Editorial

2 pages, 186 KiB

Open AccessEditorial

Editorial for the Special Issue “Bioactive Compounds of Natural Products on Metabolic Disorders and Complications”

by Wai San Cheang

Curr. Issues Mol. Biol. 2023, 45(7), 5706-5707; https://doi.org/10.3390/cimb45070359 - 05 Jul 2023

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Metabolic disorders are complex abnormalities involving impaired glucose and lipid metabolism, associated with complications such as kidney disease, cardiovascular disease, foot ulcer, retinopathy, and neuropathy [...] Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

Research

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18 pages, 6770 KiB

Open AccessArticle

Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome

by Mikhail E. Blokhin, Sergey O. Kuranov, Mikhail V. Khvostov, Vladislav V. Fomenko, Olga A. Luzina, Natalia A. Zhukova, Cham Elhajjar, Tatiana G. Tolstikova and Nariman F. Salakhutdinov

Curr. Issues Mol. Biol. 2023, 45(3), 2230-2247; https://doi.org/10.3390/cimb45030144 - 08 Mar 2023

Cited by 1 | Viewed by 1252

Abstract

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized [...] Read more.

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6^Ay) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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19 pages, 6027 KiB

Open AccessArticle

Network Pharmacological Analysis of a New Herbal Combination Targeting Hyperlipidemia and Efficacy Validation In Vitro

by Tae-Hyoung Kim, Ga-Ram Yu, Hyuck Kim, Jai-Eun Kim, Dong-Woo Lim and Won-Hwan Park

Curr. Issues Mol. Biol. 2023, 45(2), 1314-1332; https://doi.org/10.3390/cimb45020086 - 04 Feb 2023

Cited by 4 | Viewed by 2057

Abstract

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This [...] Read more.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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9 pages, 4049 KiB

Open AccessArticle

Antioxidant Efficacy of Esculetin against Tert-Butyl Hydroperoxide-Induced Oxidative Stress in HEK293 Cells

by Woo Kwon Jung, Su-Bin Park, Hwa Young Yu, Yong Hwan Kim and Junghyun Kim

Curr. Issues Mol. Biol. 2022, 44(12), 5986-5994; https://doi.org/10.3390/cimb44120407 - 29 Nov 2022

Cited by 9 | Viewed by 1799

Abstract

Esculetin is an antioxidant and anti-inflammatory compound derived from coumarin. Oxidative stress can cause overproduction of reactive oxygen species (ROS), which can lead to the development of chronic kidney failure. In this study, human embryonic kidney 293 (HEK293) cells were treated with tert-butyl [...] Read more.

Esculetin is an antioxidant and anti-inflammatory compound derived from coumarin. Oxidative stress can cause overproduction of reactive oxygen species (ROS), which can lead to the development of chronic kidney failure. In this study, human embryonic kidney 293 (HEK293) cells were treated with tert-butyl hydroperoxide (t-BHP) to determine the antioxidant effects of esculetin. HEK293 cells were treated with t-BHP to validate changes in cell viability, ROS production, and apoptosis, and then treated with esculetin to evaluate the changes. Changes in mRNA and protein levels were analyzed using a proteome kit, PCR, and Western blotting. Esculetin improved HEK293 cell viability and reduced apoptosis caused by t-BHP-induced oxidative stress. At the mRNA and protein levels, esculetin decreased pro-apoptotic factor expression as well as increased anti-apoptotic factor expression. The antioxidant efficacy of esculetin was validated when it inhibited the apoptosis caused by t-BHP-induced oxidative stress in HEK293 cells. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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15 pages, 2597 KiB

Open AccessArticle

Nitric Oxide Synthesis Metabolites—As Potential Markers in Chronic Kidney Disease in Children

by Joanna Piechowicz, Andrzej Gamian, Ositadima Chukwu and Dorota Polak-Jonkisz

Curr. Issues Mol. Biol. 2022, 44(8), 3518-3532; https://doi.org/10.3390/cimb44080242 - 07 Aug 2022

Cited by 3 | Viewed by 1717

Abstract

Nitric oxide (NO) is an important signaling molecule for many physiological and pathological processes. Diseases associated with abnormal NO synthesis include cardiovascular diseases, insulin-dependent diabetes, or chronic kidney disease (CKD). The aim of the paper was to evaluate NO synthesis metabolites, i.e., asymmetric [...] Read more.

Nitric oxide (NO) is an important signaling molecule for many physiological and pathological processes. Diseases associated with abnormal NO synthesis include cardiovascular diseases, insulin-dependent diabetes, or chronic kidney disease (CKD). The aim of the paper was to evaluate NO synthesis metabolites, i.e., asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine (DMA), arginine, citrulline in plasma of patients with different severity of CKD and to seek possible links between these parameters and the development of this disease. Forty-eight CKD children and thirty-three age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III-stage III, Group IV-stage IV, and Group RRT children on dialysis). To determine the concentrations of the above-mentioned metabolites in plasma liquid chromatography-mass spectrometry was used. There were significant differences observed in levels of ADMA, SDMA, DMA, and citrulline between control vis CKD groups (p values ranging from <0.001 to 0.029). Plasma arginine concentration was also higher in CKD patients compared to the control group but statistically insignificant. ADMA levels in CKD children were statistically significantly higher in relation to particular stages of CKD (RRT vis II stage of CKD: p = 0.01; RRT vis III-IV stages of CKD: p < 0.046). Citrulline levels in CKD children were statistically significantly higher in RRT group vis control (p < 0.001). Children with CKD develop disturbances in most metabolites of NO synthesis. Dialysis children treated show the greatest disturbances of plasma ADMA and citrulline levels. ADMA seems to be a good indicator of the gradual progression of the CKD, which is proved by the negative correlation with eGFR. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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15 pages, 3638 KiB

Open AccessArticle

Effects of Dietary Inclusion of β-Hydroxy-β-Methylbutyrate on Growth Performance, Fat Deposition, Bile Acid Metabolism, and Gut Microbiota Function in High-Fat and High-Cholesterol Diet-Challenged Layer Chickens

by Qichao Liao, Tian Wu, Qinghua Fu, Peng Wang, Yameng Zhao, Yan Li, Haihan Xiao, Lei Zhou and Ziyi Song

Curr. Issues Mol. Biol. 2022, 44(8), 3413-3427; https://doi.org/10.3390/cimb44080235 - 30 Jul 2022

Cited by 8 | Viewed by 2005

Abstract

Excessive lipid deposition in layer chickens due to inappropriate feeding adversely affects egg production; however, nutritional manipulation methods to deal with this issue are still limited. β-hydroxy-β-methylbutyrate (HMB), a metabolite of L-leucine, was recently reported as a lipid-lowering nutrient in mice and pigs, [...] Read more.

Excessive lipid deposition in layer chickens due to inappropriate feeding adversely affects egg production; however, nutritional manipulation methods to deal with this issue are still limited. β-hydroxy-β-methylbutyrate (HMB), a metabolite of L-leucine, was recently reported as a lipid-lowering nutrient in mice and pigs, although its role in layers had not been investigated. Here, we employed high-fat and high-cholesterol diet (HFHCD)−challenged growing layers as an obese model to explore HMB function in the regulation of lipid metabolism and the potential mechanisms involved. We found that dietary supplementation with (0.05% or 0.10%) HMB significantly reduced HFHCD−induced bodyweight growth in layers, mainly due to reduction in abdominal fat deposition. Mechanistically, HMB supplementation enhanced hepatic bile acid synthesis from cholesterol through elevating expression of Cyp7a1, a gene coding a key enzyme in bile acid synthesis. Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation remodeled the diversity and composition of the layers’ cecal microbiota, and the abundance of Bacteroidetes at the phylum level were especially affected. Correlation analysis further indicated a strong negative association between Bacteroidetes abundance and lipid metabolism−related parameters. Taken together, these data suggest that dietary HMB supplementation could improve abdominal fat deposition in layers, probably through modulating hepatic bile acid synthesis and gut microbiota function. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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11 pages, 1307 KiB

Open AccessArticle

3,3′,4,5′-Tetramethoxy-trans-stilbene Improves Insulin Resistance by Activating the IRS/PI3K/Akt Pathway and Inhibiting Oxidative Stress

by Yi Tan, Lingchao Miao, Jianbo Xiao and Wai San Cheang

Curr. Issues Mol. Biol. 2022, 44(5), 2175-2185; https://doi.org/10.3390/cimb44050147 - 12 May 2022

Cited by 8 | Viewed by 4261

Abstract

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS [...] Read more.

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS increased the potential of glucose consumption and glycogen synthesis in a concentration-dependent manner in IR-HepG2 cells. 3,3′,4,5′-TMS ameliorated insulin resistance by enhancing the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), inhibiting phosphorylation of insulin receptor substrate-1 (IRS-1), and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Furthermore, 3,3′,4,5′-TMS significantly suppressed levels of reactive oxygen species (ROS) with up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. To conclude, the beneficial effect of 3,3′,4,5′-TMS against insulin resistance to increase glucose consumption and glycogen synthesis was mediated through activation of IRS/PI3K/Akt signaling pathways in the IR-HepG2 cells, accomplished with anti-oxidative activity through up-regulation of Nrf2. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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Review

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17 pages, 693 KiB

Open AccessReview

Beneficial Effects of Red Wine Polyphenols on Human Health: Comprehensive Review

by Ivana Buljeta, Anita Pichler, Josip Šimunović and Mirela Kopjar

Curr. Issues Mol. Biol. 2023, 45(2), 782-798; https://doi.org/10.3390/cimb45020052 - 17 Jan 2023

Cited by 18 | Viewed by 6286

Abstract

Polyphenols are secondary plant metabolites synthesized during the development of the grape berry as a response to stress conditions. They are important constituents in red wines that contribute to the sensory properties and antioxidant activity of wines. Due to the development of highly [...] Read more.

Polyphenols are secondary plant metabolites synthesized during the development of the grape berry as a response to stress conditions. They are important constituents in red wines that contribute to the sensory properties and antioxidant activity of wines. Due to the development of highly sophisticated analytical devices, it is now possible to characterize the structure of highly polymerized polyphenols and obtain a full polyphenol profile of red wines. Red wine polyphenols include the ones present in grapes as well as new polyphenol products formed during the winemaking process. Among them, the most important groups and their representatives are flavanols (catechin), stilbenes (trans-resveratrol), flavonols (quercetin) and hydroxybenzoic acids (gallic acid). It is known that polyphenols exhibit beneficial effects on human health, such as anti-inflammatory, anticarcinogenic and cardio-protective effects. Many studies have been conducted on the health effects of red wine polyphenols in cancer chemopreventive activities, neuroprotective effects and impact on cardiovascular diseases, gut microbiota in humans, etc. This review will provide major scientific findings on the impact of red wine polyphenols on human health as well as a review of polyphenols present in red wines and their main features. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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17 pages, 3898 KiB

Open AccessPerspective

Anxiety and Metabolic Disorders: The Role of Botanicals

by Hanna Trebesova, Valentina Orlandi, Raffaella Boggia and Massimo Grilli

Curr. Issues Mol. Biol. 2023, 45(2), 1037-1053; https://doi.org/10.3390/cimb45020068 - 28 Jan 2023

Cited by 1 | Viewed by 2313

Abstract

Anxiety and anxiety-related disorders are becoming more evident every day, affecting an increasing number of people around the world. Metabolic disorders are often associated with anxiety. Furthermore, anxiety branches into metabolic disorders by playing multiple roles as a cofactor, symptom, and comorbidity. Taken [...] Read more.

Anxiety and anxiety-related disorders are becoming more evident every day, affecting an increasing number of people around the world. Metabolic disorders are often associated with anxiety. Furthermore, anxiety branches into metabolic disorders by playing multiple roles as a cofactor, symptom, and comorbidity. Taken together, these considerations open the possibility of integrating the therapy of metabolic disorders with specific drugs for anxiety control. However, anxiolytic compounds often cause disabling effects in patients. The main goal could be to combine therapeutic protocols with compounds capable of reducing side effects while performing multiple beneficial effects. In this article we propose a group of bioactive ingredients called botanicals as a healthy supplement for the treatment of metabolic disorders related to anxiety. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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