Special Issue "Potential Mechanism of Natural-Based Biomolecules for Disease Treatment"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-inspired Molecules".

Deadline for manuscript submissions: closed (22 May 2022) | Viewed by 7840

Special Issue Editor

Dr. Hang Fai Kwok
E-Mail Website
Guest Editor
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China
Interests: protease biochemistry; toxins; anti-cancer drug discovery; antibody therapy; venom-based peptides; prognostic and diagnostic biomarkers; proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of the previous Special Issue, "Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases" (https://www.mdpi.com/journal/biomolecules/special_issues/natural-based_biomolecules).

Natural-based biomolecules continuously play an important role in novel drug discovery for the treatment of various diseases. The development of natural peptide/protein-based, toxin-based, and antibody-based drugs can significantly improve the biomedical efficiency of disease-specific therapy.

This Special Issue explores the mechanisms and roles of signaling components in natural-based biomolecules, which have led to target therapy and immunotherapy for tackling diseases (e.g. cancer, diabetes, cardiovascular diseases, and rheumatoid arthritis), including but not limited to functional analysis of key genes, hormone contents, signal transduction networks, gene expression profiling, and post-translation modifications.

Prof. Dr. Hang Fai Kwok
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2100 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibody therapy
  • peptide/protein drug
  • natural toxins
  • targeted therapy
  • immunotherapy
  • combinatorial treatment
  • mode of action

Published Papers (8 papers)

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Research

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Article
Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of Pelophylax kl. esculentus, and Evaluation of Its Structure-Activity Relationships
Biomolecules 2022, 12(6), 759; https://doi.org/10.3390/biom12060759 - 29 May 2022
Viewed by 417
Abstract
Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of Pelophylax kl. esculentus and it displays a [...] Read more.
Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of Pelophylax kl. esculentus and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and Klebsiella pneumoniae, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug. Full article
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Article
Decapeptide from Potato Hydrolysate Induces Myogenic Differentiation and Ameliorates High Glucose-Associated Modulations in Protein Synthesis and Mitochondrial Biogenesis in C2C12 Cells
Biomolecules 2022, 12(4), 565; https://doi.org/10.3390/biom12040565 - 11 Apr 2022
Viewed by 684
Abstract
Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are [...] Read more.
Sarcopenia is characterized as an age-related loss of muscle mass that results in negative health consequences such as decreased strength, insulin resistance, slowed metabolism, increased body fat mass, and a substantially diminished quality of life. Additionally, conditions such as high blood sugar are known to further exacerbate muscle degeneration. Skeletal muscle development and regeneration following injury or disease are based on myoblast differentiation. Bioactive peptides are biologically active peptides found in foods that could have pharmacological functions. The aim of this paper was to investigate the effect of decapeptide DI-10 from the potato alcalase hydrolysate on myoblast differentiation, muscle protein synthesis, and mitochondrial biogenesis in vitro. The treatment of C2C12 myoblasts with DI-10 (10 µg/mL) did not induce cell death. DI-10 treatment in C2C12 myoblast cells accelerates the phosphorylation of promyogenic kinases such as ERK, Akt and mTOR proteins in a dose-dependent manner. DI-10 improves myotubes differentiation and upregulates the expression of myosin heavy chain (MyHC) protein in myoblast cells under differentiation medium with high glucose. DI-10 effectively increased the phosphorylation of promyogenic kinases Akt, mTOR, and mitochondrial-related transcription factors AMPK and PGC1α expression under hyperglycemic conditions. Further, decapeptide DI-10 decreased the expression of Murf1 and MAFbx proteins, which are involved in protein degradation and muscle atrophy. Our reports support that decapeptide DI-10 could be potentially used as a therapeutic candidate for preventing muscle degeneration in sarcopenia. Full article
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Article
Physiological Concentrations of Cimicifuga racemosa Extract Do Not Affect Expression of Genes Involved in Estrogen Biosynthesis and Action in Endometrial and Ovarian Cell Lines
Biomolecules 2022, 12(4), 545; https://doi.org/10.3390/biom12040545 - 05 Apr 2022
Viewed by 590
Abstract
In postmenopausal women, estrogen levels exclusively depend on local formation from the steroid precursors dehydroepiandrosterone sulfate and estrone sulfate (E1-S). Reduced estrogen levels are associated with menopausal symptoms. To mitigate these symptoms, more women nowadays choose medicine of natural origin, e.g., Cimicifuga racemosa [...] Read more.
In postmenopausal women, estrogen levels exclusively depend on local formation from the steroid precursors dehydroepiandrosterone sulfate and estrone sulfate (E1-S). Reduced estrogen levels are associated with menopausal symptoms. To mitigate these symptoms, more women nowadays choose medicine of natural origin, e.g., Cimicifuga racemosa (CR), instead of hormone replacement therapy, which is associated with an increased risk of breast cancer, stroke, and pulmonary embolism. Although CR treatment is considered safe, little is known about its effects on healthy endometrial and ovarian tissue and hormone-dependent malignancies, e.g., endometrial and ovarian cancers that arise during menopause. The aim of our study was to examine the effects of CR on the expression of genes encoding E1-S transporters and estrogen-related enzymes in control and cancerous endometrial and ovarian cell lines. CR affected the expression of genes encoding E1-S transporters and estrogen-related enzymes only at very high concentrations, whereas no changes were observed at physiological concentrations of CR. This suggests that CR does not exert estrogenic effects in endometrial and ovarian tissues and probably does not affect postmenopausal women’s risks of endometrial or ovarian cancer or the outcomes of endometrial and ovarian cancer patients. Full article
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Article
Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes
Biomolecules 2021, 11(12), 1764; https://doi.org/10.3390/biom11121764 - 25 Nov 2021
Cited by 3 | Viewed by 820
Abstract
Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies [...] Read more.
Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs. Full article
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Article
Postprandial Bioactivity of a Spread Cheese Enriched with Mountain Tea and Orange Peel Extract in Plasma Oxidative Stress Status, Serum Lipids and Glucose Levels: An Interventional Study in Healthy Adults
Biomolecules 2021, 11(8), 1241; https://doi.org/10.3390/biom11081241 - 19 Aug 2021
Cited by 2 | Viewed by 1131
Abstract
Postprandial lipemia, glycemia and oxidative stress may affect the occurrence of cardiovascular disease. The purpose of the present intervention study was to investigate the effect of a spread cheese enriched with mountain tea (Sideritis sp.) and orange peel (Citrus sinensis) [...] Read more.
Postprandial lipemia, glycemia and oxidative stress may affect the occurrence of cardiovascular disease. The purpose of the present intervention study was to investigate the effect of a spread cheese enriched with mountain tea (Sideritis sp.) and orange peel (Citrus sinensis) extract on postprandial metabolic biomarkers in healthy volunteers. In a cross-over design, 14 healthy subjects 20–30 years old were consumed either a meal rich in fat and carbohydrates (80 g white bread, 40 g butter and 30 g full fat spread cheese) or a meal with the spread cheese enriched with 6% mountain tea–orange peel extract. Differences in postprandial total plasma antioxidant capacity, resistance of plasma to oxidation, serum lipids, glucose and uric acid levels were evaluated at 0, 1.5 and 3 h after consumption. Plasma total antioxidant capacity was significantly increased 3 h after the consumption of the meal in the presence of the extract-enriched cheese, compared to the conventional cheese (p = 0.05). Plasma resistance to oxidation was increased at 30 min in the Functional meal compared with the Control meal. A tendency to decrease the postprandial rise in glucose and triglyceride levels, 1.5 h and 3 h, respectively, after the intake of the meal with the extract-enriched cheese was observed (p = 0.062). No significant changes in the concentrations of the remaining biomarkers studied were observed (p > 0.05). Further studies with a larger sample are needed in both healthy adults and patients with cardiovascular disease to draw safer conclusions about the postprandial effect of the extracts on metabolic biomarkers that predict cardiovascular risk. Full article
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Article
Combined Beneficial Effect of Genistein and Atorvastatin on Adipogenesis in 3T3-L1 Adipocytes
Biomolecules 2021, 11(7), 1052; https://doi.org/10.3390/biom11071052 - 18 Jul 2021
Viewed by 1076
Abstract
Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been [...] Read more.
Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been reported to possess antiadipogenic effects, their combined effects are still unclear. The aim of the current study was to explore whether the combination of genistein and atorvastatin at low concentrations significantly suppresses adipogenesis in a murine preadipocyte cell line (3T3-L1) compared to treatment with genistein or atorvastatin alone. Our results showed that cotreatment with 50 µM genistein and 50 nM atorvastatin significantly suppressed preadipocyte differentiation, whereas when each compound was used alone, there was no inhibitory effect. Additionally, cotreatment with genistein and atorvastatin significantly downregulated adipogenic marker proteins, including mitogen-activated protein kinases (MAPKs), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), glucocorticoid receptor (GR), and CCAAT/enhancer-binding protein β (C/EBPβ). This is the first evidence of the combined antiadipogenic effects of genistein and atorvastatin. Although additional experiments are required, combinational treatment with genistein and atorvastatin may be an alternative treatment for menopause-associated lipid metabolic disorders and obesity. Full article
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Review

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Review
Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age
Biomolecules 2022, 12(3), 371; https://doi.org/10.3390/biom12030371 - 25 Feb 2022
Cited by 2 | Viewed by 1005
Abstract
Alzheimer’s and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology of these disorders is not well known; however, environmental, molecular, and genetic influences play a major role in the pathogenesis of these diseases. Using Alzheimer’s disease (AD) [...] Read more.
Alzheimer’s and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology of these disorders is not well known; however, environmental, molecular, and genetic influences play a major role in the pathogenesis of these diseases. Using Alzheimer’s disease (AD) as the archetype, the pathological findings include the aggregation of Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), and cerebrovascular dysregulation. This review highlights the neuroinflammatory and neuroprotective role of epigallocatechin-3-gallate (EGCG): the medicinal component of green tea, a known nutraceutical that has shown promise in modulating AD progression due to its antioxidant, anti-inflammatory, and anti-aging abilities. This report also re-examines the current literature and provides innovative approaches for EGCG to be used as a preventive measure to alleviate AD and other neurodegenerative disorders. Full article
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Review
Potential Mechanisms of Plant-Derived Natural Products in the Treatment of Cervical Cancer
Biomolecules 2021, 11(10), 1539; https://doi.org/10.3390/biom11101539 - 18 Oct 2021
Cited by 2 | Viewed by 922
Abstract
Cervical cancer is the second most common gynecological malignancy globally; it seriously endangers women’s health because of its high morbidity and mortality. Conventional treatments are prone to drug resistance, recurrence and metastasis. Therefore, there is an urgent need to develop new drugs with [...] Read more.
Cervical cancer is the second most common gynecological malignancy globally; it seriously endangers women’s health because of its high morbidity and mortality. Conventional treatments are prone to drug resistance, recurrence and metastasis. Therefore, there is an urgent need to develop new drugs with high efficacy and low side effects to prevent and treat cervical cancer. In recent years, plant-derived natural products have been evaluated as potential anticancer drugs that preferentially kill tumor cells without severe adverse effects. A growing number of studies have shown that natural products can achieve practical anti-cervical-cancer effects through multiple mechanisms, including inhibition of tumor-cell proliferation, induction of apoptosis, suppression of angiogenesis and telomerase activity, enhancement of immunity and reversal of multidrug resistance. This paper reviews the therapeutic effects and mechanisms of plant-derived natural products on cervical cancer and provides references for developing anti-cervical-cancer drugs with high efficacy and low side effects. Full article
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