The use of plants in traditional medicine is an alternative solution to address the adverse effects of conventional anti-inflammatories. This study evaluated the phytochemistry, anti-inflammatory, analgesic and toxicity activities of the hydroethanolic extracts (HE) alone and the combination of Phyllanthus niruri Linn and Sida acuta Burm. Total phenolics were quantified using the Folin-Ciocalteu method, condensed tannin by the Butanol-HCl method, and flavonoid by the Aluminum chloride method. Gas chromatography coupled with Mass Spectrometry (GC-MS) analysis was used to identify several compounds in the extracts. Anti-inflammatory activity and analgesic activity, respectively, were carried out using the paw edema method in rats and pain method induced by intraperitoneal injection of acetic acid in the animal model. Acute, and subacute oral toxicity of extracts was conducted according to OECD n?423 for the testing of chemicals and n?407 for testing chemical products. Screening of S. acuta and P. niruri revealed that both of them contain alkaloids, phenolic compounds, terpenes and flavonoids, but P. niruri is richer in total phenols 14.69 ± 0.22 mg GAE/g; proanthocyanidins 4.42 ± 0.01 mg CE/g; and flavonoids 264.21 ± 3.64 mg RE/g. GC-MS analysis was presented for S. acuta 13 and P. niruri 19 compounds. The compounds most represented are levoglucosan (16.01%) and neophytadiene (10.48%) for S. acuta and 2-[(3,4-Dimethoxyphenyl) methyl]-4-methoxy-4-oxobutanoicacid (24%), and (3R,4R)-3-(Benzo[d][1,3] dioxol-5-ylmethyl)-4-(3,4 dimethoxybenzyl) dihydrofuran-2(3H)-one (18.34%) for P. niruri. The concentration of 400 mg/kg recorded the best anti-inflammatory activity. The analgesic effect’s results showed that the hydroethanolic compound at a concentration of 800 mg/kg recorded the highest percentage inhibition (71.60% ± 5.32%) by the oral route. Toxicity results showed that the extracts alone and in combination also did not exhibit signs of toxicity. These results therefore validate the use of S. acuta and P. niruri in traditional medicine.
References
[1]
Cavaillon, J. and Adib-Conquy, M. (2009) Compensatory Anti-Inflammatory Response Syndrome. Thrombosis and Haemostasis, 101, 36-47. https://doi.org/10.1160/th08-07-0421
[2]
Lawrence, T. and Fong, C. (2010) The Resolution of Inflammation: Anti-Inflammatory Roles for NF-κB. The International Journal of Biochemistry & Cell Biology, 42, 519-523. https://doi.org/10.1016/j.biocel.2009.12.016
[3]
Stankov, V.S. (2012) Definition of Inflammation, Causes of Inflammation and Possible Anti-Inflammatory Strategies. The Open Inflammation Journal, 5, 1-9. https://doi.org/10.2174/1875041901205010001
[4]
Placha, D. and Jampilek, J. (2021) Chronic Inflammatory Diseases, Anti-Inflammatory Agents and Their Delivery Nanosystems. Pharmaceutics, 13, Article 64. https://doi.org/10.3390/pharmaceutics13010064
[5]
Martyn Bailey, J. and Butler, J. (1985) Anti-Inflammatory Drugs in Experimental Atherosclerosis Part 6. Combination Therapy with Steroid and Non-Steroid Agents. Atherosclerosis, 54, 205-212. https://doi.org/10.1016/0021-9150(85)90179-0
[6]
Smahia, R., Nasser, B., Khaled, S. and Abdelkrim, C. (2016) Evaluation de l’activité anti-inflammatoire d’extraits aqueux de feuilles Limoniastrum feei (Plumbaginaceae). http://dspace.univ-ouargla.dz/jspui/handle/123456789/10562
[7]
Brai, B.I.C., Odetola, A.A. and Agomo, P.U. (2007) Hypoglycemic and Hypocholesterolemic Potential Ofpersea Americanaleaf Extracts. Journal of Medicinal Food, 10, 356-360. https://doi.org/10.1089/jmf.2006.291
[8]
OMS (2002) Stratégie de l’OMS pour la Médecine Traditionnelle pour 2002–2005. https://www.bing.com/search?q=OMS.+Strat%C3%A9gie+de+l+%E2%80%99+OMS+pour+la+M%C3%A9decine+Traditionnelle+pour+2002+%E2%80%93+2005.+Geneve%3B+2002.+63+p.&cvid=00e8442b1209472089cfa9f37dd578a6&aqs=edge..69i57j69i59i450l8...8.966j0j9&FORM=ANAB01&PC=U531&ntref=1
[9]
Ouedraogo, S., Yoda, J., Traore, T.K., Nitiema, M., Sombie, B.C., Diawara, H.Z., et al. (2021) Production de matières premières et fabrication des médicaments à base de plantes médicinales. International Journal of Biological and Chemical Sciences, 15, 750-772. https://doi.org/10.4314/ijbcs.v15i2.28
[10]
Agnihotri, S., Wakode, S. and Agnihotri, A. (2010) An Overview on Anti-Inflammatory Properties and Chemo-Profiles of Plants Used in Traditional Medicine. Indian Journal of Natural Products and Resources, 1, 150-167.
[11]
Bernstein, N., Akram, M., Daniyal, M., Koltai, H., Fridlender, M. and Gorelick, J. (2018) Anti-Inflammatory Potential of Medicinal Plants: A Source for Therapeutic Secondary Metabolites. In: Advances in Agronomy, Elsevier, 131-183. https://doi.org/10.1016/bs.agron.2018.02.003
[12]
Dkhil, M.A., Al-Quraishy, S., Al-Shaebi, E.M., Abdel-Gaber, R., Thagfan, F.A. and Qasem, M.A.A. (2021) Medicinal Plants as a Fight against Murine Blood-Stage Malaria. Saudi Journal of Biological Sciences, 28, 1723-1738. https://doi.org/10.1016/j.sjbs.2020.12.014
[13]
Oboh, I. and Onwukaeme, D. (2006) Analgesic, Anti-Inflammatory and Anti-Ulcer Activities of Sida Acuta in Mice and Rat. Nigerian Journal of Natural Products and Medicine, 9, 19-21. https://doi.org/10.4314/njnpm.v9i1.11827
[14]
Moreira, J., Klein-Júnior, L.C., Filho, V.C. and Buzzi, F.D.C. (2013) Anti-Hyperalgesic Activity of Corilagin, a Tannin Isolated from Phyllanthus Niruri L. (Euphorbiaceae). Journal of Ethnopharmacology, 146, 318-323. https://doi.org/10.1016/j.jep.2012.12.052
[15]
Alara, O.R., Abdurahman, N.H. and Olalere, O.A. (2018) Ethanolic Extraction of Bioactive Compounds from Vernonia Amygdalina Leaf Using Response Surface Methodology as an Optimization Tool. Journal of Food Measurement and Characterization, 12, 1107-1122. https://doi.org/10.1007/s11694-018-9726-3
[16]
Govindarajan, M. (2010) Larvicidal and Repellent Activities of Sida Acuta Burm. F. (Family: Malvaceae) against Three Important Vector Mosquitoes. Asian Pacific Journal of Tropical Medicine, 3, 691-695. https://doi.org/10.1016/s1995-7645(10)60167
[17]
Dahanayake, J., Perera, P., Galappaththy, P. and Arawwawala, M. (2020) A Mini Review on Therapeutic Potentials of Phyllanthus niruri L. Trends in Phytochemical Research, 4, 101-108.
[18]
Kumar, R.P.S., Veluswamy, B.V.M. and Rajamani, R. (2018) Phytochemical Screening of Aqueous Leaf Extract of Sida acuta Burm. F. and Its Antibacterial Activity. Journal of Emerging Technologies and Innovative Research, 5, 474-478.
[19]
Shittu, M. D, and Alagbe, J.O, (2020) Phyto-Nutritional Profiles of Broom Weed (Sida Acuta) Leaf Extract. International Journal on Integrated Education, 3, 119-124. https://doi.org/10.31149/ijie.v3i11.845
[20]
Kamruzzaman, H.M. and Hoq, M.O. (2016) A Review on Ethnomedicinal, Phytochemical and Pharmacological Properties of Phyllanthus niruri.Journal of Medicinal Plants Studies, 4, 173-180.
[21]
Lee, N.Y.S., Khoo, W.K.S., Adnan, M.A., Mahalingam, T.P., Fernandez, A.R. and Jeevaratnam, K. (2016) The Pharmacological Potential of phyllanthus Niruri. Journal of Pharmacy and Pharmacology, 68, 953-969. https://doi.org/10.1111/jphp.12565
[22]
Kaur, N., Kaur, B. and Sirhindi, G. (2017) Phytochemistry and Pharmacology Ofphyllanthus Niruril: A Review. Phytotherapy Research, 31, 980-1004. https://doi.org/10.1002/ptr.5825
[23]
Hoffman, B.R., DelasAlas, H., Blanco, K., Wiederhold, N., Lewis, R.E. and Williams, L. (2004) Screening of Antibacterial and Antifungal Activities of Ten Medicinal Plants from Ghana. Pharmaceutical Biology, 42, 13-17. https://doi.org/10.1080/1388020049050492
[24]
Tchacondo, T., Karou, S., Batawila, K., Agban, A., Ouro-Bang’na, K., Anani, K., et al. (2010) Herbal Remedies and Their Adverse Effects in Tem Tribe Traditional Medicine in Togo. African Journal of Traditional, Complementary and Alternative Medicines, 8, 45-60. https://doi.org/10.4314/ajtcam.v8i1.60522
[25]
Koukoura, K.K., Pissang, P., Hoekou, Y.P., Maman, I., Sadji, A., Effoe, S., et al. (2022) Ethnobotanical Survey of Medicinal Plants Used for The Treatment of Childhood Infections in the Central Region of Togo. African Journal of Biomedical Research, 25, 363-371.
[26]
Odeja, O., Obi, G., Ogwuche, C.E., Elemike, E.E. and Oderinlo, Y. (2016) Retraction Note: Phytochemical Screening, Antioxidant and Antimicrobial Activities of Senna Occidentalis (L.) Leaves Extract. Clinical Phytoscience, 2, 26-30. https://doi.org/10.1186/s40816-016-0028-1
[27]
Singleton, V.L., Orthofer, R. and Lamuela-Raventós, R.M. (1999) Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent. In: Methods in Enzymology, Elsevier, 152-178. https://doi.org/10.1016/s0076-6879(99)99017-1
[28]
Porter, L.J., Hrstich, L.N. and Chan, B.G. (1985) The Conversion of Procyanidins and Prodelphinidins to Cyanidin and Delphinidin. Phytochemistry, 25, 223-230. https://doi.org/10.1016/s0031-9422(00)94533-3
[29]
Andzi Barhé, T. (2015) Phytochemical Studies, Total Phenolic and Flavonoids Content and Evaluation of Antiradical Activity of the Extracts of the Leaves from Dischistocalyx sp. (Acanthacées). Journal of Pharmacognosy and Phytochemistry, 3, 174-178.
[30]
Dermane, A., Eloh, K., Palanga, K.K., Tchakinguena Adjito, D., N'nanle, O., Karou, D.S., et al. (2024) Comparative Metabolomic Profiling of Eggs from 3 Diverse Chicken Breeds Using GC-MS Analysis. Poultry Science, 103, Article 103616. https://doi.org/10.1016/j.psj.2024.103616
[31]
Winter, C.A., Risley, E.A. and Nuss, G.W. (1962) Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs. Experimental Biology and Medicine, 111, 544-547. https://doi.org/10.3181/00379727-111-27849
[32]
Siegmund, E., Cadmus, R. and Lu, G. (1957) A Method for Evaluating Both Non-Narcotic and Narcotic Analgesics. Experimental Biology and Medicine, 95, 729-731. https://doi.org/10.3181/00379727-95-23345
[33]
OECD (2002) Essai n˚423: Toxicité orale aiguë—Méthode par classe de toxicité aiguë-. Paris: Organisation for Economic Co-operation and Development. https://www.oecd-ilibrary.org/environment/essai-n-423-toxicite-orale-aigue-methode-par-classe-de-toxicite-aigue_9789264071018-fr
[34]
OCDE (2008) Essai n˚407: Toxicité orale à doses répétées—Pendant 28 jours sur les rongeurs. Lignes directrices de l’OCDE pour les essais de produits chimiques, Section 4 : Effets sur la santé. https://www.oecd-ilibrary.org/environment/essai-n-407-toxicite-orale-a-doses-repetees-pendant-28-jours-sur-les-rongeurs_9789264070691-fr
[35]
Gurib-Fakim, A. (2006) Medicinal Plants: Traditions of Yesterday and Drugs of Tomorrow. Molecular Aspects of Medicine, 27, 1-93. https://doi.org/10.1016/j.mam.2005.07.008
[36]
Dinda, B., Das, N., Dinda, S., Dinda, M. and SilSarma, I. (2015) The Genus Sida L.—A Traditional Medicine: Its Ethnopharmacological, Phytochemical and Pharmacological Data for Commercial Exploitation in Herbal Drugs Industry. Journal of Ethnopharmacology, 176, 135-176. https://doi.org/10.1016/j.jep.2015.10.027
[37]
Bagalkotkar, G., Sagineedu, S.R., Saad, M.S. and Stanslas, J. (2006) Phytochemicals from Phyllanthus Niruri Linn. and Their Pharmacological Properties: A Review. Journal of Pharmacy and Pharmacology, 58, 1559-1570. https://doi.org/10.1211/jpp.58.12.0001
[38]
Thondawada, M., Mulukutla, S., Raju, K.R.S., Dhanabal, S.P. and Wadhwani, A.D. (2016) In Vitro and In Vivo evaluation of Sida acuta Burm.f. (Malvaceae) for Its Anti-Oxidant and Anti-Cancer Activity. Der Pharma Chemica, 8, 396-402.
[39]
Krishnaveni, A., Ezhilarasan, B., Iyappan, A. and Sathali, A. (2018) Preliminary Phytochemical Screening and in Vitro Antioxidant Activity of Sida acuta Burm. International Journal of Research, Pharmacology and Pharmacotherapy, 7, 157-165. https://doi.org/10.61096/ijrpp.v7.iss2.2018.157-165.
[40]
Giribabu, N., Rao, P.V., Kumar, K.P., Muniandy, S., Swapna Rekha, S. and Salleh, N. (2014) Aqueous Extract of phyllanthus Niruri Leaves Displays in Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats. Evidence-Based Complementary and Alternative Medicine, 2014, Article 834815. https://doi.org/10.1155/2014/834815
[41]
Rusmana, D., Wahyudianingsih, R., Elisabeth, M., Balqis, B., Maesaroh, M. and Widowati, W. (2017) Antioxidant Activity of Phyllanthus Niruri Extract, Rutin and Quercetin. The Indonesian Biomedical Journal, 9, 84-90. https://doi.org/10.18585/inabj.v9i2.281
[42]
Ouadja, B., Anani, K., Djeri, B., Ameyapoh, Y.O. and Karou, D.S. (2018) Evaluation of the Phytochemical Composition, Antimicrobial and Anti-Radical Activities of Mitracarpus Scaber (Rubiaceae). Journal of Medicinal Plants Research, 12, 493-499. https://doi.org/10.5897/jmpr2018.6631
[43]
Karou, D.S. (2006) Evaluation de quelques propriétés pharmacologiques de quatre plantes de la pharmacologie traditionnelle du Burkina Faso. Université de Ouagadougou, Burkina Faso.
[44]
Di Lorenzo, C., Colombo, F., Biella, S., Stockley, C. and Restani, P. (2021) Polyphenols and Human Health: The Role of Bioavailability. Nutrients, 13, Article 273. https://doi.org/10.3390/nu13010273
[45]
Ankad, G., Bhagwat, S., Hegde, H., Subramanya, M., Upadhya, V. and Pai, S. (2015) Total Polyphenolic Contents and in Vitro Antioxidant Properties of Eight Sida Species from Western Ghats, India. Journal of Ayurveda and Integrative Medicine, 6, 24-28. https://doi.org/10.4103/0975-9476.146544
[46]
Konate, K., Souza, A., Coulibaly, A.Y., Meda, N.T.R., Kiendrebeo, M., Lamien-Med, A., et al. (2010) In Vitro Antioxidant, Lipoxygenase and Xanthine Oxidase Inhibitory Activities of Fractions from Cienfuegosia Digitata Cav., Sida Alba L. and Sida Acuta Burn F. (malvaceae). Pakistan Journal of Biological Sciences, 13, 1092-1098. https://doi.org/10.3923/pjbs.2010.1092.1098
[47]
Navarro, M., Moreira, I., Arnaez, E., Quesada, S., Azofeifa, G., Alvarado, D., et al. (2017) Proanthocyanidin Characterization, Antioxidant and Cytotoxic Activities of Three Plants Commonly Used in Traditional Medicine in Costa Rica: Petiveria Alliaceae L., Phyllanthus Niruri L. and Senna Reticulata Willd. Plants, 6, Article 50. https://doi.org/10.3390/plants6040050
[48]
Nalini, T., Keshamma, E., Ramesh Babu, H.N., Rajeshwari, N. and Sridhar, B. (2021) GC-MS Identification of Bioactive Components of Leaf Extract of Sida acuta (Burm. F). International Journal of Herbal Medicine, 9, 19-24.
[49]
Dike, C.S., Emejulu, A.A., Chukwudoruo, C.S., Akpaki, M.A., Nsofor, W.N., Edom, C.V. et al. (2023) GC-MS and FTIR Analyses of Bioactive Compounds Present in Ethanol Leaf Extract of Sida Acuta from Imo State, Nigeri. GSC Biological and Pharmaceutical Sciences, 25, 394-404. https://doi.org/10.30574/gscbps.2023.25.2.0500
[50]
Nawfetrias, W., Nurhangga, E., Reninta, R., Chotimah, S., Bidara, I.S., Maretta, D., et al. (2023) Metabolite Profiling of the Medicinal Herb Phyllanthus Niruri L. under Drought Stress. IOP Conference Series: Earth and Environmental Science, 1255, Article 012046. https://doi.org/10.1088/1755-1315/1255/1/012046
[51]
Reanmongkol, W., Noppapan, T. and Subhadhirasakul, S. (2009) Antinociceptive, Antipyretic, and Anti-Inflammatory Activities of Putranjiva Roxburghii Wall. Leaf Extract in Experimental Animals. Journal of Natural Medicines, 63, 290-296. https://doi.org/10.1007/s11418-009-0336-6
[52]
Kumar, N., Kumar, N. and Gangadhar, P.B. (2015) Anti-Inflammatory Activity of Traumeel (A Homeopathic Preparation) in Experimental Animals-Rats. Asian Journal of Pharmaceutical and Clinical Research, 8, 317-319.
[53]
Rouzer, C.A. and Marnett, L.J. (2009) Cyclooxygenases: Structural and Functional Insights. Journal of Lipid Research, 50, S29-S34.
[54]
Mostofa, R., Ahmed, S., Begum, M.M., Sohanur Rahman, M., Begum, T., Ahmed, S.U., et al. (2017) Evaluation of Anti-Inflammatory and Gastric Anti-Ulcer Activity of Phyllanthus Niruri L. (Euphorbiaceae) Leaves in Experimental Rats. BMC Complementary and Alternative Medicine, 17, Article No. 267. https://doi.org/10.1186/s12906-017-1771-7
[55]
Büyükokuroğlu, M.E. (2002) Anti-Inflammatory and Antinociceptive Properties of Dantrolene Sodium in Rats and Mice. Pharmacological Research, 45, 455-460. https://doi.org/10.1006/phrs.2002.0970
[56]
Yowtak, J., Lee, K.Y., Kim, H.Y., Wang, J., Kim, H.K., Chung, K., et al. (2011) Reactive Oxygen Species Contribute to Neuropathic Pain by Reducing Spinal GABA Release. Pain, 152, 844-852. https://doi.org/10.1016/j.pain.2010.12.034
[57]
Couto, A.G., Kassuya, C.A.L., Calixto, J.B. and Petrovick, P.R. (2013) Anti-Inflammatory, Antiallodynic Effects and Quantitative Analysis of Gallic Acid in Spray Dried Powders from Phyllanthus Niruri Leaves, Stems, Roots and Whole Plant. Revista Brasileira de Farmacognosia, 23, 124-131. https://doi.org/10.1590/s0102-695x2012005000133
[58]
McNamara, C.R., Mandel-Brehm, J., Bautista, D.M., Siemens, J., Deranian, K.L., Zhao, M., et al. (2007) TRPA1 Mediates Formalin-Induced Pain. Proceedings of the National Academy of Sciences, 104, 13525-13530. https://doi.org/10.1073/pnas.0705924104
[59]
Musa, Y., Haruna, A., Ilyas, M., Yaro, A., Ahmadu, A. and Usman, H. (2008) Phytochemical, Analgesic and Anti-Inflammatory Effects of the Ethylacetate Extract of the Leaves of Pseudocedrella Kotschyii. African Journal of Traditional, Complementary and Alternative Medicines, 5, 92-96. https://doi.org/10.4314/ajtcam.v5i1.31261
[60]
Konaté, K., Bassolé, I.H.N., Hilou, A., Aworet-Samseny, R.R., Souza, A., Barro, N., et al. (2012) Toxicity Assessment and Analgesic Activity Investigation of Aqueous Acetone Extracts of Sida Acuta Burn F. and Sida Cordifolia L. (Malvaceae), Medicinal Plants of Burkina Faso. BMC Complementary and Alternative Medicine, 12, Article No. 120. https://doi.org/10.1186/1472-6882-12-120
[61]
Asare, G.A., Bugyei, K., Sittie, A., Yahaya, E.S., Gyan, B., Adjei, S., et al. (2012) Genotoxicity, Cytotoxicity and Toxicological Evaluation of Whole Plant Extracts of the Medicinal Plant Phyllanthus Niruri (Phyllanthaceae). Genetics and Molecular Research, 11, 100-111. https://doi.org/10.4238/2012.january.13.3
[62]
Dybing, E., Doe, J., Groten, J., Kleiner, J., O’Brien, J., Renwick, A.G., et al. (2002) Hazard Characterisation of Chemicals in Food and Diet. Food and Chemical Toxicology, 40, 237-282. https://doi.org/10.1016/s0278-6915(01)00115-6