A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species
Abstract
1. Introduction
2. Results
2.1. Acute Toxicity Study
2.2. Neuropharmacological Activity
2.2.1. Anxiolytic Activity
Elevated Plus Maze Test
Hole Board Test
Light–Dark Box Test
2.2.2. Antidepressant Activity
Forced Swimming Test
Tail Suspension Test
2.2.3. Locomotor Activity
Open Field Test
Hole Cross Test
2.3. Antipyretic Activity
Yeast-Induced Pyrexia Method
2.4. Thrombolytic Activity
Human Blood Clot Lysis Method
2.5. Anthelmintic Activity
In Vitro Anthelmintic Test on Tubifex tubifex
2.6. PASS Prediction Study
2.7. In Silico Study
2.7.1. ADME/T Study
2.7.2. Molecular Docking Study
3. Discussion
4. Phytochemistry Reported from Previous Works
5. Materials and Methods
5.1. Plant Collection and Identification
5.2. Extraction Methods
5.3. Chemicals and Reagents
5.4. Experimental Animals and Ethics Statement
5.5. Experimental Design
5.6. Neuropharmacological Activity
5.6.1. Anxiolytic Activity
Elevated Plus Maze Method
Hole Board Test (HBT)
Light–Dark Box Test (LDT)
5.6.2. Antidepressant Activity
Forced Swimming Test (FST)
Tail Suspension Test (TST)
5.6.3. Locomotor Activity
Open Field Method
Hole Cross Method
5.7. Study of Antipyretic Activity
Yeast-Induced Pyrexia in Mice
5.8. Thrombolytic Activity
5.8.1. Blood Clot Lysis Method
Streptokinase (SK) Solution Preparation
5.8.2. Specimen for the Thrombolytic Test
5.9. Anthelmintic Activity
5.10. In Silico Molecular Docking Study
5.10.1. Toxicity Prediction by AdmetSAR
5.10.2. Prediction of Activity Spectra for Substances (PASS)
5.10.3. Software Tools
5.10.4. Selection of Ligands
5.10.5. Validation of the Ligands as Potential Therapeutic Agents
5.10.6. Protein Preparation and Active Site Determination
5.10.7. Validation of the Proteins as Potential Therapeutic Targets
5.10.8. Molecular Docking and Post-Docking Analysis
5.11. Statistical Analysis
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Treatment (mg/kg) | Time Spent in the Light Box (s) | Time Spent in the Dark Box (s) | Transitions |
---|---|---|---|
Control | 92.5 ± 1.69 | 205.83 ± 1.20 | 13.33 ± 1.33 |
Diazepam | 195.24 ± 3.41 *** | 104.75± 3.41 ** | 5.33 ± 0.88 * |
SIF-ME 200 | 62.73 ± 2.91 ** | 237.267 ± 2.91 ** | 9.66 ± 0.66 |
SIF-ME 400 | 132.86 ± 2.05 ** | 167.13 ± 2.05 ** | 8.66 ± 1.20 |
Treatment Dose (mg/mL) | Number of Holes Crossed | ||||
---|---|---|---|---|---|
0 min | 30 min | 60 min | 90 min | 120 min | |
Control | 17.33 ± 0.88 | 18.33 ± 0.88 | 16.33 ± 1.20 | 14 ± 1.15 | 12.33 ± 0.33 |
Diazepam | 10.66 ± 1.45 | 7.33 ± 0.88 ** | 11.66 ± 0.88 ** | 9.33 ± 0.66 | 4.33 ± 0.88 ** |
SIF-ME 200 | 15.33 ± 0.88 *** | 10.33 ± 1.20 * | 13.33 ± 1.20 *** | 10.66 ± 0.66 * | 9.33 ± 0.88 * |
SIF-ME 400 | 11.33 ± 1.20 * | 7.66b ± 1.20 ** | 10.66 ± 0.88 ** | 9.66 ± 0.88 * | 7.33 ± 0.33 ** |
Treatment | Normal Rectal Temperature (°F) | Temperature After Pyrexia (°F) | Rectal Temperature (°F) After Drug Administration | ||
---|---|---|---|---|---|
60 min | 120 min | 180 min | |||
Control | 99.06 ± 0.58 | 103.1 ± 1.92 | 99.74 ± 1.08 | 101.63 ± 1.7 | 99.53 ± 0.96 |
Paracetamol | 98.69 ± 0.42 | 100.98 ± 2.58 | 100.63 ± 2.5 | 99.1 ± 0.6 * | 99.2 ± 1.12 |
SIF-ME 200 | 98.56 ± 0.15 | 100.56 ± 1.86 | 103.86 ± 1.35 * | 101.26 ± 2.14 | 103.1 ± 0.52 * |
SIF-ME 400 | 99.15 ± 0.6 | 100.96 ± 1.68 | 101.06 ± 1.56 | 100.7 ± 2.1 | 99.3 ± 0.53 |
Compounds | Biological Activity | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Anxiolytic | Antidepressant | Locomotor | Antipyretic | Thrombolytic | Anthelmintic | |||||||
Pa | Pi | Pa | Pi | Pa | Pi | Pa | Pi | Pa | Pi | Pa | Pi | |
Butanoic acid, 3-methyl | - | - | - | - | 0.214 | 0.062 | 0.324 | 0.038 | 0.265 | 0.018 | 0.291 | 0.041 |
Phenol, 2-methoxy | 0.127 | 0.013 | 0.196 | 0.062 | 0.139 | 0.100 | 0.472 | 0.017 | 0.264 | 0.019 | 0.308 | 0.035 |
2-Methoxy-4-vinyl phenol | 0.229 | 0.005 | - | - | - | - | 0.427 | 0.022 | 0.200 | 0.073 | 0.291 | 0.041 |
Phenol, 2,6-dimethoxy | 0.097 | 0.021 | 0.155 | 0.085 | 0.167 | 0.065 | 0.395 | 0.026 | 0.291 | 0.011 | 0.278 | 0.046 |
Vanillin | 0.073 | 0.042 | - | - | 0.142 | 0.095 | 0.447 | 0.020 | 0.174 | 0.110 | 0.369 | 0.021 |
Phenol, 2-methoxy-4-propyl | 0.098 | 0.020 | - | - | - | - | 0.492 | 0.014 | 0.258 | 0.021 | 0.236 | 0.065 |
Phenol, 4-ethenyl-2,6-dimethoxy | 0.157 | 0.009 | - | - | - | - | 0.293 | 0.048 | 0.220 | 0.049 | 0.277 | 0.046 |
Benzaldehyde, 3-hydroxy-4-methoxy | 0.073 | 0.042 | - | - | 0.142 | 0.095 | 0.447 | 0.020 | 0.174 | 0.110 | 0.369 | 0.021 |
5-Methyl-3-phenyl-1,3-oxazolidine | - | - | - | - | - | - | - | - | - | - | 0.161 | 0.135 |
2,6-Dimethoxyhydroquinone | 0.111 | 0.016 | - | - | - | - | 0.344 | 0.034 | 0.292 | 0.011 | 0.293 | 0.040 |
Benzaldehyde, 4-hydroxy-3,5-dimethoxy | - | - | - | - | 0.180 | 0.053 | 0.306 | 0.043 | 0.196 | 0.079 | 0.349 | 0.025 |
Phenol, 2.6-dimethoxy-4-(2-propenyl) | 0.143 | 0.011 | - | - | - | - | 0.393 | 0.027 | 0.193 | 0.083 | 0.268 | 0.050 |
2-Propanone, 1-hydroxy-3-(4-hydroxy-3-methoxyphenyl) | 0.066 | 0.053 | - | - | - | - | 0.334 | 0.036 | 0.209 | 0.062 | 0.325 | 0.086 |
Retinoic acid | - | - | - | - | - | - | - | - | - | - | 0.306 | 0.035 |
Octahydro-9-phenanthrene methanol | 0.069 | 0.048 | 0.229 | 0.046 | - | - | 0.275 | 0.056 | - | - | 0.166 | 0.129 |
Epoxylathyrol | - | - | - | - | - | - | - | - | - | - | 0.259 | 0.054 |
Beta–Sitosterol | - | - | - | - | - | - | - | - | - | - | - | - |
24-Noroleana-3,12-diene | - | - | - | - | - | - | - | - | 0.319 | 0.007 | - | - |
Compound Name | Absorption | Distribution | Metabolism | Excretion | Toxicity | Drug Likeness | Bioavailability | |||
---|---|---|---|---|---|---|---|---|---|---|
Water Solubility (log mol/L) | Intestinal Absorption (Human) (% Absorbed) | VDss (Human) (log L/kg) | BBB Permeability (log BB) | CYP3A4 Substrate | Total Clearance (log mL/min/kg) | AMES Toxicity | Hepatotoxicity | |||
Butanoic acid, 3-methyl | −0.811 | 88.82 | −0.937 | −0.227 | No | 0.391 | No | No | Yes | 0.85 |
Phenol, 2-methoxy | −1.264 | 93.374 | 0.174 | −0.226 | No | 0.219 | No | No | Yes | 0.55 |
2-Methoxy-4-vinyl phenol | −1.958 | 91.965 | 0.118 | 0.289 | No | 0.233 | Yes | No | Yes | 0.55 |
Phenol, 2,6-dimethoxy | −1.4 | 93.789 | −0.129 | −0.204 | No | 0.213 | No | No | Yes | 0.55 |
Vanillin | −1.308 | 84.976 | −0.152 | −0.243 | No | 0.601 | No | No | Yes | 0.55 |
Phenol, 2-methoxy-4-propyl | −1.628 | 92.829 | 0.36 | 0.387 | No | 0.244 | No | Yes | Yes | 0.55 |
Phenol, 4-ethenyl-2,6-dimethoxy | −1.925 | 92.945 | 0.206 | 0.396 | No | 0.241 | No | No | Yes | 0.55 |
Benzaldehyde, 3-hydroxy-4-methoxy | −1.295 | 89.886 | −0.165 | −0.243 | No | 0.599 | No | No | Yes | 0.55 |
5-Methyl-3-phenyl-1,3-oxazolidine | −2.304 | 97.289 | 0.259 | 0.498 | No | 0.282 | No | No | Yes | 0.55 |
2,6-Dimethoxyhydroquinone | −1.715 | 85.96 | 0.169 | −0.342 | No | 0.63 | No | No | Yes | 0.55 |
Benzaldehyde, 4-hydroxy-3,5-dimethoxy | −1.481 | 90.106 | −0.042 | −0.281 | No | 0.621 | No | No | Yes | 0.55 |
Phenol, 2,6-dimethoxy-4-(2-propenyl) | −2.069 | 92.959 | 0.272 | 0.362 | No | 0.293 | No | No | Yes | 0.55 |
2-Propanone, 1-hydroxy-3-(4-hydroxy-3-methoxyphenyl) | −1.291 | 83.06 | −0.345 | −0.254 | No | 0.26 | No | No | Yes | 0.55 |
Retinoic acid | −4.924 | 94.419 | −0.51 | 0.236 | Yes | 1.443 | No | Yes | NF | NF |
Octahydro-9-phenanthrene methanol | −3.862 | 95.247 | 0.995 | 0.61 | Yes | 1.176 | No | No | Yes | 0.55 |
Epoxylathyrol | −4.273 | 97.394 | 0.16 | −0.571 | No | 0.666 | No | NO | Yes | 0.55 |
Beta–Sitosterol | −6.773 | 94.464 | 0.193 | 0.781 | Yes | 0.628 | No | No | Yes | 0.55 |
24-Noroleana-3,12-diene | −6.85 | 96.674 | 0.44 | 0.848 | Yes | 0.073 | No | No | Yes | 0.55 |
SL No. | Compounds | MW | Retention Time | Area % |
---|---|---|---|---|
1 | Butanoic acid, 3-methyl | 102.1 g/mol | 3.904 | 0.15 |
2 | Phenol, 2-methoxy | 124.1 g/mol | 6.83 | 0.37 |
3 | 2-Methoxy-4-vinyl phenol | 150.1 g/mol | 9.289 | 0.29 |
4 | Phenol, 2,6-dimethoxy | 154.1 g/mol | 9.632 | 0.38 |
5 | Vanillin | 152.1 g/mol | 10.171 | 0.3 |
6 | endo-1,5,6,7-Tetramethylbicyclo[3.2.0]hept-6-en-3-ol | 166.2 g/mol | 10.626 | 0.8 |
7 | Phenol, 2-methoxy-4-propyl | 166.2 g/mol | 10.695 | 0.24 |
8 | 3(2H)-Benzofuranone, 2.4-dimethyl | 162.1 g/mol | 10.971 | 0.2 |
9 | beta.-D-Glucopyranose, 1.6-anhydro | 162.1 g/mol | 11.031 | 0.22 |
10 | Guaiacol, 4-butyl | 180.2 g/mol | 11.35 | 0.55 |
11 | Phenol, 4-ethenyl-2,6-dimethoxy | 180.2 g/mol | 11.663 | 0.33 |
12 | Benzaldehyde, 3-hydroxy-4-methoxy | 152.1 g/mol | 11.934 | 0.28 |
13 | 5-Methyl-3-phenyl-1,3-oxazolidine | 163.2 g/mol | 12.375 | 0.41 |
14 | (3R,3aS,6S,7R)-3,6,8,8-Tetramethyloctahydro-1H3a,7-methanoazulen-6-o | 222.3 g/mol | 12.425 | 0.17 |
15 | 2,6-Dimethoxyhydroquinone | 170.1 g/mol | 12.602 | 0.32 |
16 | Benzaldehyde, 4-hydroxy-3,5-dimethoxy | 182.1 g/mol | 12.708 | 0.49 |
17 | Phenol, 2,6-dimethoxy-4-(2-propenyl) | 194.2 g/mol | 13.18 | 0.49 |
18 | 3-O-Methyl-d-glucose | 194.1 g/mol | 13.251 | 0.29 |
19 | 2-Propanone, 1-hydroxy-3-(4-hydroxy3-methoxyphenyl | 196.2 g/mol | 13.566 | 0.93 |
20 | 4-(3-Hydroxyprop-1-en-1-yl)-2-methoxyphenyl | 180.2 g/mol | 13.747 | 8.29 |
21 | Dihydroxy-4-methyldodecahydro-2H-benzo[d] oxecin-2-one | 256.3 g/mol | 14.882 | 0.38 |
22 | Sinapyl alcohol | 210.2 g/mol | 17.386 | 3.68 |
23 | 4-Hydroxy-3,5,5-trimethyl-4-(3-oxobut-1-en-1-yl) cyclohex-2-enone | 222.2 g/mol | 18.661 | 0.25 |
24 | 9,11-Octadecadienoic acid, methyl ester | 294.5 g/mol | 18.941 | 2.56 |
25 | 9,12,15-Octadecatrienoic acid, methyl ester | 292.5 g/mol | 19.046 | 6.02 |
26 | Phytol | 296.5 g/mol | 19.197 | 0.97 |
27 | Methyl stearate | 298.5 g/mol | 19.449 | 0.67 |
28 | Hexadecanamide | 255.4 g/mol | 20.421 | 0.39 |
29 | 9-Octadecenamide | 281.5 g/mol | 23.448 | 7.39 |
30 | Z,Z,Z-8,9-Epoxyeicosa-5,11,14-trienoic acid, methyl ester | 334.5 g/mol | 23.558 | 1.54 |
31 | Cyclohexanone, 5-ethenyl-5-methyl4-(1-methylethenyl)-2-(1-methylethylidene) | 218.3 g/mol | 23.75 | 0.75 |
32 | 4-Cycloocten-1-one, 8-(4-octen-4-yl) | 234.3 g/mol | 23.876 | 0.93 |
33 | 5.Beta.,7.beta.H,10.alpha.-Eudesm-11-en-1.alpha.-ol | 222.3 g/mol | 23.99 | 0.71 |
34 | Bicyclo[4.1.0]heptane, 1-(3-oxo-4-phenylthiobutyl)-2,2,6-trimethyl | 316.5 g/mol | 25.15 | 0.58 |
35 | Diethylene glycol dibenzoate | 314.3 g/mol | 25.397 | 0.39 |
36 | Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester | 330.5 g/mol | 25.849 | 0.64 |
37 | Bis(2-ethylhexyl) phthalate | 390.6 g/mol | 26.147 | 0.31 |
38 | Retinoic acid | 300.4 g/mol | 26.94 | 2.57 |
39 | S-Octahydro-9-phenanthrene methanol | 216.3 g/mol | 27.12 | 1.03 |
40 | Epoxylathyrol | 350.4 g/mol | 28.065 | 0.61 |
41 | 3,3′-Dimethoxy-4,4′-dihydroxystilbene | 272.2 g/mol | 28.195 | 0.6 |
42 | Oleic Acid | 354.6 g/mol | 28.38 | 0.39 |
43 | Retinol | 286.5 g/mol | 28.44 | 1.34 |
44 | Methyl 5,11,14-eicosatrienoate | 320.5 g/mol | 28.636 | 3.35 |
45 | 9,12,15-Octadecatrienoic acid, 2.3-dihydroxypropyl ester, (Z,Z,Z)- | 352.5 g/mol | 28.755 | 5.34 |
46 | Benzene, 1-[(4-butyl phenyl)ethynyl]-4-ethoxy2-methyl | 292.4 g/mol | 28.83 | 2.59 |
47 | 10,13-Dimethyl-3-oxo2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl 2,2,2-trifluoroacetate | 331.5 g/mol | 28.974 | 3.04 |
48 | Retinal | 284.4 g/mol | 29.323 | 1.04 |
49 | (1S,2E,4S,5R,7E,11E)-Cembra-2,7,11-trien-4,5-diol | 306.5 g/mol | 29.41 | 0.58 |
50 | Methyl 1,4a-dimethyl-6-methylidene-5-[2-(5-oxo-2Hfuran-4-yl)ethyl]-3,4,5,7,8,8a-hexahydro-2Hnaphthalene-1-carboxylate | 346.5 g/mol | 29.72 | 1.73 |
51 | 9-(Acetyloxy)-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9aH-cyclopropa | 560.7 g/mol | 30.861 | 1.7 |
52 | Cholest-22-ene-21-ol, 3.5-dehydro-6-methoxy-, pivalate | 498.8 g/mol | 31.266 | 1.96 |
53 | 1H-Cyclopropa[3,4]benz[1,2-e]azulene-4a,5,7b,9,9a (1aH)-pentol, 3-[(acetyloxy)methyl]- 1b,4,5,7a,8,9-hexahydro-1,1,6,8-tetramethyl | 492.6 g/mol | 31.842 | 2.44 |
54 | (11.xi.)-4,7-Dihydroxy-12,13-epoxytrichothec-9-en8-one | 280.3 g/mol | 33.31 | 0.22 |
55 | Spirost-5-en-3-ol, acetate, (3.beta.,25R)- | 456.7 g/mol | 34.002 | 0.24 |
56 | Nonacosan-10-ol | 424.8 g/mol | 34.551 | 0.73 |
57 | Stigmasterol | 412.7 g/mol | 37.316 | 1.18 |
58 | 22-Desoxycarpesterol | 546.8 g/mol | 37.815 | 0.33 |
59 | Beta-sitosterol | 414.7 g/mol | 38.573 | 3.5 |
60 | 24-Noroleana-3,12-diene | 394.7 g/mol | 39.627 | 5.93 |
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Mohammad, M.; Mamun, M.J.I.; Khatun, M.M.; Rasel, M.H.; Masum, M.A.A.; Suma, K.J.; Haque, M.R.; Rabbi, S.A.H.; Hossain, M.H.; Hasnat, H.; et al. A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species. Drugs Drug Candidates 2025, 4, 31. https://doi.org/10.3390/ddc4030031
Mohammad M, Mamun MJI, Khatun MM, Rasel MH, Masum MAA, Suma KJ, Haque MR, Rabbi SAH, Hossain MH, Hasnat H, et al. A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species. Drugs and Drug Candidates. 2025; 4(3):31. https://doi.org/10.3390/ddc4030031
Chicago/Turabian StyleMohammad, Mahathir, Md. Jahirul Islam Mamun, Mst. Maya Khatun, Md. Hossain Rasel, M Abdullah Al Masum, Khurshida Jahan Suma, Mohammad Rashedul Haque, Sayed Al Hossain Rabbi, Md. Hemayet Hossain, Hasin Hasnat, and et al. 2025. "A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species" Drugs and Drug Candidates 4, no. 3: 31. https://doi.org/10.3390/ddc4030031
APA StyleMohammad, M., Mamun, M. J. I., Khatun, M. M., Rasel, M. H., Masum, M. A. A., Suma, K. J., Haque, M. R., Rabbi, S. A. H., Hossain, M. H., Hasnat, H., Mahjabin, N., & Alam, S. (2025). A Multifaceted Exploration of Shirakiopsis indica (Willd) Fruit: Insights into the Neuropharmacological, Antipyretic, Thrombolytic, and Anthelmintic Attributes of a Mangrove Species. Drugs and Drug Candidates, 4(3), 31. https://doi.org/10.3390/ddc4030031