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15 pages, 3028 KiB

Open AccessArticle

Rosa canina L. Methanol Extract and Its Component Rutin Reduce Cholesterol More Efficiently than Miglustat in Niemann–Pick C Fibroblasts

by Dalanda Wanes, Sherin Al Aoua, Hadeel Shammas, Friederike Walters, Anibh M. Das, Sandra Rizk and Hassan Y. Naim

Int. J. Mol. Sci. 2024, 25(21), 11361; https://doi.org/10.3390/ijms252111361 - 22 Oct 2024

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Abstract

Niemann–Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder where 95% of the cases are caused by mutations in the Niemann–Pick C1 (NPC1) gene. Loss of function in NPC1 mutants trigger the accumulation of cholesterol in late endo-lysosomes and lysosomal [...] Read more.

Niemann–Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder where 95% of the cases are caused by mutations in the Niemann–Pick C1 (NPC1) gene. Loss of function in NPC1 mutants trigger the accumulation of cholesterol in late endo-lysosomes and lysosomal dysfunction. The current study examined the potential of polyphenol-rich methanol extracts from Rosa canina L. (RCME) and two of its components, rutin and quercitrin, to enhance protein trafficking of NPC1 and restore cholesterol levels in fibroblasts derived from NPC patients, in comparison with miglustat, a drug approved in Europe for NPC treatment. Interestingly, RCME improved the trafficking of the compound heterozygous mutant NPC1^I1061T/P887L, homozygous mutant NPC1^R1266Q, and heterozygous mutant NPC1^N1156S between the endoplasmic reticulum and the Golgi and significantly reduced the levels of cellular cholesterol in the cell lines examined. Miglustat did not affect the trafficking of the three NPC1 mutants individually nor in combination with RCME. Markedly, rutin and quercitrin exerted their effects on cholesterol, but not in the trafficking pathway of NPC1, indicating that other components in RCME are implicated in regulating the trafficking of NPC1 mutants. By virtue of its dual function in targeting the trafficking of mutants of NPC1 as well as the cholesterol contents, RCME is more beneficial than available drugs that target substrate reduction and should be therefore considered in further studies for its feasibility as a therapeutic agent for NPC patients. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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21 pages, 9245 KiB

Open AccessArticle

6-Gingerol Inhibits De Novo Lipogenesis by Targeting Stearoyl-CoA Desaturase to Alleviate Fructose-Induced Hepatic Steatosis

by Pan Li, Tingting Wang, Hongmei Qiu, Ruoyu Zhang, Chao Yu and Jianwei Wang

Int. J. Mol. Sci. 2024, 25(20), 11289; https://doi.org/10.3390/ijms252011289 - 20 Oct 2024

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Abstract

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber [...] Read more.

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber officinale Roscoe) in traditional Chinese medicine (TCM), can alleviate fructose-induced hepatic steatosis. It was found that 6-G significantly decreased hyperlipidemia caused by high-fructose diets (HFD) in rats, and reversed the increase in hepatic de novo lipogenesis (DNL) and triglyceride (TG) levels induced by HFD, both in vivo and in vitro. Mechanistically, chemical proteomics and cellular thermal shift assay (CETSA)–proteomics approaches revealed that stearoyl-CoA desaturase (SCD) is a direct binding target of 6-G, which was confirmed by further CETSA assay and molecular docking. Meanwhile, it was found that 6-G could not alter SCD expression (in either mRNA or protein levels), but inhibited SCD activity (decreasing the desaturation levels of fatty acids) in HFD-fed rats. Furthermore, SCD deficiency mimicked the ability of 6-G to reduce lipid accumulation in HF-induced HepG2 cells, and impaired the improvement in hepatic steatosis brought about by 6-G treatment in HFD supplemented with oleic acid diet-induced SCD1 knockout mice. Taken together, our present study demonstrated that 6-G inhibits DNL by targeting SCD to alleviate fructose diet-induced hepatic steatosis. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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14 pages, 3014 KiB

Open AccessArticle

Effects of Dietary Yeast β-1,3/1,6-D-Glucan on Immunomodulation in RAW 264.7 Cells and Methotrexate-Treated Rat Models

by Joohee Son, Yeseul Hwang, Eun-Mi Hong, Marion Schulenberg, Hyungyung Chai, Hee-Geun Jo and Donghun Lee

Int. J. Mol. Sci. 2024, 25(20), 11020; https://doi.org/10.3390/ijms252011020 - 14 Oct 2024

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Abstract

A new subclass of nutraceuticals, called immunoceuticals, is dedicated to immunological regulation. Although yeast-derived β-1,3/1,6-D-glucan shows promise as an immunoceutical candidate, further studies are needed to define its precise immune-enhancing processes and to standardize its use. Following methotrexate (MTX)-induced immunosuppression in rats, we [...] Read more.

A new subclass of nutraceuticals, called immunoceuticals, is dedicated to immunological regulation. Although yeast-derived β-1,3/1,6-D-glucan shows promise as an immunoceutical candidate, further studies are needed to define its precise immune-enhancing processes and to standardize its use. Following methotrexate (MTX)-induced immunosuppression in rats, we evaluated the immunomodulatory efficacy of a highly pure and standardized β-1,3/1,6-D-glucan sample (YBG) in RAW 264.7 macrophages. In in vitro and in vivo models, YBG demonstrated remarkable immunomodulatory effects, such as repair of immune organ damage, elevation of blood cytokine levels, and enhanced phagocytosis and nitric oxide production in RAW 264.7 cells. These results are consistent with the established immunostimulatory properties of β-glucan. It is noteworthy that this research indicates the potential of YBG as an immunomodulatory nutraceutical, as it is among the first to demonstrate immunological augmentation in an immunosuppression setting produced by MTX. Based on these observations, further investigation of YBG is warranted, particularly given its potential to emerge as a combination immunoceutical to mitigate immunosuppression and reduce the risk of infection in rheumatoid arthritis (RA) patients receiving long-term MTX therapy. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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19 pages, 8744 KiB

Open AccessArticle

Cucurbitacin B Inhibits the Proliferation of WPMY-1 Cells and HPRF Cells via the p53/MDM2 Axis

by Yangtao Jin, Ping Zhou, Sisi Huang, Congcong Shao, Dongyan Huang, Xin Su, Rongfu Yang, Juan Jiang and Jianhui Wu

Int. J. Mol. Sci. 2024, 25(17), 9333; https://doi.org/10.3390/ijms25179333 - 28 Aug 2024

Cited by 1 | Viewed by 775

Abstract

Modern research has shown that Cucurbitacin B (Cu B) possesses various biological activities such as liver protection, anti-inflammatory, and anti-tumor effects. However, the majority of research has primarily concentrated on its hepatoprotective effects, with limited attention devoted to exploring its potential impact on [...] Read more.

Modern research has shown that Cucurbitacin B (Cu B) possesses various biological activities such as liver protection, anti-inflammatory, and anti-tumor effects. However, the majority of research has primarily concentrated on its hepatoprotective effects, with limited attention devoted to exploring its potential impact on the prostate. Our research indicates that Cu B effectively inhibits the proliferation of human prostate stromal cells (WPMY-1) and fibroblasts (HPRF), while triggering apoptosis in prostate cells. When treated with 100 nM Cu B, the apoptosis rates of WPMY-1 and HPRF cells reached 51.73 ± 5.38% and 26.83 ± 0.40%, respectively. In addition, the cell cycle assay showed that Cu B had a G2/M phase cycle arrest effect on WPMY-1 cells. Based on RNA-sequencing analysis, Cu B might inhibit prostate cell proliferation via the p53 signaling pathway. Subsequently, the related gene and protein expression levels were measured using quantitative real-time PCR (RT-qPCR), immunocytochemistry (ICC), and enzyme-linked immunosorbent assays (ELISA). Our results mirrored the regulation of tumor protein p53 (TP53), mouse double minute-2 (MDM2), cyclin D1 (CCND1), and thrombospondin 1 (THBS1) in Cu B-induced prostate cell apoptosis. Altogether, Cu B may inhibit prostate cell proliferation and correlate to the modulation of the p53/MDM2 signaling cascade. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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12 pages, 2539 KiB

Open AccessArticle

Talaroacids A–D and Talaromarane A, Diterpenoids with Anti-Inflammatory Activities from Mangrove Endophytic Fungus Talaromyces sp. JNQQJ-4

by Guisheng Wang, Jianying Wu, Zhaokun Li, Tao Chen, Yufeng Liu, Bo Wang, Yan Chen and Zhigang She

Int. J. Mol. Sci. 2024, 25(12), 6691; https://doi.org/10.3390/ijms25126691 - 18 Jun 2024

Cited by 1 | Viewed by 720

Abstract

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A–D (1–4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by [...] Read more.

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A–D (1–4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD). Talaromarane A (5) contains a rare 2-oxabicyclo [3.2.1] octan moiety in isopimarane diterpenoids. In bioassays, compounds 1, 2, 4, and 5 displayed significant anti-inflammatory activities with the IC₅₀ value from 4.59 to 21.60 μM. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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12 pages, 4510 KiB

Open AccessArticle

Preparation of Esterified Starches with Different Amylose Content and Their Blending with Polybutylene Succinate

by Shuning Liu, Shi Tang, Yuanhao Lu, Tingting Su and Zhanyong Wang

Int. J. Mol. Sci. 2024, 25(12), 6301; https://doi.org/10.3390/ijms25126301 - 7 Jun 2024

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Abstract

Three types of starch with different amylose content were esterified and blended with polybutylene succinate (PBS) to obtain esterified manioc starch/PBS (EMS/PBS), esterified corn starch/PBS (ECS/PBS), and esterified waxy corn starch/PBS (EWS/PBS) composites. The EMS/PBS and ECS/PBS composites with high amylose content displayed [...] Read more.

Three types of starch with different amylose content were esterified and blended with polybutylene succinate (PBS) to obtain esterified manioc starch/PBS (EMS/PBS), esterified corn starch/PBS (ECS/PBS), and esterified waxy corn starch/PBS (EWS/PBS) composites. The EMS/PBS and ECS/PBS composites with high amylose content displayed typical V-type crystal structures. The original crystals of EWS, which had low amylose content, were disrupted during the esterification process. EWS exhibited the strongest interaction with PBS and the most favorable interface compatibility. The pyrolysis temperature was in order of EMS/PBS < ECS/PBS < EWS/PBS. The elongation at break of the three blends was higher than that of pure PBS. The esterification and plasticization of the EWS/PBS composite were the most comprehensive. The EWS/PBS composite showed the lowest storage modulus (G’) and complex viscosity (η*). The interfacial bonding force of the composite materials increased with more amylopectin, decreasing intermolecular forces and destroying crystal structures, which decreased G’ and η* and increased toughness. The EWS/PBS composite, with the least amylose content, had the best hydrophobicity and degradation performance. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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18 pages, 4414 KiB

Open AccessArticle

Safflower CtFLS1-Induced Drought Tolerance by Stimulating the Accumulation of Flavonols and Anthocyanins in Arabidopsis thaliana

by Xintong Ma, Yuying Hou, Abdul Wakeel Umar, Yuhan Wang, Lili Yu, Naveed Ahmad, Na Yao, Min Zhang and Xiuming Liu

Int. J. Mol. Sci. 2024, 25(10), 5546; https://doi.org/10.3390/ijms25105546 - 19 May 2024

Cited by 3 | Viewed by 1043

Abstract

Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in [...] Read more.

Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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Review

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46 pages, 2723 KiB

Open AccessReview

Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer’s Disease

by Jolanta Flieger, Alicja Forma, Wojciech Flieger, Michał Flieger, Piotr J. Gawlik, Eliasz Dzierżyński, Ryszard Maciejewski, Grzegorz Teresiński and Jacek Baj

Int. J. Mol. Sci. 2024, 25(16), 8982; https://doi.org/10.3390/ijms25168982 - 18 Aug 2024

Cited by 1 | Viewed by 1565

Abstract

Alzheimer’s disease (AD) is characterized by, among other things, dementia and a decline in cognitive performance. In AD, dementia has neurodegenerative features and starts with mild cognitive impairment (MCI). Research indicates that apoptosis and neuronal loss occur in AD, in which oxidative stress [...] Read more.

Alzheimer’s disease (AD) is characterized by, among other things, dementia and a decline in cognitive performance. In AD, dementia has neurodegenerative features and starts with mild cognitive impairment (MCI). Research indicates that apoptosis and neuronal loss occur in AD, in which oxidative stress plays an important role. Therefore, reducing oxidative stress with antioxidants is a natural strategy to prevent and slow down the progression of AD. Carotenoids are natural pigments commonly found in fruits and vegetables. They include lipophilic carotenes, such as lycopene, α- and β-carotenes, and more polar xanthophylls, for example, lutein, zeaxanthin, canthaxanthin, and β-cryptoxanthin. Carotenoids can cross the blood–brain barrier (BBB) and scavenge free radicals, especially singlet oxygen, which helps prevent the peroxidation of lipids abundant in the brain. As a result, carotenoids have neuroprotective potential. Numerous in vivo and in vitro studies, as well as randomized controlled trials, have mostly confirmed that carotenoids can help prevent neurodegeneration and alleviate cognitive impairment in AD. While carotenoids have not been officially approved as an AD therapy, they are indicated in the diet recommended for AD, including the consumption of products rich in carotenoids. This review summarizes the latest research findings supporting the potential use of carotenoids in preventing and alleviating AD symptoms. A literature review suggests that a diet rich in carotenoids should be promoted to avoid cognitive decline in AD. One of the goals of the food industry should be to encourage the enrichment of food products with functional substances, such as carotenoids, which may reduce the risk of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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