Anti-Nociceptive and Anti-Inflammatory Potential of Stem Bark Fractions of Dalbergia candenatensis (Dennst.) Prain: Insights from Experimental Models into Underlying Mechanisms
Dalbergia candenatensis (Dennst.) Prain (family: Fabaceae), a mangrove species with traditional medicinal use, was evaluated for its phytochemical composition and the in vivo anti-nociceptive and anti-inflammatory effects of its stem bark fractions in Swiss albino mice. Acute toxicity was studied at doses up to 2000 mg/kg body weight (b.wt.) and animals were observed for 14 days. Anti-nociceptive activity was evaluated using acetic acid-induced writhing (chemically induced pain), formalin-induced paw licking (neurogenic and inflammatory pain), tail immersion, and hot plate methods (thermally induced pain). Anti-inflammatory activity was evaluated in carrageenan and formalin-induced paw edema models. Results showed that mice exhibited no mortality or noticeable behavioral alterations at doses up to 2000 mg/kg b.wt. during the 14 days observation period. In comparison to control, all fractions at 200 mg/kg b.wt. showed significant (p < 0.001) anti-nociceptive activity. The n-hexane fraction produced the highest inhibition (50.86%) in the acetic acid test. In the formalin test, the ethyl acetate fraction exhibited maximum inhibition (59.69% in the early phase and 48.00% in the late phase). In the tail immersion and hot plate methods, ethyl acetate and dichloromethane fractions produced significant (p < 0.001) increases in reaction time compared with standard drugs. In the anti-inflammatory assays, the ethyl acetate fraction showed maximum inhibition of paw edema in both carrageenan (47.37%) and formalin (51.30%) models. The results suggest that stem bark fractions of D. candenatensis possess significant (p < 0.001) anti-nociceptive and anti-inflammatory activity, possibly mediated by both central and peripheral mechanisms.
References
[1]
Khanum, S., Sarwar, M.S. and Islam, M.S. (2019) In Vivo Neurological, Analgesic and in Vitro Antioxidant and Cytotoxic Activities of Ethanolic Extract of Leaf and Stem Bark of Wedelia Chinensis. Bangladesh Pharmaceutical Journal, 22, 18-26. https://doi.org/10.3329/bpj.v22i1.40021
[2]
Nimse, S.B. and Pal, D. (2015) Free Radicals, Natural Antioxidants, and Their Reaction Mechanisms. RSC Advances, 5, 27986-28006. https://doi.org/10.1039/c4ra13315c
[3]
Qian, Q., Chen, W., Cao, Y., Cao, Q., Cui, Y., Li, Y., et al. (2019) Targeting Reactive Oxygen Species in Cancer via Chinese Herbal Medicine. Oxidative Medicine and Cellular Longevity, 2019, 1-23. https://doi.org/10.1155/2019/9240426
[4]
Onen, S.H., Onen, F., Courpron, P. and Dubray, C. (2005) How Pain and Analgesics Disturb Sleep. The Clinical Journal of Pain, 21, 422-431. https://doi.org/10.1097/01.ajp.0000129757.31856.f7
[5]
Kalden, J.R. (1987) What Is Inflammation? European Heart Journal, 8, 1-5. https://doi.org/10.1093/eurheartj/8.suppl_j.1
[6]
Sulaiman, M.R., Zakaria, Z.A., Chiong, H.S., Lai, S.K., Israf, D.A. and Azam Shah, T.M. (2009) Antinociceptive and Anti-Inflammatory Effects of Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae)in Experimental Animal Models. Medical Principles and Practice, 18, 272-279. https://doi.org/10.1159/000215723
[7]
Maridass, M. and De Britto, A.J. (2008) Origins of Plant Derived Medicines. Ethnobotanical Leaflets, 2008, Article 44.
[8]
Saha, P., Rahman, F.I., Hussain, F., Rahman, S.M.A. and Rahman, M.M. (2022) Antimicrobial Diterpenes: Recent Development from Natural Sources. Frontiers inPharmacology, 12, Article 820312. https://doi.org/10.3389/fphar.2021.820312
[9]
Ernst, E. (2007) Herbal Medicines: Balancing Benefits and Risks. In: Dietary Supplements and Health, Wiley, 154-172.
[10]
Fabricant, D.S. and Farnsworth, N.R. (2001) The Value of Plants Used in Traditional Medicine for Drug Discovery. Environmental Health Perspectives, 109, 69-75. https://doi.org/10.1289/ehp.01109s169
[11]
Jiko, P., Mohammad, M., Richi, F.T., Islam, M.A., Alam, S., Taher, M.A., et al. (2024) Anti-Inflammatory, Analgesic and Anti-Oxidant Effects of Shirakiopsis Indica (Willd). Fruit Extract: A Mangrove Species in the Field of Inflammation Research. Journal of Inflammation Research, 17, 5821-5854. https://doi.org/10.2147/jir.s470835
[12]
Kundu, P., Debnath, S.L., Devnath, H.S., Saha, L. and Sadhu, S.K. (2022) Analgesic, Anti-Inflammatory, Antipyretic, and in Silico Measurements of Sonneratia caseolaris (L.) Fruits from Sundarbans, Bangladesh. BioMed Research International, 2022, Article 1405821. https://doi.org/10.1155/2022/1405821
[13]
Faridah-Hanum, I., Hakeem, A.L.K.R. and Ozturk, M. (2013) Mangrove Ecosystems of Asia: Status, Challenges and Management Strategies. Springer.
[14]
Saha, S., Shilpi, J.A., Mondal, H., Anisuzzman, M., et al. (2013) Ethnomedicinal, Phytochemical, and Pharmacological Profile of the Genus dalbergia L. (Fabaceae). https://www.researchgate.net/publication/236015007
[15]
Hamburger, M.O., Cordell, G.A., Tantivatana, P. and Ruangrungsi, N. (1987) Traditional Medicinal Plants of Thailand, VIII. Isoflavonoids of Dalbergia Candenatensis. Journal of Natural Products, 50, 696-699. https://doi.org/10.1021/np50052a020
[16]
Anisuzzman, M., Hasan, M.M., Acharzo, A.K., Das, A.K. and Rahman, S. (2017) In Vivo and in Vitro Evaluation of Pharmacological Potentials of Secondary Bioactive Metabolites of Dalbergia candenatensis Leaves. Evidence-Based Complementary and Alternative Medicine, 2017, Article 5034827. https://doi.org/10.1155/2017/5034827
[17]
Cheenpracha, S., Karalai, C., Ponglimanont, C. and Kanjana-Opas, A. (2009) Candenatenins A-F, Phenolic Compounds from the Heartwood of Dalbergia candenatensis. Journal of Natural Products, 72, 1395-1398. https://doi.org/10.1021/np900077h
[18]
Cheenpracha, S., Ritthiwigrom, T., Karalai, C. and Laphookhieo, S. (2012) Candena-tenins G-K, Phenolic Compounds from Dalbergia candenatensis Heartwood. PhytochemistryLetters, 5, 708-712. https://doi.org/10.1016/j.phytol.2012.07.007
[19]
Hamburger, M.O., Cordell, G.A., Ruangrungsi, N. and Tantivatana, P. (1988) Candenatone, a Novel Purple Pigment from Dalbergia candenatensis. The Journal of Organic Chemistry, 53, 4161-4165. https://doi.org/10.1021/jo00253a001
[20]
Sultana, S., Tareq, F.S., Rahman, K.M. and Hasan, C.M. (2019) Isolation of Two Furano Diterpenes and Two Triterpenes from the Stem Bark of Dalbergia lanceolaria L.f. Pharmacology & Pharmacy, 10, 519-527. https://doi.org/10.4236/pp.2019.1012043
[21]
Al-Snaf, P.D.A.E. (2017) Chemical Constituents and Pharmacological Effects of Dalbergia Sissoo—A Review. IOSR Journal of Pharmacy, 7, 59-71. https://doi.org/10.9790/3013-0702015971
[22]
Perez, M.R. and Garcia B. (2013) Citotoxic Activity of Isoflavan-Cinnamylphenols from Dalbergia Congestiflora on HeLa Cells. Journal of Medicinal Plants Research, 7, 2992-2998.
[23]
Islam, A.T.M.R., Hasan, M.M., Islam, M.T. and Tanaka, N. (2022) Ethnobotanical Study of Plants Used by the Munda Ethnic Group Living around the Sundarbans, the World’s Largest Mangrove Forest in Southwestern Bangladesh. Journal of Ethnopharmacology, 285, Article 114853. https://doi.org/10.1016/j.jep.2021.114853
[24]
Yin, X., Huang, A., Zhang, S., Liu, R. and Ma, F. (2018) Identification of Three Dalbergia Species Based on Differences in Extractive Components. Molecules, 23, Article 2163. https://doi.org/10.3390/molecules23092163
[25]
Ali, I., Rizwani, G.H., Rasheed, M., Ali, M., et al. (2019) Chemical Analysis of Dalbergia sissoo (ROXB.) Pod Oil by (GC-MS)/GC-FID and Evaluation of Antioxidant Potential. Pakistan Journal of Pharmaceutical Sciences, 32, 2175-2181.
[26]
South and Central America (2015) UNEP-WCMC, Overview of Dalbergia spp.
[27]
Xiang, Z., Chen, X., Zhao, Z., Xiao, X., Guo, P., Song, H., et al. (2018) Analysis of Volatile Components in Dalbergia cochinchinensis Pierre by a Comprehensive Two-Dimensional Gas Chromatography with Mass Spectrometry Method Using a Solid-State Modulator. Journal of Separation Science, 41, 4315-4322. https://doi.org/10.1002/jssc.201800636
[28]
Morris Kupchan, S. (1970) Recent Advances in the Chemistry of Terpenoid Tumor Inhibitors. Pure and Applied Chemistry, 21, 227-246. https://doi.org/10.1351/pac197021020227
[29]
Ghani, A. (1998) Medicinal Plants of Bangladesh: Chemical Constituents and Uses of the Medicinal Plants of Bangladesh. LAP LAMBERT Academic Publishing.
[30]
Chandra, S., Jena, N., Marndi, S., Kumar, S., et al. (2024) Qualitative Phytochemical Analysis of Flowers of Cassia fistula L. Biowealth India, 16, 19-27.
[31]
Lorke, D. (1983) A New Approach to Practical Acute Toxicity Testing. ArchivesofToxicology, 54, 275-287. https://doi.org/10.1007/bf01234480
Hossan, S., Agarwala, B., Sarwar, S., Karim, M., Jahan, R. and Rahmatullah, M. (2010) Traditional Use of Medicinal Plants in Bangladesh to Treat Urinary Tract Infections and Sexually Transmitted Diseases. Ethnobotany Research and Applications, 8, 61-74. https://doi.org/10.17348/era.8.0.61-74
[34]
Dubuisson, D. and Dennis, S.G. (1977) The Formalin Test: A Quantitative Study of the Analgesic Effects of Morphine, Meperidine, and Brain Stem Stimulation in Rats and Cats. Pain, 4, 161-174. https://doi.org/10.1016/0304-3959(77)90130-0
[35]
Sharma, A., Bhatia, S., Kharya, M.D., Gajbhiye, V., et al. (2010) Anti-Inflammatory and Analgesic Activity of Different Fractions of Boswellia serrata. International Journal of Phytomedicine, 2, 94-99.
[36]
Cam, A.J.T., Shanmugasundaram, P., Venkataraman, S. and Heine, S. (2005) Anti-Nociceptive Activity of Hygrophila auriculata (Schum) Heine. African Journal of Traditional, Complementary and Alternative Medicines, 2, 62-69.
[37]
Olaleye, S., Farombi, O., Adewoye, E. and Owoyele, B. (2000) Analgesic and Anti-Inflammatory Effects of Kolaviron (a Garcinia Kola Seed Extract). African Journal of Biomedical Research, 3, 171-174.
[38]
Agnel Arul John, N. and Shobana, G. (2012) Anti-Inflammatory Activity of Talinum fruticosum L. on Formalin Induced Paw Edema in Albino Rats. Journal of Applied Pharmaceutical Science, 2, 123-127.
[39]
Winter, C.A., Risley, E.A. and Nuss, G.W. (1962) Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Anti-Inflammatory Drugs. Experimental Biology and Medicine, 111, 544-547. https://doi.org/10.3181/00379727-111-27849
[40]
Açar, Y., Ağagündüz, D., De Cicco, P. and Capasso, R. (2023) Flavonoids: Their Putative Neurologic Roles, Epigenetic Changes, and Gut Microbiota Alterations in Parkinson’s Disease. Biomedicine & Pharmacotherapy, 168, Article 115788. https://doi.org/10.1016/j.biopha.2023.115788
[41]
Serafini, M., Peluso, I. and Raguzzini, A. (2010) Flavonoids as Anti-Inflammatory Agents. Proceedings of the Nutrition Society, 69, 273-278. https://doi.org/10.1017/s002966511000162x
[42]
Ignarro, L.J. (1974) Regulation of Lysosomal Enzyme Secretion: Role in Inflammation. Agents and Actions, 4, 241-258. https://doi.org/10.1007/bf01965227
[43]
Summ, O. and Evers, S. (2013) Mechanism of Action of Indomethacin in Indomethacin-Responsive Headaches. Current Pain and Headache Reports, 17, Article No. 327. https://doi.org/10.1007/s11916-013-0327-x
[44]
Akhter, F., Rahman, M.S., Amin, G.M.A., Miah, M.I. and Koh, Y. (2021) Beneficial Therapy with Natural Anti-Inflammatory Agents and Supplements. Journal of Bacteriology and Virology, 51, 149-162. https://doi.org/10.4167/jbv.2021.51.4.149
[45]
Nahar, L., Nasrin, F., Zahan, R. and Mosaddik, M.A. (2013) Anti-Nociceptive and Anti-Inflammatory Activities of Wrightia Arborea. Pakistan Journal of Biological Sciences, 16, 485-490. https://doi.org/10.3923/pjbs.2013.485.490
[46]
Filho, A.W., Filho, V.C., Olinger, L. and de Souza, M.M. (2008) Quercetin: Further Investigation of Its Antinociceptive Properties and Mechanisms of Action. Archives of Pharmacal Research, 31, 713-721. https://doi.org/10.1007/s12272-001-1217-2
[47]
Kazempor, S.F., langehbiz, S.V., Hosseini, M., Shafei, M.N., Pourganji, M. and Ghorbani, A. (2015) The Analgesic Effects of Different Extracts of Aerial Parts of Coriandrum Sativum in Mice. InternationalJournalofBiomedicalScience, 11, 23-28. https://doi.org/10.59566/ijbs.2015.11023
[48]
Ambriz-Pérez, D.L., Leyva-López, N., Gutierrez-Grijalva, E.P. and Heredia, J.B. (2016) Phenolic Compounds: Natural Alternative in Inflammation Treatment. A Review. Cogent Food & Agriculture, 2, Article 1131412. https://doi.org/10.1080/23311932.2015.1131412
[49]
Luo, P., Wong, Y.F., Ge, L., Zhang, Z.F., Liu, Y., Liu, L., et al. (2010) Anti-Inflammatory and Analgesic Effect of Plumbagin through Inhibition of Nuclear Factor-κB Activation. The Journal of Pharmacology and Experimental Therapeutics, 335, 735-742. https://doi.org/10.1124/jpet.110.170852
[50]
Kumar, T. and Jain, V. (2014) Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals. The Scientific World Journal, 2014, 1-12. https://doi.org/10.1155/2014/890151
[51]
Zhang, J. and An, J. (2007) Cytokines, Inflammation, and Pain. International Anesthesiology Clinics, 45, 27-37. https://doi.org/10.1097/aia.0b013e318034194e
[52]
Rahman, M.S., Ali, I., Arooj, M., Su, X.D., Yang, S.Y., Kim, Y.H., et al. (2020) Methyl 4-(β-D-Glucopyranosyloxy)-3-Hydroxy-5-Methoxybenzoate, Isolated from Sanguisorba Officinalis, Inhibits CpG-DNA-Induced Inflammation. Tropical Journal of Pharmaceutical Research, 19, 1993-1998. https://doi.org/10.4314/tjpr.v19i9.27
[53]
Pinheiro, B.G., Silva, A.S.B., Souza, G.E.P., Figueiredo, J.G., Cunha, F.Q., Lahlou, S., et al. (2011) Chemical Composition, Antinociceptive and Anti-Inflammatory Effects in Rodents of the Essential Oil of Peperomia serpens (Sw.) Loud. Journal of Ethnopharmacology, 138, 479-486. https://doi.org/10.1016/j.jep.2011.09.037