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Microbes & Immunity Hyphaene thebaica honey as a multitarget therapeutic product

Manuka honey. Despite this, there are only a few studies
exploring the bioactive potential of traditional Palestinian
honey. 31,32,47,52

3.2. Effects of DH on NO levels
NO, a transient bioactive free radical, functions as a
signaling molecule in numerous physiological and
pathological processes. The overproduction of NO serves
as an indicator of the severity and stage of both acute
56
and chronic inflammation. Following the incubation Figure 1. NO production by LPS-activated THP-1-derived macrophages
of TPH-1-derived macrophages with LPS, there was after 72 h of incubation with 1 mg/mL and 2 mg/mL of DH. Data are
presented as mean ± SD from three independent experiments performed
an approximately five-fold increase in NO production in triplicate. Comparisons were made between Control + LPS and DH
compared to the control (Figure 1), observed at non-toxic + LPS groups relative to Control - LPS, which was normalized to 100%.
concentrations of DH (Figure 2). Notably, the levels of NO *P < 0.05 compared to Control + LPS.
were significantly reduced by DH, with a reversion to the Abbreviations: LPS: Lipopolysaccharide; NO: Nitric oxide; DH: Doum
honey.
baseline levels observed in untreated cells.
Numerous studies have previously indicated that honey Cytotoxic Cytostatic
has the capacity to downregulate inducible NO synthase 120
expression and NO production. 57-60 The varying phenolic 100
composition of honey may elucidate the differences in
their nitrogen oxides suppression capabilities, as literature 80
has suggested a link between these compounds and NO % of viable cells 60
inhibition. 59,60 A study on Moroccan Euphorbia honey 40
revealed a strong negative correlation between the phenolic
compounds in honey and the NO scavenging activity of 20
the honey samples. This implies that a higher phenolic 0 0 0.5 1 2 4
59
content in the honey leads to more effective NO inhibition DH (mg/mL)
activity. Another study affirmed that honey possesses
anti-inflammatory properties, which could be partially Figure 2. Cytotoxic and cytostatic effects were assessed on MDA cells
using MTT Assay following treatment with honey samples ranging from
attributed to the inhibition of NO release, indicating that 0 to 4 mg/mL for 24 h (for cytotoxic effects) and 72 h (for cytostatic
the chemical constituents of honey, including its phenolic effects). The absorbance of the MTT formazan was quantified at 570 nm
compounds, may contribute to this inhibitory effect. 60 utilizing an ELISA reader. Cell viability was computed as the percentage
ratio of absorbance of honey-treated cells relative to untreated cells. Data
However, it is important to note that the specific represent the mean ± SD from three independent experiments conducted
chemical constituents of honey that contribute to this in triplicate. *P < 0.05 compared to the untreated control.
effect and the precise mechanisms involved may differ Abbreviations: DH: Doum honey; ELISA: Enzyme-linked immunosorbent
depending on the type of honey, necessitating further assay; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium
bromide.
research. While these studies suggest a correlation, they
do not establish a direct cause-and-effect relationship. The phase in various cancer cell lines, such as bladder (T24,
correlation signifies a relationship between the two factors, 253 J, RT4, and MBT-2), colon (HCT-15 and HT-29), and
but it does not definitively prove causality. human melanoma (A375) cells. 61-63 The cytostatic effects of
different types of honey have been highlighted in recent
3.3. Cytotoxic and cytostatic effects of DH in cells research, 64,65 which has focused on identifying components
from the MDA cell line in honey that can inhibit cancer cell proliferation without
Cancer cells are characterized by uncontrolled growth, eliciting cytotoxicity. For instance, an analysis of bioactive
a central focus for both traditional chemotherapy and honey samples has identified phenolic compounds such
emerging therapeutic strategies. DNA damage can lead as rosmarinic acid, tannic acid, caffeic acid, coumaric
to growth arrest at the G0/G1 or G2/M phases or may acid, gallic acid, ferulic acid, syringic acid, catechin, and
even initiate apoptosis. Many chemotherapy agents are pyrogallol. 62
designed to disrupt the cell cycle, particularly during the Figure 2 delineates the cytostatic and cytotoxic effects of
S and M phases. Studies have extensively documented DH samples on MDA cells. MDA cells are widely utilized
honey’s ability to induce cell cycle arrest at the G0/G1 models for breast cancer research, offering a relevant

Volume 2 Issue 1 (2025) 83 doi: 10.36922/mi.4994