Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
2.2. Preparation of the Different Plant Extracts
2.3. In Vivo Biological Evaluation of Different L. serriola Dried Seeds Extracts
2.3.1. Experimental Animals
2.3.2. Acute Toxicity Study
2.3.3. In Vivo Anxiolytic Activity Evaluation of Different L. serriola Dried Seeds Extracts
Hole-Board Test
Elevated Plus Maze Test
Light/Dark Box Test
2.3.4. In Vivo Sedative Activity Evaluation of Different L. serriola Dried Seeds Extracts
2.3.5. In Vivo Anti-Convulsive Activity Evaluation of Different L. serriola Dried Seeds Extracts
2.3.6. In Vivo Anti-Epileptic Activity Evaluation of Different L. serriola Dried Seeds Extracts
Pentylenetetrazol (PTZ) Induced Kindling in Mice
Evaluation of the Biochemical Parameters in Brain Tissue
Assessment of Catalase (CAT) Activity in Brain
Assessment of Malondialdehyde (MDA) Level in Brain
Assessment of Superoxide Dismutase (SOD) Level in Brain
Assessment of Total Glutathione (tGSH) Activity in Brain
2.3.7. Histopathological Examination
2.4. Phytochemical Analysis of Different L. serriola Dried Seeds Extracts
2.4.1. Estimation of Total Phenol Content
2.4.2. Estimation of Total Flavonoid Content
2.4.3. Metabolic Profiling of L. serriola Dried Seeds Chloroform Extract by GC/MS
2.5. Molecular Docking Study
2.6. Statistical Analysis
3. Results
3.1. In Vivo Biological Evaluation of Different L. serriola Dried Seeds Extracts
3.1.1. Acute Toxicity Study
3.1.2. In Vivo Anxiolytic Activity Evaluation of Different L. serriola Dried Seeds Extracts
Hole-Board Test and Effect on Number of Head Dips
Effect on Time Spent in the Elevated Plus Maze
Effect on Time Spent in Light Dark Box
3.1.3. In Vivo Sedative Activity Evaluation of Different L. serriola Dried Seeds Extracts
3.1.4. In Vivo Anti-Convulsive Activity Evaluation of Different L. serriola Dried Seeds Extracts
3.1.5. In Vivo Anti-Epileptic Activity Evaluation of Different L. serriola Dried Seeds Extracts
Effect of Different L. serriola Dried Seeds Extracts on Various Oxidative Stress Markers in Brain Tissues
3.1.6. Histopathological Examination
3.2. Phytochemical Analysis of Different L. serriola Dried Seeds Extracts
3.2.1. Estimation of Total Flavonoid and Phenol Contents
3.2.2. Metabolic Profiling of L. serriola Dried Seeds Chloroform Extract by GC/MS
3.3. Molecular Docking Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Extract | Control | Standard | 300 mg/kg | 400 mg/kg | 500 mg/kg |
---|---|---|---|---|---|
n-Hexane | 10.88 ± 0.04 | 10.06 ± 0.03 * | 10.08 ± 0.04 * | 9.98 ± 0.03 * | 9.51 ± 0.06 * |
Chloroform | 11.35 ± 0.04 | 10.98 ± 0.04 * | 9.76 ± 0.04 * | 9.06 ± 0.03 * | 8.33 ± 0.04 * |
Methanol | 10.03 ± 0.03 | 9.81 ± 0.03 * | 8.95 ± 0.04 * | 7.6 ± 0.05 * | 5.41 ± 0.04 * |
Aqueous | 10.11 ± 0.03 | 9.96 ± 0.03 * | 8.1 ± 0.02 * | 7.55 ± 0.05 * | 7 ± 0.03 * |
Extract | Control | Standard | 300 mg/kg | 400 mg/kg | 500 mg/kg |
---|---|---|---|---|---|
n-Hexane | 189.8 ± 0.60 | 202.1 ± 0.83 * | 241.6 ± 0.55 * | 263.3 ± 0.88 * | 291.1 ± 0.70 * |
Chloroform | 204.83 ± 0.47 | 214.33 ± 0.61 * | 247 ± 0.57 * | 273 ± 0.81 * | 302.3 ± 0.71 * |
Methanol | 211.3 ± 0.61 | 190.66 ± 0.49 * | 262.6 ± 0.71 * | 304.1 ± 0.70 * | 326.5 ± 1.08 * |
Aqueous | 197.5 ± 0.42 | 203.16 ± 0.47 * | 260.16 ± 0.30 * | 281.5 ± 0.67 * | 292 ± 0.57 * |
Treatment Groups | Seizure Latency | Seizure Duration | Mortality (Yes/No) |
---|---|---|---|
PCT | 679 ± 3.22 | 213.3 ± 2.44 | No |
PCT + Phenobarbitone | - | - | No |
PCT + n-hexane extract (100 mg) | 1514 ± 2.95 * | 110.8 ± 1.42 * | No |
PCT + n-hexane extract (200 mg) | 2011.1 ± 1.74 * | 20.5 ± 1.17 * | No |
PCT + n-hexane extract (300 mg) | - | - | No |
PCT + chloroform extract (100 mg) | 2253.8 ± 8.46 * | 16.7 ± 2.15 * | No |
PCT + chloroform extract (200 mg) | - | - | No |
PCT + chloroform extract (300 mg) | - | - | No |
PCT + methanol extract (100 mg) | 821.5 ± 4.12 * | 218.3 ± 2.23 | No |
PCT + methanol extract (200 mg) | 1036.1 ± 6.73 * | 184.8 ± 0.30 * | No |
PCT + methanol extract (300 mg) | 1194.5 ± 3.94 * | 120.3 ± 3.06 * | No |
PCT + aqueous extract (100 mg) | 820.6 ± 4.06 * | 214.6 ± 2.15 | No |
PCT + aqueous extract (200 mg) | 1031.1 ± 5.26 * | 168.1 ± 8.89 * | No |
PCT + aqueous extract (300 mg) | 1329.3.3 ± 8.22 * | 112.6 ± 3.26 * | No |
Treatment Groups | Seizure Latency | Seizure Duration | Mortality (Yes/No) |
---|---|---|---|
STR | 124.0 ± 0.93 | 48.33 ± 1.2 | Yes |
STR + Diazepam | 214.5 ± 0.84 * | 20.33 ± 1.87 * | Yes |
STR + n-hexane extract (100 mg) | 142.6 ± 0.88 * | 31.00 ± 0.57 * | Yes |
STR + n-hexane extract (200 mg) | 178.3 ± 1.14 * | 26.00 ± 0.44 * | Yes |
STR + n-hexane extract (300 mg) | 242.6 ± 0.84 * | 20.33 ± 0.66 * | Yes |
STR + chloroform extract (100 mg) | 194.1 ± 2.73 * | 20.50 ± 0.42 * | Yes |
STR + chloroform extract (200 mg) | 242.1 ± 0.94 * | 17.83± 0.4 * | Yes |
STR + chloroform extract (300 mg) | 254.5 ± 1.05 * | 16.10 ± 0.6 * | Yes |
STR + methanol extract (100 mg) | 147.1 ± 1.47 * | 31.30 ± 0.66 * | Yes |
STR + methanol extract (200 mg) | 170.5 ± 0.76 * | 28.83 ± 0.30 * | Yes |
STR + methanol extract (300 mg) | 190.5 ± 0.76 * | 24.66 ± 0.49 * | Yes |
STR + aqueous extract (100 mg) | 153 ± 1.03 * | 29.5 ± 0.67 * | Yes |
STR + aqueous extract (200 mg) | 162.6 ± 1.05 * | 26.50 ± 0.67 * | Yes |
STR + aqueous extract (300 mg) | 180.5 ± 0.76 * | 19.83 ± 0.60 * | Yes |
Treatment | Seizure Latency | Seizure Intensity | Mortality |
---|---|---|---|
PTZ only | 240± 0.57 | 5.75 ± 0.28 | 5/6 |
Standard (VA) | 680 ± 0.88 * | 3.25 ± 0.28 * | 1/6 * |
n-Hexane | 580 ± 1.76 * | 3.66 ± 0.33 * | 1/6 * |
Chloroform | 710 ± 1.20 * | 3.33 ± 0.33 * | 1/6 * |
Methanol | 380 ± 0.33 * | 3.75 ± 0.28 * | 3/6 * |
Aqueous | 520 ± 1.20 * | 4.33 ± 0.33 * | 3/6 * |
Treatment Group | MDA (µM/mg Tissue) | CAT (µM/mg Tissue) | SOD (U/mL) | Total GSH (mM/g) |
---|---|---|---|---|
Normal | 8.51 ± 0.28 | 40.8 ± 0.44 | 61.76 ± 0.50 | 1.44 ± 0.00 |
PTZ | 27.38 ± 0.08 | 8.50 ± 0.57 | 20.80 ± 0.19 | 0.37 ± 0.01 |
Standard | 18.75 ± 0.23 * | 16.6 ± 0.60 * | 50.88 ± 1.56 * | 1.01 ± 0.01 * |
n-Hexane | 17.04 ± 0.39 * | 16.6 ± 0.88 * | 48.89 ± 2.51 * | 0.87 ± 0.01 * |
Chloroform | 17.39 ± 0.06 * | 15.6 ± 0.92 * | 47.01 ± 0.97 * | 0.92 ± 0.00 * |
Methanol | 25.54 ± 0.05 * | 13.16 ± 0.44 * | 38.31 ± 0.39 * | 0.62 ± 0.00 * |
Aqueous | 25.52 ± 0.18 * | 11.66 ± 0.44 * | 31.38 ± 0.62 * | 0.54 ± 0.00 * |
No. | Name | Retention Time | Retention Index | Concentration (%) |
---|---|---|---|---|
1 | Octanoic acid | 7.47 | 1179 | 0.63 |
2 | p-Cumic aldehyde | 9.20 | 1239 | 0.35 |
3 | 2-Decenal, (Z)- | 9.66 | 1250 | l. 10 |
4 | p-Methoxy-.beta.-methyl styrene | 10.28 | 1303 | 0.38 |
5 | 2,4-Decadienal | 10.44 | 1309 | 4.93 |
6 | α-Terpineol acetate | I 1.85 | 1354 | 0.73 |
7 | 3-Allyl-2-methoxyphenol | 12.01 | 1392 | 1.38 |
8 | Azelaaldehydic acid, methyl ester | 13.81 | 1436 | 0.30 |
9 | Methyl tetradecanoate | 20.57 | 1706 | 0.84 |
10 | Tetradecanoic acid | 21.37 | 1770 | 1.34 |
11 | Pentadecanoic acid | 23.45 | 1857 | 0.45 |
12 | 9-Hexadecenoic acid, methyl ester, (Z)- | 24.32 | 1879 | 0.37 |
13 | Hexadecanoic acid, 15-methyl-, methyl ester | 24.78 | 1996 | 23.25 |
14 | 9,12-octadecadienoic acid methyl ester | 28.10 | 2094 | 49.03 |
15 | 6-Octadecenoic acid, methyl ester, (Z)- | 28.30 | 2104 | 1.18 |
16 | Octadecanoic acid, methyl ester | 28.64 | 2112 | 12.82 |
Total identified compounds | 97.98% |
Compound | GABA-AT (1OHV) | Number of Formed Hydrogen Bonds and C-H Bonds | Number of Formed Alkyl and π-Alkyl Bonds |
---|---|---|---|
2,4-Decadienal | −20.37 | 3; Gln75, Gly76 | - |
2-Decenal, (Z)- | −21.41 | 2; Gly76, Lys93 | - |
3-Allyl-2-methoxyphenol | −14.92 | 2; Met149 | 4; Leu206, Val196, Val78, Ala91 |
6-Octadecenoic acid, methyl ester, (Z)- | −29.92 | 3; Lys93, Glu111, Asp207 | - |
9,12-octadecadienoic acid methyl ester | −15.46 | - | 3; Lys93, Leu206 |
9-Hexadecenoic acid, methyl ester, (Z)- | −26.32 | 3; Met448, Asp150, Ala151 | 1; Ile70 |
α-TerpineoI acetate | −0.69 | 1; Ala151 | 7; Val78, Val196, Leu206, Ala91, Ile70 |
Azelaaldehydic acid, methyl ester | −36.09 | 2; Asn152, Lys193 | - |
Hexadecanoic acid, 15-methyl-, methyl ester | −51.40 | 1; Lys93 | 2; Ile124, Leu206 |
Methyl tetradecanoate | −43.56 | 2; Asn152, Lys93 | 1; Leu206 |
Octadecanoic acid, methyl ester | −44.74 | 1; Pro69 | 3; Lys58, Ile70, Ala80 |
Octanoic acid | −33.64 | 2; Asn152, Gln155 | - |
p-Cumic aldehyde | −24.44 | - | 5; Val78, Val196, Ala91, Ile70 |
p-Methoxy-.beta.-methyl styrene | −11.04 | 3; Gln155, Ile70, Ala151 | 2; Val196, Ile70 |
Pentadecanoic acid | −44.01 | 2; Lys93, Asn194 | - |
Tetradecanoic acid | −42.94 | 2; Lys93, Asn194 | - |
Valproic acid | −30.19 | 3; Glu147, Met149, Leu148 | 4; Val78, Leu206, Lys93, Met146 |
Co-crystalized ligand | −7.74 | 2; Glu147, Met149 | 11; Val78, Val196, Ala91, Ile70, Leu206 |
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Ullah, M.I.; Anwar, R.; Kamran, S.; Gul, B.; Elhady, S.S.; Youssef, F.S. Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract. Antioxidants 2022, 11, 2232. https://doi.org/10.3390/antiox11112232
Ullah MI, Anwar R, Kamran S, Gul B, Elhady SS, Youssef FS. Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract. Antioxidants. 2022; 11(11):2232. https://doi.org/10.3390/antiox11112232
Chicago/Turabian StyleUllah, Muhammad Ihsan, Rukhsana Anwar, Shahzad Kamran, Bazgha Gul, Sameh S. Elhady, and Fadia S. Youssef. 2022. "Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract" Antioxidants 11, no. 11: 2232. https://doi.org/10.3390/antiox11112232