PROPOLIS

Propolis is a complex natural substance including CAPE (caffeic acid phenethyl ester) and chrysin. It has evidence of alleviating symptoms of oncology treatments, including radiotherapy in breast cancer. Through significant decrease in radiation-induced DNA damage and restoration of healthy iron metabolism and related enzymes both extended disease free survival, and reduced metastatic progression rates (Highlight 1).

Additional studies in radiotherapy show much reduced oral mucositis after chemotherapy, a serious side effect for some.

In systemic inflammatory diseases, meta-analysis see varied results but on the whole indications of positive effects on reducing insulin resistance and key markers of inflammation. Propolis is also and active iron chelator which contributes to its positive effects in radiotherapy outcomes.

Progress more broadly on clinical trials are limited by the rapid absorption and metabolism. And, the huge variation in propolis content depending on type of and location or country of the bees producing it. Several analyses point to the importance of both sufficent doses usually at least 1g daily.

 

TYPICAL ABSORPTION LEVELS

20 – 30%

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

NO

Highlighted Studies

The supplementation of propolis 10 days pre, during and 10 days after completing radiation therapy caused a significant down-regulation of RRM2 level [marker of DNA repair levels]..after 30 months only 16% of these patients became metastatic with longer median DFS [disease free survival] in comparison to patients received radiotherapy only …. Propolis is an effective iron chelator and disturbs the di-ferric iron center that stabilizes the tyrosyl free radical, critical for catalytic fun...

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Eight weeks after intervention, the mean of FBG, fasting insulin and HOMA-IR, were significantly decreased in patients treated with propolis compared with the placebo group. Furthermore, there was a considerable enhancement in the HOMA-B as a measure of β-cell function and QUICKI index after the administration of propolis in treated group. Serum IL-6 and IL-17 were diminished remarkably in the propolis group..daily intake of 1500 mg of bee propolis supplement for 8 weeks results in improveme...

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This study showed that propolis plus bicarbonate was effective in the prevention of oral mucositis in breast cancer patients treated with doxorubicin and cyclophosphamide. Results from this study provide evidence supporting the use of propolis as complementary therapy in these patients. Such findings are important in the absence of recommendations for effective prevention of OM in this population. Patients in the experimental arm were mostly compliant and satisfied with propolis, which was sa...

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..meta-analysis regarding propolis supplementation effect on serum levels of IL-6, CRP, and TNF-α. Our results suggested that propolis supplementation decreased serum levels of IL-6, CRP, and TNF-α. These results were obtained from 11, 7, and 13 data points from 9, 7, and 11 studies evaluating propolis supplementation effect on IL-6, CRP, and TNF-α, respectively. Our findings are in consistent with the results of previous systematic reviews …Subgroup analysis showed following propoli...

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TABLE OF REFERENCES

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https://www.sciencedirect.com/science/article/pii/S1687850716300255#2.5To avoid the harmful effect of radiations, propolis was given to chemotherapy received BC patients 10 days before radiotherapy during the period of receiving radiotherapy and 10 days after completing radiotherapy. The present study demonstrated the ability of propolis to reduce significantly the radiation induced DNA damage in peripheral white blood cells of BC patients received chemotherapy and exposed to IR. This result is expected since propolis has the capability to stimulate DNA repair mechanisms which in turn counteract the damage inflicted by IRThe supplementation of propolis 10 days pre, during and 10 days after completing radiation therapy caused a significant downregulation of RRM2 level and became within the normal control level. Also it was noticed that after 30 months only 16% of these patients became metastatic with longer median DFS time (27 months) in comparison to patients received radiotherapy only (23 months). Although a number of agents have been developed as RR inhibitors, hydroxyurea has received the most attention in preclinical and clinical studies. Hydroxyurea achieved only limited success in clinical trials. Propolis is an effective iron chelator and disturbs the di-ferric iron center that stabilizes the tyrosyl free radical, critical for catalytic function of RRM2 Screenshot from 2024-11-28 08-56-53
https://journals.viamedica.pl/clinical_diabetology/article/view/969102serum IL-6 and IL-17, FBG levels, HOMA-IR, and fasting insulin were diminished remarkably in the propolis group. After 8 weeks of intervention, HOMA-B as a measure of B-cell function and QUICKI index which indicates an increase in insulin sensitivity, was significantly increased in the propolis group. Eventually, the results of this study indicate that the application of Iranian propolis significantly decreases the inflammatory condition and insulin resistance in patients with diabetes. Thus, propolis can help to decrease complications of diabetes associated with metabolic disturbances and inflammatory conditions.serum IL-6 and IL-17, FBG levels, HOMA-IR, and fasting insulin were diminished remarkably in the propolis group. After 8 weeks of intervention, HOMA-B as a measure of B-cell function and QUICKI index which indicates an increase in insulin sensitivity, was significantly increased in the propolis group. Eventually, the results of this study indicate that the application of Iranian propolis significantly decreases the inflammatory condition and insulin resistance in patients with diabetes. Thus, propolis can help to decrease complications of diabetes associated with metabolic disturbances and inflammatory conditions.
https://pubmed.ncbi.nlm.nih.gov/30022350/2Propolis mouthwash is effective and safe in the treatment of severe oral mucositis. To maintain propolis safety, propolis usage should occur under the supervision of medical staff and health professionals. Future multi-center studies and a clinical protocol are needed to confirm the current findings regarding the efficacy and safety of propolis mouthwash. hese 5 RCTs included a total of 209 participants. The Jadad score for methodological quality was 3.60 ± 0.55. No obvious publication bias was noted. The incidence of severe oral mucositis was significantly lower in the propolis group than in the control group (OR = 0.35)
https://jhpn.biomedcentral.com/articles/10.1186/s41043-024-00600-92ur results suggested that propolis supplementation decreased serum levels of IL-6, CRP, and TNF-α. These results were obtained from 11, 7, and 13 data points from 9, 7, and 11 studies evaluating propolis supplementation effect on IL-6, CRP, and TNF-α, respectively. Our findings are in consistent with the results of previous systematic reviews and meta-analyses [32, 33]. Subgroup analysis showed following propolis supplementation IL-6 significantly reduced in studies with propolis dose ≥ 830 mg/d not dose < 830 mg/d, participants age < 59 years old not ≥ 59 years old, BMI < 25 not ≥ 25, and Asian participants not AmericanAccording to our subgroup analysis results, geographical region was the critical point to get the beneficial effect. Our results revealed in studies among Asian population propolis can significantly reduce serum levels of IL-6 and TNF-α, but this effect did not indicate in American population. These results might be due to different kind of propolis which used in Asian population (Asian propolis) and American population (Brazilian propolis). Unfortunately, despite extensive research on propolis, scientific evidence comparing propolis benefits from different geographical regions are not enough
https://onlinelibrary.wiley.com/doi/10.1111/ecc.127572This study showed that propolis plus bicarbonate was effective in the prevention of oral mucositis in breast cancer patients treated with doxorubicin and cyclophosphamide. Results from this study provide evidence supporting the use of propolis as complementary therapy in these patients. Such findings are important in the absence of recommendations for effective prevention of OM in this population.No severe adverse reactions to propolis occurred. Only two mild skin rashes were reported, as suspected reactions to propolis. Taking propolis was safe in this study, in line with the literature reporting rare cases of adverse reaction to propolis (Menniti-Ippolito et al., 2008). Prevention of OM with propolis was well accepted and appreciated, in line with the increasing popularity of CAMs among cancer patient
https://www.sciencedirect.com/science/article/abs/pii/S10988823240010962 It included randomized clinical trials (RCTs) assessing the effects of propolis supplementation on inflammatory biomarkers in adults. This review included 20 RCTs with a total of 1139 participants. The propolis supplementation significantly reduced IL-6 (WMD = −2.48; 95 % CI: −4.62, −0.34; P = 0.023) and TNF-α (WMD = −0.86; 95 % CI: −1.45, −0.26; P = 0.005) compared with control groups. Although the CRP concentration was not reduced (WMD = 0.01; 95 % CI: −0.03, 0.05, P = 0.646), a significant reduction in CRP levels was revealed in supplementation durations ≥ 10 weeksOur meta-analysis of the propolis treatment effect on inflammation biomarkers summarized 20 RCTs. Our findings showed that propolis supplementation reduced IL-6 and TNF-α but not CRP. In terms of IL-6 and TNF-α, our finding was consistent with previous meta-analysis studies [15], [16], [17], but for the CRP, our results were different from the previous meta-analysis; one of the main reasons could be due to the inclusion of different diseases, duration, and dosage.
https://www.sciencedirect.com/science/article/pii/S1018364720300057?pes=vor&utm_source=wiley&getft_integrator=wiley2Prior to this work, there was no summative assessment of the effect of propolis on inflammatory markers; accordingly, we found that IL-6, CRP, and TNF-α were significantly reduced following propolis supplementation. Given that elevated inflammatory markers are associated with a plethora of non-communicable diseases, propolis may represent a viable adjunct therapy. Whilst most studies are concordant that propolis elicits a improvment impact on inflammation, and it can decrease TNF levels, its effects on interleukins levels has been inconsistently reported (Orsatti et al., 2010, Silva-Carvalho et al., 2015, Zakerkish et al., 2019a). However, in this study, the first summative assessment in the literature, we highlight that IL-6 (WMD: −17.96 pg/ml, 95% CI: −35.53, −0.38, I2 = 98%), CRP (WMD: −1.16 pg/ml, 95% CI: −2.28, −0.03, I2 = 97%), and TNF-a levels (WMD: −34.08 pg/ml, 95% CI: −60.25, −7.91, I2 = 97%) were all significantly reduced following propolis supplementation, yet IL-1 was not
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127854/2Nonetheless, we managed to identify 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects. In conclusion, propolis, as an adjunctive treatment, may have therapeutic benefits in alleviating symptoms related to breast cancers.It was found that propolis alleviated the negative impact associated with radiotherapy in breast cancer patients, namely the increase in Comet tail parameters (Tail length, % Tail DNA, Tail moment) in peripheral blood mononuclear cells, and serum malonaldehyde (MDA). Propolis also prevented the decrease in total antioxidant capacity, hemoglobin (Hb) concentration, white blood cells (WBCs), and platelets counts associated with radiotherapy. More importantly, patients supplemented with propolis had significantly longer median disease free survival time
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473390/2Our clinical trial showed that RJ exerted protective effects against TKI-induced fatigue and anorexia and lowered TKI dose reduction or discontinuation. Hence, RJ is beneficial for maintaining the quality of life and medication compliance in TKI-treated RCC patients.results demonstrated that prophylactic RJ intake is effective for the prevention and suppression of sunitinib-induced fatigue and anorexia. In addition, RJ did not affect treatment safety and compliance. Specifically, we found that the risk of TKI dose reduction or discontinuation was significantly lower in the RJ group than in the placebo group. Sunitinib remains a recommended standard agent used singly or in combination with immune therapy, low molecular weight heparin, and vaccines for the treatment of metastatic RCC
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388256/1Treatment of bCSC with CAPE (4.5-days) decreased CD44 levels by 95%, while another cell population containing 10-100-fold lower CD44 content concurrently increased. Results suggest that CAPE causes pronounced changes in bCSC characteristics manifested by inhibition of self renewal, progenitor formation, clonal growth in soft agar, and concurrent significant decrease in CD44 content, all signs of decreased malignancy potential.Here we show that CAPE inhibits growth of breast cancer stem cells (bCSC) isolated from the aggressive triple negative breast cancer cell line, MDA-231. bCSC were successfully isolated from both the MDA-231 cell line and MDA-231 cell induced nude mouse xenografts. These cells were propagated in culture in the absence of serum (Fig. 1a) and grow as mammospheres (MMS), and when dissociated into single cells, formed MMS again. This process, considered a measure of self-renewal, a CSC trait known to be responsible for regenerating tumor cell mass and cancer recurrence
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144783/1Overall, our results strongly suggest that CAPE inhibits MDA-231 and MCF-7 human breast cancer cell growth due to its cytotoxicity in tumor but not normal cells and its effects on apoptosis, cell cycle, NF-κB and angiogenesis. We propose that CAPE is a viable candidate as a new therapeutic agent by itself as well as an adjuvant to standard chemotherapeutic drugs; the ongoing research should further delineate the mechanism(s) of CAPE effects on breast cancer.CAPE also inhibits expression of the mdr-1 gene (Table 2) known to confer resistance to chemotherapeutic drugs in cancer cells. Hence, it is likely that this decrease in multi-drug resistance gene levels (~4-fold) is the reason for a strong inhibition of growth and cell-cycle arrest by a concurrent treatment of CAPE and Taxol in vitro and in vivo when each is used at suboptimal doses (37, Omene C et al, manuscript in preparation). A decline in this gene should decrease not only the risk of drug resistance, but also allow the use of lower doses of therapeutics, e.g, paclitaxel (Taxol), with greater effectiveness and fewer side effects. These results suggest that CAPE could be used in adjuvant capacity to standard chemotherapeutic drugs as well.
https://www.jcpjournal.org/journal/view.html?uid=835&vmd=Full1propolis displays potent chemoprotective or anti-cancer effect due to the presence of various phytocomponents which contribute to pro-apoptotic, cytotoxic, anti-proliferative (cell cycle arrest), anti-metastatic, anti-invasive, anti-angiogenic and anti-genotoxic or anti-mutagenic properties along with antioxidant, immunomodulatory, and anti-inflammatory functions. Hence, propolis could be used as an adjuvant for treating various cancers along with standard chemotherapeutic drugs. However, many large-scale clinical studies are needed to justify such applications.Propolis displays potent chemoprotective effects due to the presence of various phytocomponents (CAPE, galangin, chrysin, artepillins C, and nemorosone) which contributes to pro-apoptotic, cytotoxicity, anti-proliferative, anti-angiogenic and anti-genotoxic properties along with antioxidant, immunomodulatory and anti-inflammatory functions. Therefore, propolis might be recommended for adjuvant therapy along with conventional chemotherapeutic drugs to either potentiate their efficacy or to minimize adverse effects.
https://www.spandidos-publications.com/10.3892/or.2013.26671The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.In the present study, we demonstrate the ability of chrysin to decrease hypoxic survival of cancer cells, by inhibiting hypoxia-induced STAT3 activation and VEGF expression. We also provide in vivo evidence of the suppressive effect of chrysin on metastatic growth, and a potentiating effect of chrysin when combined with another antimetastatic agent, DR5 mAb. To our knowledge, this is the first study on the antimetastatic effect of chrysin in a spontaneous metastasis mouse model.
https://www.nature.com/articles/s41392-023-01689-w1In summary, our study identifies for the first time the tremendous therapeutic potential of pyrotinib combined with chrysin in treating HER2-positive breast cancer but also sheds light on the functional role of miR-16-5p/ZBTB16/G6PD axis in the anti-HER2 therapeutic process. Together, our study presents a novel treatment option, pyrotinib combined with chrysin, in treating HER2-positive breast cancer.Conversely, the co-treatment of pyrotinib plus chrysin elicited a notable increase in ER stress within breast tumor cells which was evidenced by intense fluorescence signals (Fig. 2c). In line with this, the combination therapy of pyrotinib plus chrysin significantly potentiated ER stress, as evidenced by apparently increasing ER markers, IRE1, and p-eIF2A in both mRNA and protein levels (Fig. 2d, e). Altogether, these data demonstrated that the combined treatment of pyrotinib plus chrysin could induce ER stress amplification, thereby elevating autophagy within breast cancer cells
https://jeccr.biomedcentral.com/articles/10.1186/s13046-017-0514-41After chrysin treatment, HK-2 which combined with VDAC-1 on mitochondria was significantly declined, resulting in the transfer of Bax from cytoplasm to mitochondria and induction of cell apoptosis. Chrysin-mediated cell apoptosis and glycolysis suppression were dramatically impaired in HK-2 exogenous overexpression cells. Tumor growth in HCC xenograft models was significantly restrained after chrysin treatment and significant decrease of HK-2 expression was observed in chrysin-treated tumor tissue.Since HK-2 was found to be of high expression in the majority of tested HCC cells, we examined the activity of chrysin in HCC cells with high HK-2 expression. As shown in Fig. 2b, after chrysin treatment, cell proliferation in LM-3, SMMC-7721 and Bel-7402 was substantially inhibited, and more than 50% cell growth inhibition was observed after 72 h treatment. Previous studies reported that tumor cells with high HK-2 expression often displayed high glycolytic phenomenon, we also investigated the effect of chrysin on tumor glycolysis. HCC cells exposed to chrysin (30 μM) showed significantly lower glucose consumption than the untreated
https://www.mdpi.com/2073-4409/12/12/15611Strong activation of this DNA damage response was found to be partly involved in the ability of chrysin to limit angiogenesis and may partly involve a direct interaction between the polyphenol and DNA G-quadruplex structures responsible for the replication fork collapse. Moreover, these events were associated with a marked reduction in melanoma cells’ capacity to secrete proangiogenic factor VEGF-A. The disruption of these key protein actors in tumor growth by chrysin was also confirmed in a syngeneic model of B16 melanoma. This last point is of importance to further consider the use of chrysin as a new therapeutic strategy in melanoma treatment.Chrysin was shown to decrease angiogenesis and tumor growth in vivo in this study, which limits the progression of melanoma. Nonetheless, further investigations must be performed to demonstrate the potential use of chrysin as a nutritional complement of anti-VEGF antibodies or chemotherapy in order to counteract melanoma progression, especially in preclinical models.

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