Royal Jelly Enhances the Ability of Myoblast C2C12 Cells to Differentiate into Multilineage Cells.

Royal jelly (RJ) is recognized as beneficial to mammalian health. Multilineage differentiation potential is an important property of mesenchymal stem cells (MSCs). C2C12 cells have an innate ability to differentiate into myogenic cells. Like MSCs, C2C12 cells can also differentiate into osteoblast- and adipocyte-lineage cells. We recently reported that RJ enhances the myogenic differentiation of C2C12 cells. However, the effect of RJ on osteoblast or adipocyte differentiation is still unknown. Here in this study, we have examined the effect of RJ on the osteoblast and adipocyte differentiation of C2C12 cells. Protease-treated RJ was used to reduce the adverse effects caused by RJ supplementation. To induce osteoblast or adipocyte differentiation, cells were treated with bone morphogenetic proteins (BMP) or peroxisome proliferator-activated receptor γ (PPARγ) agonist, respectively. RNA-seq was used to analyze the effect of RJ on gene expression. We found that RJ stimulates osteoblast and adipocyte differentiation. RJ regulated 279 genes. RJ treatment upregulated glutathione-related genes. Glutathione, the most abundant antioxidative factor in cells, has been shown to promote osteoblast differentiation in MSC and MSC-like cells. Therefore, RJ may promote osteogenesis, at least in part, through the antioxidant effects of glutathione. RJ enhances the differentiation ability of C2C12 cells into multiple lineages, including myoblasts, osteoblasts, and adipocytes.

Royal Jelly and Fermented Soy Extracts-A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study.

BACKGROUND: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. MATERIALS AND METHOD: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. RESULTS: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains' scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. CONCLUSIONS: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.

Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases.

Metabolic disorders, encompassing diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, etc., pose a substantial global health threat, with rising morbidity and mortality rates. Addressing these disorders is crucial, as conventional drugs often come with high costs and adverse effects. This review explores the potential of royal jelly (RJ), a natural bee product rich in bioactive components, as an alternative strategy for managing metabolic diseases. RJ exhibits diverse therapeutic properties, including antimicrobial, estrogen-like, anti-inflammatory, hypotensive, anticancer, and antioxidant effects. This review's focus is on investigating how RJ and its components impact conditions like diabetes mellitus, cardiovascular disease, and gastrointestinal illnesses. Evidence suggests that RJ serves as a complementary treatment for various health issues, notably demonstrating cholesterol- and glucose-lowering effects in diabetic rats. Specific RJ-derived metabolites, such as 10-hydroxy-2-decenoic acid (10-HDA), also known as the "Queen bee acid," show promise in reducing insulin resistance and hyperglycemia. Recent research highlights RJ's role in modulating immune responses, enhancing anti-inflammatory cytokines, and suppressing key inflammatory mediators. Despite these promising findings, further research is needed to comprehensively understand the mechanisms underlying RJ's therapeutic effects.

Research progress on rat model of drug-induced liver injury established by nonsteroidal anti-inflammatory drug (celecoxib) and royal jelly ameliorative effect.

OBJECTIVES: NSAIDs, like celecoxib, are widely used to treat pain, fever, and inflammation, with celecoxib being particularly effective in managing arthritis symptoms and acute or chronic pain especially with its favorable gastrointestinal tolerability. The study aimed at exploring the effect of chronic administration of celecoxib on hepatic tissues in male albino rats. It also examined the royal jelly celecoxib interplay. METHODS: 50 male albino rats in 5 equal groups; Group 1: received no drug. Group 2: received celecoxib (50 mg/kg/day, orally), for 30 successive days. Group 3: received celecoxib plus royal jelly (300 mg/kg/day, orally) for 30 successive days. Group 4: received celecoxib, for 30 days, then were left untreated for another 30 days. Group 5: received celecoxib plus royal jelly for 30 days, then were left untreated for another 30 days. RESULTS: Chronic celecoxib administration caused hepatotoxicity in male albino rats, with ameliorative effect of royal jelly. Celecoxib discontinuation significantly diminished the celecoxib-induced toxicity, and normal liver enzymes and serum protein levels were regained in the case of dual medications (celecoxib+RJ) discontinuation. CONCLUSIONS: Long-term celecoxib administration caused hepatotoxicity, with ameliorative effects of royal jelly against celecoxib-induced oxidative and apoptotic stress. In addition, it could be concluded that royal jelly may prove a useful adjunct in patients being prescribed celecoxib.

Effects of royal jelly on the antisenescence, mitochondrial viability and osteogenic differentiation capacity of umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent cells that have the ability to self-renew and regulate paracrine signalling and immune system processes. MSCs have extensive clinical applications in regeneration, functional reconstruction and cellular therapies. However, studies are needed to discover ways to improve the properties of MSCs, such as differentiation, and prevent senescence in culture, which are both very important for cell therapies. Royal jelly (RJ) is a nutritional substance produced by worker bees that contains a substantial amounts of proteins that are beneficial for cell growth and proliferation. RJ is widely used in traditional medicine today, and due to the specific components in its content, it has been reported to have antioxidant, antiproliferative, antimicrobial, neuroprotective, anti-inflammatory, immunomodulatory and anti-ageing properties. In our study, human Wharton's jelly mesenchymal stem cells (WJ-MSCs) derived from umbilical cord matrix were grown in culture medium supplemented with RJ. The control group comprised minimum essential medium (MEM) and 10% foetal bovine serum (FBS); RJ groups were formed using MEM, 10% FBS and 0.075 mg/ml or 0.150 mg/ml RJ. In our study, we evaluated the effect of RJ on WJ-MSC growth by MTT assay, proliferating cell nuclear antigen ELISA, ß-galactosidase activity assay, MitoTracker Green staining and differentiation tests in adipogenic, osteogenic and chondrogenic cell lines. It was observed that the number of mitochondria increased, senescence decreased and osteogenic differentiation increased after differentiation induction after the addition of RJ to MSC culture. In general, the results of this study indicate that WJ-MSCs enhance mitochondrial numbers and important cellular activities, such as antisenescence and osteogenic differentiation, and with increasing evidence from further studies, RJ supplementation may be found beneficial for the use of MSCs in bone engineering regenerative medicine or cell therapy.

A new approach for the treatment of bleomycin-induced rat pulmonary injury by combined protein fraction of major royal jelly protein 2 and its isoform X1.

Nowadays, royal jelly (RJ) has gained great interest as a functional food due to its valuable pharmacological effects. We investigated the therapeutic potency of combined protein fraction (PF50) of major RJ protein 2 and its isoform X1 on bleomycin (Bleo)-induced pulmonary injury in rats. Our study examined the impact of PF50 on pulmonary oxidative and inflammatory stress as well as smooth muscle alpha-actin (α-SMA). In addition, the predicted impacts of this PF on the activity of matrix metalloproteinase (MMP)- 8 and 15-prostaglandin dehydrogenase (15-PGDH) and the E-type prostanoid 2 (EP2) and IL-13 α2 subunit (IL13α2R) receptors, were evaluated using molecular docking. The results showed that PF50 reduced pulmonary inflammatory cells and their secreted pro-inflammatory mediators, including NF-κB, IKK, IL-4, IL-6, and NO. Additionally, the levels of IgE and mucin were diminished after treatment with PF50. Moreover, PF50 treatment improved pulmonary oxidative stress indices such as lipid peroxidation, GSH, SOD, and GPX. The histopathological findings, chest conventional X-ray, and immunohistochemistry of α-SMA confirmed the ameliorating effect of PF50. The docking outcomes reported the probable competitive inhibitory influence of PF50 on MMP-8 and a postulated blocking effect on EP2 and IL13α2R. Thus, PF50 could be a novel approach for treating pulmonary injuries.

The Composition of Fatty Acids in Bee Pollen, Royal Jelly, Buckthorn Oil and Their Mixtures with Pollen Preserved for Storage.

Honey produced by A. mellifera contains minor components present in the nectar collected from plants. Various studies of honey components and all other bee products can be informative in assessing their quality. The aim of the present study was to determine the content and composition of fatty acids (FAs) in sea buckthorn oil (SBO), royal jelly (RJ) and bee pollen (BP) and the changes in FAs content in these products during storage. The diversity of FAs and the effect of storage time on FAs content was also evaluated for the prepared-for-preservation mixtures, which included the following samples: pollen mixed with honey at a ratio of 1:2 (w/w); sample BPH, a well; BPH + 1% (w/w) SBO; and BPH + 1% (w/w) SBO + 2% (w/w) RJ. Fresh bee-collected pollen and RJ were stored at -20 °C, whereas the conserved samples were stored at +4 °C in hermetically sealed jars. The data revealed that RJ demonstrated the highest diversity of fatty acids compared to BP and BP prepared for storage with honey along with SBO and RJ. Palmitic and stearic acids were found in the highest amounts out of the eight saturated fatty acids identified in the studied SBO and RJ. The amount of these fatty acids in RJ compared to SBO was 1.27 and 6.14 times higher, respectively. In total, twenty-two unsaturated fatty acids (USFA) were identified in RJ and fourteen were found in SBO. The SBO used in this study was found to be high in linoleic acid, resulting in an increased n-6 fatty acids ratio in the prepared samples. Essential fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) were found in RJ, as well as in BP and BP mixed with honey. These FAs were not identified in the samples prepared with SBO even in the sample supplemented with RJ. The highest decrease in docosadienoic fatty acid was found in the BPH sample compared to BP, while arachidonic acid mostly decreased in BPH + 1% SBO compared to the BPH + 1% (w/w) SBO + 2% (w/w) RJ samples stored at +4 °C. Bee-collected pollen had the greatest influence on the number of FAs in its mixture with honey.

The effect of oral treatment of royal jelly on the expression of the PDGF-ß gene in the skin wound of male mice.

AIMS OF THE STUDY: Royal jelly (RJ) is one of the most widely used drugs in traditional medicine. One of its important applications is the repair of skin damage, although the path of its mechanism is still unknown. Platelet-derived growth factor-beta (PDGF-beta) is one of the important factors in wound healing and it has been observed that PDGF-ß expression decreases with increasing age. In this study, for the first time, the effect of RJ on skin wounds has been investigated through the expression of PDGF-ß and tissue studies. MATERIALS AND METHODS: 25 small laboratory male BALB/c mice were selected randomly and after creating a 5 mm wound on the back of their neck, they were treated with doses of 2.5, 10, and 40 mg/kg body weight, After sampling from the healed wound in 9th day, histopathological studies and the expression of PDGF-ß gene were performed by Real-time PCR method. RESULTS: The findings of the present study showed that royal jelly caused a significant increase in PDGF-ß (10.99 times) compared to the healthy group. Also, royal jelly increased the formation of covering tissue or epithelium, the synthesis of collagen, the presence of inflammatory cells, and the formation of new blood vessels. CONCLUSION: The oral treatment of royal jelly is probably effective in skin wound healing by changing the expression of PDGF-ß.

Effects of Sucrose Feeding on the Quality of Royal Jelly Produced by Honeybee Apis mellifera L.

Royal jelly (RJ) is a highly nutritious secretion of the honeybees' hypopharyngeal glands (HPGs). During RJ production, colonies are occasionally subjected to manual interventions, such as sucrose feeding for energy supplementation. This study aimed to assess the impact of sucrose feeding on the composition of RJ. The results indicated that RJ obtained from sucrose-fed colonies exhibited significantly higher levels of fructose, alanine, glycine, tyrosine, valine, and isoleucine compared to the honey-fed group. However, no significant differences were observed in terms of moisture content, crude protein, 10-HDA, glucose, sucrose, minerals, or other amino acids within the RJ samples. Moreover, sucrose feeding did not have a significant effect on midgut sucrase activity, HPGs development, or the expression levels of MRJP1 and MRJP3 in nurse bees. Unsealed stored food samples from sucrose-fed bee colonies demonstrated significantly higher sucrose levels compared to sealed combs and natural honey. Additionally, natural honey exhibited higher moisture and Ca levels, as well as lower levels of Zn and Cu, in comparison to honey collected from bee colonies fed sucrose solutions. Based on these findings, we conclude that sucrose feeding has only a minor impact on the major components of RJ.

Royal jelly: a predictive, preventive and personalised strategy for novel treatment options in non-communicable diseases.

Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.

The effect of Royal jelly on liver enzymes and glycemic indices: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Royal jelly (RJ) may contribute to glycemic control and liver function through various mechanisms. The present study aimed to quantify the effect of RJ supplementation on these outcomes. METHODS: A literature search of Web of Science, Scopus, and PubMed/Medline, was conducted for RCTs investigating the efficacy of RJ on plasma liver enzymes and glycemic indices. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes using a random-effects model. RESULTS: Ten RCTs were selected for inclusion in this meta-analysis. Combined estimate of effect sizes for the impact of RJ on neither the plasma liver enzymes nor the glycemic indices were statistically significant. Subgroup analysis showed a significant reduction of serum FPG in trials with intervention duration ≥ 8 weeks (WMD: -4.28 mg/dl, 95% CI -7.41 to -1.14 mg/dl, p = 0.007), and those conducted in non-healthy populations (WMD: -4.28 mg/dl, 95% CI -7.41 to -1.14, p = 0.007). CONCLUSION: RJ does not significantly affect liver function and glycemic profile of adult population. In trials with longer intervention and those conducted in non-healthy populations a significant reduction of serum FBG was observed. This meta-analysis should be repeated in the future, with more primary articles included, in order to provide conclusive results.

The Effect of Royal Jelly on Telomere Length and Some Biochemical Parameters in Wistar Albino Rats with Liver Damage Caused by Carbon Tetrachloride.

Royal jelly (RJ) is a natural bee product that has been used for therapeutic purposes since ancient times. The therapeutic properties of this product, which has rich biological content, are still being investigated with new approaches. In this study, the effect of RJ on telomere length, some antioxidant parameters, and lipid profile was examined. This study will contribute to the literature as it is the first to evaluate the effect of RJ on the length of telomeres in damaged liver tissues. In the study, the levels of serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), telomerase, 8'-hydroxy-2'-deoxyguanosine (8-OHdG), and paraoxonase-1 (PON1) were investigated with enzyme-linked immunosorbent assay method and telomere lengths were investigated by real-time quantitative polymerase chain reaction. The increased TC, LDL-C levels, and AST and ALT activities in the serum after carbon tetrachloride (CCl4) administration approached the control level after RJ administration. PON1 activity decreased in groups with CCl4. PON1 activity increased after RJ administration. The level of 8-OHdG, which increased groups with CCl4, decreased after RJ administration. According to the results of telomere length analysis in liver tissues, telomere lengths in damaged tissues were significantly shortened with CCl4 application and increased with RJ application. Based on the findings of the study, it was concluded that RJ may have therapeutic effects on telomere lengths and some biochemistry parameters.

Lyophilized royal jelly preparation in nanoscale and evaluation of its physicochemical properties and bactericidal activity.

Royal jelly, due to its unique bioactive components, has special biological activities, but a great extent of its nutritional value is lost during processing and storage. Lyophilization, an effective preservation technique, can feasibly preserve the main bioactive compounds present in royal jelly. In this study, fresh royal jelly was subjected to the freeze-drying process at a pressure and temperature of 100 Pa and - 70°C, respectively, for 40 h. The results obtained indicated that the pH, turbidity, total phenol content, and antioxidant activity of the royal jelly powder (RJP), during 3 months of storage at ambient temperature (30°C), were constant with values of 4.30, 1.634 (%A.U.), 0.617 (g/L), and 28.7 (%), respectively. Moisture content of the prepared RJP was less than 1%, while that of the fresh royal jelly was 70%. Furthermore, for the fresh royal jelly, the mentioned parameters were significantly (p < .05) decreased after 2 months of storage at freezer temperature (-20°C). GC-MS analysis indicated that the amount of 10-hydroxy-2-decanoic acid (10H2DA) in RJP was 3.85 times more than that of fresh royal jelly. The obtained results also indicated that prepared RJP had a high bactericidal effect toward Escherichia coli and Staphylococcus aureus, with clear zone diameters of 12 and 15 mm, respectively. The present study provides a foundation for research on the potential application of prepared RJP and the development of dietary supplements and functional foods.

MicroRNA profiling of royal jelly extracellular vesicles and their potential role in cell viability and reversing cell apoptosis.

MiRNAs are small non-coding RNA molecules that play important regulatory roles in diverse biological processes. Royal jelly, a milky-white substance produced by nurse honeybees (Apis mellifera), is the primary food of queen bees and plays a crucial role in their development. However, little is known about the microRNA (miRNAs) content of royal jelly and their potential functions. In this study, we isolated extracellular vesicles from the royal jelly of 36 samples through sequential centrifugation and targeted nanofiltration and performed high-throughput sequencing to identify and quantify the miRNA content of honeybee royal jelly extracellular vesicles (RJEVs). We found a total of 29 known mature miRNAs and 17 novel miRNAs. Through bioinformatic analysis, we identified several potential target genes of the miRNAs present in royal jelly, including those involved in developmental processes and cell differentiation. To investigate the potential roles of RJEVs in cell viability, RJEVs were supplemented to apoptotic porcine kidney fibroblasts induced by ethanol 6% exposure for 30 min. TUNEL assay showed a significant reduction in the apoptosis percentage after RJEV supplementation when compared with the non-supplemented control group. Moreover, the wound healing assay performed on the apoptotic cells showed a rapid healing capacity of RJEV-supplemented cells compared to the control group. We observed a significant reduction in the expression of the miRNA target genes such as FAM131B, ZEB1, COL5A1, TRIB2, YBX3, MAP2, CTNNA1, and ADAMTS9 suggesting that RJEVs may regulate the target gene expression associated with cellular motility and cell viability. Moreover, RJEVs reduced the expression of apoptotic genes (CASP3, TP53, BAX, and BAK), while significantly increasing the expression of anti-apoptotic genes (BCL2 and BCL-XL). Our findings provide the first comprehensive analysis of the miRNA content of RJEVs and suggest a potential role for these vesicles in the regulation of gene expression and cell survival as well as augmenting cell resurrection or anastasis.

Integrated microbiomic and metabolomic analyses reveal the mechanisms by which bee pollen and royal jelly lipid extracts ameliorate colitis in mice.

Bee pollen (BP) and royal jelly (RJ) have shown therapeutic effects against colitis, but the functional components contained therein remain elusive. Here, we used an integrated microbiomic-metabolomic strategy to clarify the mechanism by which bee pollen lipid extracts (BPL) and royal jelly lipid extracts (RJL) ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. Lipidomic results showed that levels of ceramide (Cer), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were significantly higher in BPL than in RJL. The anti-inflammatory efficacy of BPL surpassed that of RJL, although both BPL and RJL could attenuate DSS-induced colitis through several mechanisms: reducing the disease activity index (DAI); decreasing histopathological damage; inhibiting the expression of genes encoding proinflammatory cytokines; improving intestinal microbial community structure, and modulating host metabolism. These findings demonstrated that BPL and RJL have great potential as functional ingredients for the production of dietary supplements to prevent early colitis.

Exploring the Potential of Royal-Jelly-Incorporated Hydrogel Dressings as Innovative Wound Care Materials.

The development of multifunctional dressing materials with beneficial properties for wound healing has become a recent focus of research. Many studies are being conducted to incorporate active substances into dressings to positively impact wound healing processes. Researchers have investigated various natural additives, including plant extracts and apiproducts such as royal jelly, to enhance the properties of dressings. In this study, polyvinylpyrrolidone (PVP)-based hydrogel dressings modified with royal jelly were developed and analyzed for their sorption ability, wettability, surface morphology, degradation, and mechanical properties. The results showed that the royal jelly and crosslinking agent content had an impact on the physicochemical properties of the hydrogels and their potential for use as innovative dressing materials. This study investigated the swelling behavior, surface morphology, and mechanical properties of hydrogel materials containing royal jelly. The majority of the tested materials showed a gradual increase in swelling ratio with time. The pH of the incubated fluids varied depending on the type of fluid used, with distilled water having the greatest decrease in pH due to the release of organic acids from the royal jelly. The hydrogel samples had a relatively homogeneous surface, and no dependence between composition and surface morphology was observed. Natural additives like royal jelly can modify the mechanical properties of hydrogels, increasing their elongation percentage while decreasing their tensile strength. These findings suggest possible future applications in various fields requiring high flexibility and elasticity.

Honey-Related Treatment Strategies in Dry Eye Disease.

This systematic review and meta-analysis investigated whether honey-related treatment strategies improve the signs and symptoms of patients with dry eye disease (DED). In March 2023, the following databases were accessed for clinical trials investigating the efficacy of honey-related treatment strategies in DED: PubMed, Web of Science, Google Scholar, and EMBASE. The following data were extracted at baseline and at the last follow-up: Ocular Surface Disease Index, tear breakup time, Schirmer I test, and corneal staining. Data from 323 patients were retrieved (53.3% female, mean age 40.6 ± 18.1 years). The mean follow-up was 7.0 ± 4.2 weeks. All the endpoints of interest significantly improved from baseline to the last follow-up: tear breakup time (p = 0.01), Ocular Surface Disease Index (p < 0.0001), Schirmer I test (p = 0.0001), and corneal staining (p < 0.0001). No difference was found in tear breakup time (p = 0.3), Ocular Surface Disease Index (p = 0.4), Schirmer I test (p = 0.3), and corneal staining (p = 0.3) between the honey-related treatment strategies and the control groups. According to our main results, honey-related treatment strategies are effective and feasible to improve symptoms and signs of DED.

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.

Differential Apoptotic Effects of Bee Product Mixtures on Normal and Cancer Hepatic Cells.

Most effective anticancer drugs normally generate considerable cytotoxicity in normal cells; therefore, the preferential activation of apoptosis in cancer cells and the reduction of toxicity in normal cells is a great challenge in cancer research. Natural products with selective anticancer properties used as complementary medicine can help to achieve this goal. The aim of the present study was to analyze the effect of the addition of bee products [propolis (PR) or royal jelly (RJ) or propolis and royal jelly (PR+RJ), 2-10%] to thyme (TH) and chestnut honeys (CH) on the differential anticancer properties, mainly the cytotoxic and pro-apoptotic effects, in normal and cancer hepatic cells. The cytotoxic effects of samples were analyzed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (0-250 mg/mL) and the effects on apoptosis were analyzed using cell cycle analysis, TdT-dUTP terminal nick-end labeling (TUNEL) assay, DR5 (Death Receptor 5) and BAX (BCL-2-Associated X) activation, and caspases 8, 9, and 3 activities. Both honey samples alone and honey mixtures had no or very little apoptotic effect on normal cells. Antioxidant honey mixtures enhanced the apoptotic capacity of the corresponding honey alone via both extrinsic and intrinsic pathways. Of all the samples, chestnut honey enriched with 10% royal jelly and 10% propolis (sample 14, CH+10RJ+10PR) showed the highest apoptotic effect on tumor liver cells. The enrichment of monofloral honey with bee products could be used together with conventional anticancer treatments as a dietary supplement without side effects. On the other hand, it could be included in the diet as a natural sweetener with high added value.

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.