The Effect of Tang Forte (Royal Jelly) Capsule on Hypoglycemia and Clinical Course in COVID-19 Patients Under Corticosteroid Therapy.

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.

Exploring the potential therapeutic properties of bee products against COVID-19 (SARS CoV-2)

The new corona virus illness (COVID-19) swept around the world, quickly creating a serious international disaster. For the treatment and prevention of COVID-19, apitherapy appears to be a viable source of pharmacological and nutraceutical medicines. Honey, pollen, propolis, royal jelly, beeswax, and bee venom, for example, have been demonstrated to have significant antiviral action against infections that cause severe respiratory syndromes, including those produced by human corona viruses. Furthermore, many of these natural products are involved in the induction of antibody production, maturation of immune cells, and stimulation of innate and adaptive immunological responses and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of innate and adaptive immunological responses.

Effect of Supplemental Antioxidant-Based Therapy on the Oxidative Stress Level in COVID-19 Patients.

Background: COVID-19 is a disease in several stages starting with virus replication to dysregulation in immune system response, organ failure and recovery/death. Our aim was to determine the effect of Ganoderma lucidum, lycopene, sulforaphane, royal jelly and resveratrol extract on markers of oxidative stress, inflammation, routine laboratory analyses and duration of symptoms in COVID-19 patients. Methods: The oxidative stress parameters and interleukines 6 and 8 (IL-6, IL-8), tumor necrosis factor alpha (TNF-α) were determined in order to estimate the antioxidant and the anti-inflammatory effect of the product using a spectrophotometric and a magnetic bead-based multiplex assay in serum of 30 patients with mild form of COVID-19. Results: Statistically significant differences were obtained for all investigated parameters between the treated patients and the control group. Moreover, significant differences were observed for leukocytes, neutrophil to leukocyte ratio and iron. The average duration of the symptoms was 9.4±0.487 days versus 13.1±0.483 days in the treatment and the control group, respectively (p=0.0003). Conclusion: Our results demonstrated the promising effect of Ge132+NaturalTM on reducing the oxidative stress and the IL-6, IL-8 and TNF-α levels, and symptoms duration in COVID-19 patients. The evidence presented herein suggest that the combination of Ganoderma lucidum extract, lycopene, sulforaphane, royal jelly and resveratrol could be used as a potent an adjuvant therapy in diseases accompanied by increased oxidative stress and inflammation.

Antiviral Activity of Bee Products.

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 various 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.

Major royal jelly proteins elicited suppression of SARS-CoV-2 entry and replication with halting lung injury.

For reasons of high transmissibility and virulence, Alpha (UK, B.1.1.7) and Beta (South African, B.1.351) SARS-CoV-2 variants are classified with other types as variants of concern. Here we report on the influence of royal jelly (RJ) protein fraction (PF)50 (major RJ protein 2 and its isoform X1) on the entry of these variants into the ACE2-human embryonic kidney (HEK) 293 cells using the lentiviral system. The efficiency of PF50 on SARS-CoV-2 replication (RNA-dependent RNA polymerase "RdRp" activity), as well as its impact on bleomycin-induced lung injury in vitro, were also assessed. The PF50 efficiently inhibited infection of kidney cells with the UK and S. African variant spikes of pseudotyped lentivirus particles (IC50 = 7.25 µM and 16.92 µM, respectively) and suppressed the RdRp activity (IC50 = 29.93 µM). Moreover, PF50 displayed protective and therapeutic efficacy against lung injury due to its antioxidant, anti-inflammatory, and angiotensin II blocking activities. The current findings, taken together, offer a novel perspective on PF50 as a promising agent against COVID-19.

Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies

Periodontal diseases are caused mainly by inflammation of the gums and bones surrounding the teeth or by dysbiosis of the oral microbiome, and the Global Burden of Disease study (2019) reported that periodontal disease affects 20–50% of the global population. In recent years, more preference has been given to natural therapies compared to synthetic drugs in the treatment of periodontal disease, and several oral care products, such as toothpaste, mouthwash, and dentifrices, have been developed comprising honeybee products, such as propolis, honey, royal jelly, and purified bee venom. In this study, we systematically reviewed the literature on the treatment of periodontitis using honeybee products. A literature search was performed using various databases, including PubMed, Web of Science, ScienceDirect, Scopus, clinicaltrials.gov, and Google Scholar. A total of 31 studies were reviewed using eligibility criteria published between January 2016 and December 2021. In vitro, in vivo, and clinical studies (randomized clinical trials) were included. Based on the results of these studies, honeybee products, such as propolis and purified bee venom, were concluded to be effective and safe for use in the treatment of periodontitis mainly due to their antimicrobial and anti-inflammatory activities. However, to obtain reliable results from randomized clinical trials assessing the effectiveness of honeybee products in periodontal treatment with long-term follow-up, a broader sample size and assessment of various clinical parameters are needed.

The Effects of Royal Jelly Acid, 10-Hydroxy-trans-2-decenoic Acid, on Neuroinflammation and Oxidative Stress in Astrocytes Stimulated with Lipopolysaccharide and Hydrogen Peroxide

The increased prevalence of neurodegenerative diseases, especially during the COVID-19 outbreak, necessitates the search for natural immune- and cognitive-enhancing agents. 10-Hydroxy-trans-2-decenoic acid (10-H2DA), the main fatty acid of royal jelly, has several pharmacological activities. Given the fundamental role of astrocytes in regulating immune responses of the central nervous system, we used cortical astrocytes to examine the effect of 10-H2DA on the expression of genes associated with neuroinflammation and the production of neurotrophins, as well as cellular resistance to H2O2-induced cytotoxicity. Astrocytes, pretreated with a range of concentrations of 10-H2DA for 24 h, were exposed to lipopolysaccharide (LPS) for 3 h, after which the expression of proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)) and neurotrophic factors (BDNF, GDNF, and IGF-1) was evaluated. In the absence of LPS, 10-H2DA had no significant effect on the mRNA expression of neurotrophins or cytokines except for IL-1β, which significantly increased with low doses of 10-H2DA (3 µM). 10-H2DA (10 µM) pretreatment of LPS-stimulated cells did not significantly inhibit the expression of cytokine encoding genes;however, it significantly lowered the mRNA expression of GDNF and tended to decrease BDNF and IGF-1 expression compared with LPS alone. Additionally, 10-H2DA did not protect astrocytes against H2O2-induced oxidative stress. Our data indicate no anti-inflammatory, antioxidant, or neurotrophic effect of 10-H2DA in astrocytes undergoing inflammation or oxidative stress. The effect of IGF-1 inhibition by 10-H2DA on neuronal ketogenesis needs investigation.

Honey and royal jelly natural products as possible antiviral nominations to combat SARS-CoV-2 main protease

The new type of coronavirus called Severe Acute Respiratory Corona Virus-2 (SARS-CoV-2) has spread over the globe, left the world in lockdown, and taken more lives globally. Hence, more countries have taken restricted policies including quarantine to protect people. However, this was not a promising agent to tackle the existing crisis, so it could become burden on the scientists' shoulders to come up with noble ideas and bring high-safe vaccines and antiviral drugs to combat the COVID-19 pandemic. So far, vaccines and drugs like paxlovid and molnupiravir have been developed to effectively change the pandemic course if clinical trials will prove their efficiency. However, no FDA-approved antiviral drugs against SARS-CoV-2 yet exist. To gain these types of antiviral drugs, computer-aided drug design techniques play a notable role. Of these approaches, molecular docking can screen bio-active compounds and test their potential to specific targets. Herein, we screened bio-active compounds of royal jelly and honey against SARS-CoV-2 main protease in order to investigate their antiviral potency conducting in vivo and in vitro tests. Among the tested natural products, 4 compounds, namely Erlose, Kaempferol glucoside, Iridin, and luteolin glucoside (Cynaroside) showed the lowest binding energies of 10.2, -9.6, -9.0, and -8.4 kcal/mol, respectively. Then, two marketed drugs, i.e. Indinavir and lopinavir, were chosen as standard drugs. Among all, Erlose and Kaempferol glucoside represented excellent antiviral peculiarities against COVID-19 main protease, and may be on the call for future clinical trials to approve their potency.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

The potential antiviral effect of major royal jelly protein2 and its isoform X1 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Insight on their sialidase activity and molecular docking.

Severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 is a newly emerging type of CoV. We evaluated the predicted anti-SARS-CoV-2 effect of major royal jelly protein (MRJP)2 and MRJP2 isoform X1, which recently showed high efficacy against other enveloped RNA-viruses (HCV and HIV). Some in-silico analyses have been performed to predict the impact of these proteins on viral entry, replication, and complications. These proteins have shown a high potency in sialic acid hydrolysis from the lung cells (WI-38) surface. Docking analysis showed that these proteins have a high binding affinity to viral receptor-binding sites in the receptor-binding domain, causing attachment prevention. Moreover, MRJPs can exert an inhibitory influence, via different mechanisms, for SARS-CoV-2 non-structural proteins (main and papain proteases, RNA replicase, RNA-dependent RNA polymerase, and methyltransferase). Also, they can bind to hemoglobin-binding sites on viral-nsps and prevent their hemoglobin attack. Thus, MRJP2 and MRJP2 X1 can be a promising therapy for SARS-CoV-2 infection.

Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen.

The global pandemic of sarcopenia, skeletal muscle loss and weakness, which prevails in up to 50% of older adults is increasing worldwide due to the expansion of aging populations. It is now striking young and midlife adults as well because of sedentary lifestyle and increased intake of unhealthy food (e.g., western diet). The lockdown measures and economic turndown associated with the current outbreak of Coronavirus Disease 2019 (COVID-19) are likely to increase the prevalence of sarcopenia by promoting sedentarism and unhealthy patterns of eating. Sarcopenia has multiple detrimental effects including falls, hospitalization, disability, and institutionalization. Although a few pharmacological agents (e.g., bimagrumab, sarconeos, and exercise mimetics) are being explored in different stages of trials, not a single drug has been approved for sarcopenia treatment. Hence, research has focused on testing the effect of nutraceuticals, such as bee products, as safe treatments to prevent and/or treat sarcopenia. Royal jelly, propolis, and bee pollen are common bee products that are rich in highly potent antioxidants such as flavonoids, phenols, and amino acids. These products, in order, stimulate larval development into queen bees, promote defenses of the bee hive against microbial and environmental threats, and increase royal jelly production by nurse bees. Thanks to their versatile pharmacological activities (e.g., anti-aging, anti-inflammatory, anticarcinogenic, antimicrobial, etc.), these products have been used to treat multiple chronic conditions that predispose to muscle wasting such as hypertension, diabetes mellitus, cardiovascular disorder, and cancer, to name a few. They were also used in some evolving studies to treat sarcopenia in laboratory animals and, to a limited degree, in humans. However, a collective understanding of the effect and mechanism of action of these products in skeletal muscle is not well-developed. Therefore, this review examines the literature for possible effects of royal jelly, bee pollen, and propolis on skeletal muscle in aged experimental models, muscle cell cultures, and humans. Collectively, data from reviewed studies denote varying levels of positive effects of bee products on muscle mass, strength, and function. The likely underlying mechanisms include amelioration of inflammation and oxidative damages, promotion of metabolic regulation, enhancement of satellite stem cell responsiveness, improvement of muscular blood supply, inhibition of catabolic genes, and promotion of peripheral neuronal regeneration. This review offers suggestions for other mechanisms to be explored and provides guidance for future trials investigating the effects of bee products among people with sarcopenia.