A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease

Park, Joon Seong; Rehman, Inayat Ur; Choe, Kyonghwan; Ahmad, Riaz; Lee, Hyeon Jin; Kim, Myeong Ok

doi:10.3390/nu15133059

Cited by 12 publications

(3 citation statements)

References 118 publications

(154 reference statements)

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“…Although lupeol can be found in various fruits, consumption of ≥555 g/kg mango fruit is needed to reach the dose of 100 mg/kg lupeol in humans, which was used in the present experimental study. By contrast, the oral bioavailability of lupeol was previously reported to be #x003C;1% ( 18 ). Therefore, lupeol may be more appropriately applied as a drug instead of a dietary supplement.…”

Section: Discussionmentioning

confidence: 93%

“…It has been previously tested in clinical studies for the treatment of cancer (such as bone, liver, lung, colon, rectum and bladder), actinic keratosis and nocturnal enuresis ( 17-19 ). In a study conducted with actinic keratosis patients, the birch-bark-containing Lupeol managed to clear 75% of the lesions ( 18 ). It was determined that there was a significant decrease in the number of day frequency, nocturia and total incontinence with lupeol treatment ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of lupeol in rats with renal ischemia‑reperfusion injury

Kapisiz,

Kaya,

Eryilmaz

et al. 2024

Exp Ther Med

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Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury

Kapisiz,

Kaya,

Eryilmaz

et al. 2024

Exp Ther Med

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“…Natural-derived compounds such as flavonoids show great potential in improving learning and memory functions has been confirmed by various research studies ( 5 , 41 , 42 ). Lupeol also has a beneficial effect on memory and cognitive functions ( 43 , 44 ). Nevertheless, several studies have explored that systemic LPS administration induces memory and cognitive dysfunction ( 45–47 ).…”

Section: Resultsmentioning

confidence: 99%

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

Choe,

Park,

Park

et al. 2024

Front. Nutr.

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Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1β). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer’s symptoms as LPS treatment enhances level of amyloid beta (Aβ), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aβ, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer’s properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD.

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In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

Singh,

Joshi

et al. 2024

J of Cellular Biochemistry

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Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.

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A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease

Cited by 12 publications

References 118 publications

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury

Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus

In Silico Prediction of Potential Inhibitors for Targeting RNA CAG Repeats via Molecular Docking and Dynamics Simulation: A Drug Discovery Approach

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