties in vivo, raising the possibility that rutin might be further investigated as a therapy for S. mansoni. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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16 pages, 2297 KiB

Open AccessArticle

Fermented Lettuce Extract Containing Nitric Oxide Metabolites Attenuates Inflammatory Parameters in Model Mice and in Human Fibroblast-Like Synoviocytes

by Jisu Park, Ji Hyeon Ryu, Bo-Young Kim, Hyun Soo Chun, Min Sun Kim and Yong-Il Shin

Nutrients 2023, 15(5), 1106; https://doi.org/10.3390/nu15051106 - 23 Feb 2023

Cited by 2 | Viewed by 2817

Abstract

Lettuce (Lactuca sativa L.) contains various bioactive compounds that can reduce the severity of inflammatory diseases. This study aimed to identify therapeutic effects and underlying mechanisms of fermented lettuce extract (FLE) containing stable nitric oxide (NO) on collagen-induced arthritis (CIA) in mice [...] Read more.

Lettuce (Lactuca sativa L.) contains various bioactive compounds that can reduce the severity of inflammatory diseases. This study aimed to identify therapeutic effects and underlying mechanisms of fermented lettuce extract (FLE) containing stable nitric oxide (NO) on collagen-induced arthritis (CIA) in mice and fibroblast-like synoviocytes (MH7A line) from patients with rheumatoid arthritis (RA). DBA/1 mice were immunized with bovine type II collagen and orally administered FLE for 14 days. On day 36, mouse sera and ankle joints were collected for serological and histological analysis, respectively. Consuming FLE inhibited RA development, suppressing pro-inflammatory cytokine productions, synovial inflammation, and cartilage degradation. The therapeutic effects of FLE in CIA mice were similar to those of methotrexate (MTX), which is typically used to treat RA. In vitro, FLE suppressed the transforming growth factor-β (TGF-β)/Smad signaling pathway in MH7A cells. We also demonstrated that FLE inhibited TGF-β-induced cell migration, suppressed MMP-2/9 expression, inhibited MH7A cell proliferation, and increased the expression of autophagy markers LC3B and p62 in a dose-dependent manner. Our data suggest that FLE could induce autophagosome formations in the early of stages of autophagy while inhibiting their degradation in the later stages. In conclusion, FLE is a potential therapeutic agent for RA. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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15 pages, 4332 KiB

Open AccessArticle

Anti-Inflammatory Effect of Garcinol Extracted from Garcinia dulcis via Modulating NF-κB Signaling Pathway

by Pathanin Chantree, Pongsakorn Martviset, Nattaya Thongsepee, Kant Sangpairoj and Phornphan Sornchuer

Nutrients 2023, 15(3), 575; https://doi.org/10.3390/nu15030575 - 22 Jan 2023

Cited by 6 | Viewed by 2796

Abstract

Garcinia is a significant medicinal plant with many beneficial phytoconstituents, including garcinol. This study investigated the anti-inflammatory effect of garcinol isolated from Garcinia dulcis fruit in LPS-activated THP-1 and Raw 264.7 macrophages. The results demonstrated that the low concentration of garcinol did not [...] Read more.

Garcinia is a significant medicinal plant with many beneficial phytoconstituents, including garcinol. This study investigated the anti-inflammatory effect of garcinol isolated from Garcinia dulcis fruit in LPS-activated THP-1 and Raw 264.7 macrophages. The results demonstrated that the low concentration of garcinol did not alter cell viability. Furthermore, co-incubation of garcinol with LPS inhibited the production of pro-inflammatory cytokines, including TNF-α, IL-8, IL-6, IL-1β, and pro-inflammatory mediators, including iNOS and COX-2 at the mRNA and protein expression levels. Garcinol also decreased the secretion of TNF-α, IL-6, IL-1β, PGE2, and NO. Moreover, the anti-inflammatory effects involved an alteration in the NF-κB signaling pathway. Downregulation of pIKKα/β, pIκBα, and pNF-κB was observed, hence reducing the translocation of pNF-κB from the cytosol into the nucleus, which subsequently decreased the production of pro-inflammatory molecules. Therefore, garcinol isolated from Garcinia dulcis is a potential candidate as an anti-inflammatory agent for inflammation-related disease treatment. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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17 pages, 7426 KiB

Open AccessArticle

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

by Feng Zhang, Mengyao Wang, Yang Zha, Jie Zhou, Jihong Han and Shuang Zhang

Nutrients 2023, 15(1), 223; https://doi.org/10.3390/nu15010223 - 1 Jan 2023

Cited by 11 | Viewed by 3403

Abstract

Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) [...] Read more.

Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti−inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF−κB)/NOD−like receptor protein−3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF−κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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18 pages, 3537 KiB

Open AccessArticle

Phytate Hydrolysate Differently Modulates the Immune Response of Human Healthy and Cancer Colonocytes to Intestinal Bacteria

by Lidia Hanna Markiewicz, Anna Maria Ogrodowczyk, Wiesław Wiczkowski and Barbara Wróblewska

Nutrients 2022, 14(20), 4234; https://doi.org/10.3390/nu14204234 - 11 Oct 2022

Cited by 5 | Viewed by 1822

Abstract

(1) Phytic acid (PA) is a component of cereal seeds and legumes, therefore its consumption is much higher in a vegan and vegetarian diet compared to a conventional diet. The diet is the main driver of metabolic activity of gut microbiota, therefore, the [...] Read more.

(1) Phytic acid (PA) is a component of cereal seeds and legumes, therefore its consumption is much higher in a vegan and vegetarian diet compared to a conventional diet. The diet is the main driver of metabolic activity of gut microbiota, therefore, the ability to degrade phytates by the microbiota of vegans significantly exceeds that of the gut microbiota of omnivores. The aim of the study was to investigate the early phase of the immune response of colonocytes treated with an enzymatic hydrolysate of phytic acid (hPA120) and gut bacteria. (2) Cell lines derived from healthy (NCM460D) and cancer (HCT116) colonic tissue and fecal bacteria from vegan (V) and omnivorous (O) donors were investigated. Fecal bacteria were grown in mucin and phytic acid supplemented medium. Cultured bacteria (BM) were loaded onto colonocytes alone (V BM and O BM) or in combination with the phytate hydrolysate (V BM + hPA120 and O BM + hPA120). After a treatment of 2 h, bacterial adhesion, secretion of cytokines, and the expression of genes and proteins important for immune response were determined. (3) All bacteria-treated colonocytes increased the expression of IL8 compared to controls. The significant increase of the secreted IL-8 (p < 0.01) in both cell lines was observed for O BM and O BM + hPA120. The increase of TNF, IL-1β, and IL-10 secretion in healthy colonocytes (V BM alone and with hPA120 treatments; p < 0.05) and for TNF and IL-10 in cancer cells (treatments except O BM + hPA120 and V BM, respectively; p > 0.05) were stated. A comparison of solely the effect of hPA120 on bacteria-treated colonocytes (BM vs. BM + hPA120) showed that hPA120 decreased expression of NFkB1 and TNFR (p < 0.001) in healthy colonocytes. In cancer colonocytes, the expression of TLR4 and IL1R increased after BM + hPA120 treatment, whereas the secretion of IL-8 and MYD88 and TNFR expression decreased (p < 0.01). (4) The investigated hPA120 showed a differentiated modulatory activity on the immune response of healthy and cancer human colonocytes. Especially when analyzed independently on the gut bacteria origin, it reduced the proinflammatory response of HCT116 cells to gut bacteria, while being neutral for the bacteria-treated healthy colonocytes. Full article

(This article belongs to the Special Issue Anti-inflammatory and Immunomodulatory Properties of Plant Food Bioactives)

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