Molecular Study on the Potential Protective Effects of Bee Venom against Fructose-Induced Nonalcoholic Steatohepatitis in Rats

Abstract

Background: There is a causative relation between the increased hepatic steatohepatitis prevalence and sweeteners intake, fructose in particular. Despite an increasing understanding of the mechanisms of nonalcoholic steatohepatitis (NASH) pathogenesis, there are no drugs approved for it. Objectives: Evaluate the effect of bee venom (BV) treatment on the fructose-induced NASH in rats and demonstrate its possible molecular mechanisms. Methods: NASH was induced in rats by 10% fructose in drinking water for 8 weeks. BV was administered (0.1 mg/kg, i.p.) 3 times per week during the last 2 weeks of the experiment. Sera were used for the determination of lipids, cholesterol, glucose, insulin, and liver enzymes. Hepatic gene expressions of farnesoid X receptor (FXR)α and the liver X receptor (LXR) were determined. Hepatic sterol regulatory element-binding protein (SREBP)1/2, oxidative stress, and inflammation parameters were measured. Liver parts were used for histopathological examination. Small intestine was removed for the determination of tight junction proteins. Results: Fructose caused overt histological damage in the liver, and this was associated with parallel changes in all parameters measured. BV effectively prevented these changes, presumably through amelioration of hepatic SREBP1/2, LXR, and FXRα expression as well as intestinal tight junction proteins. Conclusion: These findings support the therapeutic usefulness of BV, a remedy with a favorable safety profile, in the prevention of fructose-induced NASH.

Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ1–42

“…In this study, we exhibited bee venom to upregulate the Nrf2 into the nucleus and to upregulate HO-1 production, which, as mentioned, is a phenomenon observed by many researchers [36][37][38]. The explanation of the mechanisms by which bee venom upregulates Nrf2 is recommended for research in the future.…”

“…Moreover, BDNF has been shown to bind to subsets of TrkB receptors, thus further upregulates neural proliferation and enhanced neurogenesis, increasing the neuronal cell's ability to combat oxidative stress [64,65]. As mentioned, in previous studies of bee venom in cell models which seem to lack the significance of BDNF/TrkB/CREB, such as studies on steatohepatitis [36], wound healing [37], and hepatitis [38], bee venom also showed a remarkable ability to upregulate the Nrf2/HO-1 pathway. If this assumption is correct, it hints that bee venom could upregulate HO-1 production as the primary effect.…”

“…As mentioned, the ability of bee venom to normalize depleted HO-1 levels and combat ROS production was mentioned in other steatohepatitis [36], wound healing [37], and hepatitis [38] studies, but has not been examined in anti-neuro-disorder research. In the current in vitro study, our results demonstrate that bee venom reversed ROS, MDA, SOD, and protein carbonyl production induced by Aβ 1-42 .…”

“…Previous cardiology and renal studies have suggested that melittin, the major component, takes up more than half of bee venom's dry weight and reinforces cellular redox balance under oxidative stress by stimulating the nuclear translocation of Nrf2 and upregulating HO-1 expression [34,35]. In addition, the proficiency of bee venom to normalize depleted HO-1 production was mentioned in other steatohepatitis [36], wound healing [37], and hepatitis [38] studies, but it has not been examined in anti-neuro-disorder research.…”

Pharmacokinetic improvement provided by microneedle patch in delivering bee venom, a case study in combating scopolamine-induced neurodegeneration in mouse model

“…Actively promote the intercellular HO-1 antioxidant enzyme to suppress oxidative stress such as ROS and MDA is an ability of bee venom and melittin proven in various studies, and not only to neurological research. Oxidative stress are the sensitive and reactive indexes, and their changes are in the forefront period to any neurodegeneration inducer or neuroprotection promoter phenomenal, therefore ROS and MDA indexes are used to monitor bee venom bioactivity level in mice brain (Hanafi et al, 2018 ; Hozzein et al, 2018 ; Abd El-Haleim, 2020 ; Kurek-Górecka et al, 2020 ; Kim et al, 2021 ; Nguyen & Lee, 2021 ; Duc Nguyen et al, 2022 ).…”