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Molecular Properties and Insilico Neuroprotective Activity of Eugenol Against Glutamate Metabotrophic Receptors

October 2016

Authors:

Nagaland University

Metabotrophic glutamate receptors were expressed abnormal in the neurodegenerative diseases. The negative regulation of the abnormal expression induce glutamate excitotoxicity has connected to interminable neurodegenerative issues for example, amyotrophic parallel sclerosis, multiple sclerosis and Parkinson's disease. The molecular target metabrophic glutamate receptors were modulated and regulated by the potent medicinal compounds. Eugenol is a medicinal value rich compound found in the buds and leaves of clove (Syzygium aromaticum (L.) Merrill and Perry), which has been accounted to have antioxidant, anticancer and neuroprotective activity. In this present study the Eugenol compound was evaluated for the neuroprotective activity through molecular docking and molecular property prediction. The eugenol compound was optimized and prepared as ligand molecule using ligprep tool. Similarly the glutamate receptors were prepared for molecular docking through auto dock tool. Prelimarily, the eugenol was evaluated for the molecular properties and drug likeliness sore. The duglikeliness score -0.60 of eugenol indicated the highest score and confirmed as potent drug like compound. Totally ten glutamate receptors were chosen and docked with eugenol ligand molecule. Among the receptors 2e4y, 3ks9, 2wjw and 3lmk were significantly inhibited by eugenol. 2e4y and 3ks9 achieved the best docking frequency (-28.01and -32.90) with atomic contact energy.

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Int. J. Pharm. Sci. Rev. Res., 40(1), September – October 2016; Article No. 58, Pages: 318-323 ISSN 0976 – 044X

International Journal of Pharmaceutical Sciences Review and Research

Available online at www.globalresearchonline.net

318

Jai Prabhu2, G.Bupesh*1, K.Prabhu2, V.S.Kalaiselvi3, K.Meenakumari1, Mudiganti Ram Krishnarao5, P.Sathyarajeswaran6,

E. Manikandan4

1 Central Research laboratory, Sree Balaji Medical College & Hospital (SBMCH), Bharath University, BIHER, Chrompet, Chennai, Tamil Nadu, India.

2 Dept of Anatomy, Sree Balaji Medical College & Hospital (SBMCH), Bharath University, BIHER, Chrompet, Chennai-600044, Tamil Nadu, India.

3Dept of Biochemistry, Sree Balaji Medical College & Hospital (SBMCH), Bharath University, BIHER, Chrompet, Chennai -600044, Tamil Nadu, India.

4 Nanosciences African Network (NANO-AFNET), Materials Research Department, iThemba LABS–National Research Foundation (NRF), 1 Old Faure

Road, Somerset West, PO BOX 722 Western Cape, South Africa.

5Dept of Industrial Biotechnology, Bharath University, BIHER, Chrompet, Chennai-600044, Tamil Nadu, India.

6Central Council for Research in Siddha, Ministry of AYUSH, Arumbakkam,Chennai, Tamil Nadu, India.

*Corresponding author’s email: bupeshgiri55@gmail.com

Accepted on: 05-07-2016; Finalized on: 31-08-2016.

ABSTRACT

Metabotrophic glutamate receptors were expressed abnormal in the neurodegenerative diseases. The negative regulation of the

abnormal expression induce glutamate excitotoxicity has connected to interminable neurodegenerative issues for example,

amyotrophic parallel sclerosis, multiple sclerosis and Parkinson's disease. The molecular target metabrophic glutamate receptors

were modulated and regulated by the potent medicinal compounds. Eugenol is a medicinal value rich compound found in the buds

and leaves of clove (Syzygium aromaticum (L.) Merrill and Perry), which has been accounted to have antioxidant, anticancer and

neuroprotective activity. In this present study the Eugenol compound was evaluated for the neuroprotective activity through

molecular docking and molecular property prediction. The eugenol compound was optimized and prepared as ligand molecule using

ligprep tool. Similarly the glutamate receptors were prepared for molecular docking through auto dock tool. Prelimarily, the eugenol

was evaluated for the molecular properties and drug likeliness sore. The duglikeliness score -0.60 of eugenol indicated the highest

score and confirmed as potent drug like compound. Totally ten glutamate receptors were chosen and docked with eugenol ligand

molecule. Among the receptors 2e4y, 3ks9, 2wjw and 3lmk were significantly inhibited by eugenol. 2e4y and 3ks9 achieved the best

docking frequency (-28.01and -32.90) with atomic contact energy.

Keywords: Eugenol, Glutamate receptors, Druglikeliness, Docking, Neuroprotective activity.

INTRODUCTION

Plants are rich wellspring of bioactive parts that have

attractive medical advantages and are traditionally useful

for various ailments. Eugenol (4-allyl-2-methoxy phenol),

is a phenolic compound found in the leaves, buds of clove

(Syzygium aromaticum (L.) Merrill and Perry1, essential

oils and is a noteworthy constituent of Ocimum,

Cinnamon, and Clove oils. Principally, eugenol is isolated

from the clove buds of Eugenia aromatica, E.

caryophyllata having a place with family Mytraceae

indigenous to the Molluca Islands, and which are likewise

developed in different parts of Indonesia, Zanzibar,

Madagascar, and Ceylon. Eugenol is a fascinating

compound inspite of its wide range of exercises like pain

relieving, calming, antifungal, antibacterial and

antihypertensive movement2. As of late, numerous

pharmacological and restorative activities of eugenol

have been explored particularly where traditional

medications are ineffectual in the treatment of infection.

Eugenol separated from the fringe activities additionally

acts at focal level. In sensory system, eugenol is acts as

neuroprotective against excitotoxicity, ischemia and

amyloid-β peptide, restrains the conduction of activity

potential in sciatic nerves and enhances neuronal and

vascular intricacies in exploratory diabetes3-7. Eugenol has

been reported to stretch bradykinin and kallikrein incited

sedation8. Old Chinese pharmacopeias uncovered that

most natural cures demonstrated for Alzheimer illness

(AD or indications reminiscent of AD) contains the organic

Rhizoma acori graminei which is rich in eugenol9.

Alzheimer's ailment (AD) is an unending and dynamic

neurodegenerative issue which was initially portrayed in

1907 by Alois Alzheimer and is described by a dynamic

loss of neurons and neurotransmitters with the nearness

of substantial quantities of extracellular amyloid plaques.

It extremely influences psychological capacity and other

behavioral angles, for example, official capacity and

dialect aptitudes. Both extracellular and intracellular

aggregation of Aβ starts a course of occasions including

synaptic and neuriticharm, microglial and astrocytic

initiation (provocative reaction), modified neuronal

ionichomeostasis, oxidative harms, changes of

kinases/phosphatases exercises, development of NFTs

and at long last cell demise. Eugenol shields neuronal cells

from NMDA-incited excitotoxic and oxidative damage4, 10.

However, no in silico reports were accessible on the

eugenol molecular mechanism on neuroprotection and

modulation. The present study investigates on the

molecular interaction, inhibition of eugenol on

metabotrophic glutamate receptors.

Molecular Properties and Insilico Neuroprotective Activity of Eugenol

Against Glutamate Metabotrophic Receptors

Research Article

Int. J. Pharm. Sci. Rev. Res., 40(1), September – October 2016; Article No. 58, Pages: 318-323 ISSN 0976 – 044X

International Journal of Pharmaceutical Sciences Review and Research

Available online at www.globalresearchonline.net

319

MATERIALS AND METHODS

Preparation of target molecules

Glutamate receptor proteins were chosen for docking

studies. The crystal structures of the proteins are

available in Protein Data Bank (http://www.rcsb.org/pdb)

and the PDB ID for the receptors is (2E4U, 2E4V, 2E4W,

2E4X, 2E4Y, 2E4Z, 2WJW, 3KS9, 3LMK, 3MQ4) was mined

and optimized for docking studies.

Ligand preparation

The identified Chemical compound namely Eugenol from

Syzygium aromaticum clove Seed and these compound

structure were retrieved from Pubchem structural

database. Both of these compounds were prepared by

Ligprep package. The ligand molecules were generated

and the three dimensional optimizations were done and

then saved as MOL file (a file format for holding

information about the atoms, bonds, connectivity and

coordinates of a molecule).

Active Site Prediction

Active site recoganization of Metabotrphic glutamate

receptors proof of human estrogen receptor The catalytic

sites of Metabotrphic glutamate receptors area and

volume of binding pocket was was done with Computed

Atlas of Surface Topography of Proteins (Castp) program

(http://cast.engr.uic.edu)11.

Molecular docking

In the present study the glutamate receptor proteins are

docked with the eugenol ligand. The molecular docking

was performed with AutoDock 4.2.1. In order to analyze

the effect of ligand association, all the water molecules

and the hetero atoms have been removed from the target

protein. All the hydrogen atoms were added to the

protein as it is required for the electrostatics and then

non polar hydrogen atoms were merged together.

RESULTS

The active compounds in many ayurvedhic drugs

constituted compounds like eugenol was treated for

neuroprotective role and neurodegenerative diseases.

The eugenol Figure 1 was chosen as the ligand and

appraised for the antagonist action against metabotropic

glutamate receptors. The eugenol was first predicted for

the quantitative structure activity relationship and drug

like lines using Molinsipiration tool Figure 2. The eugenol

structure was submitted in the molinspiration tools using

jmol chemical structure drawer. The molecular properties

and drug likeliness were shown in the Figure 3. The

molecular properties such as moleuclar formula: C10H12O2,

molecular weight-164.08, number of Hydrogen bond-1,

molecular log polarity- 2.61, molecular solubility -2.45,

molecular polar surface area- 24.42, molecular volume

181.27 and no stereo centers. The drug likeliness score

was found to be -0.60. The transport and recognization of

the drugs is very essential for the target specific therapy.

The target specific drug action can be assessed by the

parameters such as G- protein coupled receptor (GPCR),

ion channel modulator, nuclear receptor and protease

inhibitor presented in the Figure 4a and b. The

Bioproperty predictor predicts eugenol as the GPCR

ligand -0.86, Ion channel modulator -0.36, Kinase inhibitor

-1.14,Nuclear receptor ligand -0.78 , Protease inhibitor -

1.29, Enzyme inhibitor -0.41. The Insilico docking of

eugenol with metabotrophic glutamate receptors 2E4U,

2E4V, 2E4W, 2E4X, 2E4Y, 2E4Z, 2WJW, 3KS9, 3LMK,

3MQ4 were presented in the Figure 5a and b.The docking

cycles and other parameters were used according to the

Murris good self mentod and the docking score profile

were presented as shown in the figure.

The active sites residues of the metabotrophic glutamate

receptors were predicted by the active site prediction

tool. The active site residues in 2E4U-Phe 207,208,Arg-

206,Glu 518, 2E4V-Arg 206,Phe 208,Asn-209, 2E4W-Arg-

206,Phe 208,Asn 209,Val 504, 2E4X-Arg 206,Phe 208,Asn

209,Val 504, 2E4Y-Arg 206,Phe 208,2E4Z-Pro 56,Gly-

58,Lys-71,Asn 74,Ser-159,Ser-229, 2WJW-Asn-370,Glu-

391,Val-392, 3KS9-Trp-110, Gly-163, Ser-164, 165, 186,

Tyr-236, Asp-318,319,Ala-329,Gly 379, 3LMK- Arg

206,Phe 208Asn-445, Leu-455 and 3MQ4-Gly-158, Ala-

180,Ser-181,Thr-182Ser-187.

The predicted catalytic sites of 10 metabotrphic

glutamate receptors were utilized as the synergist locales

for eugenol compound were characteristic utilized for

docking studies presented in the Table 1. The effects of

the docking interaction between the dynamic site

deposits of target metabotrphic glutamate receptor

proteins and eugenol ligand were presented in the Table

2. By investigating the docking associations, Eugenol was

found to have the most noteworthy enactment vitality

with receptors 2e4y, 3ks9, 2wjw and 3lmk. The 2e4y

receptor showed the highest significant activity with the

Ligand eugenol. The atomic contact energy, Ligand

transformation and docking frequency was found to be -

28.01, 2740 Score kcal/mol and -1.09 -1.17 -0.60 -7.34

12.66 68.26. Similarly the 3ks9 significantly attained -

32.90, 3238 Score kcal/mol and -0.75 0.83 -0.89 -75.68

24.99 17.80. Further the above results could be valuable

for recognizable proof and improvement of new

preventive and remedial medication against

Neurodegenerative diseases.

DISCUSSION

At present, different phytal activities including flavors and

zest bioactive agents are broadly utilized as alternative

therapeutic compounds as reciprocal expertise

compounds in the control and management of

neurodegenerative diseases12, 13. Human Consumption of

natural product eugenol and other derived compounds

has been used in the preparation various recepies and

medicinal formulations. These bioactive compounds were

exhibited to possess different nourishment

Int. J. Pharm. Sci. Rev. Res., 40(1), September – October 2016; Article No. 58, Pages: 318-323 ISSN 0976 – 044X

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Available online at www.globalresearchonline.net

320

arrangements, antioxidant, anti-inflammatory properties

and restorative definitions14. These zest dynamic

standards have been shown to have fantastic cancer

prevention agent, anticonvulsant and local anaesthetic,

antistress, bacteriostatic and bactericidal and possess

brain calming properties. Eugenol is constituted in the

many ayurvedhic and siddha drugs especially the

saraswatarishtam an ayurvedhic drug possess 80% of this

compound12. Further, in cell models Eugenol is appeared

to improve the activities of a few glutathione –related

proteins, repress the movement of 5-lipoxygenase and

shield essential neuronal cells from excitotoxic and

oxidative harm15-17 . The previous studies reported in

perspective of Smith et al.19 the principle objectives in

drug discovery distinguishing the innovative small

molecular scaffold exhibiting high binding affinity and

selectivity for the target with a sensible retention,

conveyance, digestion system, discharge and lethality

(ADMET) profile, lead and/or drug resemblance. In the

present study the eugenol compound was evaluated for

the neuroprotective and modulatory activity through the

insilico docking of metabotrphic glutamate receptros.

There are plenty of research were carried out to screen

the bioactive compound in invivo animal models. But

none of the reports were not identified and hypothesized

the mechanism of drug action on the molecular targets of

neurodegenerative diseases and disorders. To our mind

and from the literature, we found this is the first work

emphasis the neuroprotective and modulatory activity of

eugenol by insilico computational methods through

docking. As indicated by18, molecular docking keeps on

holding awesome guarantee in the field of computational

based molecular targeting which screens small lead

molecules by orienting and scoring them in the catalytic

site of receptor protein. The docking procedure includes

the expectation of ligand affirmation and orientation

(posturing) inside focused restricting site and their

communication energies were utilized by the scoring

capacities19, 20.

Consequently the 10 glutamate receptors 2E4U, 2E4V,

2E4W, 2E4X, 2E4Y, 2E4Z, 2WJW, 3KS9, 3LMK, 3MQ4 were

evaluated completely to hypothesize the lead binding

catalytic sites for the mechanism of protective action and

modulation. The above receptors were docked with

eugenol Ligand and interesting findings attained from this

study that the motif was found in all the glutamate

receptors. The conserved amino acid sequences were

found in all the receptors such as Arg206, Phe208 and

Asn209. Hence the molecular targets of the active site

residues were identified for targeting the neurodiseases.

Finally the docking studies, suggests that eugenol

significantly inhibits the active sites of metabotrophic

glutamate receptors 2e4y, 3ks9, 2wjw and 3lmk.

Figure 1: Three dimensional Entity of Eugenol

Figure 2: Bioactivity Score prediction of Eugenol

Int. J. Pharm. Sci. Rev. Res., 40(1), September – October 2016; Article No. 58, Pages: 318-323 ISSN 0976 – 044X

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321

Figure 3: Molecular Properties and Druglikeliness score prediction of Eugenol

Figure 4: Three dimensional Entity of Glutamate receptors (a.2E4U,

b.2E4V, c.2E4W, d.2E4X, e.2E4Y, f.2E4Z, g.2WJW, h. 3KS9, i.3LMK

and j.3MQ4)

Figure 5a: Molecular interaction of eugenol with Glutamate

receptors (a.2E4U, b.2E4V, c.2E4W, d.2E4X, e.2E4Y, f.2E4Z)

Figure 5b: Molecular interaction of eugenol with Glutamate

receptors (g.2WJW, h. 3KS9, i.3LMK and j.3MQ4)

Int. J. Pharm. Sci. Rev. Res., 40(1), September – October 2016; Article No. 58, Pages: 318-323 ISSN 0976 – 044X

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322

Table 1: Catalytic Site prediction of Metabotrophic Glutamate Receptors

S.No

Glutamate Receptors

Catalytic Amino acid residues

2E4U

Phe 207,208,Arg-206,Glu 518

2E4V

Arg 206,Phe 208,Asn-209

2E4W

Arg-206,Phe 208,Asn 209,Val 504

2E4X

Arg 206,Phe 208,Asn 209,Val 504

2E4Y

Arg 206,Phe 208

2E4Z

Pro 56,Gly-58,Lys-71,Asn 74,Ser-159,Ser-229

2WJW

Asn-370,Glu-391,Val-392

3KS9

Trp-110, Gly-163, Ser-164, 165, 186, Tyr-236, Asp-318,319,Ala-329,Gly

379

3LMK

Arg 206,Phe 208Asn-445, Leu-455

3MQ4

Gly-158, Ala-180,Ser-181,Thr-182Ser-187

Table 2: Molecular Interaction and Docking scores of Eugenol –Glutamate receptors

S.No.

Eugenol with

Glutamate Receptors

Score

kcal/mol

Area

Atomic Contact Energy

(ACE)

Ligand Transformation

2E4U

3780

429.50

23.00

-0.74465 -1.39370 -2.06089 25.53879 6.43612

48.63786

2E4V

2732

293.00

-88.82

0.13 -0.38 -0.26 -3.45 1.47 -9.77

2E4W

3598

415.50

-17.00

-0.41 0.08 -2.37 29.75 -0.84 0.23

2E4X

3440

372.40

-111.28

-0.83 -0.75 0.31 16.36 -19.86 49.08

2E4Y

2740

291.80

-28.01

-1.09 -1.17 -0.60 -7.34 12.66 68.26

2e4z

3116

352.80

-178.78

-0.41 0.18 -0.93 35.08 11.39 -17.24

2WJW

2732

364.50

-57.39

-2.85 -1.54 1.23 -11.08 -36.16 -21.89

3LMK

3566

402.20

-64.26

-0.69 -0.22 -1.32 15.69 -11.19 -31.08

3MQ4

3588

405.50

-112.96

-1.11 0.33 0.46 -11.26 -41.40 -7.75

10.

4S47

3238

336.70

-32.90

-0.75 0.83 -0.89 -75.68 24.99 17.80

CONCLUSION

The significance of lead molecules from different

traditional medicines and their utilization upgrades the

protein–ligand association ponders through in-silico.

From the present investigation, we infer that the eugenol

ligand was taken for the docking study which indicated

that great interaction and inhibitory impact with the

molecular targets of neural disorders through 10

metabotrophic glutamate receptors. Consequently we

can foresee that four receptors 2e4y, 3ks9, 2wjw and

3lmk were pronouncedly inhibited by eugenol lead

molecule. Therefore, we conclude, the eugenol can be

strongly recommended and promoting as chemotherapy

drugs for neuroprotection.

Acknowledgement

We wish to thank Dr. V. Sankar, Associate Professor,

ALM.PGIMBS, Dept.of.Anatomy, University of Madras,

Chennai, India for his keen interest in this area of

research.

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Source of Support: Nil, Conflict of Interest: None.

ResearchGate has not been able to resolve any citations for this publication.

Identification of Active Biomolecules in Saraswatarishtam (An Ayurvedic Preparation) by GC-MS Analysis

Article

Full-text available

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Scientific validation of Ayurvedic, Siddha and other types of alternative medicines is very important to bring them to the main stream of medical practice. One step in this direction is to identify the active biomolecules and their roles as medicines. Bioactive molecules in standard ayurvedic medical formulations play a vital role in curing diseases. The present study deals with the GC MS analysis of one such ayurvedic nerve tonic, namely, Sarswatarishtam. It was observed that two important biomolecules, namely, eugenol and serine were predominantly present in Saraswatarishtam. These two biomolecules are well known for their neuroprotective and neuroplastic activities. This finding clearly is one step forward in the much needed scientific validation of ayurvedic medicines.

Antiviral activity of Ellagic Acid against envelope proteins from Dengue Virus through Insilico Docking

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Arbo viral infection such as dengue, chikungunya, japanese encephalitis, west nile viruses and other flaviviruses have transmemberane envelope proteins. These proteins (glycoproteins) form spike-like projections responsible for virus attachment to target cells and acid-activated membrane fusion. Further it targets numerous serologic reactions and tests including neutralization and hemagglutination inhibition. These viruses showed wide range of antigenic cross reactions and caused by seven antigenic complexes from 30 species, huge subtypes and varieties. This protein is the chief site for most neutralizing epitopes, highly conserved with cross-reactive epitopes. In the present study, the ellagic acid (4,4′,5,5′,6,6′-Hexahydroxydiphenic acid 2,6,2′,6′-dilactone) was evaluated for the antiviral activity through Insilico docking against drug target envelope proteins from dengue viruses. Ellagic acid showed good docking score with all the four glycoproteins from dengue 1-4 viruses. Among the glycoprotein receptors the glycoprotein-1 and 4 demonstrates the highest docking score with energy minimization. This highlights that the ellagic acid have potent antiviral activity against the dengue viruses.

Insilico docking study of compounds elucidated from helicteres isora fruits with ampkinase- insulin receptor

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Bioinformation

Insulin receptor (IR) proteins were essential intracellular signaling peptides in the insulin action cascade. Insulin receptor substrate proteins (IRS-1and IRS-2) serve and regulate the insulin level in the normal insulin action. The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing. Such type of proteins were cyclic adenosine monophosphate-activated protein kinase, this proteins play a key role in the insulin response and regulation. Type -2 Diabetes mellitus occurs during prolonged periods of peripheral insulin resistance due to inactivation of IRS proteins. The compounds isolated from the medicinal plants were safer than synthetic drugs and possess high bio activity. In the present study, four compounds were elucidated from fruits of Helicteres isora. The elucidated compounds were evaluated for the antidiabetic activity using Insilico docking study. The receptor was analyzed for the active site and pocket finder tools. The aminoacids such as Phenylalanine, Lysine, Glutamic acid and Asparigine were predicted as active site binding residues. Docking studies were done through Autodock 4 software. All the compounds from fruits of Helicteres isora showed good docking profiles with AMP Kinase, except compound-3 (1,2,3,4-tetrahydro-1,5,6,8-tetramethyl-7-(2-methylprop-1-enylnaphthalene-4-ylpivalate). Finally the result from the study demonstrates that the HS-1, HS-2 and HS-4 posses potent anti diabetic activity against type-2 diabetes mellitus through drug action on AMP kinase cascade system.

Eugenol—From the Remote Maluku Islands to the International Market Place: A Review of a Remarkable and Versatile Molecule

Article

Full-text available

Jun 2012
MOLECULES

Eugenol is a major volatile constituent of clove essential oil obtained through hydrodistillation of mainly Eugenia caryophyllata (=Syzygium aromaticum) buds and leaves. It is a remarkably versatile molecule incorporated as a functional ingredient in numerous products and has found application in the pharmaceutical, agricultural, fragrance, flavour, cosmetic and various other industries. Its vast range of pharmacological activities has been well-researched and includes antimicrobial, anti-inflammatory, analgesic, anti-oxidant and anticancer activities, amongst others. In addition, it is widely used in agricultural applications to protect foods from micro-organisms during storage, which might have an effect on human health, and as a pesticide and fumigant. As a functional ingredient, it is included in many dental preparations and it has also been shown to enhance skin permeation of various drugs. Eugenol is considered safe as a food additive but due to the wide range of different applications, extensive use and availability of clove oil, it is pertinent to discuss the general toxicity with special reference to contact dermatitis. This review summarises the pharmacological, agricultural and other applications of eugenol with specific emphasis on mechanism of action as well as toxicity data.

Comparison of antioxidant activity of clove (Eugenia caryophylata Thunb) buds and lavender (Lavandula stoechas L.)

Article

Full-text available

Sep 2004
FOOD CHEM

The antioxidant activity of water and ethanol extracts of clove (Eugenia carophyllata) buds and lavender (Lavandula stoechas L.) was studied. The antioxidant properties of both extracts of clove and lavender were evaluated using different antioxidant tests; reductive potential, free radical scavenging, superoxide anion radical scavenging and metal chelating activities. The both extracts of clove and lavender exhibited strong total antioxidant activity. At the concentrations of 20, 40, and 60 μg/ml, water extract of clove and lavender showed 93.3%, 95.5%, 97.9%, 86.9%, 92.3%, and 94.8% inhibition on lipid peroxidation of linoleic acid emulsion, respectively. At the same concentrations, ethanol extract of clove and lavender exhibited 94.9%, 95.5%, 98.2%, 92.5%, 93.8%, and 96.5%, respectively. Comparable, 60 μg/ml of standard antioxidant such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and α-tocopherol exhibited 96.5%, 99.2%, and 61.1% inhibition on peroxidation of linoleic acid emulsion, respectively. The both extracts of clove and lavender had effective reductive potential, free radical scavenging, superoxide anion radical scavenging, and metal chelating activities at all tested concentrations (20, 40, and 60 μg/ml). Those various antioxidant activities were compared to standard antioxidants such as BHA, BHT, and α-tocopherol. In addition, total phenolic compounds in the both extracts of clove and lavender were determined as gallic acid equivalent.

Neuroprotection by Spice-Derived Nutraceuticals: You Are What You Eat!

Article

Full-text available

Mar 2011
MOL NEUROBIOL

Numerous lines of evidence indicate that chronic inflammation plays a major role in the development of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, brain tumor, and meningitis. Why these diseases are more common among people from some countries than others is not fully understood, but lifestyle factors have been linked to the development of neurodegenerative diseases. For example, the incidence of certain neurodegenerative diseases among people living in the Asian subcontinent, where people regularly consume spices, is much lower than in countries of the western world. Extensive research over the last 10 years has indicated that nutraceuticals derived from such spices as turmeric, red pepper, black pepper, licorice, clove, ginger, garlic, coriander, and cinnamon target inflammatory pathways, thereby may prevent neurodegenerative diseases. How these nutraceuticals modulate various pathways and how they exert neuroprotection are the focus of this review.

The Anti-Inflammatory Activity of Eugenia Caryophllata Essential Oil: An animal model of anti-inflammatory activity

Article

Full-text available

Oct 2005
Eur J Gen Med

Hanefi Özbek

Aim: The aim of this study is gas chromatographic analysis of Eugenia caryaphyllata (clove) essential oil and investigation of its anti-inflammatory effects. Methods: The study involved eight groups; Serum physiologic, ethyl alcohol, indomethacin (3 mg/kg), etodolac (50 mg/kg), cardamom (0.05 mL/kg), EC-I (0.025 mL/kg), EC-II (0.050 mL/kg), EC-III (0.100 mL/kg) and EC-IV (0.200mL/kg). After measuring the volumes of right hind-paws of rats using a plethysmometer, drugs were injected intraperitoneally and lambda-carrageenan were injected subcutaneously into the plantar region. Three hours after the injections the volume measurements of the right hind-paws were repeated and the difference between the volumes were compared. Results: The composition of the essential oil was as follows: β-caryophyllen % 44.7, eugenol % 44.2, α-humulen % 3.5, eugenyl acetate % 1.3 and α-copaen % 1.0. It was found that indomethazin reduced the inflammation by 95.70%, etodolac by 43.42 %, EC-I by 46.55 %, EC-II by 90.15 %, EC-III by 66.94 % and EC-IV by 82.78 %. The essential oil of Eugenia caryophyllata had an anti-inflammatory effect matching to that of etodolac at 0.025 and 0.1 mL/kg and to that of indomethacin at 0.05 and 0.2 mL/kg doses. Conclusion: As a result Eugenia caryophyllata essential oil extract was shown to have an anti-inflammatory effect.

Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro

Article

Sep 2009

The present work is aimed at evaluating the protective effect of eugenol against in vitro nicotine-induced toxicity in murine peritoneal macrophages, compared with N-acetylcysteine. Eugenol was isolated from Ocimum gratissimum and characterized by HPLC, FTIR, (1)H NMR. To establish most effective protective support, we used five different concentrations of eugenol (1, 5, 10, 15, and 20microg/ml) and N-acetylcysteine (0.25, 0.5, 1.0, 2.0, and 5.0microg/ml) against 10mM nicotine in mice peritoneal macrophages. A dose-dependent protective effect was observed with all doses of eugenol and N-acetylcysteine, as evidenced by decreased level of superoxide anion generation and malondialdehyde, and also increased level of reduced glutathione, and superoxide dismutase activity. Moreover, maximum protection was observed at the concentration of 15.0microg/ml eugenol (0.09nM) and 1.0microg/ml N-acetylcysteine (0.006nM). Further, eugenol (15.0microg/ml) and N-acetylcysteine (1.0microg/ml) were tested against nicotine (10mM) toxicity by analyzing the radical generation, lipid, protein, DNA damage, and endogenous antioxidant status. There was a significant increase in the level of radical generation, NADPH oxidase and myeloperoxidase activity, lipid, protein, DNA damage and oxidized glutathione level in nicotine-treated group, which were significantly reduced by eugenol and N-acetylcysteine supplementation. Antioxidant status was significantly depleted in the nicotine-treated group, which was effectively restored by eugenol and N-acetylcysteine supplementation. The protection by eugenol against nicotine toxicity was merely equal effective to that of N-acetylcysteine. These findings suggest the potential use and benefit of eugenol isolated from O. gratissimum as a modulator of nicotine-induced cellular damage and it may be used as an immunomodulatory drug against nicotine toxicity.

The Effect of Eugenol on Nerve Transmission

Article

Dec 1977
Oral Surg Oral Med Oral Pathol

George Kozam

Because of its long-time use as a sedative or anodyne in dental procedures, eugenol was studied to determine its effect on evoked nerve impulse transmission. The sciatic nerve of the bullfrog was stimulated in a nerve chamber, and the compound action potential was visualized on and recorded from an oscilloscope screen. It was determined that eugenol concentrations ranging from 100 per cent to 0.01 per cent extinguished the impulse-transmission capabilities of the nerve within 3 hours. No reversal was observed within this time frame.

[Study of behavioral pharmacology on rats. Tranquilizing effects induced by endogenous or exogenous bradykinin]

Article

Nov 1989
J Tokyo Dent Coll Soc

K Yazaki

Unlabelled: This study was investigated on the mechanism of the sedative state, tranquilization induced by bradykinin (BK) and kallikrein (KAL). The drugs used in this study were as follows: KAL as endogenous BK promoter; prostaglandins (PGs) as a material of analogous action of BK; indomethacin and mepacrine as the inhibitors of PG-synthesis; eugenol as the OH- scavenger and the PGE-synthesis potentiator; angiotensin converting enzyme inhibitor as BK potentiator B. All drugs were dissolved in Hartmann's solution (lactate Ringer's solution) and 10 microliters of solution was injected into the lateral ventricle of rats, according to the Myers' procedure. Then, the rat behavior was estimated, by means of monitoring spontaneous movement. A high performance liquid chromatography (HPLC) was used for detecting alteration of monoamines and prostaglandins in the rat brain on sedative state after BK or KAL injection. Results: 1) A 2-phase alteration of spontaneous movement was occurred within 30 min after BK or KAL icv-injection with behavioral specificity as follows: two exciting states and one sedative state. 2) A great increase of spontaneous movement evoked by BK or KAL was accompanied by exciting state as follows: jumping, wet dog response, struggle and scratching response, rearing and exploration. 3) A great decrease of spontaneous movement evoked by BK or KAL was accompanied with sedative state as follows: crouching with piloerection and closed eyes, catalepsy, preening and moisturizing and grooming. 4) PGE1 icv-injection was also carried out to clarify the involvement in the BK- or KAL-induced behavioral alteration. Consequently caused PGE1 the similar result to BK or KAL. 5) ACEI elongated and enhanced the exciting state or sedative state evoked by BK or KAL. 6) It was clear that BK reduced levels of monoamines in the rat hypothalamus: levels of norepinephrine(NE), epinephrine(E), dopamine(DA) and 5-hydroxytryptamine (5-HT) were decreased to 72.5%, 53.5%, 71.2% and 75.0% of control, respectively. Reduction of catecholamines in the hypothalamus was produced by increase of PGs and subsequently occurred sedative state of rats. 7) BK- or KAL-induced exciting state was enhanced by PG- synthesis inhibitor, especially the cyclo-oxygenase inhibitor indomethacin, but the sedative state was weakened. On the contrary, eugenol, an OH- scavenger, elongated and intensified the sedative state. Detection with HPLC showed remarkable increase of levels of PGs in the rat brain during the sedative state: the level of PGE2 was 27.5% increase of control and the level of PGE2 alpha was also 54.8% increase of control, respectively.

Molecular Properties and Insilico Neuroprotective Activity of Eugenol Against Glutamate Metabotrophic Receptors

Abstract

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