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1.
Targeting hallmarks of cancer with a food-system-based approach.
Lachance, JC, Radhakrishnan, S, Madiwale, G, Guerrier, S, Vanamala, JKP
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110563
Abstract
Although extensive resources are dedicated to the development and study of cancer drugs, the cancer burden is expected to rise by about 70% over the next 2 decade. This highlights a critical need to develop effective, evidence-based strategies for countering the global rise in cancer incidence. Except in high-risk populations, cancer drugs are not generally suitable for use in cancer prevention owing to potential side effects and substantial monetary costs (Sporn, 2011). There is overwhelming epidemiological and experimental evidence that the dietary bioactive compounds found in whole plant-based foods have significant anticancer and chemopreventative properties. These bioactive compounds often exert pleiotropic effects and act synergistically to simultaneously target multiple pathways of cancer. Common bioactive compounds in fruits and vegetables include carotenoids, glucosinolates, and polyphenols. These compounds have been shown to target multiple hallmarks of cancer in vitro and in vivo and potentially to address the diversity and heterogeneity of certain cancers. Although many studies have been conducted over the past 30 y, the scientific community has still not reached a consensus on exactly how the benefit of bioactive compounds in fruits and vegetables can be best harnessed to help reduce the risk for cancer. Different stages of the food processing system, from "farm-to-fork," can affect the retention of bioactive compounds and thus the chemopreventative properties of whole foods, and there are opportunities to improve handling of foods throughout the stages in order to best retain their chemopreventative properties. Potential target stages include, but are not limited to, pre- and postharvest management, storage, processing, and consumer practices. Therefore, there is a need for a comprehensive food-system-based approach that not only taking into account the effects of the food system on anticancer activity of whole foods, but also exploring solutions for consumers, policymakers, processors, and producers. Improved knowledge about this area of the food system can help us adjust farm-to-fork operations in order to consistently and predictably deliver desired bioactive compounds, thus better utilizing them as invaluable chemopreventative tools in the fight to reduce the growing burden of cancer worldwide.
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2.
Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease.
Evans, LW, Stratton, MS, Ferguson, BS
Natural product reports. 2020;(5):653-676
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Abstract
Covering: up to 2020Chronic, low-grade inflammation is linked to aging and has been termed "inflammaging". Inflammaging is considered a key contributor to the development of metabolic dysfunction and a broad spectrum of diseases or disorders including declines in brain and heart function. Genome-wide association studies (GWAS) coupled with epigenome-wide association studies (EWAS) have shown the importance of diet in the development of chronic and age-related diseases. Moreover, dietary interventions e.g. caloric restriction can attenuate inflammation to delay and/or prevent these diseases. Common themes in these studies entail the use of phytochemicals (plant-derived compounds) or the production of short chain fatty acids (SCFAs) as epigenetic modifiers of DNA and histone proteins. Epigenetic modifications are dynamically regulated and as such, serve as potential therapeutic targets for the treatment or prevention of age-related disease. In this review, we will focus on the role for natural products that include phytochemicals and short chain fatty acids (SCFAs) as regulators of these epigenetic adaptations. Specifically, we discuss regulators of methylation, acetylation and acylation, in the protection from chronic inflammation driven metabolic dysfunction and deterioration of neurocognitive and cardiac function.
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Polyphenols: Potential Beneficial Effects of These Phytochemicals in Athletes.
D'Angelo, S
Current sports medicine reports. 2020;(7):260-265
Abstract
An athlete's dietary requirements depend on several aspects, including the environment, the sport, and the athlete's goals. Although it is recognized that regular exercise improves muscle performance and energy metabolism, unaccustomed or excessive exercise may cause cell damage and impair muscle function by triggering tissue inflammation and oxidative stress. Supplement use among athletes is widespread and recently new attention has been applied to polyphenols. Polyphenols are a class of organic chemical compounds, mainly found in plants, characterized by the presence of multiples of phenol structural units, and over recent decades, special attention has been paid to the healthy role of fruit-derived polyphenols in the human diet. This article will summarize latest knowledge on polyphenolic compounds that have been demonstrated both to exert an effect in exercise-induced muscle damage and to play a biological/physiological role in improving physical performance.
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Phytochemicals impact on osteogenic differentiation of mesenchymal stem cells.
Sharifi, S, Moghaddam, FA, Abedi, A, Maleki Dizaj, S, Ahmadian, S, Abdolahinia, ED, Khatibi, SMH, Samiei, M
BioFactors (Oxford, England). 2020;(6):874-893
Abstract
Medicinal plants have always been utilized for the prevention and treatment of the spread of different diseases all around the world. To name some traditional medicine that has been used over centuries, we can refer to phytochemicals such as naringin, icariin, genistein, and resveratrol gained from plants. Osteogenic differentiation and mineralization of stem cells can be the result of specific bioactive compounds from plants. One of the most appealing choices for therapy can be mesenchymal stem cells (MSCs) because it has a great capability of self-renewal and differentiation into three descendants, namely, endoderm, mesoderm, and ectoderm. Stem cell gives us the glad tidings of great advances in tissue regeneration and transplantation field for treatment of diseases. Using plant bioactive phytochemicals also holds tremendous promises in treating diseases such as osteoporosis. The purpose of the present review article thus is to investigate what are the roles and consequences of phytochemicals on osteogenic differentiation of MSCs.
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The Role of Exosomes in Stemness and Neurodegenerative Diseases-Chemoresistant-Cancer Therapeutics and Phytochemicals.
Beeraka, NM, Doreswamy, SH, Sadhu, SP, Srinivasan, A, Pragada, RR, Madhunapantula, SV, Aliev, G
International journal of molecular sciences. 2020;(18)
Abstract
Exosomes exhibit a wide range of biological properties and functions in the living organisms. They are nanometric vehicles and used for delivering drugs, as they are biocompatible and minimally immunogenic. Exosomal secretions derived from cancer cells contribute to metastasis, immortality, angiogenesis, tissue invasion, stemness and chemo/radio-resistance. Exosome-derived microRNAs (miRNAs) and long non-coding RNAs (lnc RNAs) are involved in the pathophysiology of cancers and neurodegenerative diseases. For instance, exosomes derived from mesenchymal stromal cells, astrocytes, macrophages, and acute myeloid leukemia (AML) cells are involved in the cancer progression and stemness as they induce chemotherapeutic drug resistance in several cancer cells. This review covered the recent research advances in understanding the role of exosomes in cancer progression, metastasis, angiogenesis, stemness and drug resistance by illustrating the modulatory effects of exosomal cargo (ex. miRNA, lncRNAs, etc.) on cell signaling pathways involved in cancer progression and cancer stem cell growth and development. Recent reports have implicated exosomes even in the treatment of several cancers. For instance, exosomes-loaded with novel anti-cancer drugs such as phytochemicals, tumor-targeting proteins, anticancer peptides, nucleic acids are known to interfere with drug resistance pathways in several cancer cell lines. In addition, this review depicted the need to develop exosome-based novel diagnostic biomarkers for early detection of cancers and neurodegenerative disease. Furthermore, the role of exosomes in stroke and oxidative stress-mediated neurodegenerative diseases including Alzheimer's disease (AD), and Parkinson's disease (PD) is also discussed in this article.
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Plant Phytochemicals in Food Preservation: Antifungal Bioactivity: A Review.
Redondo-Blanco, S, Fernández, J, López-Ibáñez, S, Miguélez, EM, Villar, CJ, Lombó, F
Journal of food protection. 2020;(1):163-171
Abstract
Synthetic food additives generate a negative perception in consumers. This fact generates an important pressure on food manufacturers, searching for safer natural alternatives. Phytochemicals (such as polyphenols and thiols) and plant essential oils (terpenoids) possess antimicrobial activities that are able to prevent food spoilage due to fungi (e.g., Aspergillus, Penicillium) and intoxications (due to mycotoxins), both of which are important economic and health problems worldwide. This review summarizes industrially interesting antifungal bioactivities from the three main types of plant nutraceuticals: terpenoids (as thymol), polyphenols (as resveratrol) and thiols (as allicin) as well as some of the mechanisms of action. These phytochemicals are widely distributed in fruits and vegetables and are very useful in food preservation as they inhibit growth of important spoilage and pathogenic fungi, affecting especially mycelial growth and germination. Terpenoids and essential oils are the most abundant group of secondary metabolites found in plant extracts, especially in common aromatic plants, but polyphenols are a more remarkable group of bioactive compounds as they show a broad array of bioactivities.
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Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials.
Rezaeiamiri, E, Bahramsoltani, R, Rahimi, R
Clinical nutrition (Edinburgh, Scotland). 2020;(2):331-342
Abstract
BACKGROUND & AIMS Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting a growing number of patients all over the world. T2DM complications are positively associated with HbA1c which is a long-term glycemic marker. Medicinal plants and their isolated phytochemicals have been extensively used as dietary supplements for the management of chronic disorders including T2DM. Current paper aims to review clinical trials evaluated the effect of phytochemicals for long-term management of T2DM considering the HbA1c level. METHODS Electronic databases including PubMed, Scopus and Cochrane were searched using the keywords "phytochemical", "extract", "herb", or "plant" and "HbA1c" or "glycosylated hemoglobin" in the title/abstract from the date of inception until May 2017. English and Persian language papers were included. References of the retrieved papers were also screened for relevant studies. RESULTS Of 2435 studies, 39 relevant clinical trials were finally included in which phytochemicals including berberine, curcumin, catechin, silymarin, resveratrol, pycnogenol, isoflavones, lignans, isohumulone, saponins, corn bran hemicellulose and pinitol were examined. Berberine and silymarin had the strongest evidence regarding their effectiveness in long-term management of HbA1c; however, lack of enough toxicological studies suggests to stay on the safe side for the administration of these agents in diabetic patients. CONCLUSIONS Current data regarding the efficacy of other phytochemicals are still controversial due to small follow-up period, methodological problems and small sample size. Future well-designed clinical trials are necessary to confirm the safety and efficacy of phytochemicals for long-term glycemic control of diabetic patients.
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Cardioprotective Effects of Dietary Phytochemicals on Oxidative Stress in Heart Failure by a Sex-Gender-Oriented Point of View.
Komici, K, Conti, V, Davinelli, S, Bencivenga, L, Rengo, G, Filippelli, A, Ferrara, N, Corbi, G
Oxidative medicine and cellular longevity. 2020;:2176728
Abstract
Dietary phytochemicals are considered an innovative strategy that helps to reduce cardiovascular risk factors. Some phytochemicals have been shown to play a beneficial role in lipid metabolism, to improve endothelial function and to modify oxidative stress pathways in experimental and clinical models of cardiovascular impairment. Importantly, investigation on phytochemical effect on cardiac remodeling appears to be promising. Nowadays, drug therapy and implantation of devices have demonstrated to ameliorate survival. Of interest, sex-gender seems to influence the response to HF canonical therapies. In fact, starting by the evidence of the feminization of world population and the scarce efficacy and safety of the traditional drugs in women, the search of alternative therapeutic tools has become mandatory. The aim of this review is to summarize the possible role of dietary phytochemicals in HF therapy and the evidence of a different sex-gender-oriented response.
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Global multi-omics and systems pharmacological strategy unravel the multi-targeted therapeutic potential of natural bioactive molecules against COVID-19: An in silico approach.
Muthuramalingam, P, Jeyasri, R, Valliammai, A, Selvaraj, A, Karthika, C, Gowrishankar, S, Pandian, SK, Ramesh, M, Chen, JT
Genomics. 2020;(6):4486-4504
Abstract
Understanding the immunological behavior of COVID-19 cases at molecular level is essential for therapeutic development. In this study, multi-omics and systems pharmacology analyses were performed to unravel the multi-targeted mechanisms of novel bioactives to combat COVID-19. Immuno-transcriptomic dataset of healthy controls and COVID-19 cases was retrieved from ArrayExpress. Phytocompounds from ethnobotanical plants were collected from PubChem. Differentially expressed 98 immune genes associated with COVID-19 were derived through NetworkAnalyst 3.0. Among 259 plant derived compounds, 154 compounds were targeting 13 COVID-19 immune genes involved in diverse signaling pathways. In addition, pharmacological properties of these phytocompounds were compared with COVID-19 drugs prescribed by WHO, and 25 novel phytocompounds were found to be more efficient with higher bioactive scores. The current study unravels the virogenomic signatures which can serve as therapeutic targets and identified phytocompounds with anti-COVID-19 efficacy. However, further experimental validation is essential to bring out these molecules as commercial drug candidates.
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The natural way forward: Molecular dynamics simulation analysis of phytochemicals from Indian medicinal plants as potential inhibitors of SARS-CoV-2 targets.
Parida, PK, Paul, D, Chakravorty, D
Phytotherapy research : PTR. 2020;(12):3420-3433
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Abstract
The pandemic COVID-19 has become a global panic-forcing life towards a compromised "new normal." Antiviral therapy against SARS-CoV-2 is still lacking. Thus, development of natural inhibitors as a prophylactic measure is an attractive strategy. In this context, this work explored phytochemicals as potential inhibitors for SARS-CoV-2 by performing all atom molecular dynamics simulations using high performance computing for 8 rationally screened phytochemicals from Withania somnifera and Azadirachta indica and two repurposed drugs docked with the spike glycoprotein and the main protease of SARS-CoV-2. These phytochemicals were rationally screened from 55 Indian medicinal plants in our previous work. MM/PBSA, principal component analysis (PCA), dynamic cross correlation matrix (DCCM) plots and biological pathway enrichment analysis were performed to reveal the therapeutic efficacy of these phytochemicals. The results revealed that Withanolide R (-141.96 KJ/mol) and 2,3-Dihydrowithaferin A (-87.60 KJ/mol) were with the lowest relative free energy of binding for main protease and the spike proteins respectively. It was also observed that the phytochemicals exhibit a remarkable multipotency with the ability to modulate various human biological pathways especially pathways in cancer. Conclusively we suggest that these compounds need further detailed in vivo experimental evaluation and clinical validation to implement them as potent therapeutic agents for combating SARS-CoV-2.