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15 pages, 2304 KiB

Open AccessArticle

How Different Dietary Methionine Sources Could Modulate the Hepatic Metabolism in Rainbow Trout?

by Chiara Ceccotti, Ilaria Biasato, Laura Gasco, Christian Caimi, Sara Bellezza Oddon, Simona Rimoldi, Fabio Brambilla and Genciana Terova

Curr. Issues Mol. Biol. 2022, 44(7), 3238-3252; https://doi.org/10.3390/cimb44070223 - 19 Jul 2022

Cited by 5 | Viewed by 1625

Abstract

In aquafeeds in which plant proteins are used to replace fishmeal, exogenous methionine (Met) sources are demanded to balance the amino acid composition of diets and meet the metabolic fish requirements. Nonetheless, since different synthetic Met sources are commercially available, it is important [...] Read more.

In aquafeeds in which plant proteins are used to replace fishmeal, exogenous methionine (Met) sources are demanded to balance the amino acid composition of diets and meet the metabolic fish requirements. Nonetheless, since different synthetic Met sources are commercially available, it is important to determine their bioavailability and efficacy. To address this issue, we conducted a two-month feeding trial with rainbow trout (Oncorhynchus mykiss), which were fed diets supplemented with five different forms of Met: Met-Met, L-Met, HMTBa, DL-Met, and Co DL-Met. No differences in growth performance were found in trout fed with different Met forms, but changes in the whole-body composition were found. In particular, Met-Met and L-Met promoted a significant body lipid reduction, whereas the protein retention was significantly increased in fish fed with HMTBa and Co DL-Met. The latter affected the hepatic Met metabolism promoting the trans-sulfuration pathway through the upregulation of CBS gene expression. Similarly, the L-Met enhanced the remethylation pathway through an increase in BHMT gene expression to maintain the cellular demand for Met. Altogether, our findings suggest an optimal dietary intake of all tested Met sources with similar promoting effects on fish growth and hepatic Met metabolism. Nevertheless, the mechanisms underlying these effects warrant further investigation. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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15 pages, 1633 KiB

Open AccessArticle

Neuropharmacological and Antidiarrheal Potentials of Duabanga grandiflora (DC.) Walp. Stem Bark and Prospective Ligand–Receptor Interactions of Its Bioactive Lead Molecules

by Israt Jahan, Mohammad Forhad Khan, Mohammed Abu Sayeed, Laiba Arshad, Md. Amjad Hossen, Md. Jakaria, Duygu Ağagündüz, Md. Areeful Haque and Raffaele Capasso

Curr. Issues Mol. Biol. 2022, 44(5), 2335-2349; https://doi.org/10.3390/cimb44050159 - 20 May 2022

Cited by 16 | Viewed by 2453

Abstract

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches [...] Read more.

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches in Swiss albino mice and a computer-aided molecular approach. The forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), and hole board test (HBT) were used to determine anti-depressant and anxiolytic activity in experimental mice. In addition, anti-diarrheal studies were performed using castor oil-induced diarrhea, castor oil-induced enter pooling, and the charcoal-induced gastrointestinal motility test. MEDG showed substantial depletions in the immobility times in both FST and TST after treatment with the MEDG extract, whereas moderate anxiolytic activity was manifested at a higher dose (400 mg/kg) compared with the control. Correspondingly, MEDG extract revealed a significant reduction in wet feces and decreased the small intestinal transit of charcoal meal in castor oil-induced diarrhea and charcoal-induced gastrointestinal motility test. In the computer-aided molecular approaches, vanillin displayed a promising binding score for both anxiolytic and anti-diarrheal activities, while duabanganal C showed a promising score for the anti-depressant activity. The present experimental findings along with a computer-aided model conclude that MEDG could be a possible Phyto therapeutic agent with potential anti-depressant, anxiolytic and anti-diarrheal activity. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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11 pages, 867 KiB

Open AccessArticle

Excessive Folic Acid Mimics Folate Deficiency in Human Lymphocytes

by Khadijah I. Alnabbat, Ali M. Fardous, Diane C. Cabelof and Ahmad R. Heydari

Curr. Issues Mol. Biol. 2022, 44(4), 1452-1462; https://doi.org/10.3390/cimb44040097 - 23 Mar 2022

Cited by 8 | Viewed by 3088

Abstract

Food fortification with synthetic folic acid (FA), along with supplementation, results in a marked increase in the population total of serum folates and unmetabolized folic acid (UMFA). Despite the success in reducing neural tube defects at birth in the intended target population (women [...] Read more.

Food fortification with synthetic folic acid (FA), along with supplementation, results in a marked increase in the population total of serum folates and unmetabolized folic acid (UMFA). Despite the success in reducing neural tube defects at birth in the intended target population (women of childbearing age), the potential deleterious effects of chronically high levels of UMFA in susceptible segments of the population require further investigation. In this study, we examine the effects of FA concentrations, ranging from depletion to supraphysiological levels, on markers of proliferation, DNA methylation, and DNA damage and repair in a human lymphoblastoid cell line (LCL). We note that both low and high levels of FA similarly impact global DNA methylation, cytome biomarkers measured through the CBMN assay, DNA damage induced by oxidative stress, and DNA base excision repair gene expression. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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10 pages, 1552 KiB

Open AccessArticle

Anti-Inflammatory Effect of Three Isolated Compounds of Physalis alkekengi var. franchetii (PAF) in Lipopolysaccharide-Activated RAW 264.7 Cells

by Hyun-Jung Park, Hyun Soo Shim, Ah-Reum Han, Eun-Kyoung Seo, Kyu-Ri Kim, Bong Hee Han and Insop Shim

Curr. Issues Mol. Biol. 2022, 44(3), 1407-1416; https://doi.org/10.3390/cimb44030094 - 21 Mar 2022

Cited by 2 | Viewed by 2375

Abstract

(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; [...] Read more.

(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; (2) Methods: To investigate the mechanisms of action of PAF extracts and their isolated compounds, their anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of Physalis alkekengi var. franchetii three isolated compounds of PAF for 30 min prior to stimulation with or without LPS for the indicated times. The inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were determined using reverse transcription-polymerase chain (RT-PCR); (3) Results Treatment of RAW 264.7 cells with LPS alone resulted in significant increases in inflammatory cytokine production as compared to the control group (p < 0.001). However, with the treatment of isophysalin B 100 μg/mL, there was a significant decrease in the mRNA expression levels of TNF-α in LPS-stimulated raw 264.7 cells (p < 0.001). With treatment of physalin 1–100 μg/mL, there was a markedly decrease in the mRNA expression levels of TNF-α in LPS stimulated raw 264.7 (p < 0.05). Moreover, TNF-α mRNA (p < 0.05) and IL-1β mRNA (p < 0.001) mRNA levels were significantly suppressed after treatment with 3′,7-dimethylquercetin in LPS stimulated Raw 264.7 cells; (4) Conclusions: These findings suggest that three isolated compounds from can suppress inflammatory responses in LPS stimulated macrophage. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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12 pages, 851 KiB

Open AccessArticle

Effects of Essential Amino Acid Deficiency on General Control Nonderepressible 2/Eukaryotic Initiation Factor 2 Signaling and Proteomic Changes in Primary Bovine Mammary Epithelial Cells

by Zulma Tatiana Ruiz-Cortés, Peter Yoder and Mark D. Hanigan

Curr. Issues Mol. Biol. 2022, 44(3), 1075-1086; https://doi.org/10.3390/cimb44030071 - 25 Feb 2022

Cited by 2 | Viewed by 2397

Abstract

We hypothesized that the general control nonderepressible 2 (GCN2)/eukaryotic initiation factor 2 (eIF2) signaling pathway and intracellular protein synthesis (PS) are regulated to maintain milk PS in primary bovine mammary epithelial cells (MECs) under essential amino acid (EAA) starvation conditions. We cultured MECs [...] Read more.

We hypothesized that the general control nonderepressible 2 (GCN2)/eukaryotic initiation factor 2 (eIF2) signaling pathway and intracellular protein synthesis (PS) are regulated to maintain milk PS in primary bovine mammary epithelial cells (MECs) under essential amino acid (EAA) starvation conditions. We cultured MECs with 0%, 2% (depletion), and 100% (control) EAA for two exposure times (8 and 24 h), followed by three refeeding (RF) times with 100% EAA (0, 8, and 24 h). Subsequently, we measured cell viability, total protein concentration, and proliferation. Western blotting was used to quantify the levels of casein and the expression of total GCN2 and eIF2, as well as phosphorylated GCN2 (GCN2P) and eIF2 (eIF2P). The ISOQuant method was used to assess MEC proteomes, and the resultant data were analyzed using the Kruskal–Wallis test, nonpaired Wilcoxon rank post-hoc test, and ANOVA–Tukey test, as well as principal component analyses and multiple regressions models. Differences in cell viability were observed between the control versus the depleted and repleted MECs, respectively, where 97.2–99.8% viability indicated low cell death rates. Proliferation (range, 1.02–1.55 arbitrary units (AU)) was affected by starvation for 12 and 24 h and repletion for 24 h, but it was not increased compared with the control. Total protein expression was unaffected by both depletion and repletion treatments (median 3158 µg/mL). eIF2P expression was significantly increased (p < 0.05) after treatment with 2% EAA for 8 and 24 h compared with 2% EAA with 8 h + 24 h RF and 2% EAA with 24 h + 8 h RF. GCN2P also showed significantly increased expression (p < 0.05) after treatment with 2% EAA for 24 h compared with the control and 2% EAA with 24 h + 8 h RF. Intracellular casein/α-tubulin expression was unaffected by 2% EAA compared with control (0.073 ± 0.01 AU versus 0.086 ± 0.02 AU, respectively). We studied 30 of the detected 1180 proteins, 16 of which were differentially expressed in starved and refed MECs. Cells faced with EAA deficiency activated the GCN2P/eIF2P pathway, and the lack of change in the levels of casein and other milk proteins suggested that the EAA deficit was mitigated by metabolic flexibility to maintain homeostasis. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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19 pages, 37700 KiB

Open AccessArticle

Phenotypic Assessment of Probiotic and Bacteriocinogenic Efficacy of Indigenous LAB Strains from Human Breast Milk

by Senbagam Duraisamy, Fazal Husain, Senthilkumar Balakrishnan, Aswathy Sathyan, Prabhu Subramani, Prahalathan Chidambaram, Selvaraj Arokiyaraj, Wahidah H. Al-Qahtani, Jothiramalingam Rajabathar and Anbarasu Kumarasamy

Curr. Issues Mol. Biol. 2022, 44(2), 731-749; https://doi.org/10.3390/cimb44020051 - 01 Feb 2022

Cited by 4 | Viewed by 2576

Abstract

Breast milk is the combination of bioactive compounds and microflora that promote newborn’s proper growth, gut flora, and immunity. Thus, it is always considered the perfect food for newborns. Amongst their bioactives, probiotic communities—especially lactic acid bacteria (LAB)—are characterized from breast milk over [...] Read more.

Breast milk is the combination of bioactive compounds and microflora that promote newborn’s proper growth, gut flora, and immunity. Thus, it is always considered the perfect food for newborns. Amongst their bioactives, probiotic communities—especially lactic acid bacteria (LAB)—are characterized from breast milk over the first month of parturition. In this study, seven LAB were characterized phenotypically and genotypically as Levilactobacillus brevis BDUMBT08 (MT673657), L. gastricus BDUMBT09 (MT774596), L. paracasei BDUMBT10 (MT775430), L. brevis BDUMBT11 (MW785062), L. casei BDUMBT12 (MW785063), L. casei BDUMBT13 (MW785178), and Brevibacillus brevis M2403 (MK371781) from human breast milk. Their tolerance to lysozyme, acid, bile, gastric juice, pancreatic juice, and NaCl and potential for mucoadhesion, auto-aggregation, and co-aggregation with pathogens are of great prominence in forecasting their gut colonizing ability. They proved their safety aspects as they were negative for virulence determinants such as hemolysis and biofilm production. Antibiogram of LAB showed their sensitivity to more than 90% of the antibiotics tested. Amongst seven LAB, three isolates (L. brevis BDUMBT08 and BDUMBT11, and L. gatricus BDUMBT09) proved their bacteriocin producing propensity. Although the seven LAB isolates differed in their behavior, their substantial probiotic properties with safety could be taken as promising probiotics for further studies to prove their in vivo effects, such as health benefits, in humans. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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14 pages, 5103 KiB

Open AccessArticle

Anti-Adhesive Properties of Calcium Alginate from Sargassum fusiforme against Particulate Matter-Induced Inflammation

by Yun-Hua Fu, Xing-Yu Tao, Di Yang, Xue Li, Dong-Yue Zhou, Yu-Lin Dai and You-Jin Jeon

Curr. Issues Mol. Biol. 2022, 44(2), 626-639; https://doi.org/10.3390/cimb44020043 - 25 Jan 2022

Cited by 5 | Viewed by 2523

Abstract

Fine dust generated by particulate matter (PM) pollution is a serious ecological issue in industrialized countries and causes disorders of the respiratory system and skin in humans. In the previous study, Sargassum fusiforme was treated with citric acid to remove heavy metals. In [...] Read more.

Fine dust generated by particulate matter (PM) pollution is a serious ecological issue in industrialized countries and causes disorders of the respiratory system and skin in humans. In the previous study, Sargassum fusiforme was treated with citric acid to remove heavy metals. In this study, the transfer of PM-mediated inflammatory responses through the skin to macrophages was evaluated. Moreover, the anti-adhesive effects of calcium alginate isolated from S. fusiforme (SFCA) against PM-induced inflammation were investigated. The structures of processing and unprocessing SFCA were then analyzed by Fourier-transform infrared spectroscopy (FT-IR), revealing minimal change after acid-processing. SFCA had protective effects both in PM-stimulated HaCaT keratinocytes and RAW 264.7 macrophages. In cellular environments, it was found that SFCA attenuated signal protein expressions such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), and pro-inflammatory cytokines. Furthermore, macrophages were added to the culture medium of PM-stimulated keratinocytes to induce inflammation. SFCA was observed to significantly inhibit inflammatory responses; additionally, SFCA showed an in vivo anti-adhesive effect in zebrafish embryos. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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24 pages, 33490 KiB

Open AccessArticle

In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease

by Hafsa Amat-ur-Rasool, Mehboob Ahmed, Shahida Hasnain, Abrar Ahmed and Wayne Grant Carter

Curr. Issues Mol. Biol. 2022, 44(1), 152-175; https://doi.org/10.3390/cimb44010012 - 29 Dec 2021

Cited by 10 | Viewed by 2534

Abstract

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. [...] Read more.

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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17 pages, 1428 KiB

Open AccessArticle

Isolation of an Extract from the Soft Coral Symbiotic Microorganism Salinispora arenicola Exerting Cytoprotective and Anti-Aging Effects

by Xanthippi P. Louka, Aimilia D. Sklirou, Géraldine Le Goff, Philippe Lopes, Eleni-Dimitra Papanagnou, Maria S. Manola, Yehuda Benayahu, Jamal Ouazzani and Ioannis P. Trougakos

Curr. Issues Mol. Biol. 2022, 44(1), 14-30; https://doi.org/10.3390/cimb44010002 - 22 Dec 2021

Cited by 1 | Viewed by 3254

Abstract

Cells have developed a highly integrated system responsible for proteome stability, namely the proteostasis network (PN). As loss of proteostasis is a hallmark of aging and age-related diseases, the activation of PN modules can likely extend healthspan. Here, we present data on the [...] Read more.

Cells have developed a highly integrated system responsible for proteome stability, namely the proteostasis network (PN). As loss of proteostasis is a hallmark of aging and age-related diseases, the activation of PN modules can likely extend healthspan. Here, we present data on the bioactivity of an extract (SA223-S2BM) purified from the strain Salinispora arenicola TM223-S2 that was isolated from the soft coral Scleronephthya lewinsohni; this coral was collected at a depth of 65 m from the mesophotic Red Sea ecosystem EAPC (south Eilat, Israel). Treatment of human cells with SA223-S2BM activated proteostatic modules, decreased oxidative load, and conferred protection against oxidative and genotoxic stress. Furthermore, SA223-S2BM enhanced proteasome and lysosomal-cathepsins activities in Drosophila flies and exhibited skin protective effects as evidenced by effective inhibition of the skin aging-related enzymes, elastase and tyrosinase. We suggest that the SA223-S2BM extract constitutes a likely promising source for prioritizing molecules with anti-aging properties. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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13 pages, 2334 KiB

Open AccessArticle

Evaluation of Anti-Inflammatory Effects of Celery Leaf and Stem Extracts in LPS-Induced RAW 264.7 Cells Using Nitric Oxide Assay and LC-MS Based Metabolomics

by Hazel Lau, Nengyi Ni, Hiranya Dayal, Si-Ying Lim, Yi Ren and Sam Fong-Yau Li

Curr. Issues Mol. Biol. 2021, 43(3), 1876-1888; https://doi.org/10.3390/cimb43030131 - 05 Nov 2021

Cited by 1 | Viewed by 3308

Abstract

The present work demonstrated and compared the anti-inflammatory effects of celery leaf (CLE) and stem (CSE) extracts. LC-MS-based metabolomics were an effective approach to achieve the biomarker identification and pathway elucidation associated with the reduction in inflammatory responses. The celery extracts suppressed LPS-induced [...] Read more.

The present work demonstrated and compared the anti-inflammatory effects of celery leaf (CLE) and stem (CSE) extracts. LC-MS-based metabolomics were an effective approach to achieve the biomarker identification and pathway elucidation associated with the reduction in inflammatory responses. The celery extracts suppressed LPS-induced NO production in RAW 264.7 cells, and CLE was five times more effective than CSE. Distinct differences were revealed between the control and celery-treated samples among the 24 characteristic metabolites that were identified. In celery-treated LPS cells, reversals of intracellular (citrulline, proline, creatine) and extracellular (citrulline, lysine) metabolites revealed that the therapeutic outcomes were closely linked to arginine metabolism. Reversals of metabolites when treated with CLE (aspartate, proline) indicated targeted effects on the TCA and urea cycles, while, in the case of CSE (histidine, glucose), the glycolysis and the pentose phosphate pathways were implicated. Subsequently, apigenin and bergapten in CLE were identified as potential biomarkers mediating the anti-inflammatory response. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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15 pages, 2932 KiB

Open AccessArticle

Geraniol Averts Methotrexate-Induced Acute Kidney Injury via Keap1/Nrf2/HO-1 and MAPK/NF-κB Pathways

by Nancy S. Younis, Heba S. Elsewedy, Tamer M. Shehata and Maged E. Mohamed

Curr. Issues Mol. Biol. 2021, 43(3), 1741-1755; https://doi.org/10.3390/cimb43030123 - 24 Oct 2021

Cited by 20 | Viewed by 3323

Abstract

Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol [...] Read more.

Objectives: Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways. Methods: Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg). Results: Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues. Conclusion: The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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17 pages, 933 KiB

Open AccessArticle

Impact of Vitamin D Supplementation on Inflammatory Markers’ Levels in Obese Patients

by Michał Wiciński, Mateusz Ozorowski, Eryk Wódkiewicz, Stephan Walter Otto, Karol Kubiak and Bartosz Malinowski

Curr. Issues Mol. Biol. 2021, 43(3), 1606-1622; https://doi.org/10.3390/cimb43030114 - 14 Oct 2021

Cited by 2 | Viewed by 2446

Abstract

In view of research suggesting a possible beneficial impact of vitamin D on systemic inflammatory response, the authors decided to investigate an influence of vitamin D supplementation on serum levels of certain inflammatory markers in obese patients. The current study included such biomarkers [...] Read more.

In view of research suggesting a possible beneficial impact of vitamin D on systemic inflammatory response, the authors decided to investigate an influence of vitamin D supplementation on serum levels of certain inflammatory markers in obese patients. The current study included such biomarkers as interleukin-6 (IL-6), pituitary adenylate cyclase-activating peptide (PACAP), advanced oxidation protein products (AOPP), C-X3-C Motif Chemokine Ligand 1 (CX3CL1), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO). The measurements were performed with the ELISA method before and after 3-month-long supplementation of 2000 IU of vitamin D orally. The results showed that the therapy did not induce any statistically significant changes in serum levels of MCP-1, IL-6, CX3CL1, and PACAP. The supplementation was related to a significant increase in measurements of NO and AOPP levels, although the correlation analysis between vitamin D concentration after its supplementation and the concentration of the molecular parameters did not show significant relation. In conclusion, our study seems to contradict certain aspects of findings available in the literature regarding the vitamin D’s impact. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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11 pages, 1927 KiB

Open AccessArticle

Effect of Ducrosia flabellifolia and Savignya parviflora Extracts on Inhibition of Human Colon and Prostate Cancer Cell Lines

by Youssef Saeed Alghamdi, Osama Moseilhy Saleh, Nada Alqadri, Mutaib Mosaued Mashraqi, Omar Bahattab and Nabil Saied Awad

Curr. Issues Mol. Biol. 2021, 43(3), 1518-1528; https://doi.org/10.3390/cimb43030107 - 10 Oct 2021

Cited by 1 | Viewed by 2067

Abstract

The goal of this study was to investigate whether Ducrosia flabellifolia and Savignya parviflora methanol extract the have effect on colon and prostate cancer cell lines. Analysis of total content of phenolics and flavonoids of each plant extract was carried out. Cytotoxic effect, [...] Read more.

The goal of this study was to investigate whether Ducrosia flabellifolia and Savignya parviflora methanol extract the have effect on colon and prostate cancer cell lines. Analysis of total content of phenolics and flavonoids of each plant extract was carried out. Cytotoxic effect, cell cycle analysis, induction of apoptosis and gene expression of Bcl-2 and Bax genes were studied. Obtained results indicated that, the plant extracts exhibit growth inhibition of used cancer cell lines and induced apoptosis as well as arresting of cell cycle. At the molecular level, changes in gene expression were detected via qPCR and confirmed by western blotting. The exhibited anticancer potentialities of plant extracts against utilized cancer cell lines are due to its containing bioactive compounds. Further detailed isolation, fractionation and characterization of bioactive compounds are needed. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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13 pages, 3996 KiB

Open AccessArticle

Dexpanthenol Promotes Cell Growth by Preventing Cell Senescence and Apoptosis in Cultured Human Hair Follicle Cells

by Jae Young Shin, Jaeyoon Kim, Yun-Ho Choi, Nae-Gyu Kang and Sanghwa Lee

Curr. Issues Mol. Biol. 2021, 43(3), 1361-1373; https://doi.org/10.3390/cimb43030097 - 28 Sep 2021

Cited by 14 | Viewed by 10500

Abstract

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were [...] Read more.

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; β-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-β1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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15 pages, 746 KiB

Open AccessArticle

Potential DPP IV Inhibitory Peptides from Dry-Cured Pork Loins after Hydrolysis: An In Vitro and In Silico Study

by Paulina Kęska and Joanna Stadnik

Curr. Issues Mol. Biol. 2021, 43(3), 1335-1349; https://doi.org/10.3390/cimb43030095 - 27 Sep 2021

Cited by 8 | Viewed by 2153

Abstract

Peptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes, and inhibitors of this enzyme are an important class of drugs for the treatment of type 2 diabetes. In the present study, peptides (<7 kDa) isolated from dry-cured pork loins after [...] Read more.

Peptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes, and inhibitors of this enzyme are an important class of drugs for the treatment of type 2 diabetes. In the present study, peptides (<7 kDa) isolated from dry-cured pork loins after pepsin and pancreatin hydrolysis were identified by mass spectrometry and tested as potential inhibitors of DPP-IV by the in silico method. Two peptides, namely WTIAVPGPPHS from myomesin (water-soluble fraction, A = 0.9091) and FKRPPL from troponin (salt-soluble fraction, A = 0.8333), were selected as the most promising inhibitors of DPP-IV. Both peptides were subjected to ADMET analysis. Fragments of these peptides showed promising drug-likeness properties as well as favorable absorption, distribution, metabolism, excretion, and toxicity functions, suggesting that they are novel leads in the development of DPP-IV inhibitors from food. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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14 pages, 2394 KiB

Open AccessArticle

Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-A^y/Ta Mice with Hyperglycemia and Hyperuricemia

by Shinji Kondo, Shin-ichi Adachi, Fumiaki Yoshizawa and Kazumi Yagasaki

Curr. Issues Mol. Biol. 2021, 43(3), 1293-1306; https://doi.org/10.3390/cimb43030092 - 26 Sep 2021

Cited by 11 | Viewed by 2660

Abstract

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 [...] Read more.

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-A^y/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5’-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-A^y/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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17 pages, 7191 KiB

Open AccessArticle

Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract

by Min Hye Kang, Gwi Yeong Jang, Yun-Jeong Ji, Jeong Hoon Lee, Su Ji Choi, Tae Kyung Hyun and Hyung Don Kim

Curr. Issues Mol. Biol. 2021, 43(2), 1171-1187; https://doi.org/10.3390/cimb43020083 - 18 Sep 2021

Cited by 12 | Viewed by 4351

Abstract

Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is [...] Read more.

Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is used as a natural treatment for skin whitening. We aimed to confirm the potential of Wongam, a new cultivar of licorice developed by the Rural Development Administration (RDA), as a whitening agent in cosmetics. In addition, we verified the effect of heat treatment on the bioactivity of licorice by comparing antioxidant and anti-melanogenic activities of licorice extract before and after heating (130 °C). The heat-treated licorice extract (WH-130) showed higher radical-scavenging activities in the ABTS⁺ (2,2′-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays. In addition, WH-130 inhibited melanogenesis more effectively due to downregulation of tyrosinase in B16F10 melanoma cells than non-heated licorice extract. Moreover, heat treatment increased total phenolic content. In particular, isoliquiritigenin, an antioxidant and anti-melanogenic compound of licorice, was produced by heat treatment. In conclusion, WH-130, with increased levels of bioactive phenolics such as isoliquiritigenin, has potential for development into a novel skin whitening material with applications in cosmetics. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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16 pages, 2264 KiB

Open AccessArticle

Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling

by Sally K. Hammad, Rana G. Eissa, Mohamed A. Shaheen and Nahla N. Younis

Curr. Issues Mol. Biol. 2021, 43(2), 1057-1071; https://doi.org/10.3390/cimb43020075 - 05 Sep 2021

Cited by 12 | Viewed by 6695

Abstract

Postmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, there is a [...] Read more.

Postmenopausal women are at an increased risk of vascular calcification which is defined as the pathological deposition of minerals in the vasculature, and is strongly linked with increased cardiovascular disease risk. Since estrogen-replacement therapy is associated with increased cancer risk, there is a strong need for safer therapeutic approaches. In this study we aimed to investigate the protective and therapeutic effects of the phytoestrogen resveratrol against vascular calcification in ovariectomized rats, a preclinical model of postmenopause. Furthermore, we aimed to compare the effects of resveratrol to those of estrogen and to explore the mechanisms underpinning those effects. Treatment with resveratrol or estrogen ameliorated aortic calcification in ovariectomized rats, as shown by reduced calcium deposition in the arterial wall. Mechanistically, the effects of resveratrol and estrogen were mediated via the activation of SIRT1 signaling. SIRT1 protein expression was downregulated in the aortas of ovariectomized rats, and upregulated in rats treated with resveratrol or estrogen. Moreover, resveratrol and estrogen reduced the levels of the osteogenic markers: runt-related transcription factor 2 (RUNX2), osteocalcin and alkaline phosphatase (ALP) which have been shown to play a role during vascular calcification. Additionally, the senescence markers (p53, p16 and p21) which were also reported to play a role in the pathogenesis of vascular calcification, were reduced upon treatment with resveratrol and estrogen. In conclusion, the phytoestrogen resveratrol may be a safer alternative to estrogen, as a therapeutic approach against the progression of vascular calcification during postmenopause. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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23 pages, 2650 KiB

Open AccessArticle

Active Ingredients from Euodia ruticarpa Steam Distilled Essential Oil Inhibit PC-3 Prostate Cancer Cell Growth via Direct Action and Indirect Immune Cells Conditioned Media In Vitro

by Tzu-He Yeh and Jin-Yuarn Lin

Curr. Issues Mol. Biol. 2021, 43(2), 996-1018; https://doi.org/10.3390/cimb43020071 - 28 Aug 2021

Cited by 5 | Viewed by 2251

Abstract

Active constituents isolated from Euodia ruticarpa (ER) steam distilled essential oil (SDEO) against PC-3 prostate cancer cell growth remain unclear. To clarify the puzzle, ER SDEO was extracted and further resolved into six isolated fractions ERF1–F6 with Sephadex LH-20 gel filtration chromatography to [...] Read more.

Active constituents isolated from Euodia ruticarpa (ER) steam distilled essential oil (SDEO) against PC-3 prostate cancer cell growth remain unclear. To clarify the puzzle, ER SDEO was extracted and further resolved into six isolated fractions ERF1–F6 with Sephadex LH-20 gel filtration chromatography to analyze their biological activities. Active ingredients in the isolated fractions were analyzed with GC-MS. Potential isolated fractions were selected to treat PC-3 cells with direct action and indirect treatment by mouse splenocyte- (SCM) and macrophage-conditioned media (MCM). The relationship between PC-3 cell viabilities and corresponding total polyphenols, flavonoid contents as well as Th1/Th2 cytokine profiles in SCM was analyzed using the Pearson product–moment correlation coefficient (r). As a result, ERF1–F3 was abundant in total polyphenols and flavonoids contents with diverse active ingredients. Treatments with ERF1–F3 at appropriate concentrations more or less inhibit PC-3 cell growth in a direct action manner. Only SCM, respectively, cultured with ER SDEO and ERF1–F3 markedly enhanced the effects to inhibit PC-3 cell growth, suggesting that secretions by splenocytes might involve anti-PC-3 effects. There are significantly negative correlations between PC-3 cell viabilities and IL-2, IL-10 as well as IL-10/IL-2 ratios in the corresponding SCM. Total polyphenol and flavonoid contents in the media cultured with ER SDEO isolated fractions positively correlated with IL-10 (Th2) and IL-10/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, indicating that polyphenol and flavonoid components in ER SDEO isolated fractions promote Th2-polarized and anti-inflammatory characteristics. These new findings concluded that the inhibitory effects against PC-3 prostate cancer cell growth are attributed to active anti-inflammatory ingredients in ER SDEO and its active ERF1–F3 fractions through direct action and indirect treatment by modulating splenocytes’ cytokine secretion profiles. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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9 pages, 1086 KiB

Open AccessArticle

Prostate Apoptotic Induction and NFκB Suppression by Dammarolic Acid: Mechanistic Insight into Onco-Therapeutic Action of an Aglycone Asiaticoside

by Ahmed Alafnan, Talib Hussain, Syed Mohd Danish Rizvi, Afrasim Moin and Abdulwahab Alamri

Curr. Issues Mol. Biol. 2021, 43(2), 932-940; https://doi.org/10.3390/cimb43020066 - 10 Aug 2021

Cited by 7 | Viewed by 2501

Abstract

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different [...] Read more.

Prostate cancer (PCa) is addressed as the second most common form of onco-threat worldwide and is usually considered as the major cause of mortality in men. Recent times have seen a surge in exploration of plant-derived components for alternative therapeutical interventions against different oncological malignancies. Dammarolic acid or Asiatic acid (AsA) is an aglycone asiaticoside that has been reported for its efficacy in several ailments including cancer. The current study aimed to investigate the anti-proliferative potency of AsA against human prostate cancer PC-3 cells. Purified AsA was diluted and PC-3 cells were exposed to 20, 40, and 80 µM concentration and incubated for 24 h. Post-exposure, PC-3 cells showcased a substantial loss of their viability at 20 µM (p < 0.05), moreover, this reduction in cell viability escalated proportionally with an increase in AsA at concentrations of 40 and 80 µM (p < 0.01; p < 0.001) respectively. AsA-impelled loss of cellular viability was also evident from the acridine orange-stained photomicrographs, which was also used to quantify the viable and apoptotic cells using Image J software. Additionally, quantification of ROS within PC-3 cells also exhibited an increase in DCF-DA-mediated fluorescence intensity post-exposure to AsA in a dose-dependent manner. AsA-induced apoptosis in PC-3 cells was shown to be associated with augmented activity of caspase-3 proportionally to the AsA concentrations. Thus, initially, this exploratory study explicated that AsA treatment leads to anti-proliferative effects in PC-3 cells by enhancing oxidative stress and inciting apoptosis en route to onset of nuclear fragmentation. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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13 pages, 807 KiB

Open AccessArticle

A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins

by Alkistis Kapelouzou, Michalis Katsimpoulas, Christos Kontogiannis, Irene Lidoriki, Georgios Georgiopoulos, Christos Kourek, Christos Papageorgiou, Konstantinos S. Mylonas, Spyridon Dritsas, Alexandros Charalabopoulos and Dennis V. Cokkinos

Curr. Issues Mol. Biol. 2021, 43(2), 818-830; https://doi.org/10.3390/cimb43020059 - 26 Jul 2021

Cited by 4 | Viewed by 2651

Abstract

Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit [...] Read more.

Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. Methods: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. Results: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. Conclusions: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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12 pages, 1476 KiB

Open AccessArticle

Anti-Inflammatory Effects of Resveratrol on Human Retinal Pigment Cells and a Myopia Animal Model

by Yu-An Hsu, Chih-Sheng Chen, Yao-Chien Wang, En-Shyh Lin, Ching-Yao Chang, Jamie Jiin-Yi Chen, Ming-Yen Wu, Hui-Ju Lin and Lei Wan

Curr. Issues Mol. Biol. 2021, 43(2), 716-727; https://doi.org/10.3390/cimb43020052 - 16 Jul 2021

Cited by 20 | Viewed by 3795

Abstract

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on [...] Read more.

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-β, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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23 pages, 3132 KiB

Open AccessArticle

Computational and Pharmacological Studies on the Antioxidant, Thrombolytic, Anti-Inflammatory, and Analgesic Activity of Molineria capitulata

by Mohammad Ashiqur Rahman Bhuiyan Shovo, Marzia Rahman Tona, Jannatul Mouah, Fayza Islam, Md. Helal Uddin Chowdhury, Tuhin Das, Arkajyoti Paul, Duygu Ağagündüz, Md. Masudur Rahman, Talha Bin Emran, Raffaele Capasso and Jesus Simal-Gandara

Curr. Issues Mol. Biol. 2021, 43(2), 434-456; https://doi.org/10.3390/cimb43020035 - 22 Jun 2021

Cited by 23 | Viewed by 3875

Abstract

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental [...] Read more.

Molineria capitulata is an ornamental plant that has traditionally been used to treat several chronic diseases. The present study was designed to examine the antioxidant, cytotoxic, thrombolytic, anti-inflammatory, and analgesic activities of a methanolic extract of M. capitulata leaves (MEMC) using both experimental and computational models. Previously established protocols were used to perform qualitative and quantitative phytochemical screening in MEMC. A computational study, including molecular docking and ADME/T analyses, was performed. The quantitative phytochemical analysis revealed the total phenolic and flavonoid contents as 148.67 and 24 mg/g, respectively. Antioxidant activity was assessed by examining the reducing power of MEMC, resulting in absorbance of 1.87 at 400 µg/mL, demonstrating a strong reduction capacity. The extract exhibited significant protection against blood clotting and showed the highest protein denaturation inhibition at 500 µg/mL. In both the acetic acid-induced writhing and formalin-induced paw-licking models, MEMC resulted in significant potential pain inhibition in mice. In the computational analysis, 4-hydroxybenzaldehyde, orcinol glucoside, curcapital, crassifogenin C, and 2,6-dimethoxy-benzoic acid displayed a strong predictive binding affinity against the respective receptors. These findings indicated that M. capitulata possesses significant pharmacological activities to an extent supported by computational studies. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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18 pages, 3192 KiB

Open AccessArticle

Immature Persimmon Suppresses Amyloid Beta (Aβ) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice

by Seul-Ki Yoo, Jong-Min Kim, Uk Lee, Jin-Yong Kang, Seon-Kyeong Park, Hye-Ju Han, Hyo-Won Park, Hyun-Jin Kim, Chul-Woo Kim, Mahn-Jo Kim and Ho-Jin Heo

Curr. Issues Mol. Biol. 2021, 43(1), 405-422; https://doi.org/10.3390/cimb43010033 - 21 Jun 2021

Cited by 3 | Viewed by 2345

Abstract

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aβ)_1–42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aβ_1–42-induced mice by improving the [...] Read more.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aβ)_1–42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aβ_1–42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aβ_1–42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3β, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS²). Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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19 pages, 3528 KiB

Open AccessArticle

Water Extract of Mixed Mushroom Mycelia Grown on a Solid Barley Medium Is Protective against Experimental Focal Cerebral Ischemia

by Ji Heun Jeong, Shin Hye Kim, Mi Na Park, Jong Yea Park, Hyun Young Park, Chan Eui Song, Ji Hyun Moon, Ah La Choi, Ki Duck Kim, Nam Seob Lee, Young Gil Jeong, Do Kyung Kim, Bong Ho Lee, Yung Choon Yoo and Seung Yun Han

Curr. Issues Mol. Biol. 2021, 43(1), 365-383; https://doi.org/10.3390/cimb43010030 - 15 Jun 2021

Cited by 5 | Viewed by 3527

Abstract

Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed [...] Read more.

Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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18 pages, 5001 KiB

Open AccessArticle

Histological Evidence of Wound Healing Improvement in Rats Treated with Oral Administration of Hydroalcoholic Extract of Vitis labrusca

by Tarsizio S. Santos, Izabella D. D. dos Santos, Rose N. Pereira-Filho, Silvana V. F. Gomes, Isabel B. Lima-Verde, Maria N. Marques, Juliana C. Cardoso, Patricia Severino, Eliana B. Souto and Ricardo L. C. de Albuquerque-Júnior

Curr. Issues Mol. Biol. 2021, 43(1), 335-352; https://doi.org/10.3390/cimb43010028 - 11 Jun 2021

Cited by 27 | Viewed by 4539

Abstract

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of Vitis labrusca are rich in phenolic acids and flavonoids. The goal of this study was to assess [...] Read more.

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of Vitis labrusca are rich in phenolic acids and flavonoids. The goal of this study was to assess the healing properties of the oral administration of hydroalcoholic extract of V. labrusca leaves (HEVL) in a murine model. HEVL was obtained by Soxhlet and dynamic maceration, and their yield and phenolic acids and flavonoid contents were determined. For the wound healing assay, 8 mm wounds were performed on the back of 48 Wistar rats, assigned into four groups (n = 12): CTR (distilled water), HEVL100, HEVL200, and HEVL300 (HEVL at 100, 200, and 300 mg/kg, respectively). On days 7 and 14, wound closure rates were assessed, and the healing wounds were subjected to histological analysis. Soxhlet-obtained extract was selected for the wound healing assay because it provided a higher yield and phenolic acid and flavonoid contents. HEVL significantly reduced leukocytosis in the peripheral blood (p < 0.05), accelerated wound closure (p < 0.05), and improved collagenization (p < 0.05) on day 7, as well as enhanced the epidermal tissue thickness (p < 0.001) and elastic fiber deposition on day 14 (p < 0.01). Furthermore, HEVL promoted an increase in the histological grading of wound healing on both days 7 and 14 (p < 0.01). The doses of 200 and 300 mg/kg provided better results than 100 mg/Kg. Our data provide histological evidence that the oral administration of HEVL improves wound healing in rodents. Therefore, the extract can be a potential oral medicine for healing purposes. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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14 pages, 9395 KiB

Open AccessArticle

Vitamin D Deficiency Reduces Vascular Reactivity of Coronary Arterioles in Male Rats

by Zoltán Fontányi, Réka Eszter Sziva, Éva Pál, Leila Hadjadj, Anna Monori-Kiss, Eszter Mária Horváth, Rita Benkő, Attila Magyar, Andrea Heinzlmann, Zoltán Benyó, György L. Nádasy, Gabriella Masszi and Szabolcs Várbíró

Curr. Issues Mol. Biol. 2021, 43(1), 79-92; https://doi.org/10.3390/cimb43010007 - 07 May 2021

Cited by 5 | Viewed by 2710

Abstract

Background: Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of [...] Read more.

Background: Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of male rats in cases of different vitamin D supply. Methods: Four-week-old male Wistar rats were divided into a control group (n = 11) with optimal vitamin D supply (300 IU/kgbw/day) and a VDD group (n = 11, <0.5 IU/kgbw/day). After 8 weeks of treatment, intramural coronary artery segments were microprepared, their pharmacological reactivity was examined by in vitro microangiometry, and their receptor expression was investigated by immunohistochemistry. Results: Thromboxane A₂ (TXA₂)-agonist induced reduced vasoconstriction, testosterone (T) and 17-β-estradiol (E2) relaxations were significantly decreased, a significant decrease in thromboxane receptor (TP) expression was shown, and the reduction in estrogen receptor-α (ERα) expression was on the border of significance in the VDD group. Conclusions: VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA₂ and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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14 pages, 10206 KiB

Open AccessArticle

Network Pharmacology and Molecular Docking Combined to Analyze the Molecular and Pharmacological Mechanism of Pinellia ternata in the Treatment of Hypertension

by Zhaowei Zhai, Xinru Tao, Mohammad Murtaza Alami, Shaohua Shu and Xuekui Wang

Curr. Issues Mol. Biol. 2021, 43(1), 65-78; https://doi.org/10.3390/cimb43010006 - 01 May 2021

Cited by 12 | Viewed by 5230

Abstract

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination [...] Read more.

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination with western medicine has played an important role in traditional Chinese medicine. Although P. ternata is used clinically to treat hypertension, its functional molecular mechanism and pharmacological mechanism have not been elucidated. Therefore, in this study, the potentially effective components, and targets of P. ternata in the treatment of hypertension were screened by the method of network pharmacology, and the mechanism of P. ternata in the treatment of hypertension was analyzed by constructing a component-target relationship network, PPI interaction network, targets’ function analysis, and molecular docking. In the study, 12 potentially effective components and 88 targets were screened, and 3 potential protein modules were found and analyzed after constructing a PPI network using targets. In addition, 10 targets were selected as core targets of the PPI network. After that, the targets were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the molecular docking method is used to study the interaction between the targets and the active components. The above evidence shows that the mechanism of P. ternata in the treatment of hypertension is complicated, as it acts in many ways, mainly by affecting nerve signal transmission, cell proliferation, and apoptosis, calcium channels, and so on. The binding between targets and active components mainly depends on Pi bonds and hydrogen bonds. Using the method of network pharmacology and molecular docking to analyze the mechanism of P. ternata in the treatment of hypertension will help to provide a better scientific basis for the combined use of traditional Chinese medicine and western medicine, and will better help to improve the quality of P. ternata and point out its direction. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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16 pages, 705 KiB

Open AccessReview

Genistein: A Potent Anti-Breast Cancer Agent

by Smitha S. Bhat, Shashanka K. Prasad, Chandan Shivamallu, Kollur Shiva Prasad, Asad Syed, Pruthvish Reddy, Charley A. Cull and Raghavendra G. Amachawadi

Curr. Issues Mol. Biol. 2021, 43(3), 1502-1517; https://doi.org/10.3390/cimb43030106 - 10 Oct 2021

Cited by 51 | Viewed by 5173

Abstract

Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of [...] Read more.

Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of tyrosine kinases, regulation of Hedgehog-Gli1 signaling, modulation of epigenetic activities, seizing of cell cycle and Akt and MEK signaling pathways, among others via which the cancer cell proliferation can be controlled. Notwithstanding, the observed activities have been time- and dose-dependent. In addition, genistein has also shown varying results in women depending on the physiological parameters, such as the early or post-menopausal states. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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15 pages, 570 KiB

Open AccessReview

Antioxidant Supplements versus Health Benefits of Brief/Intermittent Exposure to Potentially Toxic Physical or Chemical Agents

by Rafael Franco, Berta Casanovas, Jordi Camps, Gemma Navarro and Eva Martínez-Pinilla

Curr. Issues Mol. Biol. 2021, 43(2), 650-664; https://doi.org/10.3390/cimb43020047 - 10 Jul 2021

Cited by 7 | Viewed by 3995

Abstract

Although antioxidants can act locally to react with an oxidant, oral administration of “antioxidants” is quite useless in treating oxidative stress in tissues. Furthermore, it does not make sense to consider a vitamin as an antioxidant, but vitamin B3 leads to the in [...] Read more.

Although antioxidants can act locally to react with an oxidant, oral administration of “antioxidants” is quite useless in treating oxidative stress in tissues. Furthermore, it does not make sense to consider a vitamin as an antioxidant, but vitamin B3 leads to the in vivo formation of compounds that are essential for reducing this stress. A rigorous treatment of the subject indicates that to deal with oxidative stress, the most direct approach is to enhance the innate antioxidant mechanisms. The question is whether this is possible through daily activities. Diets can contain the necessary components for these mechanisms or may induce the expression of the genes involved in them. Another possibility is that pro-oxidant molecules in food increase the sensitivity and power of the detoxification pathways. This option is based on well-known DNA repair mechanisms after exposure to radiation (even from the Sun), or strong evidence of induction of antioxidant capacity after exposure to powerful pro-oxidants such as H₂O₂. More experimental work is required to test whether some molecules in food can increase the expression of antioxidant enzymes and/or improve antioxidant mechanisms. Identifying effective molecules to achieve such antioxidant power is critical to the food and nutraceutical industries. The potential of diet-based interventions to combat oxidative stress must be viewed from a new perspective. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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32 pages, 1581 KiB

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Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

by Wamidh H. Talib, Asma Ismail Mahmod, Ayah Kamal, Hasan M. Rashid, Aya M. D. Alashqar, Samar Khater, Duaa Jamal and Mostafa Waly

Curr. Issues Mol. Biol. 2021, 43(2), 558-589; https://doi.org/10.3390/cimb43020042 - 03 Jul 2021

Cited by 39 | Viewed by 18955

Abstract

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet [...] Read more.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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15 pages, 2029 KiB

Open AccessReview

Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

by Matúš Čoma, Veronika Lachová, Petra Mitrengová and Peter Gál

Curr. Issues Mol. Biol. 2021, 43(1), 127-141; https://doi.org/10.3390/cimb43010011 - 17 May 2021

Cited by 11 | Viewed by 3065

Abstract

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed [...] Read more.

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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