Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. Cardiovascular diseases, kidney damage and neuropathy are the main cause of high mortality rates among individuals with diabetes. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target alpha-amylase and alpha-glucosidase, enzymes that catalyzes starch hydrolysis in the intestine. At present, approved inhibitors for these enzymes are restricted to acarbose, miglitol and voglibose. Although these inhibitors retard glucose absorption, undesirable gastrointestinal side effects impede their application. Therefore, research efforts continue to seek novel inhibitors with improved efficacy and minimal side effects. Natural products of plant origin have been a valuable source of therapeutic agents with lesser toxicity and side effects. The anti-diabetic potential through alpha-glucosidase inhibition of plant-derived molecules are summarized in this review. Eight molecules (Taxumariene F, Akebonoic acid, Morusin, Rhaponticin, Procyanidin A2, Alaternin, Mulberrofuran K and Psoralidin) were selected as promising drug candidates and their pharmacokinetic properties and toxicity were discussed where available.

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A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes.

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development.

https://doi.org/10.1016/j.apsb.2022.01.002

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

https://www.mdpi.com/2076-2607/9/2/292/pdf

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways

The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue “Recent Advances in Herpesviruses Research: What’s in the Pipeline?” aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.

https://www.mdpi.com/1999-4915/12/4/476/pdf

Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19.

Multiple In vitro biological effects of phenolic compounds from Morus alba root bark.

The review presents prenylated flavonoids as potential therapeutic agents for the treatment of topical skin infections and wounds, as they can restore the balance in the wound microenvironment. A thorough two-stage search of scientific papers published between 2000 and 2022 was conducted, with independent assessment of results by two reviewers. The main criteria were an MIC (minimum inhibitory concentration) of up to 32 µg/mL, a microdilution/macrodilution broth method according to CLSI (Clinical and Laboratory Standards Institute) or EUCAST (European Committee on Antimicrobial Susceptibility Testing), pathogens responsible for skin infections, and additional antioxidant, anti-inflammatory, and low cytotoxic effects. A total of 127 structurally diverse flavonoids showed promising antimicrobial activity against pathogens affecting wound healing, predominantly Staphylococcus aureus strains, but only artocarpin, diplacone, isobavachalcone, licochalcone A, sophoraflavanone G, and xanthohumol showed multiple activity, including antimicrobial, antioxidant, and anti-inflammatory along with low cytotoxicity important for wound healing. Although prenylated flavonoids appear to be promising in wound therapy of humans, and also animals, their activity was measured only in vitro and in vivo. Future studies are, therefore, needed to establish rational dosing according to MIC and MBC (minimum bactericidal concentration) values, test potential toxicity to human cells, measure healing kinetics, and consider formulation in smart drug release systems and/or delivery technologies to increase their bioavailability.

https://www.mdpi.com/1420-3049/27/14/4491/pdf?version=1657767298

Prenylated Flavonoids in Topical Infections and Wound Healing

Antimicrobial resistance is a public health threat and the increasing number of multidrug-resistant bacteria is a major concern worldwide. Common antibiotics are becoming ineffective for skin infections and wounds, making the search for new therapeutic options increasingly urgent. The present study aimed to investigate the antibacterial potential of prenylated phenolics in wound healing. Phenolic compounds isolated from the root bark of Morus alba L. were investigated for their antistaphylococcal potential both alone and in combination with commonly used antibiotics. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined by microdilution and agar method. Synergy was investigated using the checkerboard titration technique. Membrane-disrupting activity and efflux pump inhibition were evaluated to describe the potentiating effect. Prenylated phenolics inhibited bacterial growth of methicillin-resistant Staphylococcus aureus (MRSA) at lower concentrations (MIC 2–8 μg/ml) than commonly used antibiotics. The combination of active phenolics with kanamycin, oxacillin, and ciprofloxacin resulted in a decrease in the MIC of the antimicrobial agent. Kuwanon C, E, T, morusin, and albafuran C showed synergy (FICi 0.375–0.5) with oxacillin and/or kanamycin. Prenylated phenolics disrupted membrane permeability statistically significantly (from 28 ± 16.48% up to 73 ± 2.83%), and membrane disruption contributes to the complex antibacterial activity against MRSA. In addition, kuwanon C could be considered an efflux pump inhibitor. Despite the antibacterial effect on MRSA and the multiple biological activities, the prenylated phenolics at microbially significant concentrations have a minor effect on human keratinocyte (HaCaT) viability. In conclusion, prenylated phenolics in combination with commonly used antibiotics are promising candidates for the treatment of MRSA infections and wound healing, although further studies are needed.

Marie Čulenová

Papers

Multiple In vitro biological effects of phenolic compounds from Morus alba root bark.

Prenylated Flavonoids in Topical Infections and Wound Healing

Prenylated phenolics from Morus alba against MRSA infections as a strategy for wound healing