Special Issue "Biological Efficacy of Natural Products against Noncommunicable Diseases"

A special issue of Medicines (ISSN 2305-6320).

Deadline for manuscript submissions: closed (30 June 2020).

Special Issue Editors

Prof. Dr. Marcello Iriti
Website
Guest Editor
Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy
Interests: crop protection; plant diseases; agrochemicals; abiotic stresses; food production; food security; food safety; global climate change; bioactive phytochemicals; agrochemicals; mycotoxins; medicinal plants; ethnobotany
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Special Issue Information

Dear colleagues,

According to the World Health Organization, noncommunicable diseases (NCDs), including cardiovascular diseases, cancers, respiratory diseases and diabetes, are responsible for almost 70% of all deaths worldwide. The rapid rise of NCDs has been driven by a number of (modifiable) behavioral risk factors, such as unhealthy diets, physical inactivity, exposure to tobacco smoke and the harmful use of alcoholic beverages, in addition to environmental (air pollutants), occupational (carcinogens, particulates, gases, fumes) and metabolic (hypertension, overweight/obesity, hyperglycemia, hypercholesterolemia) risk factors. Nowadays, the epidemic of NCDs poses devastating health consequences for individuals, families and communities, threatening to overwhelm health systems, particularly in low-income countries.

In this complex scenario, innovative therapeutic approaches are more than ever of paramount importance, including the use of natural products as the lead compounds for drug discovery, adjuvant agents in combination with conventional therapeutics to increase efficacy and/or reduce adverse effects, chemosensitizers or radiosensitizers in anticancer therapies. It is noteworthy that the rationale for using natural products relies on their multitarget mechanisms of action, which are of particular interest in the treatment of diseases with a multistage pathogenesis.

In this very wide context, we invite investigators to submit both original research and review articles that explore all these aspects, including preclinical (in vitro/in vivo) and in human studies (clinical trials, epidemiological studies, systematic reviews and meta-analyses).

Potential topics include, but are not limited to: formulation, evaluation of efficacy and mechanism of action, oral bioavailability, pharmacokinetics and the pharmacodynamics of natural products.

Dr. Sara Vitalini
Prof. Dr. Marcello Iriti
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 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

  • chronic degenerative diseases
  • medicinal plants
  • herbal remedies
  • bioactive phytochemicals
  • phytotherapeutics
  • botanicals
  • nutraceuticals
  • marine drugs
  • fungal metabolites
  • animal metabolites

Published Papers (9 papers)

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Research

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Open AccessArticle
A Double-Blind Randomized Placebo-Controlled Study Assessing the Safety, Tolerability and Efficacy of a Herbal Medicine Containing Pycnogenol Combined with Papain and Aloe vera in the Prevention and Management of Pre-Diabetes
Medicines 2020, 7(4), 22; https://doi.org/10.3390/medicines7040022 - 22 Apr 2020
Abstract
Background: Herbal medicines present attractive options to patients with chronic diseases. Undertaking clinical studies with patients presenting with symptomless pre-T2D can lead to significant limitations. Methods: A 12-week randomized double-blind placebo-controlled clinical study was conducted that investigated the safety and efficacy of an [...] Read more.
Background: Herbal medicines present attractive options to patients with chronic diseases. Undertaking clinical studies with patients presenting with symptomless pre-T2D can lead to significant limitations. Methods: A 12-week randomized double-blind placebo-controlled clinical study was conducted that investigated the safety and efficacy of an herbal formulation administered orally for the treatment of pre-type 2 diabetes (pre-T2D). Results: A numerically greater proportion of subjects in the interventional arm had impaired fasting glucose (IFG) at week 12 compared to the control arm (71.0% vs. 69.0%, p = 0.75). Fewer participants had impaired glucose tolerance (IGT) at 12 weeks in the intervention arm compared to the control arm (unadjusted 58.3% vs. 66.7%, p = 0.65; adjusting for baseline IGT, p = 0.266). In a subgroup analysis, subjects with a baseline fasting plasma glucose (FPG) level in the range of 6.1–6.9 mmol/L demonstrated a non-significant lower proportion of IFG at week 12 in the intervention arm compared to the control arm (60.0% vs. 41.7% p = 0.343). Total blood cholesterol and triglyceride levels remained unchanged from baseline to week 12 in both treatment groups. Conclusions: This study suggests that a polyherbal medicine was not effective for reducing the metabolic markers associated with pre-T2D over a 12-week period. Therefore, larger studies with well-defined endpoints and of longer duration are warranted. Full article
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Open AccessArticle
Piperine Inhibits TGF-β Signaling Pathways and Disrupts EMT-Related Events in Human Lung Adenocarcinoma Cells
Medicines 2020, 7(4), 19; https://doi.org/10.3390/medicines7040019 - 08 Apr 2020
Cited by 3
Abstract
Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular [...] Read more.
Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders. Full article
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Open AccessArticle
Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue
Medicines 2020, 7(4), 18; https://doi.org/10.3390/medicines7040018 - 02 Apr 2020
Abstract
Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has [...] Read more.
Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects. Full article
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Open AccessArticle
The Antioxidant and Antihyperglycemic Activities of Bottlebrush Plant (Callistemon lanceolatus) Stem Extracts
Medicines 2020, 7(3), 11; https://doi.org/10.3390/medicines7030011 - 04 Mar 2020
Cited by 3
Abstract
Background: Diabetes mellitus, a metabolic disease, is a major health concern today throughout the world. Callistemon lanceolatus (Myrtaceae), commonly known as bottlebrush, has been used by Indian tribal communities for the treatment of many diseases. The purpose of this study was to explore [...] Read more.
Background: Diabetes mellitus, a metabolic disease, is a major health concern today throughout the world. Callistemon lanceolatus (Myrtaceae), commonly known as bottlebrush, has been used by Indian tribal communities for the treatment of many diseases. The purpose of this study was to explore antioxidant and antihyperglycemic potential of methanolic and aqueous extracts of the stem of C. lanceolatus in vitro and in vivo. Methods: Phytoconstituents of C. lanceolatus stem were extracted in methanol and water sequentially followed by phytochemical analysis. The in vitro antioxidant potential of aqueous and methanolic extracts was assessed by metal ion chelating, free radical scavenging, and reducing power assays. The in vivo antihyperglycemic activity of the oral methanolic extract was studied in alloxan-induced diabetic rats. Bodyweight and blood glucose were monitored regularly. After the treatment period, serum was examined for total cholesterol, triglycerides, high-density lipoprotein (HDL), bilirubin, creatinine, urea, glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatase (ALP). Results: Methanolic extract exhibited superior antioxidant activity to aqueous extract. A marked increase in levels of serum markers, viz., glucose, triglycerides, total cholesterol, bilirubin, urea, creatinine, SGOT, SGPT, and ALP along with a reduction in HDL was observed in diabetic rats. Methanol extract treatment for 28 days accounted for a decrease in blood glucose and other metabolic markers accompanied by an improvement in body weight and HDL level in hyperglycemic rats. Conclusions: The present study suggests that C. lanceolatus methanolic stem extract possesses antioxidant and antihyperglycemic activities and has potential as a therapeutic agent in diabetes. Full article
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Open AccessArticle
Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets
Medicines 2019, 6(3), 89; https://doi.org/10.3390/medicines6030089 - 12 Aug 2019
Cited by 3
Abstract
Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits [...] Read more.
Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation. Full article
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Open AccessArticle
Reduction of Inflammation and Colon Injury by a Spearmint Phenolic Extract in Experimental Bowel Disease in Mice
Medicines 2019, 6(2), 65; https://doi.org/10.3390/medicines6020065 - 06 Jun 2019
Cited by 3
Abstract
Background: Inflammatory Bowel Diseases (IBD) encompasses both Crohn’s Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint (Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have [...] Read more.
Background: Inflammatory Bowel Diseases (IBD) encompasses both Crohn’s Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint (Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have mainly focused on the essential oil suggesting an anti-inflammatory activity. This work aimed to perform a preliminary screening of the in vivo anti-inflammatory effects of a spearmint phenolic extract in an acute inflammation model, in a chronic inflammation model of colitis, and also study the effects in vitro on a colon cancer model. Methods: Spearmint extract was administered to rats of a paw oedema model (induced by carrageenan) and to mice from a TNBS-induced colitis model in parallel with studies using HT-29 CRC cells. Results: Administration of the extract led to reduced paw inflammation, reduction of colon injury and inflammation, with attenuation of histological markers, and reduction of iNOS expression. It repressed the in vitro movement of HT-29 cells in a wound healing assay. Conclusions: These findings suggest that spearmint extract exhibits acute and chronic anti-inflammatory activity and is able to inhibit migration of cancer cells, suggesting a potential role in the supplementary therapy of IBD patients. Full article
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Review

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Open AccessReview
Medicinal Herbs Used in Traditional Management of Breast Cancer: Mechanisms of Action
Medicines 2020, 7(8), 47; https://doi.org/10.3390/medicines7080047 - 14 Aug 2020
Abstract
Background: Breast cancer is one of the principal causes of death among women and there is a pressing need to develop novel and effective anti-cancer agents. Natural plant products have shown promising results as anti-cancer agents. Their effectiveness is reported as decreased [...] Read more.
Background: Breast cancer is one of the principal causes of death among women and there is a pressing need to develop novel and effective anti-cancer agents. Natural plant products have shown promising results as anti-cancer agents. Their effectiveness is reported as decreased toxicity in usage, along with safety and less recurrent resistances compared with hormonal targeting anti-cancer agents. Methods: A literature search was conducted for all English-language literature published prior to June 2020. The search was conducted using electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library. The search strategy included keywords such as breast cancer, herbs, anti-cancer biologically active components, clinical research, chemotherapy drugs amongst others. Results: The literature provides documented evidence of the chemo-preventative and chemotherapeutic properties of Ginseng, garlic (Allium sativum), Black cohosh (Actaea racemose), Tumeric (Curcuma longa), Camellia sinenis (green tea), Echinacea, Arctium (burdock), Flaxseed (Linum usitatissimum) and Black Cumin (Nigella sativa). Conclusions: The nine herbs displayed anti-cancer properties and their outcomes and mechanisms of action include inhibition of cell proliferation, angiogenesis and apoptosis as well as modulation of key intracellular pathways. However, more clinical trials and cohort human studies should be conducted to provide key evidence of their medical benefits. Full article
Open AccessReview
Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications
Medicines 2020, 7(8), 45; https://doi.org/10.3390/medicines7080045 - 30 Jul 2020
Abstract
Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions [...] Read more.
Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine. Full article
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Open AccessReview
Zebrafish as an Emerging Model for Bioassay-Guided Natural Product Drug Discovery for Neurological Disorders
Medicines 2019, 6(2), 61; https://doi.org/10.3390/medicines6020061 - 30 May 2019
Cited by 9
Abstract
Most neurodegenerative diseases are currently incurable, with large social and economic impacts. Recently, there has been renewed interest in investigating natural products in the modern drug discovery paradigm as novel, bioactive small molecules. Moreover, the discovery of potential therapies for neurological disorders is [...] Read more.
Most neurodegenerative diseases are currently incurable, with large social and economic impacts. Recently, there has been renewed interest in investigating natural products in the modern drug discovery paradigm as novel, bioactive small molecules. Moreover, the discovery of potential therapies for neurological disorders is challenging and involves developing optimized animal models for drug screening. In contemporary biomedicine, the growing need to develop experimental models to obtain a detailed understanding of malady conditions and to portray pioneering treatments has resulted in the application of zebrafish to close the gap between in vitro and in vivo assays. Zebrafish in pharmacogenetics and neuropharmacology are rapidly becoming a widely used organism. Brain function, dysfunction, genetic, and pharmacological modulation considerations are enhanced by both larval and adult zebrafish. Bioassay-guided identification of natural products using zebrafish presents as an attractive strategy for generating new lead compounds. Here, we see evidence that the zebrafish’s central nervous system is suitable for modeling human neurological disease and we review and evaluate natural product research using zebrafish as a vertebrate model platform to systematically identify bioactive natural products. Finally, we review recently developed zebrafish models of neurological disorders that have the potential to be applied in this field of research. Full article
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