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Antiviral Activities of Honey, Royal Jelly, and Acyclovir Against HSV-1
Abstract
Herpes simplex virus type 1 (HSV-1) belongs to the Herpesviridae family and genus simplex virus. This virus is usually acquired during childhood and is transmitted through direct mucocutaneous contact or droplet infection from infected secretions. The aim of the present study was to compare antiviral effects of honey, royal jelly, and acyclovir on herpes simplex virus-1 in an extra-somatic environment.
Vero cells were cultured in the Dulbecco's Modified Eagle's Medium (DMEM) along with 10% fetal bovine serum (FBS) in 12-welled microplates. Various dilutions of honey, royal jelly, and acyclovir (5, 10, 50, 100, 2500, 500, and 800 μg/mL) were added to the Vero cells along with a 100-virus concentration of TCID50. The plaque assay technique was used to evaluate the antiviral activities.
The results showed that honey, royal jelly, and acyclovir have the highest inhibitory effects on HSV-1 at concentrations of 500, 250, and 100 μg/mL, respectively. In addition, honey, royal jelly, and acyclovir decreased the viral load from 70 795 to 43.3, 30, and 0 PFU/mL at a concentration of 100 μg/mL, respectively.
The results of the present study showed that honey and royal jelly, which are natural products with no reports about their deleterious effect at least in laboratory conditions, can be considered alternatives to acyclovir in the treatment of herpetic lesions. However, it should be pointed out that further studies are necessary to substantiate their efficacy because hard evidence on their effectiveness is not available at present.
... 59 The in vitro studies were more heterogeneous in terms of studied pathogens: Eick et al. 60 studied 20 strains of Porphyromonas gingivalis, while Aggregatibacter actinomycetemcomitans, Campylobacter rectus and Eubacterium nodatum were studied by Aparna et al. 58 Two unique studies in our review concerned Streptococcus gordonii 61 and Campylobacter spp.; 62 C. albicans was studied by Al-Waili, 59 Ansari et al., 63 Irish et al. 64 Koc et al., 65 Anyanwu 66 and Theunissen et al. 67 The current review includes three studies on HSV susceptibility, one of which is an in vitro trial. 28,59,68 An overview of the main characteristics of these publications is detailed in Tables 3 and 4. ...
... Concerning the included in vitro studies, interventions included the following eligible microorganisms according to the adopted inclusion criteria: A. actinomycetemcomitans as a reference strain; 58,69 P. gingivalis as clinical isolates and a reference strain; 57,58,60,69 S. gordonii as a reference strain; 61 Campylobacter spp. as clinical isolates; 62 C. rectus as a reference strain; 58 E. nodatum as a reference strain; 58 C. albicans as clinical isolates and a reference strain; [63][64][65]67,70 and HSV type 1 (HSV-1) as a reference strain. 68 The incubation duration varied between 42 h and 3 days for A. actinomycetemcomitans and P. gingivalis, 57,58,60,69 was 24-72 h for C. albicans [63][64][65]67,70 and was 48 h for HSV-1. 68 The growth conditions were heterogeneous among the included studies. ...
... 68 The incubation duration varied between 42 h and 3 days for A. actinomycetemcomitans and P. gingivalis, 57,58,60,69 was 24-72 h for C. albicans [63][64][65]67,70 and was 48 h for HSV-1. 68 The growth conditions were heterogeneous among the included studies. The control solutions were also variable and varied between chlorhexidine 0.2%, 58,69 sterile physiological saline, 58,69 multifloral honey, 69 artificial honey, 64 ethanol, 61 sodium chloride, 60 fluconazole 65 and hypertonic sugar solution. ...
Background:
Honey has shown positive antimicrobial and anti-inflammatory actions in several dermatological studies; however, it is unclear if it could be effective in the treatment of periodontal disease.
Objectives:
To answer the question: Does honey have antimicrobial activity against periodontopathogens?
Methods:
Six electronic databases were screened from initiation to 31 January 2019 for randomized clinical trials (RCTs) and controlled in vitro studies exploring the antimicrobial effect of honey against periodontopathogens. Honey's botanical origin, periopathogens that showed microbial susceptibility to honey, MICs, microbial growth conditions, control product and clinical follow-up were the main investigated outcomes. The risk of bias (RoB) of included RCTs was assessed using the Cochrane Collaboration RoB tool. The RoB of in vitro studies was evaluated based on the Sarkis-Onofre judgement model adapted to the context of honey.
Results:
A total of 1448 publications were found as search results in the screened databases. Sixteen eligible papers were included based on predetermined inclusion criteria. Retained studies included 5 RCTs and 11 in vitro controlled trials. Manuka and multifloral honeys were the most studied varieties. The tested honeys showed a significant antimicrobial action, with different MICs, against eight periopathogens. Four of the five RCTs showed a high RoB, while 4 of the 11 retained in vitro studies showed a medium RoB.
Conclusions:
Honey showed a significant antimicrobial activity against all targeted periopathogens. Additional experiments are required to explore the entire antimicrobial spectrum of honey towards all pathogens involved in periodontal disease.
... Interestingly, manuka honey could inhibit HSV-1 replication slightly more efficiently than acyclovir in Vero cells (manuka honey SI = 10.7/ acyclovir SI = 9.7) [32]. ...
... The SI values for royal jelly, manuka honey, and acyclovir were 9.6, 10.7, and 9.7, respectively. Honey and royal jelly demonstrated higher activity than acyclovir at concentrations 5, 10 and 50 µg/ml [32]. ...
Honey bees provide many products exerting a wide range of benefits to humans. Honey, propolis, royal jelly, beeswax, bee venom, bee pollen and bee bread have been used as natural medicines since ancient times because of their therapeutic effects. These products have demonstrated healing properties against wounds, diabetes, gastrointestinal diseases, cancer, asthma, neurological diseases, bacterial and viral infections. The antibacterial and antibiofilm activity of honey bee products is widely studied and a huge body of evidence supports it. On the other hand, their antiviral effect has not been extensively studied. However, recent research has demonstrated their potential against diverse viral infections including SARS-CoV-2. Hence, honey bee products could be alternatives to treat viral diseases, especially when there is no effective treatment available. This narrative review aims to present up to date data (including ongoing clinical trials) regarding the antiviral activity of honey bee products, aiming to elucidate how honey bee product supplementation contributes to antiviral treatment.
... Overall reports indicate that honey is a prospective sources of antiviral compounds with excellent in vitro efficacy against varicella zoster virus (VZV) [158] and rubella virus [159]. Honey, either in a single use or in a combination with other products, has also been reported to demonstrate antiviral activity against influenza virus [13], herpes simplex virus (HSV)-1 [160], and respiratory syncytial virus (RSV) [14]. In addition, honey can improve the life of patients infected with human immunodeficiency virus (HIV) by promoting the proliferation of lymphocytes and by maintaining the hematological and biochemical parameters at optimal conditions [160,161]. ...
... Honey, either in a single use or in a combination with other products, has also been reported to demonstrate antiviral activity against influenza virus [13], herpes simplex virus (HSV)-1 [160], and respiratory syncytial virus (RSV) [14]. In addition, honey can improve the life of patients infected with human immunodeficiency virus (HIV) by promoting the proliferation of lymphocytes and by maintaining the hematological and biochemical parameters at optimal conditions [160,161]. ...
Bee products have long been used in traditional healing practices to treat many types of disorders, including cancer and microbial-related diseases. Indeed, several chemical compounds found in bee products have been demonstrated to display anticancer, antibacterial, antiviral, and antiparasitic properties. With the improvement of research tools and in view of recent advances related to bee products, this review aims to provide broad yet detailed insight into the pharmaceutical prospects of bee products such as honey, propolis, bee pollen, royal jelly, bee bread, beeswax, and bee venom, in the domain of cancer and infectious disease management. Available literature confirms the efficacy of these bee products in the alleviation of cancer progression, inhibition of bacterial and viral proliferation, and mitigation of parasitic-related symptoms. With such potentials, bioactive components isolated from the bee products can be used as an alternative approach in the long-run effort to improve humans' health at a personal and community level.
... Several investigations have determined the therapeutic impact of honey and its bioactive compounds against many viral infections. They may protect against the respiratory syncytial virus, varicella-zoster virus (VZV), influenza, herpes simplex viruses, immunodeficiency virus, rubella virus, AIDS, rhinoconjunctivitis, gingivostomatitis, viral hepatitis, rabies, and SARS-CoV-2 (Table 1) [49][50][51][52][53][54][55][56][57][58][59]. The exact mechanism of action of honey and its bioactive compounds is immense and still unknown. ...
Bee products have been extensively employed in traditional therapeutic practices to treat several diseases and microbial infections. Numerous bioactive components of bee products have exhibited several antibacterial, antifungal, antiviral, anticancer, antiprotozoal, hepatoprotective, and immunomodulatory properties. Apitherapy is a form of alternative medicine that uses the bioactive properties of bee products to prevent and/or treat different diseases. This review aims to provide an elaborated vision of the antiviral activities of bee products with recent advances in research. Since ancient times, bee products have been well known for their several medicinal properties. The antiviral and immunomodulatory effects of bee products and their bioactive components are emerging as a promising alternative therapy against several viral infections. Numerous studies have been performed, but many clinical trials should be conducted to evaluate the potential of apitherapy against pathogenic viruses. In that direction, here, we review and highlight the potential roles of bee products as apitherapeutics in combating numerous viral infections. Available studies validate the effectiveness of bee products in virus inhibition. With such significant antiviral potential, bee products and their bioactive components/extracts can be effectively employed as an alternative strategy to improve human health from individual to communal levels as well.
... Honey and its major components are proved effective in treating a variety of viral infections in numerous investigations. Herpes zoster (Hashemipour et al., 2014), rubella (Zeina et al., 1996) influenza (Watanabe et al., 2014), herpes disease (Semprini et al., 2017), respiratory syncytial virus (Zareie, 2011), AIDS (Behbahani, 2014), immunodeficiency virus (Al-Waili et al., 2006), viral hepatitis (Abdulrhman et al., 2016), gingivostomatitis (Awad and Hamad, 2018), rabies rhinoconjunctivitis (Igado et al., 2010), and COVID-19 are among the diseases that honey and its main components can combat (Filipe, 2020). Honey's antiviral activities and their primary components have a large and unknown method of action. ...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners’ safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics’ data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are noncarcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.
... According to [56] investigated the antiviral activities of honey, royal jelly and acyclovir against HSV-1 (Herpes simplex virus type 1). As a result of the study, it was determined that the mentioned natural products did not have harmful effects in laboratory conditions, and they stated that these products could be considered as an alternative to acyclovir in the treatment of herpetic lesions. ...
The new type of coronavirus infection (COVID-19), caused by coronavirus-2 (SARS-CoV-2), has led to a world pandemic due to severe acute respiratory syndrome. In addition to drug and vaccine studies for COVID-19, studies on various foods maintain to increase immunity and alternative treatment, and in this context, bee products are also being researched. Although many studies are showing that bee products have antimicrobial properties and immune-enhancing effects, there are limited studies on the effectiveness of these products against coronavirus. Some peptides in royal jelly are reported to be potent antibacterial and antifungal agents that may be beneficial for avoiding co-infections in COVID-19 patients. Positive results have been found Pollen, a fine and powder-like substance produced by flowering plants and collected by bees, in many studies investigating the effects of pollen on health such as antimicrobial, antiviral and anti-inflammatory. Bee venom; It is a yellowish-colored, bitter-sweet, pungent-smelling substance that is produced in the venom sac of bees, normally in liquid form, but dries up and crystallizes after contact with air. Melittin, the primary component of bee venom having more than 40 biologically and pharmacologically active compounds including phospholipase A2, histamine, epinephrine, free amino acids, peptide and apamin, has been stated to have antitumor, antimicrobial, anti-nociceptive and anti-inflammatory activities. Phospholipase A2 (PLA2) secreted from bee and snake venom is known to have strong anti-HIV activities. Melittin, phosphorylase A2 and hyaluronidan, which are the most significant components of bee venom, constitute 50% of bee venom. Moreover, researches on the relationship between bee venom and COVID-19 are limited. The target of this review is to bring together the studies on the health effects of royal jelly, bee pollen and bee venom, and to contribute to the existing studies.
... Even, researches on regular honey have revealed its antimicrobial activities. [19,20] Evaluation of the population in two subgroups with first 4-month and other month period patients showed no difference in demographic, clinical, or ECG findings. Hence, the incidence of intoxication in the winter period should only depend on the frequency of mad-honey consumption. ...
Objectives:
Mad-honey intoxication (MHI) often presents with all kinds of bradyarrhythmias. Despite numerous publications focused on clinical findings, we aim to evaluate poor prognostic implications, ischemia likely electrocardiography (ECG) changes, and detailed ECG findings of MHI in the largest series.
Methods:
This is a retrospective single-center study of 117 MHI patients admitted to emergency service.
Results:
The study had 26 (22.2%) females (median 52.5 years) and 91 (77.8%) males (median 51.0 years). Fifty-six (47.9%) patients had ischemia likely changes on ECG. Multivariate model demonstrated that beta-blocker usage (odds ratio (OR): 52.871; 95% confidence interval (CI): 3.618-772.554 (p=0.004)), atrioventricular junctional rhythm (AVJR) (OR: 5.319; 95%CI: 1.090-25.949 (p=0.039)), and quantity of mad-honey consumption (OR: 1.035; 95% CI: 1.008-1.063 (p=0.011)) are predictors of hospitalization. ROC curve analysis showed cutoff value of mad-honey consumption quantity 24.79 g had 57% sensitivity and 68% specificity for predicting hospitalization (AUC: 0.7, 95% CI: 0.55-0.816, p=0.027). In addition, all hospitalized cases were male.
Conclusion:
Our study has shown that male gender, AVJR, the quantity of mad-honey consumption, and beta-blocker usage are high-risk criteria for hospitalization in MHI patients. Furthermore, ischemia likely ECG changes is often observed with MHI even independently from hypotension or bradycardia.
... The antiviral effect of royal jelly has been proved against many viruses such as hepatitis C virus and hepatitis B virus; it has been found in vitro that major royal-jelly protein (MRJP) 2 and its isoform X1 have proved their ability to inhibit the viral receptors CD81 and scavenger receptor class B type I (SR-B1), and also, they targeted HCVNS3/NS4A protease, HCV-NS5B polymerase and HBV polymerase (DNA-dependent DNA polymerase and reverse transcriptase) [72]. In addition, Hashemipour et al. [73] studied the effect of royal jelly on herpes simplex virus type 1 (HSV-1) and found that can inhibit the virus at a concentration of 250 µg/mL and can decrease the viral load from 70,795 to 30 PFU/mL at a concentration of 100 µg/mL. Importantly, in silico analyses revealed that (MRJP) 2 and the isoform X1 MRJP2 may be a promising therapy against SARS-CoV-2. ...
The coronavirus disease 2019 (COVID-19) is an epidemic caused by SARS-CoV-2 (severe
acute respiratory syndrome coronavirus 2). Populations at risk as well as those who can develop
serious complications are people with chronic diseases such as diabetes, hypertension, and the elderly.
Severe symptoms of SARS-CoV-2 infection are associated with immune failure and dysfunction. The
approach of strengthening immunity may be the right choice in order to save lives. This review
aimed to provide an overview of current information revealing the importance of bee products in
strengthening the immune system against COVID-19. We highlighted the immunomodulatory and
the antiviral effects of zinc and polyphenols, which may actively contribute to improving symptoms
and preventing complications caused by COVID-19 and can counteract viral infections. Thus, this
review will pave the way for conducting advanced experimental research to evaluate zinc and
polyphenols-rich bee products to prevent and reduce the severity of COVID-19 symptoms.
... The use of honey for treating wounds, skin burns, eczema, and several other skin infections are among the most prevalent therapeutic applications. It exhibits strong antibacterial, antiviral and antifungal properties (Agbaje et al., 2006;Anyanwu, 2012;Hannan et al., 2014;Hashemipour et al., 2014;Irish et al., 2006;Johnston et al., 2018;Lu et al., 2013;Shahzad & Cohrs, 2012;Watanabe et al., 2014). It acts as a potent antioxidative agent which alleviates levels of antioxidative enzymes thus providing protection against many diseases where oxidative stress is the key player for instance in neurodegenerative disorders (Al-Mamary et al., 2002;Erejuwa et al., 2012a;Mijanur Rahman et al., 2014;Mohamed et al., 2010). ...
Honey is a delicious, sweet liquid with infinite nutritional properties. Being a cherished human food, honey had been utilized by Homo since the dawn of time. It is a highly saturated and viscous sugar solution with a variety of additional ingredients including organic acids, proteins, minerals, vitamins, amino acids, polyphenols, aroma compounds, and approximately 500 enzymes. This diversified chemical profile of honey accounts for its immense dietary and medicinal uses in both present and historic generations and civilizations. The literature archive suggests that honey exerts numerous health-constructive effects including hypocholesterolemic, cardioprotective, antihypertensive, hepatoprotective, gastroprotective, neuroprotective, nephroprotective, antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, antiarrhythmic, antileishmanial, antithrombotic, antinociceptive, and immune-boosting properties. Oxidative stress is the key player in the progression of degenerative changes in many vital organs such as skin, liver, pancreas, and reproductive organs. Honey has the distinct advantage of carrying components that can help with regenerative healing by acting as an anti-bacterial, antioxidant, and anti-inflammatory agent. Keeping in view the regenerative potential of honey, this review is envisioned to apprehend the potential role of honey in boosting the regeneration of various vital organ systems. Promoting the natural regenerative abilities of tissues can help in mitigating the progression of degenerative changes and abate the burden of various degenerative maladies.
... The natural products of both plant and animal origin have wide range of pharmacological activities such as; antimicrobial, antiinflammatory and anti-modulatory [14][15][16][17]. Currently the use of natural products has increased due to reduction in number of effective antibiotics provided by the pharmaceutical industries as well as due to the increasing drug resistance among microorganisms [18][19][20][21][22]. Microbes are evolving various mechanisms of antibiotics resistance and in some cases become multi drug resistant [23][24][25][26]. ...
Microorganisms and helminthes can cause serious diseases in humans as well as in animals. The use of antimicrobial and antihelminthic drugs have created selective pressure and caused resistance to antibiotics used against them, thus it necessitates the use of honey bee’s derived natural products. One such bee derived product is pollen, collected by worker honey bees from the flowering plants and modify it by adding its salivary secretions. The present study embodies use of pollen as antimicrobial and antihelminthic substance. Among microorganisms 4 Gram (+ve) bacteria; (Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae) and 3 Gram (-ve) bacteria; (Escherichia Coli, Pseudomonas aeruginosa, Salmonella enteric) and 2 yeasts (Candida albicans and Saccharomyces cerevisiae) were used and the methodology used disc diffusion assay and broth dilution method. The antihelminthic effect was observed among amphistomes via bioassay method under in vitro conditions. For observations three types of pollen extracts (ethanolic, methanolic and water extract) were prepared and positive controls used were; Ampicillin for antibacterial, Amphotericin B for antifungal and Albendazole for anti-helminthes. The antimicrobial activities were determined by measuring the zones of inhibition diameters in millimeters after 24 hours of incubation at optimum temperature for each microbe and also by broth dilution method. Results obtained showed that the water extract of pollen was found to be most effective against bacteria used in the present study where; Gram (+ve) bacteria were more susceptible as compared to the Gram (-ve) bacteria. It was also observed that among yeasts; Saccharomyces cerevisiae was more susceptible towards ethanolic extract of pollen while Candida albicans showed more inhibitions towards water extract of pollen. Results also demonstrated that none of the extracts of pollen was found to be effective against Helminthes (amphistomes) used in the present study.
... Właściwości przeciwwirusowe miodu są słabo rozpoznane [32,61], ale jest on zalecany jako środek na kaszel w wirusowych chorobach układu oddechowego [52]. Potencjał miodu w leczeniu choroby COVID-19 może być analizowany dwukierunkowo: poprzez poszukiwanie dowodów na bezpośrednie działanie przeciwwirusowe miodu i jego składników oraz poprzez wykazanie wpływu miodu na choroby współistniejące, które przyczyniają się do cięższego przebiegu COVID-19 i zwiększonej śmiertelności wśród chorych. ...
COVID-19 to nowa choroba zakaźna układu oddechowego wywoływana przez wirus SARS-CoV-2, patogen należący do rodziny koronawirusów, odpowiedzialny za wywołanie światowej pandemii. Obecnie nie ma zatwierdzonych metod leczenia, a jedynym sposobem zapobiegania pandemii są masowe szczepienia. Równocześnie na całym świecie trwają poszukiwania leku na COVID-19, testowane są głównie znane substancje lecznicze, w tym produkty naturalne. Do grupy tej zalicza się miód, produkt znany z właściwości przeciwbakteryjnych, przeciwwirusowych i immunomodelujących. Właściwości przeciwwirusowe miodu obejmują działanie wirusobójcze, hamowanie replikacji wirusa, blokowanie adhezji i wnikania do komórek gospodarza, aktywację układu odpornościowego i indukcję przeciwciał oraz wzmacnianie leków przeciwwirusowych. Za aktywność przeciwwirusową miodu odpowiadają występujące w nim składniki, głównie flawonoidy, kwasy fenolowe i nadtlenek wodoru. Aktywność przeciwutleniająca miodów jest skorelowana z całkowitą zawartością polifenoli i zróżnicowana odmianowo. Ciemne miody odmianowe jednokwiatowe (gryczany, wrzosowy, faceliowy) wykazują silniejsze właściwości przeciwutleniające w porównaniu z miodami wielokwiatowymi i miodami odmianowymi jednokwiatowymi o jasnej barwie (nawłociowym, mniszkowym, rzepakowym, akacjowym). W badaniach in vitro i in silico wykazano skuteczność miodu i jego składników bioaktywnych w unieszkodliwianiu wirusa SARS-CoV-2, ale wciąż brakuje dowodów na skuteczność miodu w zwalczaniu COVID-19. Potencjalne mechanizmy działania miodu w terapii COVID-19 obejmują: redukcję stresu oksydacyjnego, wzmacnianie układu odpornościowego, zapobieganie wtórnym infekcjom oraz łagodzenie objawów chorób współistniejących. W pracy dokonano przeglądu aktualnych badań naukowych, w tym klinicznych, obejmujących zastosowanie miodu w leczeniu COVID-19.
... Manuka honey from New Zealand is said to possess antiviral activities against influenza virus (H1N1) strain A/WSN/33 in MDCK cells. Another in vitro study also showed the effectiveness of commercial manuka honey against a HSV-1 isolate using Vero cells (69). Charyasriwong et al. (70) reported that an active ingredient, methylglyoxal, present in manuka honey showed an activity against H3N2, H1N1, H5N2, and also oseltamivir-resistant H1N1. ...
Nowadays, despite enormous scientific advances, viral diseases remain the leading cause of morbidity worldwide, and their potential to spread is escalating, eventually turning into pandemics. Nutrition can play a major role in supporting the immune system of the body and for the optimal functioning of the cells of the immune system. A healthy diet encompassing vitamins, multi-nutrient supplements, functional foods, nutraceuticals, and probiotics can play a pivotal role in combating several viral invasions in addition to strengthening the immune system. This review provides comprehensive information on diet-based scientific recommendations, evidence, and worldwide case studies in light of the current pandemic and also with a particular focus on virus-induced respiratory tract infections. After reviewing the immune potential of nutraceuticals based on the lab studies and on human studies, it was concluded that bioactive compounds such as nutraceuticals, vitamins, and functional foods (honey, berries, etc.) with proven antiviral efficacy, in addition to pharmaceutical medication or alone as dietary supplements, can prove instrumental in treating a range of virus-induced infections in addition to strengthening the immune system. Milk proteins and peptides can also act as adjuvants for the design of more potent novel antiviral drugs.
... Royal jelly administration showed promising results in patients undergoing radio-and chemotherapy, improving the signs and symptoms of oral mucositis and shortening the healing time [122]. Royal jelly has also been tested for the treatment of herpetic lesions as a natural alternative to acyclovir, showing inhibitory effects on HSV-1 at 250 µg/mL concentration [123]. ...
Oral health is an essential element in maintaining general well-being. By preserving the complex equilibrium within the oral microbial community, commensal microorganisms can protect against extrinsic pathogenic threats. However, when an imbalance occurs, the organism is susceptible to a broad range of infections. Synthetic drugs can be administered to help the body fight against the fungal, bacterial, or viral burden. Nonetheless, they may produce undesirable consequences such as toxicity, adverse effects, and drug resistance. In this respect, research has focused on finding safer and more efficient alternatives. Particularly, increasing attention has been drawn towards developing novel formulations based on natural compounds. This paper reviews the plant-based, algae-based, and beehive products investigated for their antimicrobial properties, aiming to thoroughly present the state of the art on oral infection prevention in the ear, nose, and throat (ENT) field.
... These factors reduce the severity and duration of infection, maintain the integrity of epithelial cells, cause stimulation of granulation and angiogenesis as well [150]. When studied in comparison with available pharmacological antiviral drug "acyclovir", honey showed least to no deleterious effects in treating infection of herpes simplex virus [151]. Since the infection of SARS-CoV-2 proliferate due to protease enzyme present in the viral structure, a recent in-silico study showed strong binding of constituents of honey to the active site of protease, making it a potential candidate for further in-vitro and in-vivo studies to check it's efficacy against SARS-CoV-2 [152]. ...
Recently, the outbreak of severe acute respiratory syndrome cornoavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become a great perturbation all around the globe and has many devastating effects on every aspect of life. Apart from the oxygen therapy and extracorporeal membrane oxygenation, Remdesivir and Dexamethasone have been proven to be efficacious against COVID-19, along with various vaccine candidates and monoclonal antibody cocktail therapy for Regeneron. All of these are currently at different stages of clinical trials. People with weak immunity are more prone to a severe infection of SARS-CoV-2. Therefore, early and judicious nutritional supplementation along with pharmacological treatment and clinician collaborations are critical in restituting the current situation. Nutritional supplements help in acquiring strong immunity to prevent the progression of disease any further. Vitamin C, vitamin D, selenium, zinc and many other nutritional and dietary supplements inhibit the production of inflammatory cytokines during a viral infection and prevents several unwanted symptoms of infection. Many dietary components like citrus fruits, black elderberry, ginger, and probiotics have the ability to attack viral replication. These supplements can also tame the overriding immune system during coronavirus infection. Keeping in view these facts, nutritional and dietary supplements can be used along with other management modalities. These nutritional and dietary supplements are potential candidates to curb the convulsive unfolding of novel COVID-19, in combination with other standard treatment protocols. In this review, various search engines were used to exploit available literature in order to provide a comprehensive review on nutritional and dietary supplements with respect to the viral infections. It will also provide a brief overview on some of the clinical trials that are in progress to assess the role of nutritional supplements, either alone or in combination with other pharmacological drugs, in fight against COVID-19.
... In addition, honey acts as a broad-spectrum antiviral agent, e.g., against varicella zoster virus and herpes simplex virus 1 (HSV-1). Indeed, in vitro and clinical trials show that honey can be used as an efficient alternative of acyclovir for the treatment of HSV-1 [66,67]. Moreover, folk medicine in many parts of the world considers natural honey as a first line of treatment for acute cough caused by upper respiratory tract infection, which is a key symptom in COVID-19 [68]. ...
Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible treatments. Bee honey and propolis are rich in bioactive compounds that express strong antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant activities. This review examined the literature for the anti-COVID-19 effects of bee honey and propolis, with the aim of optimizing the use of these handy products as prophylactic or adjuvant treatments for people infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Molecular simulations show that flavonoids in propolis and honey (e.g., rutin, naringin, caffeic acid phenyl ester, luteolin, and artepillin C) may inhibit viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replica-tion. Similar to the potent antiviral drug remdesivir, rutin, propolis ethanolic extract, and propolis liposomes inhibited non-structural proteins of SARS-CoV-2 in vitro, and these compounds along with naringin inhibited SARS-CoV-2 infection in Vero E6 cells. Propolis extracts delivered by nanocarriers exhibit better antiviral effects against SARS-CoV-2 than ethanolic extracts. In line, hospitalized COVID-19 patients receiving green Brazilian propolis or a combination of honey and Ni-gella sativa exhibited earlier viral clearance, symptom recovery, discharge from the hospital as well as less mortality than counterparts receiving standard care alone. Thus, the use of bee products as an adjuvant treatment for COVID-19 may produce beneficial effects. Implications for treatment outcomes and issues to be considered in future studies are discussed.
... 25 Similarly, royal jelly was also established to possess potent antiviral effect against herpes simplex virus (HSV). 26,27 Royal jelly's viricidal activity has been attributed to 10-HAD (10-Hydroxy-2-Decenoic Acid).By the action of this compound, the activity of white blood cells (WBCs) is increased, especially against HSV and hepatitis viruses. Ultimately, causing increased viral destruction. ...
p>The outbreak of pneumonia that broke out in Wuhan, in December 2019, later rapidly spread to the rest of the world. This was identified as Coronavirus disease 2019 (COVID-19) [officially renamed severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)] caused by a zoonotic beta Coronavirus entitled 2019 novel Coronavirus (2019-nCoV). The aim of this study was to summarize the biological features of SARSCoV-2, its clinical features and the possible antiviral effect of honey against SARS-CoV-2. For this purpose, recently published literature, official documents and selected up-to-date preprint studies were reviewed. The initial source of SARS-CoV-2 is still unknown but a possible animal-to-human transmission is indicated. Human spread of SARS-CoV-2 is due to droplet spread. The infected individual may present as symptomatic or asymptomatic, this varies from patient to patient mainly depending upon his/her immunity. To combat the current pandemic various modalities are under study, an important and harmless way of treatment might be the use of honey. Various studies have demonstrated antiviral effects of honey. Propolis and honey have shown promising anti-viral effect against SARS-CoV-2. Thus, the combined effect of honey and its products might open a door for developing a safe and highly efficient natural drug against COVID-19
infection.</p
... Fatty acids such as 3,10-HDA, 11S, 10-HDA and 10-acetooxy-2-DEA could strongly inhibit the growth of yeasts, such as C. tropicalis, C. albicans, and C. glabrata [71]. Moreover, RJ could fight against herpes 2 virus, influenza virus, heart virus coxsackie B3, herpes simplex virus type 1 (HSV-1), and certain rhabdoviruses [118,119]. ...
Royal jelly (RJ) is a yellowish-white and acidic secretion of hypopharyngeal and mandibular glands of nurse bees used to feed young worker larvae during the first three days and the entire life of queen bees. RJ is one of the most appreciated and valued natural product which has been mainly used in traditional medicines, health foods, and cosmetics for a long time in different parts of the world. It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials. It is commonly used to supplement various diseases, including cancer, diabetes, cardiovascular, and Alzheimer's disease. Here, we highlight the recent research advances on the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolics, for a comprehensive understanding of the biochemistry, biological, and pharmaceutical responses to human health promotion and life benefits. This is potentially important to gain novel insight into the biological and pharmaceutical properties of RJ.
... 12 The mechanisms of a therapeutic benefit for honey could include physiochemical properties such as low pH and high osmolality and mechanistically independent bioactive factors that vary between honeys; these bioactives may be anti-inflammatory, antiviral and promote wound healing. [13][14][15] Kanuka honey is derived from the kanuka tree (Kunzea ericoides) of the same family as the better studied manuka tree strengths and limitations of this study ► One of the largest randomised controlled trials for herpes simplex labialis. ► Highly generalisable data from a national cohort. ...
Objective
To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis.
Design
Prospective parallel randomised controlled open-label superiority trial.
Setting
76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017.
Participants
952 adults randomised within the first 72 hours of a herpes simplex labialis episode.
Interventions
Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily.
Outcome measures
The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability.
Results
Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported.
Conclusion
There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis.
Trial registration number
ACTRN12615000648527;Post-results
... Phage impairment in H&T might also be due to the presence of RJ, whose antiviral activity had already been reported 7,27 . This substance is produced in the head by the hypopharyngeal glands. ...
Bacteriophages (phages) or viruses that specifically infect bacteria have widely been studied as biocontrol agents against animal and plant bacterial diseases. They offer many advantages compared to antibiotics. The American Foulbrood (AFB) is a bacterial disease affecting honeybee larvae caused by Paenibacillus larvae. Phages can be very significant in fighting it mostly due to European restrictions to the use of antibiotics in beekeeping. New phages able to control P. larvae in hives have already been reported with satisfactory results. However, the efficacy and feasibility of administering phages indirectly to larvae through their adult workers only by providing phages in bees’ feeders has never been evaluated. This strategy is considered herein the most feasible as far as hive management is concerned. This in vivo study investigated the ability of a phage to reach larvae in an infective state after oral administration to honeybees. The screening (by direct PFU count) and quantification (by quantitative PCR) of the phage in bee organs and in larvae after ingestion allowed us to conclude that despite 104 phages reaching larvae only an average of 32 were available to control the spread of the disease. The fast inactivation of many phages in royal jelly could compromise this therapeutic approach. The protection of phages from hive-derived conditions should be thus considered in further developments for AFB treatment.
... Overall, there is a paucity of data on the function of royal jelly proteins, especially on its therapeutic effects in human. Collectively, royal jelly shows various pharmacological effects including hypocholesterolemic [39], anti-fibrotic [40], anti-tumor [41], anti-obesity, anti-hyperglycemic [42], immunomodulatory [43], anti-diabetic, anti-oxidative [44], hepatoprotective [45], anti-fatigue [46], anti-lipidemic [47], cardioprotective [48], metabolic activity [49], nephroprotective [50], anti-inflammatory and antioxidant effects [51], bone stimulatory properties [52], anti-aging [53], anti-viral [54], anti-diabetic [55], neuro-protective [56], antibacterial [57], antidepressant [58] and cosmetic effects [59]. Since there are many specific roles of royal jelly proteins in human reported, there is an urgent need to identify the key components for specific therapeutics (such as antidiabetics, anticancer, anti-inflammatory, anti-obesity and in the treatment of neurodegenerative diseases). ...
Background
To date, there is no x-ray crystallography or structures from nuclear magnetic resonance (NMR) on royal jelly proteins available in the online data banks. In addition, characterization of proteins in royal jelly is not fully accomplished to date. Although new investigations unravel novel proteins in royal jelly, the majority of a protein family is present in high amounts (80-90%).
Objective
In this review, we attempted to predict the three-dimensional structure of royal jelly proteins (especially the major royal jelly proteins) to allow visualization of the four protein surface properties (aromaticity, hydrophobicity, ionizability and (hydrogen (H)-bond) by using bioinformatics tools. Furthermore, we gathered the information on available therapeutic activities of crude royal jelly and its proteins.
Methods
For protein modeling, prediction and analysis, the Phyre2 web portal systematically browsed in which the modeling mode was intensive. On the other side, to build visualized understanding of surface aromaticity, hydrophobicity, ionizability and H-bond of royal jelly proteins, the Discovery Studio 4.1 (Accelrys Software Inc.) was used.
Results
Our in silico study confirmed that all proteins treasure these properties, including aromaticity, hydrophobicity, ionizability and (hydrogen (H)-bond. Another finding was that newly discovered proteins in royal jelly do not belong to the major royal jelly protein group.
Conclusion
In conclusion, the three dimensional structure of royal jelly proteins along with its major characteristics were successfully elucidated in this review. Further studies are warranted to elucidate the detailed physiochemical properties and pharmacotherapeutics of royal jelly proteins.
... These properties can ameliorate issues of antibiotic resistance against Pseudomonas aeruginosa which is increasingly encountered (Gunaldi et al., 2014). Moreover, it is reported that RJ, positively decreased viral load when supplemented at a concentration of 100 μg/ml (Hashemipour et al., 2014). ...
Royal Jelly (RJ) is product from bees that is used to feed larvae in the hive as well as a main nutritional source for the queen honey bee. It has various important biological activities including as an antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, cholesterol-lowering, and growth promoter activities and has the ability for inhibition of certain enzymatic degradation. It can be used for the improvement of growth performance, gut health and quality and safety of animal products in poultry due to its antioxidant and immune modulating properties. The antioxidant activity of RJ is mainly due to the presence of polyphenolic compounds. It is an excellent source of B and C vitamins and folic acid. The mineral profile of RJ is useful as it contains major macro and micro minerals. Studies conducted on supplementation with RJ in poultry diets have shown a significant increase in body weight, egg production, and immune levels and is especially useful in organic production. Supplementation of RJ at the level of 10 and 15 mg/kg in layer diets positively influenced egg weight (by 5.0% and 4.8% respectively), egg production (10.5% and 11.0% respectively), weight gain of hens (7.0% and 6.5% respectively) and yolk pigmentation (9.5% and 9.7% respectively). Total leukocyte and erythrocyte counts in the diet containing 200 mg/kg RJ were significantly higher than the diet contained 100 mg/kg or the unsupplemented control group. However, the heterophil/lymphocyte ratio and heterophil percent were reduced in RJ-fed groups. Supplementing poultry diets with RJ offers an opportunity to maximise profit from safe and high quality poultry production.
... The bioactive compounds and healthpromoting properties are described by Ramadan and Al-Ghamdi (2012). It has been reported that RJ has shown different pharmacological activities such as antimicrobial (Bílikova et al., 2015), antiviral (Hashemipour et al., 2014), antitumor (Guo et Royal jelly (RJ) is one of the most attractive bee products. RJ has long been used in traditional medicine. ...
Royal jelly (RJ) is one of the most attractive bee products. RJ has long been used in traditional medicine. Due to various pharmacological properties, including antioxidative, anti-inflammatory and antibacterial properties, RJ has been widely consumed in daily diets in numerous countries. The purpose of the present study is to find out some correlations of physicochemical parameters, antioxidant activity and total polyphenol content of fresh RJ samples. The following parameters were analyzed in fresh RJ samples: water content, proteins, pH, total acidity, electrical conductivity, sugars (glucose, fructose, sucrose), trans-10-hydroxy-2-decenoic acid (10-HDA). The antioxidant activity of RJ was examined by two methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power (FRAP) assay. Total phenolic content was determined according to Folin Ciocalteu procedure. High positive linear correlations between the total antioxidant activity determined by the DPPH method and 10-HDA (r=0.858, p<0.05) and FRAP method and total polyphenols (r=0.812, p<0.05) were found.
... A number of studies suggest that some varieties of honey have strong activity against certain viruses (Shahzad and Cohrs, 2012;Watanabe et al., 2014) A. In 1996, Zeina suggest that honey has effective role against rubella virus (Sankum et al., 2002). Similar study on royal jelly suggested strong antiviral activity against herpes simplex virus (HSV) (Hashemipour et al., 2014). The antiviral activity of royal jelly is greater than honey (Izuta et al., 2009). ...
... A number of studies suggest that some varieties of honey have strong activity against certain viruses (Shahzad and Cohrs, 2012;Watanabe et al., 2014) A. In 1996, Zeina suggest that honey has effective role against rubella virus (Sankum et al., 2002). Similar study on royal jelly suggested strong antiviral activity against herpes simplex virus (HSV) (Hashemipour et al., 2014). The antiviral activity of royal jelly is greater than honey (Izuta et al., 2009). ...
Honey is a natural food item produced by honey bees. Ancient civilizations considered honey as a God gifted prestigious product. Therefore, a huge literature is available regarding honey importance in almost all religions. Physically, honey is a viscous and jelly material having no specific color. Chemically, honey is a complex blend of many organic and inorganic compounds such as sugars, proteins, organic acids, pigments, minerals, and many other elements. Honey use as a therapeutic agent is as old as human civilization itself. Prior to the appearance of present day drugs, honey was conventionally used for treating many diseases. At this instant, the modern research has proven the medicinal importance of honey. It has broad spectrum anti-biotic, anti-viral and anti-fungal activities. Honey prevents and kills microbes through different mechanism such as elevated pH and enzyme activities. Till now, no synthetic compound that works as anti-bacterial, anti-viral and anti-fungal drugs has been reported in honey yet it works against bacteria, viruses and fungi while no anti-protozoal activity has been reported. Potent anti-oxidant, anti-inflammatory and anti-cancerous activities of honey have been reported. Honey is not only significant as. anti-inflammatory drug that relieve inflammation but also protect liver by degenerative effects of synthetic anti-inflammatory drugs. This article reviews physico-chemical properties, traditional use of honey as medicine and mechanism of action of honey in the light of modern scientific medicinal knowledge.
... Honey has a range of anti-inflammatory as well as antibacterial, antifungal and antiviral effects. [5][6][7] These properties have led to the use of medical grade honey in a wide range of conditions. Honey is efficacious in the treatment of wounds, burns, infections and rosacea. ...
Introduction
Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as ‘cold sores’, which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban).
Methods and analysis
This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution.
Ethics and dissemination
New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants.
Trial registration number
Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results. SCOTT Registration: 15/SCOTT/14
Protocol version
4.0 (12 June 2017)
... With respect to its antiviral activity, different investigations reported that honey could be efficient against Rubella virus (Zeina, Othman, & Al-Assad, 1996) and Herpes virus (Al-Waili, 2004;Hashemipour, Tavakolineghad, Arabzadeh, Iranmanesh, & Nassab, 2014). Honey has also exhibited activity against several parasites, such as Leishmania (Zeina, Zohra, & Al Assad, 1997) and the nematode Caenorhabditis elegans (Sajid & Azim, 2012), being the major nematicidal component a glycoconjugate with the molecular mass of 5511. ...
Honey is a natural sweetener with a complex composition. Honey features vary depending on the botanical source and geographical origin, as well as climatic, processing and storage conditions. Honey is mainly composed of carbohydrates and water, parameters that influence its shelf life and some of its properties, including color, flavor, density, viscosity, hygroscopicity, and crystallization. Honey also contains small amounts of other components, such as nitrogen compounds, organic acids, minerals, vitamins, Maillard reaction products, volatile compounds, and several bioactive substances that affect sensory and physical characteristics, as well as biological potential. This review summarizes the literature about the composition and main properties of honey. It also describes the use of honey as a biomonitor for collecting information about the environment, identifying environmental contamination and assessing the level of soil, water, plant and air pollution.
... 189 Manuka and clover honey were also effective in vitro against varicella zoster virus using human malignant melanoma cells (MeWo). 190 Furthermore, commercial and manuka honey seem to act against herpes simplex virus (HSV-1) isolates in vitro (using Vero cells), 191,192 and honey solutions act against rubella virus also in vitro (using monkey kidney cell cultures). 193 Al-Waili 194 showed that topical honey application was effective in healing labial and genital recurrent herpes lesions. ...
The beneficial effects of honey on human health have long been recognized. Today, many of those positive effects have been studied to elucidate its mode of action. This review briefly summarizes the best studied features of honey, highlighting it as an appealing alternative medicine. In these reports, the health benefits of honey range from antioxidant, immunomodulatory, and anti-inflammatory activity to anticancer action, metabolic and cardiovascular benefits, prebiotic properties, human pathogen control, and antiviral activity. These studies also support that the honey’s biological activity is mainly dependent on its floral or geographic origin. In addition, some promising synergies between honey and antibiotics have been found, as well as some antiviral properties that require further investigation. Altogether, these studies show that honey is effectively a nutraceutical foodstuff.
Honey bee products comprise various compounds, including honey, propolis, royal jelly, bee pollen, bee wax and bee venom, which have long been recognized for their pharmacological and health-promoting benefits. Scientists have discovered that periodontal disorders stem from dental biofilm, an inflammatory response to bacterial overgrowth produced by dysbiosis in the oral microbiome. The bee products have been investigated for their role in prevention of oral diseases, which are attributed to a myriad of biologically active compounds including flavonoids (pinocembrin, catechin, caffeic acid phenethyl ester (CAPE) and galangin), phenolic acids (hydroxybenzoic acid, hydroxycinnamic acid, p-coumaric, ellagic, caffeic and ferulic acids) and terpenoids. This review aims to update the current understanding of role of selected bee products, namely, honey, propolis and royal jelly, in preventing oral diseases as well as their potential biological activities and mechanism of action in relation to oral health have been discussed. Furthermore, the safety of incorporation of bee products is also critically discussed. To summarize, bee products could potentially serve as a therapy option for people suffering from a variety of oral disorders.
The benefits of honey have been recognized since ancient times for treating numerous diseases. However, in today's modern era, the use of traditional remedies has been rapidly diminishing due to the complexities of modern lifestyles. While antibiotics are commonly used and effective in treating pathogenic infections, their inappropriate use can lead to the development of resistance among microorganisms, resulting in their widespread prevalence. Therefore, new approaches are constantly required to combat drug-resistant microorganisms, and one practical and useful approach is the use of drug combination treatments.
Manuka honey, derived from the manuka tree (Leptospermum scoparium) found exclusively in New Zealand, has garnered significant attention for its biological potential, particularly due to its antioxidant and antimicrobial properties. Moreover, when combined with antibiotics, it has demonstrated the ability to enhance their effectiveness. In this review, we delve into the chemical markers of manuka honey that are currently known, as well as detail the impact of manuka honey on the management of infectious diseases up to the present.
Corticosteroids improve the complications of Covid-19 but may cause some side effects such as hyperglycemia. Royal jelly is one of the bee products that exert anti-inflammatory, insulin-like, and hypoglycemic activities. The present study was conducted to investigate the effect of royal jelly capsules on blood sugar and the clinical course of Covid-19 in the patients receiving corticosteroid therapy. In this clinical trial, 72 Covid-19 patients with positive reverse transcription polymerase chain reaction (RT-PCR) test and pulmonary involvement hospitalized in Shahrekord Hajar Hospital were enrolled and randomized into two groups: treatment (receiving corticosteroids and Royal Jelly 1000 mg capsules daily for 7 days) and placebo (given corticosteroids and placebo). Laboratory tests, blood sugar, and clinical courses were determined and compared. Data was analyzed using SPSS version 16. On day 7 after the onset of the intervention, the dosage and frequency of insulin, FBS level, and required corticosteroid showed a decrease in both groups but the inter-group difference was not significant (P > .05). As well, the Spo2 level indicated a non-significant increase and hospital stay length indicated a non-significant decrease in the intervention group (P > .05). Among the symptoms, only headache, cough, and dyspnea indicated an improvement in the intervention group (P < .05). Overall, the results indicated the short-term consumption of royal jelly could not significantly improve blood sugar and the clinical course of Covid-19; however, it could significantly improve headache, cough, and dyspnea in the patients.
SARS-CoV-2/novel coronavirus is a fresh virus strain that was first detected in the city of Wuhan located at Hubei province of China in December, 2019. Within a couple of months the virus has spread rapidly to different geographical regions through human transmission leading to serious disease burden worldwide. Although research is under progress to develop effective vaccine and drugs for the disease, a unified approach between conventional and traditional medicine system may prove to be beneficial in early prevention and management of the disease. Joint efforts are being put up at global scientific community level to enhance the research on advancement of meticulous diagnostics, antiviral measures and finally leading to development of an effective vaccine against the novel coronavirus. Some basic and safe measures from AYUSH systems of medicine have also been advocated for prophylaxis and treatment of COVID-19 which can be used independently or with integrated approach. The rationale of this review paper is to provide the details regarding disease spectrum, modes of transmission, social & economic consequences, and role of AYUSH systems of medicine in prevention and management of COVID-19. Based on the signs and symptoms of COVID-19, list of herbs and drugs of AYUSH systems of medicine were also searched and are being reported here.
Keywords: AYUSH systems of medicine, Coronavirus, COVID-19, SARS-CoV-2, Unani Medicine
Honey is a complex and variable mixture that contains more than 180 biochemical compounds from various molecule families. This mixture is achieved after processing the nectar out of plant food sources at the level of the bees’ abdomen. The bioactive components found in this natural product are in charge of its antimicrobial properties. Honey is used for its antibacterial actions over Gram+ and Gram-; their anti-fungal and antimycotic actions against melds and yeasts, along with its protozoal and antiviral activities. This literature review outlines its naturally antimicrobial potential of honey; explains the factors responsible for this potential; and spell out their mechanisms of action. Osmotic pressure, water activity, acid content of honey, presence of bioactive compounds like: hydrogen peroxide, phenolic acids, flavonoids, the MGO, defensin-1, lysozyme, volatile compounds as well as antibacterial products secreted from the lactic bacteria that are behind this antimicrobial activity. This potential basically depends on the biological activities of the initially harvested floral source, its geographical origin, the season, the storage conditions, the honey age, the health of bees’ colonies and the suitable beekeeping practices.
Hospital-acquired infections and treatment-related wound complications constitute a tremendous burden for the health care system, particularly given the serious increase in multidrug resistant pathogens. Imagine that a large part of nosocomial infections can be prevented using a simple treatment. In this respect, honey is used mainly in topical cutaneous wound care because of its potent broad-spectrum antibacterial and wound healing activities. However, therapeutic use outside this scope has been limited. The current review provides an in-depth view of studies using honey outside the conventional wound care indications. Non-conventional routes of honey application include subcutaneous, intra-socket, abdominal, and oral administration in novel indications, such as post colon surgery, mucositis, and tooth extraction. Honey consistently demonstrates beneficial therapeutic activities in these novel applications, orchestrating antimicrobial and prophylactic activity, reducing inflammation and wound dehiscence, and inducing healing, epithelialization, and analgesic activity. Several molecular mechanisms are responsible for these beneficial clinical effects of honey during the course of wound healing. Pro-inflammatory effects of honey, such as induction of iNOS, IL-1β, and COX-2, are mediated by TLR4 signaling. In contrast, honey's anti-inflammatory actions and flavonoids induce anti-inflammatory and antioxidant pathways by inducing NRF2 target genes, including HO-1 and PRDX1. The molecular and biochemical pathways activated by honey during the different phases of wound healing are also discussed in more detail in this review. Variation between different honey origins exists, and therefore standardized medical-grade honey may offer an optimized and safe treatment. Honey is a valuable alternative to conventional antimicrobial and anti-inflammatory therapies that can strongly reduce nosocomial infections.
COVID-19 pandemic has passed to the front all the contradictions of the beekeeping sector: the valuable role of bee products as immune enhancers and antiviral agents and the impact that unsustainability of human activities has on bees’ health and survival. The COVID-19 emergency led several countries to adopt severe restriction measures to contrast the infection. The lowering of industrial and commercial activities, transports, and the general lockdown had immediate consequences on the air quality, significantly improving environmental conditions. This had a positive impact on honeybees’ life’s quality. On the other hand, the bee and beehive transportation limitations threaten to hit food production by affecting the pollinator service, and this is particularly true in large, food-exporting countries like the USA and China where due to the few numbers of local bees, beekeepers import them by other countries and convey by truck hives for thousands of kilometers to pollinate crops. Furthermore, honeybee products, focusing on their natural pharmacological properties, can play an essential role as a potential natural contrast to the virus by enhancing the immunity defenses of both humans and animals, and their demand by consumers is expected to increase. Several researchers in the last months focused their attention on bee products to evaluate their effect in the cure of COVID-19 patients to ameliorate the symptoms or to contrast the coronavirus directly. This review reports these preliminary results.
Headings ethnopharmacological relevance
Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results.
Aim of the study
Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes.
Materials and methods
The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library.
Results
This search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against HSV-induced wounds (95% CI: 3.58 to −0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to −0.42; p = 0.18).
Conclusions
Overall, these results confirm the use of honey and propolis as potent antiherpetic agents.
Cold sores are nasolabial blisters caused by herpes simplex virus (HSV) infections. Novel therapies demonstrating simultaneously antiviral activity and improved wound healing are warranted. The aim of this study was to investigate the efficacy of medical-grade honey (MGH) for treating HSV-induced cold sores. A crossover trial was performed in patients with recurrent cold sores (n = 29). The majority (65.6%) of these patients experience four or more episodes per year, thus forming a valid self-control group. In this study, patients applied an MGH-based formulation (L-Mesitran Soft) on their cold sore at the onset of symptoms (62.1%) or appearing of blister (37.9%) and compared it to their conventional treatments. After complete healing, patients filled in a questionnaire evaluating healing, pain, and itching. The average absolute healing time was 72.4% slower with conventional treatment (10.0 days) compared to MGH (5.8 days). After MGH treatment, 86.2% of all patients experienced faster objective healing (6.9% similar and 6.9% slower) and the subjective healing score was higher in 79.3% of the patients (20.7% similar). If the patients normally experience pain and itching during their cold sores, these levels were lower with MGH therapy compared to conventional treatment in 72.7% and 71.4% of the patients, respectively. Moreover, 100% of the patients prefer MGH treatment over conventional treatment and will use it again on future cold sores. MGH is a promising alternative treatment for cold sores, likely by combining both increased antiviral and wound healing activities while alleviating pain and itching.
Coronavirus disease 2019 (COVID-19) is a viral pneumonia that is spreading rapidly worldwide. The main feature of this disease is a severe acute respiratory syndrome and caused by coronavirus 2 (SARS-CoV-2). There are several unknowns about the pathogenesis and therapeutically treatment of COVID-19 infection. In addition, available treatment protocols have not been effective in managing COVID-19 infection. It is proposed that natural anti-oxidants such as lemon, green tea, saffron, curcuma longa, etc. with high flavonoids like safranal, crocin, crocetin, catechins, resveratrol, calebin A, curcumin have therapeutic potential against viral infections. In this context, honey and its main components are being investigated as an option for patients with COVID-19. The present study may indicate that honey and its main components inhibit the entry of the virus into the host cell and its replication as well as modulate the inflammatory cascade. This review provides basic information for the possible potential effects of honey and its main components for fighting with SARS-CoV-2.
Honey is a well-known and historically important sweet food which possesses immense antimicrobial properties. Numerous varieties of honey are present in nature, and all of these honey varieties contain certain key ingredients, which confer upon them various antimicrobial properties. These antimicrobial key ingredients include polyphenolic compounds, hydrogen peroxide, methylglyoxal, and bee-defensin among several others. Honey is nowadays used extensively in modern medicine as potent antibiotic for the treatment of surface wounds and burns. It is also used in combination with other antibiotics to treat antibiotic resistance. As an antifungal agent, honey is used to treat the athlete’s foot (tinea pedis), jock itch (tinea cruris), and ringworm of face, scalp, nail, and hand (tinea corporus). In this chapter, we aim to provide a brief overview of various types of honey and their composition and describe extensively its various antimicrobial properties and how these properties are exploited in modern medicine as an alternative to popular therapeutics or in conjunction with it.
Currently, researchers are oriented to the use of several natural products as alternatives in curing various ailments. Among natural products, honey occupies a great position as a sweetening agent as well as a magic remedy for a large list of diseases. Several studies had been conducted on different types of honeys. At first, most of the studies were focused on the use of honey as a natural antimicrobial. Afterwards, many pharmaceutical applications have been knocked. The well-known anti-inflammatory, antioxidant, and antimicrobial characteristics of honey suggest its use to promote wound healing, relief oxidative stress in case of cardiovascular diseases and cure several infectious and inflammatory diseases. Honey has proved its effectiveness in eradication of multidrug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), controlling blood sugar in diabetic patients, accelerating healing of wounds and chronic ulcers, improving cough and asthma, treatment of different types of cancers, and reducing symptoms associated with periodontal diseases.
Use of honey is advocated by the people of all religions, traditions, and cultural beliefs, and it is one of the most valued natural products owing to its nutritional and medicinal properties. Honey is known to be the rich in sugars, phenolic compounds, free organic acids, and enzymes. It also contains lipids, amino acids, trace elements, vitamins, and few toxic compounds. It has been known to exert neuroprotective, cardioprotective, gastroprotective, antidiabetic, antioxidant, antimicrobial, anticancer, and anti-inflammatory activities. This chapter focusses on the positive influence of honey on human health and the mechanisms involved in the same. It also sheds light on the chemical composition and the ongoing clinical trials on honey.
Honey has been broadly recognized as a source of nourishment and medication by both old and new generations. It has been utilized by people to treat numerous illnesses through topical application for at least 2700 years, but recent researches have revealed the antiseptic and antimicrobial activities of honey. It has been seen as a powerful agent that can be used in various human pathologies. Different clinical examinations have affirmed that the use of honey to cutaneous injuries which are severely infected removes contamination from the injury and enhances tissue healing. Honey has been perceived as a successful antioxidant and antimicrobial agent for centuries. Utilized mainly for treating burns and surface wounds, it has thus been developed into clinical medicine, as medical grade honey. In spite of this, the underlying interest in the utilization of honey for antimicrobial treatment was significantly reduced, as antibiotics were discovered and used. Nonetheless, due to the alarming increment in the occurrence of organisms with antimicrobial resistance, specifically the expansion in multidrug resistance (MDR), the quantity of efficient antibiotics is decreasing at a larger rate than new medications are created. This serious situation has made numerous scientists to think back to the pre-antibiotic period for creating solutions, directing their consideration towards the mechanisms of action of antimicrobial activity of honey.
Coronavirus Disease (COVID-19) has infected people in 210 nations and has been declared a pandemic on March 12, 2020 by the World Health Organization (WHO). In the absence of effective treatment and/or vaccines for COVID-19, natural products of known therapeutic and antiviral activity could offer an inexpensive, effective option for managing the disease. Benefits of products of honey bees such as honey, propolis, and bee venom, against various types of diseases have been observed. Honey bees products are well known for their nutritional and medicinal values, they have been employed for ages for various therapeutic purposes. In this review, promising effects of various bee products against the emerging pandemic COVID-19 are discussed. Products of honey bees that contain mixtures of potentially active chemicals, possess unique properties that might help to protect, fight, and alleviate symptoms of COVID-19 infection.
Honey dressings attract attention as a therapeutic alternative for wound care due to its antibacterial, antioxidant, and immunomodulatory action. To obtain better medicinal properties, the formulation of honey requires the characterization of physicochemical and mechanical properties. This chapter aims to provide an in-depth account of the value of characterizing the honey dressing. Physical tests, such as swelling capacity, water vapor transmission rate, and thermal studies, are described. Therapeutic testings of honey wound dressings and their clinical applications have been covered. Recent developments in the formulation of honey dressings are also discussed in this chapter.
The new coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has recently put the world under stress, resulting in a global pandemic. Currently, there are no approved treatments or vaccines, and this severe respiratory illness has cost many lives. Despite the established antimicrobial and immune-boosting potency described for honey, to date there is still a lack of evidence about its potential role amid COVID-19 outbreak. Based on the previously explored antiviral effects and phytochemical components of honey, we review here evidence for its role as a potentially effective natural product against COVID-19. Although some bioactive compounds in honey have shown potential antiviral effects (i.e., methylglyoxal, chrysin, caffeic acid, galangin and hesperidinin) or enhancing antiviral immune responses (i.e., levan and ascorbic acid), the mechanisms of action for these compounds are still ambiguous. To the best of our knowledge, this is the first work exclusively summarizing all these bioactive compounds with their probable mechanisms of action as antiviral agents, specifically against SARS-CoV-2.
COVID-19 was originated from Wuhan city of Hubei Province in China in December 2019. Since then it has spread in more than 210 countries and territories. It is a viral disease due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The patients show flu-like symptoms with a dry cough, sore throat, high fever, and breathing problems. The disease due to SARS-CoV-2 was named as COVID-19. About 2.2 million people have been infected with more than 0.15 million deaths globally. The United States of America is the most affected country with the highest patients of about 0.7 million. Despite great efforts, there is no treatment of this disease. However, prevention and management are the best options. This article describes SARS-CoV-2, disease, prevention and management, treatment and social impact on society. It was analyzed that a combination of antiviral drugs with hydroxyl-chloroquine and azithromycin (with the consultation of a medical practitioner) may be the best option to treat the patients, depending on the patient's conditions and symptoms. However, Unani therapy may be useful along with allopathic treatment. It is urgently advised and requested that all the persons should follow the preventive measures, managements and quarantine strictly without any religious discrepancy otherwise the situation may be the worst. Also, there is an urgent requirement to educate our new generation for science and technology to fight against any such disaster in future; if any. There is no need to be panic and proper prevention and management are essential to combat this disease. This article may be useful to create awareness among the public, to prevent, manage and treat COVID-19.
Objectives
To assess the value of bee products with respect to antiviral efficacy against herpes viruses.
Design
A systematic review was done using the JUSTfind System of the Justus-Liebig-University Gießen and Scopus.
Results
Three trials on honey and 6 trials on propolis were conducted. Each trial provided evidence that these two bee products are interesting alternatives to acyclovir, especially propolis, which was found to be superior to acyclovir in 4 trials.
Conclusions
The evidence from these trials suggests that propolis is the best of all natural possibilities in the treatment of herpetic skin lesions, especially those related to HSV-1. Future studies should analyse if propolis could be an adjunct to treatment with acyclovir. For lesions in the oral cavity, honey could be an interesting alternative.
Honey has been used as a folk medicine since 2100 BC; however, mad honey is different from normal natural or commercially available honey as it is contaminated with grayanotoxins, which leads to intoxication / poisoning upon consumption. Grayanotoxin is generally found in Rhododendron genus (family: Ericaceae) and is extracted by bees from nectar and pollens of flowers. Mad honey has been commonly used as an aphrodisiac (sexual stimulant), in alternative therapy for gastrointestinal disorders (peptic ulcer disease, dyspepsia, and gastritis), and for hypertension for a long time. Grayanotoxin acts on sodium ion channels and muscarinic receptors, leading to cardiac disorders (hypotension and different rhythm disorders including bradycardia, bradydysrhythmias, atrial fibrillation, nodal rhythm, atrioventricular block, and complete atrioventricular block) and respiratory depression. Patients may also exhibit any one symptom out of or combination of dizziness, blurred vision, diplopia, nausea, vomiting, vertigo, headache, sweating/excessive perspiration, extremity paresthesia, impaired consciousness, convulsion, hypersalivation, ataxia, inability to stand, and general weakness. Mad honey intoxication is diagnosed with honey intake history before the appearance of the signs and symptoms (clinical presentation), and the treatment is symptomatic. Prompt treatment includes intravenous infusions of atropine sulfate and fluids (saline infusions or simultaneous infusion of saline with atropine sulfate) if the patient presents bradycardia and severe hypotension. In case of a complete atrioventricular block, a temporary pacemaker is employed. Except for a single case from Lanping County (Southwest China), the prognosis for mad honey intoxication is very good, and no fatalities have been reported in modern medical literature excluding a few in the 1800s. Although fatalities are very rare, mad honey ingestion may still lead to arrhythmias, which can be life-threatening and hard to recognize. This article provides a brief introduction to honey, mad honey and its uses, the effects of mad honey intoxication/poisoning, and its diagnosis, prognosis, and treatment.
Royal jelly (RJ) has been reported to possess several physiological and pharmacological properties such as the ability to prevent osteoporosis in rats and anti-inflammatory effects. We hypothesized that RJ could have beneficial effects on the prevention or treatment of periodontal diseases, which are chronic inflammatory diseases caused by bacterial infection that result in resorption of the tooth-supporting bone. We assessed the effect of RJ on mineralization in mouse periodontal ligament cell clone 22 (MPDL22 cells), which are of an osteogenic and cementogenic lineage. The mRNA expression of osteopontin, osteocalcin and osterix, and mineralized nodule formation were significantly enhanced in RJ-treated MPDL22 cells. In addition, we investigated the effects of RJ on the production of inflammatory cytokines from MPDL22 cells stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a periodontopathic bacterium. RJ suppressed LPS-induced interleukin-6 and CXC chemokine ligand 10 production from MPDL22 cells. Furthermore, RJ suppressed the expression of CD54 in MPDL22 cells: CD54 is the adhesion molecule involved in the accumulation of leukocytes in periodontal lesions. These findings suggest that the osteoinductive and anti-inflammatory effects of RJ can provide benefits for the treatment and prevention of periodontal diseases.
This project aimed to assess the antibacterial potential of various brands of honey sold in Muscat area on some isolates of H. pylori and to determine if there is any synergy between honey and amoxycillin or clarithromycin used in the treatment of H. pylori gastritis and duodenal ulcer.
Eight samples of commercial honey were used in the experiment after they were checked for purity by sub-culturing on blood agar and incubating for 48 hours at 37°c. Honey samples showing gross contamination were discarded. Purified culture isolates of H. pylori from our laboratory stock cultures were swabbed on chocolate plate using 1x 10(4) cfu/ml. One hundred microlitres (100μl) of various honey samples were placed on each plate which was subsequently incubated microaerophilically at 37ºc for 3 days. The presence or absence of growth inhibition zones on each plate was noted and an average zone size of each honey was taken. Honey samples with high zone sizes were further diluted from 1:2-1:8 to find the end-points of their growth inhibition concentrations and the experiment was repeated in triplicates. The synergistic effect between honey, amoxycillin and clarithromycin was done in triplicates by placing honey at various distances between each antibiotic after swabbing chocolate agar with 1x 10(4) cfu/ml of H. pylori. The plates were incubated as before.
All honey samples produced growth inhibition zones with H. pylori no at dilution of honey but had different zone sizes at 1:2-1:8 dilutions. Black Forest honey had the highest antibacterial activity followed by Langnese honey. None of the honeys had a synergistic effect with either clarithromycin or amoxycillin.
We conclude that, in vitro, some honey brands possess antibacterial activity against H. pylori and that no synergy or antagonism was observed between honey and clarithromycin or honey and amoxicillin using H. pylori as a test organism. Though no synergy or antagonism was observed between honey, amoxicillin or clarithromycin, it has been suggested that the use of honey with triple therapy regimen may help shorten the time required to eliminate H. pylori from stomach lining of patients with gastritis or duodenal ulcer caused by H. pylori infection.
To evaluate the synergistic action of starch on the antibacterial activity of royal jelly (RJ), a comparative method of adding RJ with and without starch to culture media was used.
Strains of Staphylococcus aureus and Escherichia coli have been used to determine the minimum inhibitory concentration (MIC) of a variety of freshly reaped RJ. In a second step, lower concentrations of RJ than the MIC were incubated with a set of concentrations of starch and then were added to media to determine the minimum synergistic inhibitory concentration.
The MIC of RJ without starch was 1.7% (vol/vol) and 2% (vol/vol) against S. aureus and E. coli, respectively. When starch was incubated with RJ and then added to media, a significant MIC drop has been noticed against both strains. This MIC drop was 61% and 30% against S. aureus and E. coli, respectively.
The effectiveness of RJ against bacteria has been extensively reviewed, but this bee product remains unaffordable in most countries. Our findings suggest that combined mixture of RJ and starch could be used to treat infections that are resistant to conventional drugs, at a lower cost.
Vascular endothelial growth factor (VEGF) is reported to be a potent pro-angiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. Royal jelly (RJ) is a honeybee product containing various proteins, sugars, lipids, vitamins and free amino acids. 10-Hydroxy-2-decenoic acid (10HDA), a major fatty acid component of RJ, is known to have various pharmacological effects; its antitumor activity being especially noteworthy. However, the mechanism underlying this effect is unclear. We examined the effect of 10HDA on VEGF-induced proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Our findings showed that, 10HDA at 20 microM or more significantly inhibited such proliferation, migration and tube formation. Similarly, 10 microM GM6001, a matrix metalloprotease inhibitor, prevented VEGF-induced migration and tube formation. These findings indicate that 10HDA exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell proliferation and migration. Further experiments will be needed to clarify the detailed mechanism.
We have developed a rapid, sensitive, and inexpensive method for measuring the cellular protein content of adherent and suspension cultures in 96-well microtiter plates. The method is suitable for ordinary laboratory purposes and for very large-scale applications, such as the National Cancer Institute's disease-oriented in vitro anticancer-drug discovery screen, which requires the use of several million culture wells per year. Cultures fixed with trichloroacetic acid were stained for 30 minutes with 0.4% (wt/vol) sulforhodamine B (SRB) dissolved in 1% acetic acid. Unbound dye was removed by four washes with 1% acetic acid, and protein-bound dye was extracted with 10 mM unbuffered Tris base [tris (hydroxymethyl)aminomethane] for determination of optical density in a computer-interfaced, 96-well microtiter plate reader. The SRB assay results were linear with the number of cells and with values for cellular protein measured by both the Lowry and Bradford assays at densities ranging from sparse subconfluence to multilayered supraconfluence. The signal-to-noise ratio at 564 nm was approximately 1.5 with 1,000 cells per well. The sensitivity of the SRB assay compared favorably with sensitivities of several fluorescence assays and was superior to those of both the Lowry and Bradford assays and to those of 20 other visible dyes. The SRB assay provides a colorimetric end point that is nondestructive, indefinitely stable, and visible to the naked eye. It provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening. SRB fluoresces strongly with laser excitation at 488 nm and can be measured quantitatively at the single-cell level by static fluorescence cytometry.
The concept of growing crops for health rather than for food or fiber is slowly changing plant biotechnology and medicine. Rediscovery of the connection between plants and health is responsible for launching a new generation of botanical therapeutics that include plant-derived pharmaceuticals, multicomponent botanical drugs, dietary supplements, functional foods and plant-produced recombinant proteins. Many of these products will soon complement conventional pharmaceuticals in the treatment, prevention and diagnosis of diseases, while at the same time adding value to agriculture. Such complementation can be accelerated by developing better tools for the efficient exploration of diverse and mutually interacting arrays of phytochemicals and for the manipulation of the plant's ability to synthesize natural products and complex proteins. This review discusses the history, future, scientific background and regulatory issues related to botanical therapeutics.
Royal jelly (RJ) is known to have a variety of biological activities toward various types of cells and tissues of animal models, but nothing is known about its effect on brain functions. Hence, we examined the effect of oral administration of RJ on the mRNA expression of various neurotrophic factors, their receptors, and neural cell markers in the mouse brain. Our results revealed that RJ selectively facilitates the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that RJ shows neurotrophic effects on the mature brain via stimulation of GDNF production, and that enhanced expression of neurofilament H mRNA is involved in events subsequently caused by GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain through GDNF.
Graves' disease is an organ-specific autoimmune disease with unknown etiology. TSHR Ab plays the most important role for the pathogenesis of Graves' disease. Recently, the role of cytokines for the pathogenesis of Graves' disease has been studied extensively. Royal jelly (RJ) is a creamy product secreted by young nurse worker bees (Apis mellifera), and it is synthesized in the hypopharyngeal and mandibular glands. RJ has been reported to have such pharmacological characteristics as antitumor, antibacterial, antihypercholesterolemic, antiallergic, antiinflammatory, and immunomodulatory properties. The major aim of the present study is to evaluate the effect of RJ on autoimmunity in peripheral lymphocyte culture and to establish the therapeutic doses.
In the first phase, lymphocyte cell isolation from four voluntary healthy subjects was performed to find the effective concentration of RJ on immunity. Serial dilutions of the RJ were prepared (0-5 mg/mL). All isolated lymphocyte cells were treated with the above diluted samples. MTT test was carried out after incubation of 72 h. In the second phase, six patients with Graves' disease, newly diagnosed by clinical and laboratory methods and admitted to my hospital and untreated were identified. RJ samples of 0 and 4 mg/mL were incubated in a culture medium for 72 h with isolated lymphocytes obtained from the patients. After incubation, MTT test in lymphocyte cell culture, Th1 cytokines IFN-gamma, TNF-alpha, and IL-12, and Th2 cytokines IL-4 and IL-10 levels by the enzyme amplified sensitivity immunoassay (EASIA) method and TSHR Ab by the radioreceptor method were determined.
The concentration causing lymphocytes to proliferate was found to be 4 mg/mL by MTT test after incubation of 72 h in cell culture medium. Of the cytokines produced and secreted from lymphocytes, IFN-gamma increased, whereas, other cytokines decreased in RJ concentration of 4 mg/mL. Significant differences were found only for IFN-gamma and TNF-alpha. IL-4 concentrations were kept near the level of significancy. Of Th1/Th2 ratios, IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios also exhibited significant differences between 0 and 4 mg/mL. RJ treatment in lymphocytes from patients with Graves' disease shifted the Th1/Th2 cytokine ratio to the side of Th1 cytokine. Therefore, RJ using the treatment and establishing a remission of Graves' disease may be effective as an antithyroid drug treatment. TSHR Ab levels of lymphocyte cell culture supernatants treated with RJ showed significant decreases. Also, the result may suggest that RJ may exert an effect similar to an antithyroid drug for decreasing TSHR Ab levels.
RJ may be effective as an immunomodulatory agent in Graves' disease.
Unlabelled:
Introduction. Ulcers are one of the most frequent diseases af- fecting the oral cavity. The aim of this study was to assess the effects of omega-3 fatty acid (topical and systemic) on oral mucosa wound healing in rats.
Methods and materials:
In this study, adult male rats in 5 groups (n = 16 per group) were used (L: local, S: systemic, LB: local blank, SB: systemic blank, and C: control.) A wound (2 mm di- ameter) was punched into the hard palate of each rat. A mucosal de- fect (2 mm in diameter and 0.2 mm in wall thickness) was made to the depth of the periosteum in the palate with a round stainless steel blade designed for punch biopsy. For topical application, a swab was soaked in L omega-3 or LB and packed into the wound. For systemic treatment, 2 cc of the S omega-3 acid or SB was guided into the stom- ach by gastric gavage. The control group was not treated. Histological samples were harvested on post-injury days 2, 4, 6, and 8.
Results:
The highest amount of polymorphonuclear (PMN) cells was observed on days 2 and 4 in the LB group. The control group had the highest inflammation score on days 2 and 4, and the lowest reepithelialization score on days 2, 4, 6, and 8. The thickest epithelium was observed in the L and S groups on days 6 and 8.
Conclusion:
Omega-3 fatty acid (L and S) increases fibroblast counts and decreases PMN cell counts. Moreover, this compound causes an increase in reepithelialization and epithelial thickness. .
To synthesise the evidence regarding honey's role in health care and to identify whether this evidence applies more specifically to cancer care.
Systematic review.
The inclusion and exclusion criteria were agreed by two reviewers and a keyword strategy was developed. EMBASE, CINAHL, AMED, MEDLINE, COCHRANE and PUBMED databases were screened to identify suitable articles. The citation list from each included study was also screened for potentially suitable papers. The key findings from each study were entered onto a data extraction sheet.
In total, 43 studies were included in the systematic review, which included studies in relation to wounds (n = 19), burns (n = 11), skin (n = 3), cancer (n = 5) and others (n = 5). In addition, a systematic review regarding honey use in wound care was also included. While the majority of studies noted the efficacy of honey in clinical use, five studies found honey to be equally as effective as the comparator and three found honey to be less effective than the comparator treatment. Other research did not illustrate any significant difference between standard treatment regimes vs. honey treatment. Studies were generally poor in quality because of small sample sizes, lack of randomisation and absence of blinding.
Honey was found to be a suitable alternative for wound healing, burns and various skin conditions and to potentially have a role within cancer care.
In the cancer setting, honey may be used for radiation-induced mucositis, radiotherapy-induced skin reactions, hand and foot skin reactions in chemotherapy patients and for oral cavity and external surgical wounds.
The use of honey in wound management has enjoyed a resurgence. This is largely due to the growing clinical problem of antibiotic-resistant bacteria and the combined difficulties for the practitioner in managing chronic wound types, such as burns, leg ulcers or surgical wounds, that may become infected, for example, with methicillin-resistant Staphylococcus aureus or Pseudomonas. The associated costs of treating such wounds are escalating as a result. While the use of honey as a wound dressing has been recognized, at least since Egyptian times circa 2000 BC, it is only more recently, due to the development and licensing of modern honey wound dressings, that such dressings have become more widely available and used in wound management. This article focuses on the use of honey in the treatment of infected wounds and burns. It will examine the effects of honey at the wound bed and its clinical applications, along with the current dressings available. Also discussed are the practical considerations, if, like any wound dressing, honey is to be used safely, appropriately and for the benefit of the patient.
The use of herbal medicine in the United States has been increasing at a steady pace over the past decade. Most recent estimates suggest that the US population spends $5 billion per year for herbal supplements alone. Herbal supplements are receiving increasing exposure through national media, in lay journals, and more recently in the scientific press. Interest in herbal medicine has been facilitated by multiple factors, including the perception that pharmaceutical medications are expensive, overprescribed, and often dangerous. Alternatively, herbal medicine is often perceived as being "natural" and is therefore considered safe. While the growth of the herbal medicine industry in the United States can probably not continue at this accelerated pace indefinitely, there is little indication of any major slowing. Therefore, patients will continue to use herbal medications. Knowledge of these preparations (including their potential benefits and risks as well as their ability to interact with pharmaceutical medications) will enable physicians to provide a balanced and objective view to patients seeking information on herbal therapy.
Honey has antibacterial, antifungal and antioxidants activities and has high nutrient value. In this study we investigated the potential use of topical application of crude honey in the management of seborrheic dermatitis and dandruff. Thirty patients with chronic seborrheic dermatitis of scalp, face and front of chest were entered for study. Twenty patients were males and 10 were females, their ages ranged between 15 and 60 years. The patients had scaling, itching and hair loss. The lesions were scaling macules, papules and dry white plaques with crust and fissures. The patients were asked to apply diluted crude honey (90% honey diluted in warm water) every other day on the lesions with gentle rubbing for 2-3 mins. Honey was left for 3 hr before gentle rinsing with warm water. The patients were followed daily for itching, scaling, hair loss and the lesions were examined. Treatment was continued for 4 weeks. The improved patients were included in a prophylactic phase, lasting six months. Half patients were treated with the topical honey once weekly and the other half served as control. All the patients responded markedly with application of honey. Itching was relieved and scaling was disappeared within one week. Skin lesions were healed and disappeared completely within 2 weeks. In addition, patients showed subjective improvement in hair loss. None of the patients ( 15 patients) treated with honey application once weekly for six months showed relapse while the 12/15 patients who had no prophylactic treatment with honey experienced a relapse of the lesions 2-4 months after stopping treatment. It might be concluded that crude honey could markedly improve seborrheic dermatitis and associated hair loss and prevent relapse when applied weekly.
10-Hydroxy-Delta(2)-decenoic acid, the major component of the lipide fraction of royal jelly, exhibits antibiotic activity against many bacteria and fungi. This fatty acid is less than one-fourth as active as penicillin against Micrococcus pyogenes and less than one-fifth as active as chlortetracycline against Escherichia coli. It also slows the growth rate of Neurospora sitophila and some unidentified molds. The salt of this compound is considerably less active than the free acid.
To evaluate the possible role of honey, olive oil and beeswax in the treatment of skin fungal infections.
Thirty-seven patients with pityriasis versicolor, tinea cruris, tinea corporis and tinea faciei were studied. After clinical evaluation of redness, scaling, pruritus and burning/pain sensation and mycological assessment, honey mixture containing honey, olive oil and beeswax (1:1:1) was applied to the lesions three times daily for a maximum of 4 weeks.
Clinical response was obtained in 86% of patients with pityriasis versicolor, 78% of patients with tinea cruris and in 75% of patients with tinea corporis. Mycological cure was obtained in 75, 71 and 62% of patients with PV, tinea cruris and tinea corporis, respectively. The patient with tinea faciei showed clinical and mycological cure 3 weeks after commencement of therapy.
Honey mixture may have place in the management of these skin conditions and rigorous, controlled trials are justified.
The objective of this research was to investigate the effect of the topical application of honey on recurrent attacks of herpes lesions, labial and genital, as compared to acyclovir cream.
Sixteen adult patients with a history of recurrent attacks of herpetic lesions, 8 labial and 8 genital, were treated by topical application of honey for one attack and acyclovir cream for another attack.
For labial herpes, the mean duration of attacks and pain, occurrence of crusting, and mean healing time with honey treatment were 35%, 39%, 28% and 43% better, respectively, than with acyclovir treatment. For genital herpes, the mean duration of attacks and pain, occurrence of crusting, and mean healing time with honey treatment were 53%, 50%, 49% and 59% better, respectively, than with acyclovir. Two cases of labial herpes and one case of genital herpes remitted completely with the use of honey. The lesions crusted in 3 patients with labial herpes and in 4 patients with genital herpes. With acyclovir treatment, none of the attacks remitted, and all the lesions, labial and genital, developed crust. No side effects were observed with repeated applications of honey, whereas 3 patients developed local itching with acyclovir.
Topical honey application is safe and effective in the management of the signs and symptoms of recurrent lesions from labial and genital herpes.
An attempt is made to review the prevalence of medicinal herb use in different societies and the various lines of evidence for its effectiveness for particular health needs and the alleviation of disease conditions.
Published scientifically collected data and anecdotal reports representing numerous populations are compiled and evaluated. Original research findings from Caribbean, American, and Caribbean-American samples are included in the comparisons.
Medicinal plant products have been successfully administered both externally and internally in several different forms for a wide range of health problems cross-culturally since prehistoric times. Certain toxic effects and contraindications have also been recorded.
Many botanical medications contain curative bioactive chemical ingredients which have proven to be valuable as primary or supplemental therapies when carefully applied. Further research will ultimately clarify their appropriate roles in the treatment of diseases and injuries as well as in preventive health maintenance.
The herpes inhibitory effect of Dunbaria bella Prain (Fabaceae), a Thai medicinal plant traditionally used to treat viral infections was investigated. Using a bioassay-guided fractionation procedure, tertiary fractionation of a dichloromethane-methanol plant extract afforded a partially purified fraction (Fr.372) equally active against replication of herpes simplex virus (HSV) types 1 and 2. The 50% inhibitory concentration determined by a viral yield-inhibition assay was 1.21-1.25 microg/ml and the antiviral selectivity was about 17-fold. Treatment of HSV with high concentrations of Fr.372 followed by removal before infection had little effect on subsequent viral yield indicating the active principle(s) were not inactivating the virus. Concentrations greater than 0.5 microg/ml significantly inhibited viral release more than cell-associated virus suggesting that one or more active ingredients may inhibit viral release. Furthermore, the antiviral activity was dependent on multiplicity of infection and the type of host cell. Preliminary chemical analysis showed that Fr.372 contained neither phenolic compounds nor alkaloids.
Neural stem/progenitor cells (NSCs) proliferate vigorously as neurospheres in medium containing basic fibroblast growth factor (FGF-2), but start differentiating into neurons, astrocytes or oligodendrocytes in FGF-2-free medium. An extract of royal jelly (RJ) significantly increased the percentage in the total cell population of not only neurons immunoreactive for class III beta-tubulin (Tuj1) but also astrocytes immunoreactive for glial fibrillary acidic protein (GFAP), and oligodendrocytes immunoreactive for 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) generated from NSCs, but decreased that of nestin-positive NSCs. These results highlight a novel and outstanding property of the RJ, i.e., that it facilitates the differentiation of all types of brain cells (neurons, astrocytes, and oligodendrocytes). On the other hand, 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid characteristic of RJ, increased the generation of neurons and decreased that of astrocytes from NSCs. These observations suggest that RJ contains plural components that differently influence neuronal and/or glial lineages and that HDEA is one of such components of RJ that facilitates neurogenesis by NSCs.
This article reviews the laboratory and clinical evidence that relates to the antimicrobial properties of honey. Observations show it is a broad spectrum antimicrobial agent with efficacy against bacteria, fungi, protozoa and viruses. It is also capable of eliminating malodours from wounds, eradicating antibiotic-resistant strains of bacteria from wounds and acting as an effective prophylactic agent at the exit sites of medical devices.
The aim of this study was to evaluate the effects of bee products such as honey, royal jelly and propolis on 5-fluorouracil-induced experimental oral mucositis in hamsters. Oral mucositis was induced in hamsters through a combination of 5-fluorouracil and mild abrasions that were made on the cheek pouch. Honey, royal jelly and propolis were thereafter topically administered to the oral mucosa, and then the healing process was examined by measuring the size of the mucositis. Honey (1%, 10% and 100%) and propolis (0.3%, 1% and 3%) ointments did not reduce the size of the mucositis in comparison to the vaseline-treated control group. However, the royal jelly (3%, 10% and 30%) ointments significantly improved the recovery from 5-fluorouracil-induced damage in a dose-dependent manner. These results suggest the possibility that the topical application of royal jelly has a healing effect on severe oral mucositis induced by chemotherapy.
To investigate the effects of honey, olive oil and beeswax mixture on patients with atopic dermatitis (AD) or psoriasis vulgaris (PV).
Twenty-one patients with dermatitis and 18 patients with psoriasis were entered for patient-blinded, partially controlled study; 11 patients with dermatitis used topical betamethasone esters and 10 patients with psoriasis used clobetasol propionate. Honey mixture contained honey, beeswax and olive oil (1:1:1). Mixtures A, B, and C contained honey mixture with the corticosteroids ointment in a ratio of 1:1, 2:1, and 3:1 respectively. Patients with dermatitis were subjected to controlled bilateral half-body comparison to evaluate the efficacy of honey mixture against Vaseline, or mixture A against Vaseline-betamethasone esters mixture (1:1) in patients using topical corticosteroid treatment. In patients with psoriasis, the effect of honey mixture was compared with paraffin in an individual right/left-sites comparison, or mixture A against paraffin-clobetasol propionate mixture (1:1) in patients using corticosteroid topical therapy. In dermatitis, body lesions on right or left half-body were assessed for erythema, scaling, lichenification, excoriation, indurations, oozing and itching on a 0-4 points scale. In psoriasis, lesions of selected site were assessed for redness, scaling, thickening and itching, on a 0-4 points scale.
In honey mixture group, 8/10 patients with dermatitis showed significant improvement after 2 weeks, and 5/11 patients pretreated with betamethasone esters showed no deterioration upon 75% reduction of corticosteroid doses with use of mixture C. In psoriasis, 5/8 patients showed a significant response to honey mixture. In patients using clobetasol propionate, 5/10 patients showed no deterioration upon 75% reduction of corticosteroid doses with use of mixture C.
Honey mixture appears useful in the management of dermatitis and psoriasis vulgaris.