PMID: 

Biol Trace Elem Res. 2019 Feb 19. Epub 2019 Feb 19. PMID: 30783919

Abstract Title: 

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats.

Abstract: 

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group(14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renalinjury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through actingas an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

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PMID: 

Int Immunopharmacol. 2019 Apr ;69:270-278. Epub 2019 Feb 8. PMID: 30743203

Abstract Title: 

Genistein suppresses psoriasis-related inflammation through a STAT3-NF-κB-dependent mechanism in keratinocytes.

Abstract: 

Psoriasis is a chronic recurrent skin inflammatory disease, and inhibition of inflammation may be an effective means of treating psoriasis. The flavonoid genistein has a clear anti-inflammatory effect. However, the anti-psoriatic effects of genistein and their underlying mechanisms remain unclear. In this study, we investigated the effects of genistein on imiquimod (IMQ)-induced psoriasis-like skin lesions in vivo and explored the mechanisms underlying those effects in vitro. It was found that genistein can significantly improve IMQ-induced pathological scores of cutaneous skin lesions in mice, reduce epidermal thickness, and inhibit the expression of inflammatory factors，including interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), IL-17 and IL-23. In vitro studies, genistein inhibited the proliferation of human keratinocyte HaCaT cells and inhibited the expression of inflammatory factors in a dose-dependent manner whichinduced by TNFα. Further researches showed that genistein could also significantly inhibit phosphorylated STAT3 (pSAT3) expression in IMQ mice dorsal skin and in TNF-α-induced HaCaT cells. The inhibitory effect of genistein on the expression of IL-6, IL-23 and TNF-α was weakened after Stat3 siRNAin HaCaT cells. Genistein could also significantly inhibit TNF-α induced the nuclear translocation of NF-κB, and inhibit the phosphorylation of I-kBα (pI-kBα). After combining with NF-κB blocker BAY 11-7082, the effect of genistein down-regulate the expression of TNF-α and VEGFA was attenuated in HaCaT cells. The results suggest that genistein may be developed for the treatment of psoriasis lesions.

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PMID: 

Eur J Cancer Care (Engl). 2017 Nov ;26(6). Epub 2017 Aug 25. PMID: 28840622

Abstract Title: 

Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: A pilot randomised controlled trial.

Abstract: 

Chemo-induced oral mucositis (OM) is associated with significant symptoms, treatment delays and increased costs. This pilot randomised controlled trial aimed at evaluating the safety, tolerability and compliance with propolis in breast cancer patients receiving doxorubicin and cyclophosphamide, testing preliminary clinical efficacy of propolis in the prevention of OM, and prospectively evaluating the incidence of OM. Sixty patients were randomised to receive either a dry extract of propolis with 8%-12% of galangin plus mouth rinsing with sodium bicarbonate (experimental arm), or mouth rinsing with sodium bicarbonate (control arm). OM was evaluated with the NCI-CTCAE v4.0 after 5, 10, 15 and 21 days of treatment. Compliance with, tolerability of propolis and adverse events were recorded. The incidence of OM was also prospectively evaluated for 6 months. Two patients (6.7%) manifested a suspected skin reaction to propolis. No patient in the experimental arm developed OM>G1, while in the control arm OM > G1 was 16.7% (p = .02). The incidence of OM ≥ G1 at the end of cycles 2-8 was higher at the second (25%) and fifth cycles (45.8%). Propolis plus bicarbonate was safe, well tolerated and promisingly effective in the prevention of OM in patients with breast cancer.

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PMID: 

Biomed Pharmacother. 2017 Nov ;95:252-263. Epub 2017 Sep 12. PMID: 28846983

Abstract Title: 

Indian propolis ameliorates the mitomycin C-induced testicular toxicity by reducing DNA damage and elevating the antioxidant activity.

Abstract: 

Development of excellent curative therapy for most of the malignancies has resulted in a growing population of cancer survivors who are at increased risk for a variety of health problems including infertility. Therefore, fertility preservation has become an important issue during cancer treatment in recent years. Combination therapy with natural agents such as vitamins, antioxidants, dietary supplements, and plant products are considered as an attractive option to mitigate normal tissue toxicity imparted by chemotherapy. The aim of the present study was to explore the beneficial effect of hydroethanolic extract of Indian propolis (HEIP) on mitigating mitomycin C (MMC)-induced testicular damage and its mechanism of action. Healthy adult male mice were injected intraperitoneally with saline, MMC, HEIP and HEIP followed by MMC after 1h. The animals were dissected at 35days after various treatments to analyze testicular function. MMC administration resulted in significant reduction in testicular function in a dose-dependent manner at 35days after treatment which significantly improved by HEIP pre-treatment. At 24h after treatment, MMC induced significant increase in oxidative stress,γ-H2AX foci and expression of RAD51 and KU80 in testicular cells. Prior treatment with HEIP decreased the oxidative stress, reduced DNA damage and restored the testicular testosterone and inhibin B level. In conclusion, co-administration of Indian propolis extract may play a promising beneficial role in fertility preservation of males undergoing chemotherapy.

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PMID: 

Anticancer Agents Med Chem. 2018 ;18(3):375-387. PMID: 29318976

Abstract Title: 

Algerian Propolis Potentiates Doxorubicin Mediated Anticancer Effect Against Human Pancreatic PANC-1 Cancer Cell Line through Cell Cycle Arrest, Apoptosis Induction and P-Glycoprotein Inhibition.

Abstract: 

BACKGROUND: Pancreatic cancer is one of the most aggressive and lethal cancers, with poor prognosis and high resistance to current chemotherapeutic agents. Therefore, new therapeutic strategies and targets are underscored. Propolis has been reported to exhibit a broad spectrum of biological activities including anticancer activity.OBJECTIVE: This study was carried out to assess the possible efficacy of Algerian propolis on the antitumor effect of doxorubicin on human pancreatic cancer cell line (PANC-1).METHODS: Modifications in cell viability, apoptosis and cell cycle progression, Pgp activity and intracellular accumulation of DOX were monitored to study the synergistic effect of Algerian propolis on the antitumor effects of DOX in PANC-1 cell line.RESULTS: Both propolis and its combination with doxorubicin inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. In the presence of 100μg/ml of propolis, the IC50 of DOX against PANC-1 cells decreased by 10.9-fold. Propolis combined with DOX increased after 48h, the number of cells in the G0G1 phase with dramatical increase in sub-G1 phase to reach 47% of total cells, corresponding to an increase of senescence or apoptotic state of the cells. Dead cell assay with annexinV/PI staining demonstrated that propolis and propolis-DOX treatment resulted in a remarkable induction of apoptosis as detected by flow cytometry. It was interesting to note that propolis at its 5IC50 was found as the most potent inducer of apoptosis. Our finding revealed that induced apoptosis in our conditions was caspase-3 and caspase-9 dependent. Flow cytometry showed that propolis increased the accumulation of doxorubicin within PANC-1 cells. Moreover, fluorescent intensity detection revealed that propolis remarkably increased the retention of rhodamine-123, 7- fold compared to 3-fold of verapamil, the most effective P-gp inhibitor.CONCLUSION: In conclusion, propolis sensitize pancreatic cancer cells to DOX via enhancing the intracellular retention of DOX due to blocking the efflux activity of P-gp pump, inducing cell cycle arrest and increasing apoptosis, finding that improuve the synergism of antitumor effect of Algerian propolis and DOX in pancreatic cancer cell line. Therefore, Algerian propolis may be an effective agent in a combined treatment with doxorubicin for increased therapeutic efficacy against pancreatic cancer.

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PMID: 

Crit Rev Food Sci Nutr. 2019 Jul 10:1-15. Epub 2019 Jul 10. PMID: 31290343

Abstract Title: 

Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials.

Abstract: 

Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption.PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects.A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; 

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PMID: 

J Hum Nutr Diet. 2019 Jul 15. Epub 2019 Jul 15. PMID: 31305957

Abstract Title: 

Dietary intake of isoflavones is associated with a lower prevalence of subclinical cardiovascular disease in postmenopausal women: cross-sectional study.

Abstract: 

BACKGROUND: Menopause has been associated with an increased risk of cardiovascular disease. It has been shown that isoflavones protect vascular endothelial cells against induced oxidative stress injury. Therefore, the present study aimed to investigate the association between the dietary intake of isoflavones and the presence of subclinical cardiovascular disease (CVD) in postmenopausal women.METHODS: Ninety-six postmenopausal women [mean (SD) age 55.2 (4.9) years, body mass index (BMI) 27.2 (4.6) kg m] completed the study protocol. Habitual physical activity was assessed using a digital pedometer, resting metabolic rate was measured by indirect calorimetry and dietary intake was assessed via a validated food frequency questionnaire. Subclinical CVD was defined as carotid artery intima-media thickness (C-IMT)>0.9 mm and/or the presence of one or more atherosclerotic plaques in any of the studied segments.RESULTS: Mean (SD) C-IMT was 0.74 (0.2) mm, 25% of participants were found to have atherosclerotic plaques and the prevalence of subclinical CVD was 35%. Participants with subclinical CVD were more likely to consume less selenium, magnesium, folate and isoflavones, even after adjusting for total energy intake. A multivariate-adjusted regression model showed that a BMI>27 kg mwas associated with 90% higher risk of having≥1 plaque and/or C-IMT>0.9 mm (P = 0.017). Higher oestradiol levels (P = 0.004) and isoflavone intake (P = 0.021) were independently associated with a lower risk of having subclinical CVD.CONCLUSIONS: In the present study, we observed that a higher isoflavone dietary intake was associated with a lower risk of subclinical CVD in postmenopausal women, independent of BMI and endogenous oestradiol levels.

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PMID: 

J Cardiovasc Pharmacol. 2019 Jul 22. Epub 2019 Jul 22. PMID: 31356541

Abstract Title: 

Soy isoflavones inhibit endothelial cell dysfunction and prevent cardiovascular disease.

Abstract: 

Soybeans are among the most popular foods worldwide, and intake of soy-containing foods has been associated with many health benefits, in part because of it structure similar to estrogen. Epidemiologic studies have demonstrated that soy consumption improves serum profiles of hypercholesterolemic patients. Several studies have also indicated an inverse relationship between the consumption of soy isoflavones and the incidence of cardiovascular diseases (CVD). Soy is a rich dietary source of isoflavones. The main soy isoflavones are daidzein and genistein; equol, another isoflavone and a major intestinal bacterial metabolite of daidzein, is generated by enterobacterial effects. Many isoflavones have anti-oxidative effects and anti-inflammatory actions, as well as induce nitric oxide production to maintain a healthy endothelium and prevent endothelial cell dysfunction. These effects may limit the development of atherosclerosis and CVD and restore healthy endothelial function in altered endothelia. Although the evidence supporting the benefits of soy isoflavones in CVD prevention continues to increase, the association between soy isoflavones and disease is not fully understood. This review summarized recent progress in identifying the preventive mechanisms of action of dietary soybean isoflavones on vascular endothelial cells. Furthermore, it describe the beneficial roles that these isoflavones may have on endothelial dysfunction-related atherosclerosis.

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PMID: 

Phytother Res. 2018 Apr ;32(4):750-754. Epub 2018 Jan 29. PMID: 29377427

Abstract Title: 

Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.

Abstract: 

Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a unique Apis melifera type of propolis botanically originated from Dalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole-genome expression in human tumor cells, particularly cancer-related target proteins. HeLa cells were exposed to the compounds at ICand genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC = 214.7 μM) reduced the expression of genes enrolled with the alpha tubulin (fold -3.7), tubulin in microtubules (fold -3.7), and histone h3 (fold = -3.03), and that treatment with neovestitol (IC = 102.91 μM) downregulated prostaglandin E synthase gene (fold = -3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non-clinical, and clinical validation of the findings presented herein is needed.

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PMID: 

Biosci Biotechnol Biochem. 2018 Mar ;82(3):417-421. Epub 2018 Jan 26. PMID: 29370717

Abstract Title: 

Chemical constituents of Brazilian Propolis from the state of Bahia and their growth inhibitory activities against cancer cells.

Abstract: 

A novel 2-phenoxychromone (1) and five known flavones (2-6) were isolated from northeastern Brazilian propolis in the state of Bahia. The chemical structures of these six compounds were determined by spectroscopic investigations and single-crystal X-ray analysis. The isolated compounds showed growth-inhibitory activities, in varying degrees, against human tumor cell lines. This is the first report on the discovery of a novel 2-phenoxychromone from propolis.

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