Influence of chrysin on D‐galactose induced‐aging in mice: Up regulation of AMP kinase/liver kinase B1/peroxisome proliferator‐activated receptor‐γ coactivator 1‐α signaling pathway
Abstract:Adenosine monophosphate kinase/liver kinase B1/peroxisome proliferator‐activated receptor‐γ coactivator 1‐α (AMPK/LKB1/PGC1α) pathway has a vital role in regulating age‐related diseases. It controls neurogenesis, cell proliferation, axon outgrowth, and cellular energy homeostasis. AMPK pathway also regulates mitochondrial synthesis. The current study evaluated the effect of chrysin on D‐galactose (D‐gal) induced‐aging, neuron degeneration, mitochondrial dysfunction, oxidative stress, and neuroinflammation in m… Show more
“…Serum insulin and HOMA-β levels were significantly increased in Chr-PLs-treated diabetic rats, whereas FBG and HOMA-IR were markedly decreased. These results were coordinated with the results obtained by Salama et al [ 50 ], and Kim et al [ 71 ]. Increased peripheral uptake of glucose, suppression of hepatic glucose production [ 71 ], and improved insulin sensitivity may all contribute to chrysin’s powerful hypoglycemic impact.…”
Section: Discussionsupporting
confidence: 91%
“…This results in persistently high blood sugar levels and difficulty metabolizing carbohydrates, proteins, and fats [ 49 ]. Nephropathy and neurologic consequences are included in this illness [ 50 ]. In this study, our findings demonstrate the significant involvement of the ER stress and autophagy signaling pathway in the capacity of Chr-PLs to safeguard against advancing diabetic neuropathy.…”
Section: Discussionmentioning
confidence: 99%
“…This finding agreed with Kang et al [ 83 ], who treated glucose-stimulated human RPE cells with chrysin and observed that ER stress-related sensors such as BiP, ATF6, and the IRE1 pathway were less induced. In a study using a D-galactose model of aging in mice, Salama et al [ 50 ] found that chrysin prevented neurodegeneration, boosted mitochondrial autophagy and biogenesis, and reduced oxidative stress and neuroinflammation. The increased ER stress response and the suppression of autophagy in the alloxan model of DN may be the outcomes of hyperglycemia’s enhancement of oxidative stress.…”
Background
Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats.
Methods
Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs’ antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis.
Results
According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration.
Conclusion
The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.
Graphical Abstract
“…Serum insulin and HOMA-β levels were significantly increased in Chr-PLs-treated diabetic rats, whereas FBG and HOMA-IR were markedly decreased. These results were coordinated with the results obtained by Salama et al [ 50 ], and Kim et al [ 71 ]. Increased peripheral uptake of glucose, suppression of hepatic glucose production [ 71 ], and improved insulin sensitivity may all contribute to chrysin’s powerful hypoglycemic impact.…”
Section: Discussionsupporting
confidence: 91%
“…This results in persistently high blood sugar levels and difficulty metabolizing carbohydrates, proteins, and fats [ 49 ]. Nephropathy and neurologic consequences are included in this illness [ 50 ]. In this study, our findings demonstrate the significant involvement of the ER stress and autophagy signaling pathway in the capacity of Chr-PLs to safeguard against advancing diabetic neuropathy.…”
Section: Discussionmentioning
confidence: 99%
“…This finding agreed with Kang et al [ 83 ], who treated glucose-stimulated human RPE cells with chrysin and observed that ER stress-related sensors such as BiP, ATF6, and the IRE1 pathway were less induced. In a study using a D-galactose model of aging in mice, Salama et al [ 50 ] found that chrysin prevented neurodegeneration, boosted mitochondrial autophagy and biogenesis, and reduced oxidative stress and neuroinflammation. The increased ER stress response and the suppression of autophagy in the alloxan model of DN may be the outcomes of hyperglycemia’s enhancement of oxidative stress.…”
Background
Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats.
Methods
Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs’ antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis.
Results
According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration.
Conclusion
The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.
Graphical Abstract
“…In addition, brain levels of adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), liver kinase B1 (LKB1), neurotrophin-3 (NT-3), NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), and serotonin (5-HT) were increased and the proinflammatory mediators TNF-α, NF-κB, and glial fibrillary acidic protein (GFAP) were reduced. Chrysin also alleviated neuronal degeneration in the white matter and cerebral cortex [ 85 ]. Fig.…”
Section: Dietary Small Molecules and Neuroprotection – A Overview Of ...mentioning
The long and rich history of herbal therapeutic nutrients is fascinating. It is incredible to think about how ancient civilizations used plants and herbs to treat various ailments and diseases. One group of bioactive phytochemicals that has gained significant attention recently is dietary polyphenols. These compounds are commonly found in a variety of fruits, vegetables, spices, nuts, drinks, legumes, and grains. Despite their incredible therapeutic properties, one challenge with polyphenols is their poor water solubility, stability, and bioavailability. This means that they are not easily absorbed by the body when consumed in essential diets. Because of structural complexity, polyphenols with high molecular weight cannot be absorbed in the small intestine and after arriving in the colon, they are metabolized by gut microbiota. However, researchers are constantly working on finding solutions to enhance the bioavailability and absorption of these compounds. This study aims to address this issue by applying nanotechnology approaches to overcome the challenges of the therapeutic application of dietary polyphenols. This combination of nanotechnology and phytochemicals could cause a completely new field called nanophytomedicine or herbal nanomedicine.
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