International Journal of Molecular Sciences

Research

13 pages, 13375 KiB

Open AccessArticle

Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima)

by Fu Ou-Yang, I-Hsuan Tsai, Jen-Yang Tang, Ching-Yu Yen, Yuan-Bin Cheng, Ammad Ahmad Farooqi, Shu-Rong Chen, Szu-Yin Yu, Jun-Kai Kao and Hsueh-Wei Chang

Int. J. Mol. Sci. 2019, 20(13), 3238; https://doi.org/10.3390/ijms20133238 - 1 Jul 2019

Cited by 18 | Viewed by 4119 | Correction

Abstract

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa [...] Read more.

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

17 pages, 2279 KiB

Open AccessArticle

Dietary Supplementation with Sea Bass (Lateolabrax maculatus) Ameliorates Ulcerative Colitis and Inflammation in Macrophages through Inhibiting Toll-Like Receptor 4-Linked Pathways

by Jiali Chen, Muthukumaran Jayachandran, Wenxia Zhang, Lingyuqing Chen, Bin Du, Zhiling Yu and Baojun Xu

Int. J. Mol. Sci. 2019, 20(12), 2907; https://doi.org/10.3390/ijms20122907 - 14 Jun 2019

Cited by 25 | Viewed by 4523

Abstract

Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological [...] Read more.

Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

16 pages, 2708 KiB

Open AccessArticle

Skullcapflavone II Inhibits Degradation of Type I Collagen by Suppressing MMP-1 Transcription in Human Skin Fibroblasts

by Young Hun Lee, Eun Kyoung Seo and Seung-Taek Lee

Int. J. Mol. Sci. 2019, 20(11), 2734; https://doi.org/10.3390/ijms20112734 - 4 Jun 2019

Cited by 27 | Viewed by 6587

Abstract

Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, a herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in [...] Read more.

Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, a herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in foreskin fibroblasts. Skullcapflavone II did not affect the secretion of type I collagen but reduced the secretion of MMP-1 in a dose- and time-dependent manner. Real-time reverse transcription-PCR and reporter gene assays showed that skullcapflavone II reduced MMP-1 expression at the transcriptional level. Skullcapflavone II inhibited the serum-induced activation of the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways required for MMP-1 transactivation. Skullcapflavone II also reduced tumor necrosis factor (TNF)-α-induced nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activation and subsequent MMP-1 expression. In three-dimensional culture of fibroblasts, skullcapflavone II down-regulated TNF-α-induced MMP-1 secretion and reduced breakdown of type I collagen. These results indicate that skullcapflavone II is a novel biomolecule that down-regulates MMP-1 expression in foreskin fibroblasts and therefore could be useful in therapies for maintaining the integrity of extracellular matrix. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

14 pages, 1997 KiB

Open AccessArticle

In Vitro Study of the Anticancer Effects of Biotechnological Extracts of the Endangered Plant Species Satureja Khuzistanica

by Abbas Khojasteh, Isidoro Metón, Sergio Camino, Rosa M. Cusido, Regine Eibl and Javier Palazon

Int. J. Mol. Sci. 2019, 20(10), 2400; https://doi.org/10.3390/ijms20102400 - 15 May 2019

Cited by 13 | Viewed by 3526

Abstract

Many medicinal plant species are currently threatened in their natural habitats because of the growing demand for phytochemicals worldwide. A sustainable alternative for the production of bioactive plant compounds are plant biofactories based on cell cultures and organs. In addition, plant extracts from [...] Read more.

Many medicinal plant species are currently threatened in their natural habitats because of the growing demand for phytochemicals worldwide. A sustainable alternative for the production of bioactive plant compounds are plant biofactories based on cell cultures and organs. In addition, plant extracts from biofactories have significant advantages over those obtained from plants, since they are free of contamination by microorganisms, herbicides and pesticides, and they provide more stable levels of active ingredients. In this context, we report the establishment of Satureja khuzistanica cell cultures able to produce high amounts of rosmarinic acid (RA). The production of this phytopharmaceutical was increased when the cultures were elicited with coronatine and scaled up to a benchtop bioreactor. S. khuzistanica extracts enriched in RA were found to reduce the viability of cancer cell lines, increasing the sub-G0/G1 cell population and the activity of caspase-8 in MCF-7 cells, which suggest that S. khuzistanica extracts can induce apoptosis of MCF-7 cells through activation of the extrinsic pathway. In addition, our findings indicate that other compounds in S. khuzistanica extracts may act synergistically to potentiate the anticancer activity of RA. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

17 pages, 1468 KiB

Open AccessArticle

Curcumin Treatment in Combination with Glucose Restriction Inhibits Intracellular Alkalinization and Tumor Growth in Hepatoma Cells

by So Won Kim, Min-Ji Cha, Seul-Ki Lee, Byeong-Wook Song, Xinghai Jin, Jae Myun Lee, Jeon Han Park and Jong Doo Lee

Int. J. Mol. Sci. 2019, 20(10), 2375; https://doi.org/10.3390/ijms20102375 - 14 May 2019

Cited by 17 | Viewed by 4430

Abstract

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, [...] Read more.

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein–protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GβL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

14 pages, 1887 KiB

Open AccessArticle

β3-Adrenoreceptor Activity Limits Apigenin Efficacy in Ewing Sarcoma Cells: A Dual Approach to Prevent Cell Survival

by Amada Pasha, Marina Vignoli, Angela Subbiani, Alessio Nocentini, Silvia Selleri, Paola Gratteri, Annalisa Dabraio, Tommaso Casini, Luca Filippi, Ilaria Fotzi, Claudio Favre and Maura Calvani

Int. J. Mol. Sci. 2019, 20(9), 2149; https://doi.org/10.3390/ijms20092149 - 30 Apr 2019

Cited by 9 | Viewed by 3780

Abstract

Ewing Sarcoma (ES) is an aggressive paediatric tumour where oxidative stress and antioxidants play a central role in cancer therapy response. Inhibiting antioxidants expression, while at the same time elevating intracellular reactive oxygen species (ROS) levels, have been proposed as a valid strategy [...] Read more.

Ewing Sarcoma (ES) is an aggressive paediatric tumour where oxidative stress and antioxidants play a central role in cancer therapy response. Inhibiting antioxidants expression, while at the same time elevating intracellular reactive oxygen species (ROS) levels, have been proposed as a valid strategy to overcome ES cancer progression. Flavonoid intake can affect free radical and nutritional status in children receiving cancer treatment, but it is not clear if it can arrest cancer progression. In particular, apigenin may enhance the effect of cytotoxic chemotherapy by inducing cell growth arrest, apoptosis, and by altering the redox state of the cells. Little is known about the use of apigenin in paediatric cancer. Recently, β3-adrenergic receptor (β3-AR) antagonism has been proposed as a possible strategy in cancer therapy for its ability to induce apoptosis by increasing intracellular levels of ROS. In this study we show that apigenin induces cell death in ES cells by modulating apoptosis, but not increasing ROS content. Since ES cells are susceptible to an increased oxidative stress to reduce cell viability, here we demonstrate that administration of β3-ARs antagonist, SR59230A, improves the apigenin effect on cell death, identifying β3-AR as a potential discriminating factor that could address the use of apigenin in ES. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

11 pages, 2043 KiB

Open AccessArticle

Theaflavin-Enriched Fraction Stimulates Adipogenesis in Human Subcutaneous Fat Cells

by Phil June Park, Chan-Su Rha and Sung Tae Kim

Int. J. Mol. Sci. 2019, 20(8), 2034; https://doi.org/10.3390/ijms20082034 - 25 Apr 2019

Cited by 10 | Viewed by 4923

Abstract

Skin provides the first defense line against the environment while preserving physiological homeostasis. Subcutaneous tissues including fat depots that are important for maintaining skin structure and alleviating senescence are altered during aging. This study investigated whether theaflavin (TF) in green tea (GT) has [...] Read more.

Skin provides the first defense line against the environment while preserving physiological homeostasis. Subcutaneous tissues including fat depots that are important for maintaining skin structure and alleviating senescence are altered during aging. This study investigated whether theaflavin (TF) in green tea (GT) has skin rejuvenation effects. Specifically, we examined whether high ratio of TF contents can induce the subcutaneous adipogenesis supporting skin structure by modulating lipid metabolism. The co-fermented GT (CoF-GT) fraction containing a high level of TF was obtained by co-fermentation with garland chrysanthemum (Chrysanthemum coronarium) and the conventionally fermented GT (F-GT) fraction was also obtained. The effects of the CoF- or F-GT fractions on adipogenesis were assessed using primary human subcutaneous fat cells (hSCF). Adipogenesis was evaluated based on lipid droplet (LD) formation, as visualized by Oil Red O staining; by analyzing of adipogenesis-related factors by real-time quantitative polyperase chain reaction (RT-qPCR); and by measuring the concentration of adiponectin released into the culture medium by enzyme-linked immunosorbent assay. TF-enriched CoF-GT fraction did not adversely affect hSCF cell viability but induced their adipogenic differentiation, as evidenced by LD formation, upregulation of adipogenesis-related genes, and adiponectin secretion. TF and TF-enriched CoF-GT fraction promoted differentiation of hSCFs and can therefore be used as an ingredient in rejuvenating agents. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

15 pages, 2659 KiB

Open AccessArticle

Ginsenoside Rh2 Ameliorates Doxorubicin-Induced Senescence Bystander Effect in Breast Carcinoma Cell MDA-MB-231 and Normal Epithelial Cell MCF-10A

by Jin-Gang Hou, Byeong-Min Jeon, Yee-Jin Yun, Chang-Hao Cui and Sun-Chang Kim

Int. J. Mol. Sci. 2019, 20(5), 1244; https://doi.org/10.3390/ijms20051244 - 12 Mar 2019

Cited by 28 | Viewed by 6121

Abstract

The anthracycline antibiotic doxorubicin is commonly used antineoplastic drug in breast cancer treatment. Like most chemotherapy, doxorubicin does not selectively target tumorigenic cells with high proliferation rate and often causes serve side effects. In the present study, we demonstrated the cellular senescence and [...] Read more.

The anthracycline antibiotic doxorubicin is commonly used antineoplastic drug in breast cancer treatment. Like most chemotherapy, doxorubicin does not selectively target tumorigenic cells with high proliferation rate and often causes serve side effects. In the present study, we demonstrated the cellular senescence and senescence associated secretory phenotype (SASP) of both breast tumor cell MDA-MB-231 and normal epithelial cell MCF-10A induced by clinical dose of doxorubicin (100 nM). Senescence was confirmed by flattened morphology, increased level of beta galactose, accumulating contents of lysosome and mitochondrial, and elevated expression of p16 and p21 proteins. Similarly, SASP was identified by highly secreted proteins IL-6, IL-8, GRO, GM-CSF, MCP-1, and MMP1 by antibody array assay. Reciprocal experiments, determined by cell proliferation and apoptosis assays and cell migration and cell invasion, indicated that SASP of MDA-MB-231 cell induces growth arrest of MCF-10A, whereas SASP of MCF-10A significantly stimulates the proliferation of MDA-MB-231. Interestingly, SASP from both cells powerfully promotes the cell migration and cell invasion of MDA-MB-231 cells. Treatment with the natural product ginsenoside Rh2 does not prevent cellular senescence or exert senolytic. However, SASP from senescent cells treated with Rh2 greatly attenuated the above-mentioned bystander effect. Altogether, Rh2 is a potential candidate to ameliorate this unwanted chemotherapy-induced senescence bystander effect. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

15 pages, 2307 KiB

Open AccessArticle

Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes

by Seok Hee Seo, Sang-Mi Jo, Jiyoung Kim, Myoungsook Lee, Yunkyoung Lee and Inhae Kang

Int. J. Mol. Sci. 2019, 20(5), 1216; https://doi.org/10.3390/ijms20051216 - 11 Mar 2019

Cited by 20 | Viewed by 5036

Abstract

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were [...] Read more.

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [³H]-oleic acid (OA) to [³H]-H₂O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

22 pages, 3132 KiB

Open AccessArticle

Isodon rugosus (Wall. ex Benth.) Codd In Vitro Cultures: Establishment, Phytochemical Characterization and In Vitro Antioxidant and Anti-Aging Activities

by Bilal Haider Abbasi, Aisha Siddiquah, Duangjai Tungmunnithum, Shankhamala Bose, Muhammad Younas, Laurine Garros, Samantha Drouet, Nathalie Giglioli-Guivarc’h and Christophe Hano

Int. J. Mol. Sci. 2019, 20(2), 452; https://doi.org/10.3390/ijms20020452 - 21 Jan 2019

Cited by 39 | Viewed by 6963

Abstract

Isodon rugosus (Wall. ex Benth.) Codd accumulates large amounts of phenolics and pentacyclic triterpenes. The present study deals with the in vitro callus induction from stem and leaf explants of I. rugosus under various plant growth regulators (PGRs) for the production of antioxidant [...] Read more.

Isodon rugosus (Wall. ex Benth.) Codd accumulates large amounts of phenolics and pentacyclic triterpenes. The present study deals with the in vitro callus induction from stem and leaf explants of I. rugosus under various plant growth regulators (PGRs) for the production of antioxidant and anti-ageing compounds. Among all the tested PGRs, thidiazuron (TDZ) used alone or in conjunction with α-napthalene acetic acid (NAA) induced highest callogenesis in stem-derived explants, as compared to leaf-derived explants. Stem-derived callus culture displayed maximum total phenolic content and antioxidant activity under optimum hormonal combination (3.0 mg/L TDZ + 1.0 mg/L NAA). HPLC analysis revealed the presence of plectranthoic acid (373.92 µg/g DW), oleanolic acid (287.58 µg/g DW), betulinic acid (90.51 µg/g DW), caffeic acid (91.71 µg/g DW), and rosmarinic acid (1732.61 µg/g DW). Complete antioxidant and anti-aging potential of extracts with very contrasting phytochemical profiles were investigated. Correlation analyses revealed rosmarinic acid as the main contributor for antioxidant activity and anti-aging hyaluronidase, advance glycation end-products inhibitions and SIRT1 activation, whereas, pentacyclic triterpenoids were correlated with elastase, collagenase, and tyrosinase inhibitions. Altogether, these results clearly evidenced the great valorization potential of I. rugosus calli for the production of antioxidant and anti-aging bioactive extracts for cosmetic applications. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

17 pages, 2046 KiB

Open AccessArticle

Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo

by Min-Chi Cheng, Tzong-Huei Lee, Yi-Tzu Chu, Li-Ling Syu, Su-Jung Hsu, Chia-Hsiung Cheng, Jender Wu and Ching-Kuo Lee

Int. J. Mol. Sci. 2018, 19(12), 3994; https://doi.org/10.3390/ijms19123994 - 11 Dec 2018

Cited by 31 | Viewed by 6283

Abstract

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we [...] Read more.

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC₅₀ values of 78.9 and 31.1 μM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 μM) compared to arbutin (20 μM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

Review

Jump to: Research, Other

21 pages, 1356 KiB

Open AccessReview

Costunolide—A Bioactive Sesquiterpene Lactone with Diverse Therapeutic Potential

by Dae Yong Kim and Bu Young Choi

Int. J. Mol. Sci. 2019, 20(12), 2926; https://doi.org/10.3390/ijms20122926 - 14 Jun 2019

Cited by 87 | Viewed by 8096

Abstract

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, [...] Read more.

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Graphical abstract

31 pages, 2816 KiB

Open AccessReview

Phytochemicals as Novel Therapeutic Strategies for NLRP3 Inflammasome-Related Neurological, Metabolic, and Inflammatory Diseases

by Carolina Pellegrini, Matteo Fornai, Luca Antonioli, Corrado Blandizzi and Vincenzo Calderone

Int. J. Mol. Sci. 2019, 20(12), 2876; https://doi.org/10.3390/ijms20122876 - 13 Jun 2019

Cited by 83 | Viewed by 8486

Abstract

Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in the pathophysiology of several neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis [...] Read more.

Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in the pathophysiology of several neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and major depressive disorder), metabolic disorders (i.e., obesity and type 2 diabetes) and chronic inflammatory diseases (i.e., intestinal inflammation, arthritis, and gout). Intensive research efforts are being made to achieve an integrated view about the pathophysiological role of NLRP3 inflammasome pathways in such disorders. Evidence is also emerging that the pharmacological modulation of NLRP3 inflammasome by phytochemicals could represent a promising molecular target for the therapeutic management of neurological, psychiatric, metabolic, and inflammatory diseases. The present review article has been intended to provide an integrated and critical overview of the available clinical and experimental evidence about the role of NLRP3 inflammasome in the pathophysiology of neurological, psychiatric, metabolic, and inflammatory diseases, including PD, AD, MS, depression, obesity, type 2 diabetes, arthritis, and intestinal inflammation. Special attention has been paid to highlight and critically discuss current scientific evidence on the effects of phytochemicals on NLRP3 inflammasome pathways and their potential in counteracting central neuroinflammation, metabolic alterations, and immune/inflammatory responses in such diseases. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

18 pages, 1452 KiB

Open AccessReview

The Anti-inflammatory Effects of Dietary Anthocyanins against Ulcerative Colitis

by Shiyu Li, Binning Wu, Wenyi Fu and Lavanya Reddivari

Int. J. Mol. Sci. 2019, 20(10), 2588; https://doi.org/10.3390/ijms20102588 - 27 May 2019

Cited by 96 | Viewed by 14272

Abstract

Ulcerative colitis (UC), which is a major form of inflammatory bowel disease (IBD), is a chronic relapsing disorder of the gastrointestinal tract affecting millions of people worldwide. Alternative natural therapies, including dietary changes, are being investigated to manage or treat UC since current [...] Read more.

Ulcerative colitis (UC), which is a major form of inflammatory bowel disease (IBD), is a chronic relapsing disorder of the gastrointestinal tract affecting millions of people worldwide. Alternative natural therapies, including dietary changes, are being investigated to manage or treat UC since current treatment options have serious negative side effects. There is growing evidence from animal studies and human clinical trials that diets rich in anthocyanins, which are pigments in fruits and vegetables, protect against inflammation and increased gut permeability as well as improve colon health through their ability to alter bacterial metabolism and the microbial milieu within the intestines. In this review, the structure and bioactivity of anthocyanins, the role of inflammation and gut bacterial dysbiosis in UC pathogenesis, and their regulation by the dietary anthocyanins are discussed, which suggests the feasibility of dietary strategies for UC mitigation. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

14 pages, 808 KiB

Open AccessReview

MicroRNA-Mediated Health-Promoting Effects of Phytochemicals

by Hara Kang

Int. J. Mol. Sci. 2019, 20(10), 2535; https://doi.org/10.3390/ijms20102535 - 23 May 2019

Cited by 33 | Viewed by 4412

Abstract

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by [...] Read more.

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by which phytochemicals affect cellular functions. It has recently been shown that phytochemicals may regulate the expression of microRNAs (miRNAs). MiRNAs are responsible for the fine-tuning of gene expression by controlling the expression of their target mRNAs in both normal and pathological cells. This review summarizes the recent findings regarding phytochemicals that modulate miRNA expression and promote human health by exerting anticancer, photoprotective, and anti-hepatosteatosis effects. Identifying miRNAs modulated by phytochemicals and understanding the regulatory mechanisms mediated by their target mRNAs will facilitate the efforts to maximize the therapeutic benefits of phytochemicals. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

13 pages, 1359 KiB

Open AccessReview

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers

by Durray Shahwar, Muhammad Javed Iqbal, Mehr-un Nisa, Milica Todorovska, Rukset Attar, Uteuliyev Yerzhan Sabitaliyevich, Ammad Ahmad Farooqi, Aamir Ahmad and Baojun Xu

Int. J. Mol. Sci. 2019, 20(8), 2010; https://doi.org/10.3390/ijms20082010 - 24 Apr 2019

Cited by 18 | Viewed by 3483

Abstract

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer [...] Read more.

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

15 pages, 499 KiB

Open AccessReview

DA-9701 (Motilitone): A Multi-Targeting Botanical Drug for the Treatment of Functional Dyspepsia

by Mirim Jin and Miwon Son

Int. J. Mol. Sci. 2018, 19(12), 4035; https://doi.org/10.3390/ijms19124035 - 13 Dec 2018

Cited by 13 | Viewed by 11393

Abstract

Functional dyspepsia (FD) is the most common functional gastrointestinal disorder (FGID). FD is characterized by bothersome symptoms such as postprandial fullness, early satiety, and epigastric pain or burning sensations in the upper abdomen. The complexity and heterogeneity of FD pathophysiology, which involves multiple [...] Read more.

Functional dyspepsia (FD) is the most common functional gastrointestinal disorder (FGID). FD is characterized by bothersome symptoms such as postprandial fullness, early satiety, and epigastric pain or burning sensations in the upper abdomen. The complexity and heterogeneity of FD pathophysiology, which involves multiple mechanisms, make both treatment and new drug development for FD difficult. Current medicines for FD targeting a single pathway have failed to show satisfactory efficacy and safety. On the other hand, multicomponent herbal medicines that act on multiple targets may be a promising alternative treatment for FD. DA-9701 (Motilitone), a botanical drug consisting of Corydalis Tuber and Pharbitidis Semen, has been prescribed for FD since it was launched in Korea in 2011. It has multiple mechanisms of action such as prokinetic effects, fundus relaxation, and visceral analgesia, which are mediated by dopamine D₂ and several serotonin receptors involved in gastrointestinal (GI) functions. In clinical studies, DA-9701 has been found to be beneficial for improvement of FD symptoms and GI functions in FD patients, while showing better safety compared to that associated with conventional medicines. In this review, we provide updated information on the pharmacological effects, safety, and clinical results of DA-9701 for the treatment of FGIDs. Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

Other

Jump to: Research, Review

3 pages, 677 KiB

Open AccessCorrection

Correction: Ou-Yang, F. et al. Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima). Int. J. Mol. Sci. 2019, 20, 3238

by Fu Ou-Yang, I-Hsuan Tsai, Jen-Yang Tang, Ching-Yu Yen, Yuan-Bin Cheng, Ammad Ahmad Farooqi, Shu-Rong Chen, Szu-Yin Yu, Jun-Kai Kao and Hsueh-Wei Chang

Int. J. Mol. Sci. 2021, 22(2), 668; https://doi.org/10.3390/ijms22020668 - 12 Jan 2021

Cited by 1 | Viewed by 1920

Abstract

The authors would like to make corrections to their published paper [...] Full article

(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Health Promoting Effects of Phytochemicals

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (18 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI