Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer's Disease: Findings from a Rat Model Study – PubMed Black Hawk Supplements

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Alzheimer’s disease (AD) poses a major worldwide health challenge because of its profound impact on cognitive abilities and overall well-being. Despite extensive research and numerous clinical trials, therapeutic options remain limited. Our study aimed to investigate the potential of Kelulut honey (KH) as a novel therapeutic agent for addressing the multifactorial pathology of AD. We tried to evaluate the disease-attenuating and neuroprotective potential of KH in the intrahippocampally induced…
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Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer's Disease: Findings from a Rat Model Study - PubMed

Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer’s Disease: Findings from a Rat Model Study

Ammara Shaikh et al. Antioxidants (Basel). .

Abstract

Alzheimer’s disease (AD) poses a major worldwide health challenge because of its profound impact on cognitive abilities and overall well-being. Despite extensive research and numerous clinical trials, therapeutic options remain limited. Our study aimed to investigate the potential of Kelulut honey (KH) as a novel therapeutic agent for addressing the multifactorial pathology of AD. We tried to evaluate the disease-attenuating and neuroprotective potential of KH in the intrahippocampally induced AD rat model by utilizing histochemistry and enzyme-linked immunosorbent assay (ELISA) studies. A total of 26 male Sprague Dawley rats weighing ~280-380 g were randomly divided into three groups: Control, AD-induced (Aβ), and AD-induced and treated with KH (Aβ+KH). The latter two groups underwent stereotaxic surgery, where 6.25 µg of amyloid β1-42 peptides were injected intrahippocampally. One-week post-surgery, KH was administered to the treatment group at a dose of 1 g/kg body weight for a period of four weeks, after which the rats went through behavior tests. After completion of behavior analysis, the rats were sacrificed, and the brains were processed for histochemistry and ELISA studies. The open field test analysis demonstrated that KH improved the locomotion of Aβ+KH compared to Aβ (p = 0.0013). In comparison, the Morris water maze did not show any nootropic effects on cognition with a paradoxical increase in time spent in the target quadrant by the Aβ group (p = 0.029). Histochemical staining showed markedly increased Congo-red-stained amyloid plaques, which were significantly reduced in dentate gyrus of Aβ+KH compared to Aβ (p < 0.05). Moreover, significantly higher apoptosis was seen in the Aβ group compared to Aβ+KH (p < 0.01) and control groups (p < 0.001). Furthermore, the ELISA studies deduced more phosphorylated tau in the diseased group compared to Aβ+KH (p = 0.038) and controls (p = 0.016). These findings suggest that KH consumption for twenty-eight days has the potential to attenuate the pathological burden of disease while exerting neuroprotective effects in rodent models of AD.

Keywords: neurodegenerative disease; neuroprotection; pot-honey; stingless bee honey; β-amyloid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Path length and time spent in peripheral vs. central zone in OFT arena. ** p < 0.01.

Figure 2
Figure 2

Results of the training days. (a) Total distance (b), escape latency, (c) swim speed, and probe test (d) total distance covered, (e) number of times the platform area was crossed, and (f) the time spent in target quadrant. * p < 0.05.

Figure 3
Figure 3

Congo-red-stained human brain with (AD brain) and without AD (control brain). The orange-red stained amyloid plaques can be seen in 40× and 100× magnification (red arrows).

Figure 4
Figure 4

(a) Congo-red-stained control, Aβ, Aβ+KH groups (magnification 40×). The areas CA1, CA3, and DG are further enlarged (magnification 100×) to show the amyloid plaques (green arrows). Congo-red-stained amyloid plaque count in areas (b) CA1, (c) CA3, (d) DG and (e) the total count in all regions combined. * p < 0.05.

Figure 5
Figure 5

(a) TUNEL assay of area CA1 of control, Aβ, Aβ+KH groups (magnification 100×). Bright green TUNEL-positive cells appear turquoise green after merging with DAPI (yellow arrows). Number of TUNEL-positive cells in areas (b) CA1, (c) CA3, (d) DG, and (e) the total count in all three regions. * p < 0.05, ** p < 0.01, # p < 0.001.

Figure 6
Figure 6

The ELISA results of Aβ42 (amyloid β42), p-tau, NF-κB p65, SOD1, and MDA in rat hippocampus. * p < 0.05.

Figure 7
Figure 7

Current FDA-approved treatment options targeting pathology and symptoms of AD.

Figure 8
Figure 8

Possible mechanism of action of KH to ameliorate AD burden in amyloid β1–42 (Aβ1–42)-induced models. Figure showing Aβ1–42 intrahippocampal injection initiating amyloid and tau pathologies with subsequent formation of amyloid plaques and p-tau (leading to microtubule dysfunction); both the pathological markers later cause DNA damage (evident as increased TUNEL-positive signals). The KH treatment likely targets plaque formation and tau hyperphosphorylation (shown with the red cross) that ultimately results in decreased neuronal apoptosis (shown with dotted green line).

References

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Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer's Disease: Findings from a Rat Model Study – PubMed