Pain Alleviating Potential of Ethanol Extract of <i>Vernonia amygdalina</i> Del. on Writhing in Male Wistar Rats

Authors

  • Oluwapelumi M. Ajiboye Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • Aderiike Adewumi Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • Kayode O. Ogunwenmo Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • Rufus Animashaun Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • David O. Jegede Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • Folasade O. Aina Department of Maternal and Child Health, School of Nursing, Babcock University, Ilishan-Remo, Ogun State, Nigeria

DOI:

https://doi.org/10.26538/tjnpr/v8i4.35

Keywords:

Traditional Medicine, Acetic Acid-induced, Anti-inflammatory, Analgesic, Pain

Abstract

Non-steroidal anti-inflammatory drugs and central analgesics are both effective pain relievers, but they have limitations and possible adverse effects. In African, Indian, and Chinese folkloric medicine, Vernonia amygdalina (VA) is known widely for its pharmacological benefits including antioxidant, antibacterial, and anti-cancer properties. The models, acetic acid-induced writhing, hot-plate latency, and tail-flick response, were utilized in this study for assessing the anti-inflammatory and analgesic potential of VA, alongside its toxicological study. The toxicology results showed no sign of toxicity, including mortality, salivation, diarrhea, or abnormal weight loss or gain. The serum AST and ALT were within the reference range (ALT:7-45 U/l; AST: 6-38 U/l). The analgesic effect of VA extract was highly demonstrated after 3 days of pretreatment at the two highest doses (400 and 800 mg/kg) in a dose-dependent manner. Despite being less effective than the larger doses, an analgesic effect was also observed at 200 mg/kg, which implies that VA may still have some analgesic effects at lower doses. The higher doses of VA were as effective and provided a prolonged analgesic effect that was comparable to the conventional medications (Diclofenac and Aspirin) used. The analgesic effect of VA has been suggested to be associated with its rich alkaloid constituent, which has been reported to exert an analgesic effect via mechanisms such as opioid receptor activation, neurotransmitter modulation, inhibition of pro-inflammatory cytokines, and ion channel modulation, among others. Hence, this study supports the utilization of VA as alternative therapeutic approach for the alleviation of pain and its symptoms.

References

Clark LM, Wrona S. A Sensory and Emotional Experience: Pediatric Chronic Pain & Mental Health Pain Manag Nurs. 2016; 17: 97

Perrot S, Cohen M, Barke A, Korwisi B, Rief W, Treede R-D. The IASP classification of chronic pain for ICD-11: chronic secondary musculoskeletal pain. Pain. 2019; 160: 77–82.

Craig KD, MacKenzie NE. What is pain: Are cognitive and social features core components? Paediatr Neonatal Pain. 2021; 3: 106–118.

Luo Y, Wang C-Z, Sawadogo R, Tan T, Yuan C-S. Effects of Herbal Medicines on Pain Management. Am J Chin Med. 2020; 48: 1–16.

Williams AC de C, Craig KD. Updating the definition of pain. Pain. 2016; 157: 2420–2423.

Toth LA. Interacting Influences of Sleep, Pain, and Analgesic Medications on Sleep Studies in Rodents Comp Med. 2019; 69: 571–578.

McCann C. Preoperative analgesia for children and adolescents to reduce pain associated with dental treatment. Evid Based Dent. 2017; 18: 17–18.

Panayotova GS, Dimitrov DA. Modeling from Time Series of Complex Brain Signals. Int J Signal Process Syst. 2021; 9: 1–6.

Lim RKS, Armstrong D, Pardo EG. Pharmacology of Pain, Vol. 9. Pergamon Press: Elsevier; 2016. 250p.

Vanegas H, Vazquez E, Tortorici V. NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System Pharmaceuticals. 2010; 3: 1335–1347.

Gargya I, Singh B, Talnia S. NSAIDS (Non- Steroidal Anti- Inflammatory Drugs)- Their Effects and Side Effects in Orthodontic Therapy- A Review Dent J Adv Stud. 2017; 05: 8–13.

Fokunang C. Overview of non-steroidal anti-inflammatory drugs (NSAIDs) in resource limited countries. MOJ Toxicol. 2018; 4(1): 5–13.

Drini M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Aust Prescr. 2017; 40(3): 91-93.

Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020; 180: 114147

Jahnavi K, Pavani Reddy P, Vasudha B, Narender B. Non-steroidal anti-inflammatory drugs: an overview. J Drug Deliv Ther. 2019; 9: 442–448.

Kumar P, Shah S, Gupta A. Emerging role of cannabinoids and synthetic cannabinoid receptor 1/cannabinoid receptor 2 receptor agonists in cancer treatment and chemotherapy-associated cancer management. J Cancer Res Ther. 2021; 17: 1-9.

Reed MD. The Balance Between Effective Opioid-Based Pain Management and Patient Safety: Can It Be Achieved? J Pediatr Pharmacol Ther. 2013; 18: 264–268.

Mauritz MD, Hasan C, Dreier LA, Schmidt P, Zernikow B. Opioid-Induced Respiratory Depression in Pediatric Palliative Care Patients with Severe Neurological Impairment—A Scoping Literature Review and Case Reports. Children. 2020; 7: 312.

Anne S, Finestone SA, Paisley A, Monjur TM. Plain Language Summary: Opioid Prescribing for Analgesia After Common Otolaryngology Operations. Otolaryngol Head Neck Surg. 2021; 164: 704–711.

Chen H, Chen H, Wang C, Gong Y, Xiang X, Zhang H. Current application of commonly-used traditional Chinese herbal medicine and formulae for preventing severe infectious diseases. Pharm Care Res. 2020; 20: 291–295.

Mohankumar R, Prakash SEL, Irfan N, Mohanraj S, Kumarappan C. Evaluation of analgesic, anti-inflammatory, and antipyretic activities of Ziziphus mauritania Lam leaves in animal models. Pharmacol Res - Mod Chin Med. 2022; 4: 100153.

Zhou F, Lan K, Li X, Mei Y, Cai S, Wang J. The complete chloroplast genome sequence of Vernonia amygdalina Delile. Mitochondrial DNA B Resour. 2021; 6: 1134–1135.

Nguyen PAT, Khang DT, Nguyen PTT, Do HDK. The complete chloroplast genome of Elephantopus scaber L. (Vernonioideae, Asteraceae), a useful ethnomedicinal plant in asia. Mitochondrial DNA B: Resour. 2023; 8(9): 936–941

Liu X, Yang R, Xu Q, Zhou M, Feng J, Wang G, Lin T, Tian W, Chen H. Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity. Bioorg Chem. 2022; 128: 106068.

Burkill HM. The useful plants of west tropical Africa, Vols. 1-3. (2nd ed.). Kew: Royal Botanical Garden; 1995.

Adejumo TO, Vögele RT. Biopesticides. Berlin: Logos Verlag Berlin GmbH; 2021. 300p.Oladele JO, Oyeleke OM, Oladele OT, Olaniyan M. Neuroprotective mechanism of Vernonia amygdalina in a rat model of neurodegenerative diseases. Toxicol Rep. 2020; 7: 1223–1232.

Alozie EU, Iheanacho KM, Alisi CS, Asiwe ES, Iweala E. Comparative Hepatoprotective Activity of Vernonia amygdalina Leaf Solvent Extracts in Alloxan-Induced Diabetic Rats. Trop J Nat Prod Res. 2023; 7(7): 3517-3523.

Koffi JA, Silué KD, Tano DK, Dable TM, Yavo W. Evaluation of in vitro antiplasmodial effect of extracts from seven medicinal plants used to treat malaria in Côte d’Ivoire. BioImpacts. 2020; 10: 151–157.

Olamoyegun MA, Omisore NO, Yusuf AO, Odewale TE. Assessment of Pharmacodynamic Interactions and Toxicological Effects of Vernonia amygydalina –Metformin Co-Administration on Streptozotocin-Induced Diabetic Wistar Rats. Trop J Nat Prod Res. 2022; 6 (12): 2073-2080.

Adedayo BC, Ajiboye OM, Oyeleye IS, Ojo RO, Oboh G. Effect of alkaloid extract from Andrographis paniculata (Burm. f.) Nees and Phyllanthus amarus Schumach. & Thonn. on cognitive related biochemicals in the brain of streptozotocin-induced diabetic rats. Pharmacol Res - Mod Chin Med. 2023; 9: 100314.

Owoyele BV, Adebukola OM, Funmilayo AA, Soladoye AO. Anti-inflammatory activities of ethanol extract of Carica papaya leaves. Inflammopharmacology. 2008; 16: 168–173.

Koster R. Acetic acid for analgesics screening. In: Fed Proc. 1959; 18: 412-417.

Shehu A, Olurishe TO, Zezi AU, Ahmed A. Acute Toxicological, Analgesic and Anti-Inflammatory Effects of Methanol Extract of Laggera aurita Linn F (Compositae) in Mice and Rats. Afr J Pharmacol Ther. 2016; 5(2): 65-73.

Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl-and dithienylbutylamines. J Pharmacol Exp Ther. 1953; 107(3): 385-393.

Hayashi G, Takemori AE. The type of analgesic-receptor interaction involved in certain analgesic assays. Eur J Pharmacol. 1971; 16: 63–66.

Onasanwo S, Oyebanjo O, Ajayi A, Olubori M. Mechanisms of action of the anti-nociceptive and anti-inflammatory effects of leaf extract of Vernonia amygdalina. J Intercult Ethnopharmacol. 2017; 6(1): 192-198.

Adiukwu PC, Kayanja FIB, Rugera S, Murokore B, Nambatya GK, Ezeonwumelu JOC, Tanayen JK, Murokore BJ, Twikirize O, Twinomujuni S, Byamugisha D, Imanirampa L. Antipyretic and antinociceptive properties of the aqueous extract and saponin from an edible vegetable: Vernonia amygdalina leaf. Afr J Food Agric Nutr Dev. 2013; 13: 7587–7606.

Alara OR, Abdurahman NH, Abdul Mudalip SK, Olalere OA. Phytochemical and Pharmacological Properties of Vernonia amygdalina: A Review J Chem Eng Ind Biotechnol. 2017; 2: 80–96.

Njan AA, Adzu B, Agaba AG, Byarugaba D, Díaz-Llera S, Bangsberg DR. The Analgesic and Antiplasmodial Activities and Toxicology of Vernonia amygdalina. J Med Food. 2008; 11: 574–581.

Purnamasari O, Azizah Z, Misfadhila S. Phytochemical and Pharmacological Activities of African Leaf (Vernonia Amygdalina): A Review. Int J Res Pub Rev. 2023; 4: 1752–1758.

Abubakar A, Nazifi A, Hassan F, Duke K, Edoh T. Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae): Acute and sub-acute toxicity studies in Wistar rats. J. Acute Dis. 2019; 8: 21-27.

Rahman SMM, Atikullah Md, Islam MdN, Mohaimenul Md, Ahammad F, Islam MdS, Saha B, Rahman MdH. Anti-inflammatory, antinociceptive and antidiarrhoeal activities of methanol and ethyl acetate extract of Hemigraphis alternata leaves in mice. Clin Phytoscience. 2019; 5:16.

Olajumoke E, Ibrahim O, Akinwunmi A, Viola N. Acute Toxicity of Aqueous Leaf Extract of Euphorbia heterophylla L. in Sprague Dawley Rats. J Complement Med Res. 2016; 1: 1–10.

Lala V. Liver Function Tests. StatPearls - NCBI Bookshelf 2023. https://www.ncbi.nlm.nih.gov/books/NBK482489/.

Cantalapiedra-Hijar G, Abo-Ismail M, Carstens GE, Guan LL, Hegarty R, Kenny DA, McGee M, Plastow G, Relling A, Ortigues-Marty I. Review: Biological determinants of between-animal variation in feed efficiency of growing beef cattle. Animal. 2018; 12: 321–335.

Eslam M, El-Serag HB, Francque S, Sarin SK, Wei L, Bugianesi E, George J. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol. 2022; 19: 638–651.

Esmaeili N, Carter CG, Wilson R, Walker SP, Miller MR, Bridle AR, Symonds JE. Proteomic investigation of brain, liver and intestine in high feed intake and low feed intake Chinook salmon (Oncorhynchus tshawytscha). Aquaculture 2022; 551: 737915.

Kumar A, Kaur H, Singh A. Neuropathic Pain models caused by damage to central or peripheral nervous system. Pharmacol Rep. 2018; 70: 206–216.

Saganuwan SA. Piroxicam: Source for Synthesis of Central Nervous System (CNS) Acting Drugs. Cent Nerv Syst Agents Med Chem. 2017; 17(2): 135-140.

Mazo I, Roza C, Zamanillo D, Merlos M, Vela JM, Lopez‐Garcia JA. Effects of centrally acting analgesics on spinal segmental reflexes and wind‐up. Eur J Pain 2014; 19: 1012–1020.

Martini M, Perez‐Marcos D, Sanchez‐Vives MV. Modulation of pain threshold by virtual body ownership. Eur. J. Pain. 2014; 18: 1040–1048.

Kress HG. Tapentadol and its two mechanisms of action: Is there a new pharmacological class of centrally-acting analgesics on the horizon? Eur J Pain. 2010; 14: 781–783.

Martínez V, Abalo R. Peripherally acting opioid analgesics and peripherally-induced analgesia. Behav Pharmacol. 2020; 31: 136–158.

Stein C. Targeting pain and inflammation by peripherally acting opioids. Front. Pharmacol. 2013; 4.

Sehgal N. Peripherally Acting Opioids and Clinical Implications for Pain Control. Pain Physician. 2011; 14: 249–258.

Rohdewald P, Neddermam E, Handwerker HO. Dose dependency of the analgesic effect of metamizole to painful tooth pulp stimulation. Pain. 1987; 30: S53.

Patil A, Konda VCR. Dose-dependent analgesic activity of mexiletine on thermally induced pain in rats. Int J Basic Clin Pharmacol. 2018; 8: 90-94.

Rai N, Vyas S, Phadnis P. Evaluation of analgesic activity of Ficus racemosa leaf extract using acetic acid induced writhing method in mice. Int J Basic Clin Pharmacol. 2016: 60–64.

Jo H-G, Lee G-Y, Baek CY, Song HS, Lee D. Analgesic and Anti-Inflammatory Effects of Aucklandia lappa Root Extracts on Acetic Acid-Induced Writhing in Mice and Monosodium Iodoacetate-Induced Osteoarthritis in Rats. Plants 2020; 10: 42.

Olela B, Mbaria J, Wachira T, Moriasi G. Acute Oral Toxicity and Anti-inflammatory and Analgesic Effects of Aqueous and Methanol Stem Bark Extracts of Piliostigma thonningii (Schumach.). Evid Based Complement Alternat Med. 2020; 2020: 1–10.

Sharma S, Khare S, Dubey BK, Joshi A, Jain A. Analgesic activity of poly herbal formulation in experimental rats by acetic acid induced writhing test model and Hot plate model. J Drug Deliv Ther. 2019; 9(Suppl. 2): 276-280.

Alzahrani AR, Shahid I. Determination of Analgesic Potential of Ethanol Extract of Brassica campestris Leaves in Rats.Pharmacognosy Res. 2022; 14: 297–303.

Oboh G, Adedayo BC, Adetola MB, Oyeleye IS, Ogunsuyi OB. Characterization and neuroprotective properties of alkaloid extract of Vernonia amygdalina Delile in experimental models of Alzheimer’s disease. Drug Chem Toxicol. 2020; 45: 731–740.

Shareef H, Naeem S, Zaheer E. Comparative Analgesic Activity of Selected Medicinal Plants from Pakistan: Analgesics from plants. Proc Pak Acad Sci B. 2019; 56(3): 57-67.

Tian B, Tian M, Huang S-M. Advances in phytochemical and modern pharmacological research of Rhizoma corydalis. Pharm Biol. 2020; 58: 265–275.

Wang M, Zhang X-M, Fu X, Zhang P, Hu W-J, Yang B-Y, Kuang H-X. Alkaloids in genus stephania (Menispermaceae): A comprehensive review of its ethnopharmacology, phytochemistry, pharmacology and toxicology. J Ethnopharmacol. 2022; 293: 115248.

Le HM, Huynh NT, Vo TT, Nguyen TT, Nguyen QM. Evaluation of Pain-relieving effect of the herbal remedy “Hoang Ky Que Chi Ngu Vat Thang” in Animal Model. Trop J Nat Prod Res. 2023; 7(6): 3153-3157.

Jiang W, Tang M, Yang L, Zhao X, Gao J, Jiao Y, Li T, Tie C, Gao T, Han Y, Jiang J-D. Analgesic Alkaloids Derived from Traditional Chinese Medicine in Pain Management. Front Pharmacol. 2022; 13: 851508.

Feng J, Chen K, Shen S, Luo Y, Liu X, Chen X, Gao W, Tong Y-R. The composition, pharmacological effects, related mechanisms and drug delivery of alkaloids from Corydalis yanhusuo. Biomed Pharmacother. 2023; 167: 115511.

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Published

2024-05-01

How to Cite

Ajiboye, O. M., Adewumi, A., Ogunwenmo, K. O., Animashaun, R., Jegede, D. O., & Aina, F. O. (2024). Pain Alleviating Potential of Ethanol Extract of <i>Vernonia amygdalina</i> Del. on Writhing in Male Wistar Rats. Tropical Journal of Natural Product Research (TJNPR), 8(4), 7000–7005. https://doi.org/10.26538/tjnpr/v8i4.35