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11 pages, 13036 KiB

Open AccessArticle

Vitamin D and Beta-Glucans Synergically Stimulate Human Macrophage Activity

by Loredana Bergandi, Giulia Apprato and Francesca Silvagno

Int. J. Mol. Sci. 2021, 22(9), 4869; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094869 - 04 May 2021

Cited by 5 | Viewed by 2985

Vitamin D and beta-glucans are both immunostimulants. Vitamin D exerts its beneficial effects on many components of the immune system. In macrophages, the hormone modulates both phagocytic activity and cytokine production; therefore, it plays an important role in mediating the innate immune response [...] Read more.

Vitamin D and beta-glucans are both immunostimulants. Vitamin D exerts its beneficial effects on many components of the immune system. In macrophages, the hormone modulates both phagocytic activity and cytokine production; therefore, it plays an important role in mediating the innate immune response to infection. The immunomodulatory properties of beta-glucans are attributed to the ability of these fungal cell wall polysaccharides to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes and macrophages. The intracellular signaling pathways activated by beta-glucans lead to enhanced phagocytosis and cytokine response. In this study we investigated the possible potentiation of immunomodulatory properties of the combined treatment with vitamin D and beta-glucans. The effects of 100 nM 1,25-dihydroxyvitamin D3 or 100 µg/mL beta-glucans were evaluated in human macrophages in terms of cytokine production, intracellular vesicle acidification and changes in energy metabolism, three hallmarks of macrophage antimicrobial activation. We found that all the analyzed parameters were enhanced by the co-treatment compared to the response to single molecules. The results of this study support the validity of a novel therapeutic approach that could boost the immune response, taking advantage of the synergy between two natural compounds. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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11 pages, 10002 KiB

Open AccessArticle

Protocatechuic Aldehyde Inhibits α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells via PKA/CREB-Associated MITF Downregulation

by Seok-Chun Ko and Seung-Hong Lee

Int. J. Mol. Sci. 2021, 22(8), 3861; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083861 - 08 Apr 2021

Cited by 17 | Viewed by 2722

Abstract

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis [...] Read more.

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of −527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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25 pages, 8280 KiB

Open AccessArticle

Marine Collagen Hydrolysates Promote Collagen Synthesis, Viability and Proliferation While Downregulating the Synthesis of Pro-Catabolic Markers in Human Articular Chondrocytes

by Bastien Bourdon, Frédéric Cassé, Nicolas Gruchy, Pierre Cambier, Sylvain Leclercq, Sarah Oddoux, Antoine Noël, Jérôme E. Lafont, Romain Contentin and Philippe Galéra

Int. J. Mol. Sci. 2021, 22(7), 3693; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073693 - 01 Apr 2021

Cited by 7 | Viewed by 3207

Abstract

Cartilage is a non-innervated and non-vascularized tissue. It is composed of one main cell type, the chondrocyte, which governs homeostasis within the cartilage tissue, but has low metabolic activity. Articular cartilage undergoes substantial stresses that lead to chondral defects, and inevitably osteoarthritis (OA) [...] Read more.

Cartilage is a non-innervated and non-vascularized tissue. It is composed of one main cell type, the chondrocyte, which governs homeostasis within the cartilage tissue, but has low metabolic activity. Articular cartilage undergoes substantial stresses that lead to chondral defects, and inevitably osteoarthritis (OA) due to the low intrinsic repair capacity of cartilage. OA remains an incurable degenerative disease. In this context, several dietary supplements have shown promising results, notably in the relief of OA symptoms. In this study, we investigated the effects of collagen hydrolysates derived from fish skin (Promerim^®30 and Promerim^®60) and fish cartilage (Promerim^®40) on the phenotype and metabolism of human articular chondrocytes (HACs). First, we demonstrated the safety of Promerim^® hydrolysates on HACs cultured in monolayers. Then we showed that, Promerim^® hydrolysates can increase the HAC viability and proliferation, while decreasing HAC SA-β-galactosidase activity. To evaluate the effect of Promerim^® on a more relevant model of culture, HAC were cultured as organoids in the presence of Promerim^® hydrolysates with or without IL-1β to mimic an OA environment. In such conditions, Promerim^® hydrolysates led to a decrease in the transcript levels of some proteases that play a major role in the development of OA, such as Htra1 and metalloproteinase-1. Promerim^® hydrolysates downregulated HtrA1 protein expression. In contrast, the treatment of cartilage organoids with Promerim^® hydrolysates increased the neosynthesis of type I collagen (Promerim^®30, 40 and 60) and type II collagen isoforms (Promerim^®30 and 40), the latter being the major characteristic component of the cartilage extracellular matrix. Altogether, our results demonstrate that the use of Promerim^® hydrolysates hold promise as complementary dietary supplements in combination with the current classical treatments or as a preventive therapy to delay the occurrence of OA in humans. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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30 pages, 6277 KiB

Open AccessArticle

Marine Collagen Hydrolysates Downregulate the Synthesis of Pro-Catabolic and Pro-Inflammatory Markers of Osteoarthritis and Favor Collagen Production and Metabolic Activity in Equine Articular Chondrocyte Organoids

by Bastien Bourdon, Romain Contentin, Frédéric Cassé, Chloé Maspimby, Sarah Oddoux, Antoine Noël, Florence Legendre, Nicolas Gruchy and Philippe Galéra

Int. J. Mol. Sci. 2021, 22(2), 580; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020580 - 08 Jan 2021

Cited by 20 | Viewed by 4334

Abstract

Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the [...] Read more.

Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen^® hydrolyzed fish collagens from skin (Promerim^®30 and Promerim^®60) and cartilage (Promerim^®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cytotoxicity and the beneficial effect of Promerim^® hydrolysates on eAC metabolic activity under physioxia; further, Promerim^®30 also delayed eAC senescence. To assess the effect of Promerim^® in a cartilage-like tissue, eACs were cultured as organoids under hypoxia with or without BMP-2 and/or IL-1β. In some instances, alone or in the presence of IL-1β, Promerim^®30 and Promerim^®40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely Htra1, and the metalloproteinases Mmp1-3, Adamts5, and Cox2. Both Promerim^® hydrolysates also decreased Htra1 protein amounts, particularly in inflammatory conditions. The effect of Promerim^® was enhanced under inflammatory conditions, possibly due to a decrease in the synthesis of inflammation-associated molecules. Finally, Promerim^® favored in vitro repair in a scratch wound assay through an increase in cell proliferation or migration. Altogether, these data show that Promerim^®30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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12 pages, 2573 KiB

Open AccessArticle

1-Cinnamoyltrichilinin from Melia azedarach Causes Apoptosis through the p38 MAPK Pathway in HL-60 Human Leukemia Cells

by Hoibin Jeong, SeonJu Park, Seo-Young Kim, Su-Hyeon Cho, Myeong Seon Jeong, Song-Rae Kim, Jong Bok Seo, Seung Hyun Kim and Kil-Nam Kim

Int. J. Mol. Sci. 2020, 21(20), 7506; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207506 - 12 Oct 2020

Cited by 10 | Viewed by 2259

Abstract

Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating [...] Read more.

Acute myeloid leukemia (AML) is an aggressive type of human leukemia with a low survival rate, and its complete remission remains challenging. Although chemotherapy is the first-line treatment of AML, it exerts toxicity in noncancerous cells when used in high doses, thus necessitating the development of novel compounds with a high therapeutic window. This study aimed to investigate the anticancer effects of several compounds derived from the fruits of Melia azedarach (a tree with medicinal properties). Among them, 1-cinnamoyltrichilinin (CT) was found to strongly suppress the viability of HL-60 human leukemia cells. CT treatment induced apoptosis and increased nuclear fragmentation and fractional DNA content in HL-60 cells in a dose-dependent manner. CT induced phosphorylation of p38 mitogen-activated protein kinases (p38), though not of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), and activated Bcl-2 family proteins towards the proapoptosis and cleavage of caspase-3 and poly (ADP-ribose) polymerase. Both CT-mediated apoptosis and apoptotic protein expression were reversed by treatment with the p38 inhibitor, thereby indicating the p38 pathway to be critical in CT-stimulated apoptosis. The results collectively indicated CT to suppress HL-60 survival by activating the p38 pathway and inducing apoptosis, hence being a novel potential therapeutic agent for AML. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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16 pages, 1990 KiB

Open AccessArticle

Protocatechuic Aldehyde Attenuates UVA-induced Photoaging in Human Dermal Fibroblast Cells by Suppressing MAPKs/AP-1 and NF-κB Signaling Pathways

by Yuling Ding, Chanipa Jiratchayamaethasakul and Seung-Hong Lee

Int. J. Mol. Sci. 2020, 21(13), 4619; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134619 - 29 Jun 2020

Cited by 25 | Viewed by 5659

Abstract

Ultraviolet radiation (UV) is a major causative factor of DNA damage, inflammatory responses, reactive oxygen species (ROS) generation and a turnover of various cutaneous lesions resulting in skin photoaging. The purpose of this study is to investigate the protective effect of protocatechuic aldehyde [...] Read more.

Ultraviolet radiation (UV) is a major causative factor of DNA damage, inflammatory responses, reactive oxygen species (ROS) generation and a turnover of various cutaneous lesions resulting in skin photoaging. The purpose of this study is to investigate the protective effect of protocatechuic aldehyde (PA), which is a nature-derived compound, against UVA-induced photoaging by using human dermal fibroblast (HDF) cells. In this study, our results indicated that PA significantly reduced the levels of intracellular ROS, nitric oxide (NO), and prostaglandins-E₂ (PGE₂) in UVA-irradiated HDF cells. It also inhibited the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Besides, PA significantly suppressed the expression of matrix metalloproteinases-1 (MMP-1) and pro-inflammatory cytokines and promoted collagen synthesis in the UVA-irradiated HDF cells. These events occurred through the regulation of activator protein 1 (AP-1), nuclear factor-κB (NF-κB), and p38 signaling pathways in UVA-irradiated HDF cells. Our findings suggest that PA enhances the protective effect of UVA-irradiated photoaging, which is associated with ROS scavenging, anti-wrinkle, and anti-inflammatory activities. Therefore, PA can be a potential candidate for the provision of a protective effect against UVA-stimulated photoaging in the pharmaceutical and cosmeceutical industries. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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Review

Jump to: Research

16 pages, 1285 KiB

Open AccessReview

Natural Polyphenols as Modulators of Etoposide Anti-Cancer Activity

by Magdalena Kluska and Katarzyna Woźniak

Int. J. Mol. Sci. 2021, 22(12), 6602; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126602 - 20 Jun 2021

Cited by 23 | Viewed by 3778

Abstract

Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and treatment of many human diseases, including cancer, have been known for years. Many anti-cancer drugs are derived from these natural compounds. [...] Read more.

Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and treatment of many human diseases, including cancer, have been known for years. Many anti-cancer drugs are derived from these natural compounds. Etoposide, which is a semi-synthetic derivative of podophyllotoxin, a non-alkaloid lignan isolated from the dried roots and rhizomes of Podophyllum peltatum or Podophyllum emodi (Berberidaceae), is an example of such a compound. In this review, we present data on the effects of polyphenols on the anti-cancer activity of etoposide in in vitro and in vivo studies. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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24 pages, 1747 KiB

Open AccessReview

Epigallocatechin Gallate for Management of Heavy Metal-Induced Oxidative Stress: Mechanisms of Action, Efficacy, and Concerns

by Iwona Zwolak

Int. J. Mol. Sci. 2021, 22(8), 4027; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084027 - 14 Apr 2021

Cited by 39 | Viewed by 3827

Abstract

In this review, we highlight the effects of epigallocatechin gallate (EGCG) against toxicities induced by heavy metals (HMs). This most active green tea polyphenol was demonstrated to reduce HM toxicity in such cells and tissues as testis, liver, kidney, and neural cells. Several [...] Read more.

In this review, we highlight the effects of epigallocatechin gallate (EGCG) against toxicities induced by heavy metals (HMs). This most active green tea polyphenol was demonstrated to reduce HM toxicity in such cells and tissues as testis, liver, kidney, and neural cells. Several protective mechanisms that seem to play a pivotal role in EGCG-induced effects, including reactive oxygen species scavenging, HM chelation, activation of nuclear factor erythroid 2-related factor 2 (Nrf2), anti-inflammatory effects, and protection of mitochondria, are described. However, some studies, especially in vitro experiments, reported potentiation of harmful HM actions in the presence of EGCG. The adverse impact of EGCG on HM toxicity may be explained by such events as autooxidation of EGCG, EGCG-mediated iron (Fe³⁺) reduction, depletion of intracellular glutathione (GSH) levels, and disruption of mitochondrial functions. Furthermore, challenges hampering the potential EGCG application related to its low bioavailability and proper dosing are also discussed. Overall, in this review, we point out insights into mechanisms that might account for both the beneficial and adverse effects of EGCG in HM poisoning, which may have a bearing on the design of new therapeutics for HM intoxication therapy. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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27 pages, 1759 KiB

Open AccessReview

The Potential Anticancer Activity of Phytoconstituents against Gastric Cancer—A Review on In Vitro, In Vivo, and Clinical Studies

by Sylwia Nakonieczna, Aneta Grabarska and Wirginia Kukula-Koch

Int. J. Mol. Sci. 2020, 21(21), 8307; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218307 - 05 Nov 2020

Cited by 12 | Viewed by 3011

Abstract

Gastric cancer belongs to the heterogeneous malignancies and, according to the World Health Organization, it is the fifth most commonly diagnosed cancer in men. The aim of this review is to provide an overview on the role of natural products of plant origin [...] Read more.

Gastric cancer belongs to the heterogeneous malignancies and, according to the World Health Organization, it is the fifth most commonly diagnosed cancer in men. The aim of this review is to provide an overview on the role of natural products of plant origin in the therapy of gastric cancer and to present the potentially active metabolites which can be used in the natural therapeutical strategies as the support to the conventional treatment. Many of the naturally spread secondary metabolites have been proved to exhibit chemopreventive properties when tested on the cell lines or in vivo. This manuscript aims to discuss the pharmacological significance of both the total extracts and the single isolated metabolites in the stomach cancer prevention and to focus on their mechanisms of action. A wide variety of plant-derived anticancer metabolites from different groups presented in the manuscript that include polyphenols, terpenes, alkaloids, or sulphur-containing compounds, underlines the multidirectional nature of natural products. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy)

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