Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies

The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.

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Anticancer Activities of Citrus Peel Polymethoxyflavones Related to Angiogenesis and Others

BioMed Research International ◽

10.1155/2014/453972 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 41

Author(s):

Liwen Wang ◽

Jinhan Wang ◽

Lianying Fang ◽

Zuliang Zheng ◽

Dexian Zhi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Plant Secondary Metabolites ◽

In Vivo Studies ◽

Protective Effects ◽

Human Beings ◽

Anticancer Activities ◽

Citrus Peel ◽

Citrus Flavonoids

Citrus is a kind of common fruit and contains multiple beneficial nutrients for human beings. Flavonoids, as a class of plant secondary metabolites, exist in citrus fruits abundantly. Due to their broad range of pharmacological properties, citrus flavonoids have gained increased attention. Accumulative in vitro and in vivo studies indicate protective effects of polymethoxyflavones (PMFs) against the occurrence of cancer. PMFs inhibit carcinogenesis by mechanisms like blocking the metastasis cascade, inhibition of cancer cell mobility in circulatory systems, proapoptosis, and antiangiogenesis. This review systematically summarized anticarcinogenic effect of citrus flavonoids in cancer therapy, together with the underlying important molecular mechanisms, in purpose of further exploring more effective use of citrus peel flavonoids.

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Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

Current Alzheimer Research ◽

10.2174/1567205014666171128102557 ◽

2018 ◽

Vol 15 (6) ◽

pp. 531-543 ◽

Cited By ~ 4

Author(s):

Dominik Szwajgier ◽

Ewa Baranowska-Wojcik ◽

Kamila Borowiec

Keyword(s):

Phenolic Acids ◽

Ex Vivo ◽

Amyloid Β ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Amyloid Β Peptide ◽

Beneficial Effects ◽

Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

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Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients

Pharmaceuticals ◽

10.3390/ph14040336 ◽

2021 ◽

Vol 14 (4) ◽

pp. 336

Author(s):

Annalisa Noce ◽

Maria Albanese ◽

Giulia Marrone ◽

Manuela Di Lauro ◽

Anna Pietroboni Zaitseva ◽

...

Keyword(s):

Adjuvant Treatment ◽

Pulmonary Involvement ◽

In Vivo Studies ◽

Pharmacological Treatments ◽

Beneficial Effects ◽

Coronavirus Infection ◽

Ultramicronized Palmitoylethanolamide ◽

Potential Use

The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection.

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Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

Journal of Personalized Medicine ◽

10.3390/jpm11050336 ◽

2021 ◽

Vol 11 (5) ◽

pp. 336

Author(s):

Mohammed Ghiboub ◽

Ahmed M. I. Elfiky ◽

Menno P. J. de Winther ◽

Nicola R. Harker ◽

David F. Tough ◽

...

Keyword(s):

Histone Deacetylases ◽

Inflammatory Diseases ◽

Selective Inhibition ◽

In Vivo Studies ◽

Beneficial Effects ◽

Domain Specific ◽

Recent Advances ◽

Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

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The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽

10.3390/cancers13133169 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3169

Author(s):

Kevin Doello ◽

Cristina Mesas ◽

Francisco Quiñonero ◽

Gloria Perazzoli ◽

Laura Cabeza ◽

...

Keyword(s):

Pancreatic Cancer ◽

Sodium Selenite ◽

Molecular Mechanisms ◽

Combined Therapy ◽

Significant Inhibition ◽

In Vivo Studies ◽

C57bl Mice ◽

Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

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Health Beneficial Effects of Moomiaii in Traditional Medicine

Galen Medical Journal ◽

10.31661/gmj.v9i0.1743 ◽

2020 ◽

Vol 9 ◽

pp. 1743

Author(s):

Solmaz Rahmani Barouji ◽

Amir Saber ◽

Mohammadali Torbati ◽

Seyyed Mohammad Bagher Fazljou ◽

Ahmad Yari Khosroushahi

Keyword(s):

Traditional Medicine ◽

English Language ◽

Modern Medicine ◽

In Vivo Studies ◽

Beneficial Effects ◽

Anticancer Properties ◽

Language Studies ◽

Health Complications

raditional medicine (TM) that developed over the years within various societies consists of medical experimental knowledge and practices, which apply natural methods and compounds for general wellness and healing. Moomiaii as a pale-brown to blackish-brown natural exudate is one of the natural compounds in traditional medicine that has been used over 3000 years in many countries of the world especially in India, China, Russia, Iran, Mongolia, Kazakhstan and Kirgizstan. We reviewed all English-language studies about Moomiaii that we accessed them. In traditional medicine, many beneficial activities have been attributed to Moomiaii and to its main constituents, Humic acid and Fulvic acid, which are widely used to prevent and treatment of different diseases. Some modern scientific investigations showed that Moomiaii as a safe dietary supplement can be beneficial in various health complications. Even though the beneficial effects of Moomiaii have been confirmed in traditional and modern medicine, it seems that additional in-vitro/in-vivo studies and comprehensive clinical trials are necessary to explain the whole mechanisms of action and to determine the effective doses in various diseases. We discuss and clarify the claimed health beneficial effects of Moomiaii in some wide-spread diseases regarding its anti-ulcerogenic, immunomodulatory, antidiabetic, antioxidative and anticancer properties. [GMJ.2020;9:e1743]

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Flavonoid constituents of Amomum tsao-ko Crevost et Lemarie and its antioxidant, antidiabetic effects in diabetic rats–in vitro and in vivo studies

Food & Function ◽

10.1039/d1fo02974f ◽

2021 ◽

Author(s):

Xiaofeng Zhang ◽

Yujun Tang ◽

Xiaoxian Guan ◽

Xin Lu ◽

Jiao Li ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Diabetic Rats ◽

In Vivo Studies ◽

Antidiabetic Effects

Amomum tsao-ko Crevost et Lemarie (A. tsao-ko) is a well-known dietary spice and traditional Chinese medicine. This study aimed to identify the flavonoids in A. tsao-ko and evaluate its antioxidant...

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Progress to Improve Oral Bioavailability and Beneficial Effects of Resveratrol

International Journal of Molecular Sciences ◽

10.3390/ijms20061381 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1381 ◽

Cited By ~ 50

Author(s):

Adele Chimento ◽

Francesca De Amicis ◽

Rosa Sirianni ◽

Maria Sinicropi ◽

Francesco Puoci ◽

...

Keyword(s):

Solid Dispersions ◽

Aqueous Solubility ◽

In Vivo Studies ◽

Beneficial Effects ◽

Lipid Nanocarriers ◽

Methodological Approaches ◽

Neuroprotective Actions ◽

Synthetic Derivatives

Resveratrol (3,5,4′-trihydroxystilbene; RSV) is a natural nonflavonoid polyphenol present in many species of plants, particularly in grapes, blueberries, and peanuts. Several in vitro and in vivo studies have shown that in addition to antioxidant, anti-inflammatory, cardioprotective and neuroprotective actions, it exhibits antitumor properties. In mammalian models, RSV is extensively metabolized and rapidly eliminated and therefore it shows a poor bioavailability, in spite it of its lipophilic nature. During the past decade, in order to improve RSV low aqueous solubility, absorption, membrane transport, and its poor bioavailability, various methodological approaches and different synthetic derivatives have been developed. In this review, we will describe the strategies used to improve pharmacokinetic characteristics and then beneficial effects of RSV. These methodological approaches include RSV nanoencapsulation in lipid nanocarriers or liposomes, nanoemulsions, micelles, insertion into polymeric particles, solid dispersions, and nanocrystals. Moreover, the biological results obtained on several synthetic derivatives containing different substituents, such as methoxylic, hydroxylic groups, or halogens on the RSV aromatic rings, will be described. Results reported in the literature are encouraging but require additional in vivo studies, to support clinical applications.

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Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

Antioxidants ◽

10.3390/antiox8060188 ◽

2019 ◽

Vol 8 (6) ◽

pp. 188 ◽

Cited By ~ 10

Author(s):

Filip Vlavcheski ◽

Mariah Young ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Pathological Condition ◽

Current Treatment ◽

In Vivo Studies ◽

Olive Leaves ◽

Treatment And Prevention ◽

Antidiabetic Effects

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

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Phytoestrogens: Dietary Intake, Bioavailability, and Protective Mechanisms against Colorectal Neoproliferative Lesions

Nutrients ◽

10.3390/nu11081709 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1709 ◽

Cited By ~ 7

Author(s):

Maria Teresa Viggiani ◽

Lorenzo Polimeno ◽

Alfredo Di Leo ◽

Michele Barone

Keyword(s):

Dietary Intake ◽

Intestinal Microbiota ◽

Estrogen Receptor Beta ◽

Epidemiological Data ◽

In Vivo Studies ◽

Beneficial Effects ◽

Natural Substances

Phytoestrogens are natural substances that have been extensively studied for their beneficial effect on human health. Herein, we analyzed the data of the literature on the role of phytoestrogens in the prevention of colorectal neoproliferative lesions (CNL). Both in vitro and in vivo studies suggest that the beneficial effects of phytoestrogens on CNL mainly depend on their ability to bind estrogen receptor beta (ERβ) in the intestinal mucosa and counter ER-alpha (ERα) activity. Epidemiological data demonstrate a correlation between the low prevalence of CNL in Eastern populations and the consumption of soy products (phytoestrogen-enriched diet). However, both observational and interventional studies have produced inconclusive results. In our opinion, these discrepancies depend on an inadequate evaluation of phytoestrogen intake (dietary questionnaires were not aimed at establishing phytoestrogen intake) and absorption (depending mainly on the intestinal microbiota of the analyzed subjects). For this reason, in the present review, we performed an overview of phytoestrogen dietary intake and metabolism to offer the reader the opportunity for a better interpretation of the literature. Future prospective trials focusing on the protective effect of phytoestrogens against CNL should take into account both their dietary intake and absorption, considering the effective role of the intestinal microbiota.

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