Inhibitory and Enzyme-Kinetic Investigation of Chelerythrine and Lupeol Isolated from<i>Zanthoxylum rhoifolium</i>Against Krait Snake Venom Acetylcholinesterase

Ahmad, Mustaq; Weber, Andréia D.; Zanon, Graciane; Tavares, Luciana de Carvalho; Ilha, Vinícius; Dalcol, Ionara I.; Morel, Ademir F.

doi:10.5935/0103-5053.20130274

Cited by 3 publications

(4 citation statements)

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“…In agreement with the previous findings, the present study also showed significant increase in AChE activity in Aβ infused brains [6][7][8][9][10]. However, the treatment of lupeol was able to significantly decrease AChE activity as reported earlier [17]. The finding of the current study suggest that lupeol contributes to the restoration of ACh level by reducing the level of AChE in Aβ (1-42) infused rat's hippocampus.…”

Section: Conflict Of Interestsupporting

confidence: 82%

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Lupeol Isolated from Betula alnoides Ameliorates Amyloid Beta Induced Neuronal Damage via Targeting Various Pathological Events and Alteration in Neurotransmitter Levels in Rat’s Brain

Kaundal¹,

Akhtar²,

Deshmukh³

2017

J Neurol Neurosci

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Lupeol, a natural active constituent of Betula alnoides (BA), is well known for its anti-inflammatory, anti-oxidant and neuroprotective activities. In present study the therapeutic potential of lupeol was investigated against amyloid beta (Aβ (1-42) ) induced cognitive deficit, neurochemical and biochemical abnormalities in rats. Lupeol was isolated from the BA and its structure was confirmed through nuclear magnetic resonance spectra. Aβ (1-42) (4 μg/4 μL) intracerebroventrically (icv) was administered to rats for the induction of Alzheimer's disease (AD). Lupeol treatment (25 mg/kg/day, 50 mg/kg/day and 100 mg/kg/day per orally) was started one week after Aβ (1-42) infusion up to the 21 st days. Morris water maze from day 16 to 21 and object recognition tasks on day 14 and 15 were performed for memory assessment. On 22 nd day, animals were sacrificed and hippocampi were isolated for analysis of biochemical (acetylcholinesterase, lipid hydroperoxide, glutathione and nitrite) and neuro-inflammatory (tumor necrosis factor -α, interleukin (IL)-1β, and IL-6) parameters. In the present study Aβ (1-42) infusion was significantly impaired behavioral memory, increased oxidative stress, decreased antioxidant enzyme and increased pro-inflammatory markers. Treatment of lupeol significantly restored Aβ (1-42) induced behavioral and biochemical abnormalities in rats brain. The findings of the present study suggest that lupeol act through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders of AD.

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Section: Conflict Of Interestsupporting

confidence: 82%

“…inhibition, anti-inflammatory and anti-oxidant actions [16][17][18]. Further, it has been reported to be effective in various pathologies and recently its neuroprotective effect has been studied [19,20].…”

Section: Archivos De Medicina Issn 1698-9465 Journal Of Neurology Andmentioning

confidence: 99%

Lupeol Isolated from Betula alnoides Ameliorates Amyloid Beta Induced Neuronal Damage via Targeting Various Pathological Events and Alteration in Neurotransmitter Levels in Rat’s Brain

Kaundal¹,

Akhtar²,

Deshmukh³

2017

J Neurol Neurosci

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“…In this case the K m increased from 0.108 to 0.310 mM (45.74 to 318.35%) and the V max was unchanged ( Table 2 ). This behavior was indicated by the line weaver Burk double reciprocal plot [ 47 ]. Pd(II) complex inhibited AChE in Bungarus sindanus (krait) venom using ACh as a substrate.…”

Section: Discussionmentioning

confidence: 99%

“…In such type of inhibition, the inhibitor competes with the substrate for binding to the active site of the enzyme, and thus; adequate substrate molecules can move the inhibitor from the enzyme active site. The results of the Lineweaver-Burk analysis indicate that Pd(II) complex inhibited snake venom AChE in a dose-dependent mode [ 47 ]. The Pd(II) complex compete with substrate ACh for binding at the active site of the enzyme and it does not react with the active site but its function is to occupy or prevent the binding of any other molecule of the substrate.…”

Section: Discussionmentioning

confidence: 99%

Kinetic and toxicological effects of synthesized palladium(II) complex on snake venom (Bungarus sindanus) acetylcholinesterase

Ahmed¹,

Khan²,

Sher³

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: The venom of the krait ( Bungarus sindanus ), an Elapidae snake, is highly toxic to humans and contains a great amount of acetylcholinesterase (AChE). The enzyme AChE provokes the hydrolysis of substrate acetylcholine (ACh) in the nervous system and terminates nerve impulse. Different inhibitors inactivate AChE and lead to ACh accumulation and disrupted neurotransmission. Methods: The present study was designed to evaluate the effect of palladium(II) complex as antivenom against krait venom AChE using kinetics methods. Results: Statistical analysis showed that krait venom AChE inhibition decreases with the increase of Pd(II) complex (0.025-0.05 µM) and exerted 61% inhibition against the AChE at a fixed concentration (0.5 mM) of ACh. Kinetic analysis using the Lineweaver Burk plot showed that Pd(II) caused a competitive inhibition. The compound Pd(II) complex binds at the active site of the enzyme. It was observed that K m (Michaelis-Menten constant of AChE-ACh into AChE and product) increased from 0.108 to 0.310 mM (45.74 to 318.35%) and V max remained constant with an increase of Pd(II) complex concentrations. In AChE K Iapp was found to increase from 0.0912 to 0.025 µM (29.82-72.58%) and did not affect the V maxapp with an increase of ACh from (0.05-1 mM). K i (inhibitory constant) was estimated to be 0.029 µM for snake venom; while the K m was estimated to be 0.4 mM. The calculated IC 50 for Pd(II) complex was found to be 0.043 µM at constant ACh concentration (0.5 mM). Conclusions: The results show that the Pd(II) complex can be deliberated as an inhibitor of AChE.

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Promising inhibition of krait snake’s venom acetylcholinesterase by <italic>Salix nigra</italic> and its role as anticancer, antioxidant agent

Ahmed

Ahmad

Khan

et al. 2016

IJAR

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Snakebites are considered a neglected tropical disease that affects thousands of people worldwide. The available antivenoms are associated with numerous side effects. As an alternative, researchers have extensively studied the plants in order to obtain some unusual treatment. The current study was conceded to evaluate the effects of salix nigra (Black willow) against krait snake venom acetylcholinesterase and its role as anti-cancer, anti-oxidant agent. Standard protocols of Ellman, Meyer, Gyamfi and Ruch were used for enzyme inhibition, anti-cancer and free radicals scavenging assays respectively. The methanolic extract of Salix nigra proved to possess neutralization properties against krait snake (Bungarus Sindanus) venom acetylcholinesterase. Statistical data of the results showed that Salix nigra extract inhibited the krait venom acetylcholinesterase through concentration dependent manner. Kinetic analysis using Lineweaver Burk plot revealed that Salix nigra caused competitive type of inhibition i.e. k m value increased while V max remain constant with an increase of extract's concentration. The calculated IC 50 value of Salix nigra was found to be 177µg/ml. In DPPH free radical scavenging assay, extract showed good scavenging potential with IC 50 value of 317µg/ml. Similarly, using H 2 O 2 free radicals, the % scavenging of the extract at 100, 250, 500 and 1000µg/ml was 41, 54, 69 and 74% in comparison with ascorbic acid. Moreover, the extract exhibited good cytotoxic activity against brine shrimps in a dose dependent manner. The present work suggests, for the first time, that Salix nigra extract can be used not only as a potent inhibitor of snake venom acetylcholinesterase but also for the eradication of free radicals along with significant anticancer activity.

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Inhibitory and Enzyme-Kinetic Investigation of Chelerythrine and Lupeol Isolated fromZanthoxylum rhoifoliumAgainst Krait Snake Venom Acetylcholinesterase

Cited by 3 publications

References 1 publication

Lupeol Isolated from Betula alnoides Ameliorates Amyloid Beta Induced Neuronal Damage via Targeting Various Pathological Events and Alteration in Neurotransmitter Levels in Rat’s Brain

Lupeol Isolated from Betula alnoides Ameliorates Amyloid Beta Induced Neuronal Damage via Targeting Various Pathological Events and Alteration in Neurotransmitter Levels in Rat’s Brain

Kinetic and toxicological effects of synthesized palladium(II) complex on snake venom (Bungarus sindanus) acetylcholinesterase

Promising inhibition of krait snake’s venom acetylcholinesterase by <italic>Salix nigra</italic> and its role as anticancer, antioxidant agent

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