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19 pages, 5089 KiB

Open AccessArticle

Dieckol Inhibits Autophagic Flux and Induces Apoptotic Cell Death in A375 Human Melanoma Cells via Lysosomal Dysfunction and Mitochondrial Membrane Impairment

by Min-Hee Jo, Yong-Tae Kim and Sun Joo Park

Int. J. Mol. Sci. 2022, 23(22), 14149; https://doi.org/10.3390/ijms232214149 - 16 Nov 2022

Cited by 9 | Viewed by 1615

Abstract

Dieckol is a natural brown algal-derived polyphenol and its cytotoxic potential against various types of cancer cells has been studied. However, the effects of dieckol on autophagy in cancer cells remain unknown. Here, we show that dieckol inhibits the growth of A375 human [...] Read more.

Dieckol is a natural brown algal-derived polyphenol and its cytotoxic potential against various types of cancer cells has been studied. However, the effects of dieckol on autophagy in cancer cells remain unknown. Here, we show that dieckol inhibits the growth of A375 human melanoma cells by inducing apoptotic cell death, which is associated with lysosomal dysfunction and the inhibition of autophagic flux. Dieckol induces autophagosome accumulation by inhibiting autophagosome-lysosome fusion. Moreover, dieckol not only triggers lysosomal membrane permeabilization, followed by an increase in lysosomal pH and the inactivation of cathepsin B and D, but also causes the loss of mitochondrial membrane potential. Importantly, a cathepsin D inhibitor partially relieved dieckol-induced mitochondrial membrane impairment and caspase-mediated apoptosis. Collectively, our findings indicate that dieckol is a novel autophagy inhibitor that induces apoptosis-mediated cell death via lysosomal dysfunction and mitochondrial membrane impairment in A375 human melanoma cells. This suggests the novel potential value of dieckol as a chemotherapeutic drug candidate for melanoma treatment. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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15 pages, 3852 KiB

Open AccessArticle

Hair-Growth-Promoting Effects of the Fish Collagen Peptide in Human Dermal Papilla Cells and C57BL/6 Mice Modulating Wnt/β-Catenin and BMP Signaling Pathways

by Su Bin Hwang, Hyeon Ju Park and Bog-Hieu Lee

Int. J. Mol. Sci. 2022, 23(19), 11904; https://doi.org/10.3390/ijms231911904 - 7 Oct 2022

Cited by 21 | Viewed by 7239

Abstract

Fish-derived collagen has recently emerged as an alternative collagen source with bioactive properties, including the enhancement of hair and skin health. It is also cost-effective and has high bioavailability, in addition to having fewer side-effects compared to collagen from porcine skin or bovine [...] Read more.

Fish-derived collagen has recently emerged as an alternative collagen source with bioactive properties, including the enhancement of hair and skin health. It is also cost-effective and has high bioavailability, in addition to having fewer side-effects compared to collagen from porcine skin or bovine skin. Collagen peptides (CPs) extracted from the scales of Mozambique tilapia (Oreochromis mossambicus) reportedly promote hair and skin health. This study sought to evaluate the effects of CPs on hair growth using in vitro and in vivo models. CP significantly enhanced hair regrowth and the proliferation of human dermal papilla cells (hDPCs) in vitro. CP was orally administered to C57BL/6 mice for 6 weeks to confirm the hair-growth-promoting effects. The mice were divided into four groups: negative control (distilled water), positive control (1 mg/kg of finasteride), CP500 (500 mg/kg of CP), and CP1000 (1000 mg/kg of CP). CP treatment significantly enhanced the proliferation of hDPCs compared to 0.2 μM finasteride, in addition to enhancing hair regrowth. Particularly, CP1000 treatment achieved a hair-growth index similar to that of the PC. In H&E staining, the CP groups exhibited a high A/T ratio. Furthermore, CP increased the expression of hair growth factors (IGF-1, VEGF, krt27, Gprc5d, and Ki67) and decreased the growth inhibitory factor (TGF-β1). Furthermore, CP significantly upregulated the Wnt/β-catenin pathways and downregulated the BMP pathways. Therefore, these results indicate that CP could be used as food supplements and nutraceuticals for hair loss prevention as well as hair regrowth during alopecia. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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14 pages, 2694 KiB

Open AccessArticle

Pepper Alkaloid Piperine Increases Radiation Sensitivity of Cancer Cells from Glioblastoma and Hypopharynx In Vitro

by Sascha Diehl, Guido Hildebrandt and Katrin Manda

Int. J. Mol. Sci. 2022, 23(15), 8548; https://doi.org/10.3390/ijms23158548 - 1 Aug 2022

Cited by 3 | Viewed by 1788

Abstract

In our study, our aim was to examine the cytotoxic and radio-sensitizing effect of the alkaloid piperine, a major pungent of black pepper, on two different human epithelial tumor cell lines in vitro. The growth of the human cell lines T98G (glioblastoma) and [...] Read more.

In our study, our aim was to examine the cytotoxic and radio-sensitizing effect of the alkaloid piperine, a major pungent of black pepper, on two different human epithelial tumor cell lines in vitro. The growth of the human cell lines T98G (glioblastoma) and FaDu (hypopharyngeal carcinoma) was examined under the influence of piperine in different concentrations. In addition, after combined treatment with ionizing radiation, long-term survival was investigated with a colony formation assay. The proliferation was analyzed using the BrdU-assay, while the DNA repair capacity was examined via the γH2AX assay. Piperine reduced the growth of both cell lines in a concentration-dependent manner as well as a time-dependent one. After combined treatment with piperine and ionizing radiation, an inhibition of clonogenic survival could be proven. A reduced proliferation capacity and an additive effect on DNA damage 24 h after irradiation are possible causal mechanisms, which were also demonstrated for both cell lines. Based on the results presented in this study, piperine was shown to have cytotoxic antitumor activity and a radio-sensitizing effect in micromolar concentrations in the human tumor cells that were tested. Based on these results piperine represents a potential therapeutic option in radio-oncological treatment. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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11 pages, 2888 KiB

Open AccessArticle

Co-Application with Tannic Acid Prevents Transdermal Sensitization to Ovalbumin in Mice

by Eri Izumi, Nana Tanahashi, Serina Kinugasa, Shota Hidaka, Nobuhiro Zaima and Tatsuya Moriyama

Int. J. Mol. Sci. 2022, 23(7), 3933; https://doi.org/10.3390/ijms23073933 - 1 Apr 2022

Cited by 2 | Viewed by 2371

Abstract

Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic [...] Read more.

Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic stromal lymphopoietin and thymus and activation-regulated chemokine are also involved. In this study, we investigated the suppressive effect of tannic acid (TA) on transdermal sensitization using ovalbumin (OVA), a major egg-white allergen. We also analyzed the mechanisms associated with the inhibitory effects of TA. The results showed that the co-application with TA prevents transdermal sensitization to OVA. As possible mechanisms, its anti-inflammatory and astringent effect on the skin and binding ability with the protein were considered. These results indicate that TA could be applied to cosmetics and lotions, which could suppress the transdermal sensitization to allergens. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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28 pages, 14018 KiB

Open AccessArticle

The Nutritional Supplement L-Alpha Glycerylphosphorylcholine Promotes Atherosclerosis

by Zeneng Wang, Jennie Hazen, Xun Jia, Elin Org, Yongzhong Zhao, Lucas J. Osborn, Nisreen Nimer, Jennifer Buffa, Miranda K. Culley, Daniel Krajcik, Bert-Jan H. van den Born, Koos Zwinderman, Bruce S. Levison, Max Nieuwdorp, Aldons J. Lusis, Joseph A. DiDonato and Stanley L. Hazen

Int. J. Mol. Sci. 2021, 22(24), 13477; https://doi.org/10.3390/ijms222413477 - 15 Dec 2021

Cited by 16 | Viewed by 7271

Abstract

L-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic [...] Read more.

L-alpha glycerylphosphorylcholine (GPC), a nutritional supplement, has been demonstrated to improve neurological function. However, a new study suggests that GPC supplementation increases incident stroke risk thus its potential adverse effects warrant further investigation. Here we show that GPC promotes atherosclerosis in hyperlipidemic Apoe^−/− mice. GPC can be metabolized to trimethylamine N-oxide, a pro-atherogenic agent, suggesting a potential molecular mechanism underlying the observed atherosclerosis progression. GPC supplementation shifted the gut microbial community structure, characterized by increased abundance of Parabacteroides, Ruminococcus, and Bacteroides and decreased abundance of Akkermansia, Lactobacillus, and Roseburia, as determined by 16S rRNA gene sequencing. These data are consistent with a reduction in fecal and cecal short chain fatty acids in GPC-fed mice. Additionally, we found that GPC supplementation led to an increased relative abundance of choline trimethylamine lyase (cutC)-encoding bacteria via qPCR. Interrogation of host inflammatory signaling showed that GPC supplementation increased expression of the proinflammatory effectors CXCL13 and TIMP-1 and activated NF-κB and MAPK signaling pathways in human coronary artery endothelial cells. Finally, targeted and untargeted metabolomic analysis of murine plasma revealed additional metabolites associated with GPC supplementation and atherosclerosis. In summary, our results show GPC promotes atherosclerosis through multiple mechanisms and that caution should be applied when using GPC as a nutritional supplement. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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14 pages, 3130 KiB

Open AccessArticle

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

by Madamanchi Geethangili, Chiao-Wei Lin, Harry J. Mersmann and Shih-Torng Ding

Int. J. Mol. Sci. 2021, 22(18), 10062; https://doi.org/10.3390/ijms221810062 - 17 Sep 2021

Cited by 13 | Viewed by 3312

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results [...] Read more.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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Review

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21 pages, 1431 KiB

Open AccessReview

Camel (Camelus spp.) Urine Bioactivity and Metabolome: A Systematic Review of Knowledge Gaps, Advances, and Directions for Future Research

by Carlos Iglesias Pastrana, Juan Vicente Delgado Bermejo, Maria Noemi Sgobba, Francisco Javier Navas González, Lorenzo Guerra, Diana C. G. A. Pinto, Ana M. Gil, Iola F. Duarte, Giovanni Lentini and Elena Ciani

Int. J. Mol. Sci. 2022, 23(23), 15024; https://doi.org/10.3390/ijms232315024 - 30 Nov 2022

Cited by 5 | Viewed by 7243

Abstract

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence [...] Read more.

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis. Additionally, medium osmolarity is not experimentally adjusted prior to bioactivity assays. In this scenario, the methodological standardization and interdisciplinary approach of such processes will strengthen the interpretation, repeatability, and replicability of the empirical results on the compounds with bioactive properties present in camel urine. Furthermore, sample enlargement would also permit the evaluation of camel urine’s intra- and interindividual variability in terms of chemical composition, bioactive effects, and efficacy, while it may also permit researchers to discriminate potential animal-intrinsic and extrinsic conditioning factors. Altogether, the results would help to evaluate the role of camel urine as a natural source for the identification and extraction of specific novel bioactive substances that may deserve isolated chemical and pharmacognostic investigations through preclinical tests to determine their biological activity and the suitability of their safety profile for their potential inclusion in therapeutic formulas for improving human and animal health. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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17 pages, 835 KiB

Open AccessReview

Current Development and Future Application Prospects of Plants-Derived Polyphenol Bioactive Substance Curcumin as a Novel Feed Additive in Livestock and Poultry

by Shifeng Pan, Jie Yan, Xingyu Xu, Yongfang Chen, Xinyu Chen, Fei Li and Hua Xing

Int. J. Mol. Sci. 2022, 23(19), 11905; https://doi.org/10.3390/ijms231911905 - 7 Oct 2022

Cited by 13 | Viewed by 2613

Abstract

Curcumin (CUR) is a kind of natural orange-yellow phenolic compound mainly extracted from the stems and roots of turmeric plants and other species in the genus Curcuma, furthermore, it is also the most important active ingredient exerting pharmacological functions in turmeric. In [...] Read more.

Curcumin (CUR) is a kind of natural orange-yellow phenolic compound mainly extracted from the stems and roots of turmeric plants and other species in the genus Curcuma, furthermore, it is also the most important active ingredient exerting pharmacological functions in turmeric. In recent years, CUR has been frequently reported and has attracted widespread attention from scholars all over the world due to its numerous biological functions and good application prospects, such as anti-inflammatory, anticancer, antioxidant and providing lipid-lowering effects, etc. In addition, adding a certain dose of CUR to livestock and poultry feed is important for animal growth and development, which plays a key role in animal metabolism, reproduction, immunity and clinical health care. This review aims to summarize, based on the published papers and our own observations, the physical and chemical properties and the biological functions of the plant-derived bioactive ingredient CUR, especially regarding the latest research progress in regulating intestinal health as well as its current development and future application prospects in livestock and poultry as a novel feed additive, so as to provide theoretical and practical references for the further study of the application of CUR as a novel feed additive and a potential new antibiotic substitute, thereby improving the research field of plant-derived bioactive ingredients and promoting the healthy development of livestock and poultry. Full article

(This article belongs to the Special Issue Advances in Natural Products for Application in Biomedicine and Pharmacotherapy 2.0)

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