Oral delivery of proteins and peptides: Challenges, status quo and future perspectives.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease (COVID-19), is a contagion that has rapidly spread around the globe. COVID-19 has caused significant loss of life and disrupted global society at a level never before encountered. While the disease was predominantly characterized by respiratory symptoms initially, it became clear that other systems including the cardiovascular and neurological systems were also involved. Several thrombotic complications were reported including venous thrombosis, vasculitis, cardiomyopathy, and stroke. Thrombosis and inflammation are implicated in various non-communicable diseases (NCDs). This is of significant concern as people with pre-existing conditions such as cardiovascular disorders, renal disorders, obesity, metabolic syndrome, and diabetes are at greater risk of severe COVID-19 infection. Consequently, the research surrounding the use of anticoagulants, antiplatelet, and antithrombotic strategies for prophylaxis and treatment of COVID-19 is of critical importance. The adoption of a healthy diet, physical exercise, and lifestyle choices can reduce the risk factors associated with NCDs and the thrombo-inflammatory complications. In this review, these thrombotic complications and potential foods, nutraceuticals, and the antithrombotic constituents within that may prevent the onset of severe thrombotic complications as a result of infection are discussed. While nutrition is not a panacea to tackle COVID-19, it is apparent that a patient’s nutritional status may affect patient outcomes. Further intensive research is warranted to reduce to incidence of thrombotic complications.

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Thrombosis and COVID-19: The Potential Role of Nutrition

Low-cost plant and algal biomass are increasingly demanded as a source of proteins, and also, peptides and amino acids are gaining interest for their biological and functional properties. The reduction in chemicals, time and energy, and the integral valorization of the raw materials in the framework of biorefineries are major concerns in the development of environmentally friendly processes. Subcritical water technology is an efficient green technique useful both for extraction and for hydrolysis of protein and other fractions (lipid, carbohydrates, phenolics). However, adequate selection of operational conditions is needed in order both to maximize their extraction yield and to avoid degradation into monomeric units and decomposition products. This review summarizes the major features of subcritical water–based processes for the extraction/hydrolysis of protein. In order to valorizate other valuable fractions from agro-food wastes and algal biomass, optimal conditions should be established as a compromise solution. Alternatively, stagewise operation to sequentially obtain the target fractions could be desirable.

Subcritical Water for the Extraction and Hydrolysis of Protein and Other Fractions in Biorefineries from Agro-food Wastes and Algae: a Review

Targeting cell cycle by β-carboline alkaloids in vitro: Novel therapeutic prospects for the treatment of cancer.

Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin “resistance”; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an a...

Aspirin: Promise and Resistance in the New Millennium

Antiplatelet drugs reduce the risks associated with atherothrombotic events and show various applications in diverse cardiovascular diseases including myocardial infarctions. Efficacy of the current antiplatelet medicines including aspirin, clopidogrel, prasugrel and ticagrelor, and the glycoprotein IIb/IIIa antagonists, are limited due to their increased risks of bleeding, and antiplatelet drug resistance. Hence, it is important to develop new effective antiplatelet drugs, with fewer side-effects. The vast repertoire of natural peptides can be explored towards this goal. Proteins and peptides derived from snake venoms and plants represent exciting candidates for the development of novel and potent antiplatelet agents. Consequently, this review discusses multiple peptides that have displayed antiplatelet aggregation activity in preclinical drug development stages. This review also describes the antiplatelet mechanisms of the peptides, emphasizing the signaling pathways intervened by them. Also, the hurdles encountered during the development of peptides into antiplatelet drugs have been listed. Finally, hitherto unexplored peptides with the potential to prevent platelet aggregation are explored.

Bioactive peptides and proteins as alternative antiplatelet drugs.

Fever or Pyrexia means abnormal rise in body temperature above the usual range of normal in response to a variety of infectious, immunological and neoplastic stimuli. To normalize these febrile conditions, several synthetic agents are in clinical practice such as acetaminophen, ibuprofen, and aspirin. However, they are having many side effects which sometimes challenge their applications. The various sources are under investigation worldwide to overcome issues of unwanted effects and to better therapeutic response. In this scenario botanicals such as alkaloids, the most widely distributed and studied plant secondary metabolites, could effectively produce the molecules with better antipyretic effect and safety profile. The current review deals with 21 isolated alkaloids from 14 plants species having some antipyretic effect in preliminary screening/preclinical studies with the possible mechanism and structural edges. Therefore, these alkaloids of plant origin are candidates for further detail studies to ascertain their mechanism(s) and clinical utility or as lead compounds for future drugs.

Potential of Plant Alkaloids as Antipyretic Drugs of Future.

Tangeretin is one of the many polymethoxyflavones (PMFs) mostly found in fruits and fruit peels of citrus plants. In view of its importance as a nutraceutical it has received extensive scientific scrutiny with regards to its suspected diverse bioactivities including anti-oxidant, anti-diabetes, anti-inflammatory, neuroprotection, efflux pump inhibition, anti-microbial, and mitochondrial biogenesis just to mention but a few have been confirmed in both in vitro and in vivo studies. Importantly, tangeretin and other PMFs have demonstrated anti-cancer properties, which have stimulated renewed efforts among natural product scientists to explore the possibility of finding a natural anti-cancer template for development of diverse and readily available natural anti-cancer therapies. Nonetheless, current knowledge on the anti-cancer properties of tangeretin and other PMFs, particularly their natural sources, chemistry, pharmacokinetics, anti-cancer efficacy and most importantly their anti-cancer mechanisms remain limited. The current review provides an expanded overview of anti-cancer effects of tangeretin on many cancer subtypes, current knowledge, knowledge gaps, and future prospects. Specifically, the review highlights interaction of tangeretin with cell signaling pathways implicated in inflammation-related cancers and hormone-sensitive cancers as well as their downstream mediators. Information on tangeretin and PMFs in major electronic scientific databases including Scopus, Web of science, Web of science core collection, PubMed, PubMed central, just to mention but a few were accessed. Pre-clinically, tangeretin has enjoyed extensive scientific scrutiny, however, it was sad to discover that the quantum of pre-clinical data on tangeretin could not translate into a strong rationale for clinical trial on tangeretin or other PMFs either as monotherapy or as a combination with conventional chemotherapeutics. Although, tangeretin has low oral bioavailability but it was encouraging to find many studies exploring new tangeretin formulations and other improved drug delivery strategies. Tangeretin per current knowledge demonstrates a wide and diverse spectrum of bioactivities crucial for cancer pharmacotherapy. Tangeretin ameliorated most of the key hallmarks of cancer in various cancer subtypes through diverse signaling pathways and mediators including PI3K/Akt/Mtor, JNK/Bcl-2/BECLIN1, MAPK, Wnt/B-catenin, cyclin B1, p53, p27 and p21, activation of Caspase-3, Bad, and Bax proteins while decreasing anti-apoptotic factors (Bcl-2, Bcl-xL), prostate specific antigen, and mitochondrial membrane potential. The volume of pre-clinical data on tangeretin provides a compelling rationale for clinical trials to be initiated on tangeretin either as a monotherapy or as a combination with conventional chemotherapeutics.

Incipient citrus polymethoxylated flavone Tangeretin as anticancer drug candidate: Mechanistic insights, limitations and possible solutions

https://www.techscience.com/oncologie/v23n3/44590/pdf

Imad Ahmad

Papers

Targeting cell cycle by β-carboline alkaloids in vitro: Novel therapeutic prospects for the treatment of cancer.

Bioactive peptides and proteins as alternative antiplatelet drugs.

Potential of Plant Alkaloids as Antipyretic Drugs of Future.

Incipient citrus polymethoxylated flavone Tangeretin as anticancer drug candidate: Mechanistic insights, limitations and possible solutions

An Overview on the Anticancer Potential of Punarnavine: Prediction of Drug-Like Properties