Conventional medications used to treat ulcers are not easily accessible to remote areas, costly and not without side effects, thus causing many patients residing in rural areas to resort to herbal means of treatment. World Health Organization records that at least 80% of the world’s population depends on herbal medicinal products. Herbal therapy is the belief that it will promote healthier living. Azadirachta indica is a tree extensively spread in the Northern parts and sparsely distributed in the Northwest Region of Cameroon, used as a remedy for several pathologies, amongst which we have gastric ulcers which is our area of interest. The objective of this study was to evaluate the acute oral toxicity (420 OECD guidelines), systemic exposure and biochemical parameters of toxicity of Azadirachta indica. A. Juss on Wistar rats. Various biochemical parameters such as the: MDA, Catalase, Glutathione, Pepsin, SOD, ASAT, ALAT, Creatinine, XO, and total proteins, were quantified. The acute oral toxicity was of 2000 mg/Kg single dose and compared to a control group which was administered tap water. The administration of 2000 mg/Kg was well tolerated and no death was recorded throughout the fourteen days of observation. No toxic effects were recorded in the organs, implying that at the dose of 2000 mg/Kg, Azadirachta indica was safe. Azadirachta indica aqueous leaf extract contains active metabolites coumarins, catechic tannins, polyphenols, tannins, flavonoids and phlobotannins that were bioavailable in systemic circulation. Showed bioavailability at the tested doses (12.5, 25 and 50 mg/Kg), with the presence of phytochemicals being dose dependent. A clean toxicity profile, with just a slight increase in the level of creatinine.
| Published in | Journal of Drug Design and Medicinal Chemistry (Volume 5, Issue 1) |
| DOI | 10.11648/j.jddmc.20190501.12 |
| Page(s) | 10-17 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Azdiracthta Indica, Systemic Exposure, Toxicity Bioactive Compounds Wistar Rats
| [1] | WHO | About us [Internet]. WHO. [cited 2018 Apr 25]. Available from: http://www.who.int/traditional-complementary-integrative-medicine/about/en/. |
| [2] | Wachtel-Galor S, Benzie IFF. Herbal Medicine: An Introduction to Its History, Usage, Regulation, Current Trends, and Research Needs. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects [Internet]. 2nd ed. Boca Raton (FL): CRC Press/Taylor & Francis; 2011 [cited 2018 Apr 25]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK92773/. |
| [3] | Jo R, Am L, R C. Use of Herbal Medicines and Implications for Conventional Drug Therapy Medical Sciences. Altern Integr Med. 2013 Jul 19; 2 (6): 1–6. |
| [4] | Petrovska BB. Historical review of medicinal plants’ usage. Pharmacogn Rev. 2012; 6 (11): 1–5. |
| [5] | Jain A, Choubey S, Singour PK, Rajak H, Pawar RS. Journal of Applied Pharmaceutical Science. Sida cordifolia Linn - Overv. 2011; 01 (02): 23–31. |
| [6] | Kumar VS, Navaratnam V. Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pac J Trop Biomed. 2013 Jul; 3 (7): 505–14. |
| [7] | Ankoane F., Ngatcha G., Tagni-Sartre M., Biwolé S., Ndjitoyap N. Helicobacter pylori infection and peptic ulcer disease in children and adolescents. 2015 Dec; 1–4. |
| [8] | Bhusan Mohapatra B, Charan Das M, Dinda S, E. V. Nagoji K. Anti-ulcer activity of aqueous and ethanolic leaf extract of neem (Azadirachta indica) in albino rats. 2012 Feb 18; |
| [9] | Sylvia. s Mader. The Digestive System. Understanding Human Anatomy & Physiology. 5th ed. The McGraw-Hill Companies; 2004. p. 299–301. |
| [10] | Gregory M. Gibbons. The Stomach [Internet]. Making Life Better through Research Education & Healthcare; 2008 Nov 10; University of South Florida. Available from: http://health.usf.edu/nocms/medicine/internalmedicine/emergencymed/stomach.pdf. |
| [11] | David I. Soybel. Anatomy And Physiology of the Stomach. Surgical Clinics of North America. North America: Elselvier Saunders; 2005. p. 875–94. |
| [12] | Ian R. Daniels, William H. Allum. Anatomy and Physiology of the stomach [Internet]. 2017. Available from: http://eknygos.lsmuni.lt/springer/463/17-37.pdf. |
| [13] | O’Connor A, O’Moráin C. Digestive Function of the Stomach. Dig Dis. 2014; 32 (3): 186–91. |
| [14] | Farrar GE, Bower IL, and RJ. Gastric Juice and Secretion: Physiology and Variations in Disease. Annu Rev Physiol. 1967; 29 (1): 141–68. |
| [15] | Helander HF. Physiology and pharmacology of the parietal cell. Baillières Clin Gastroenterol. 1988 Jul 1; 2 (3): 539–54. |
| [16] | McQuaid KR. Drugs Used in the Treatment of Gastrointestinal Diseases. BASIC & CLINICAL PHARMACOLOGY. 13th ed. McGraw-Hill Education Lange; 2014. p. 1052–83. |
| [17] | Prabhu V, Shivani A. An Overview of History, Pathogenesis and Treatment of Perforated Peptic Ulcer Disease with Evaluation of Prognostic Scoring in Adults. Ann Med Health Sci Res. 2014; 4 (1): 22–9. |
| [18] | Mertz HR, Walsh JH. Peptic ulcer pathophysiology. Med Clin North Am. 1991 Jul; 75 (4): 799–814. |
| [19] | Kusters JG, van Vliet AHM, Kuipers EJ. Pathogenesis of Helicobacter pylori Infection. Clin Microbiol Rev. 2006 Jul; 19 (3): 449–90. |
| [20] | Drini M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Aust Prescr. 2017 Jun; 40 (3): 91–3. |
| [21] | Shier David, Lewis Ricki, Butler Jackie, Hole John. Hole’s Human Anatomy and Physiology. Hole’s Human Anatomy & Physiology. 9th ed. McGraw-Hill, Boston; 2001. |
| [22] | Bode CJ. Alcohol’s Role in Gastrointestinal Tract Disorders [Internet]. Alcohol Rehab. [cited 2017 Nov 3]. Available from: http://alcoholrehab.com/alcoholism/alcohol-and-ulcers/. |
| [23] | AL-Wajeeh NS, Hajerezaie M, Noor SM, Halabi MF, Al-Henhena N, Azizan AHS, et al. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats. BMC Vet Res. 2017 Jan 19; 13: 27. |
| [24] | Li LF, Chan RLY, Chan RLY, Lu L, Lu L, et al. Cigarette smoking and gastrointestinal diseases: The causal relationship and underlying molecular mechanisms (Review). Int J Mol Med. 2014 Aug 1; 34 (2): 372–80. |
| [25] | Berndt V, Götz E, Schönleben K, Langhans P. [Stress-induced peptic ulcer; pathogenesis, clinical features, prevention and treatment (author’s transl)]. Prakt Anasthesie Wiederbeleb Intensivther. 1978 Apr; 13 (2): 108–22. |
| [26] | Zollinger-Ellison Syndrome: Background, Pathophysiology, Etiology [Internet]. [cited 2017 Nov 6]. Available from: https://emedicine.medscape.com/article/183555-overview. |
| [27] | Tomassetti P, Campana D, Piscitelli L, Mazzotta E, Brocchi E, Pezzilli R, et al. Treatment of Zollinger-Ellison Syndrome. World J Gastroenterol WJG. 2005 Sep 21; 11 (35): 5423–32. |
| [28] | Yang R-H, Chu Y-K. Zollinger-Ellison syndrome: Revelation of the gastrinoma triangle. Radiol Case Rep [Internet]. 2015 Dec 3 [cited 2017 Nov 6]; 10 (1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921170/. |
| [29] | Milosavljevic T, Kostić-Milosavljević M, Jovanović I, Krstić M. Complications of Peptic Ulcer Disease. Dig Dis. 2011; 29 (5): 491–3. |
| [30] | Dubero Sime. Gastroprotective Effect of Crude Ethanol Extract of Ethopian Propolis Against Chemical Induced Gastric Mucosal Lesion in Mice [Internet]. [Addis Ababa]: Addis Ababa University; 2007. Available from: http://etd.aau.edu.et/bitstream/123456789/2982/3/Microsoft%20Word%20-%20final.pdf. |
| [31] | Fashner J, Alfred C. Gitu. Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection. American Acadamy of Family Physician. 2015 Feb; 91 (4): 236–42. |
| [32] | Roche VF. The Chemically Elegant Proton Pump Inhibitors. Am J Pharm Educ [Internet]. 2006 Oct 15 [cited 2018 Apr 9]; 70 (5). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1637016/. |
| [33] | Koelz HR. Protective drugs in the treatment of gastroduodenal ulcer disease. Scand J Gastroenterol Suppl. 1986; 125: 156–64. |
| [34] | Bi W-P, Man H-B, Man M-Q. Efficacy and safety of herbal medicines in treating gastric ulcer: A review. World J Gastroenterol WJG. 2014 Dec 7; 20 (45): 17020–8. |
| [35] | Shail Bala Sanghi. Diversity of Tree Flora at Tendukheda, District Narshinghpur, Madhya Pradesh. International Journal of Pharmacy & Life Sciences. 2015 Jun; 6: 4562–4. |
| [36] | El-Hawary SS, El-Tantawy ME, Rabeh MA, Badr WK. DNA fingerprinting and botanical study of Azadirachta indica A. Juss. (neem) family Meliaceae. Beni-Suef Univ J Basic Appl Sci. 2013 Mar 1; 2 (1): 1–13. |
| [37] | Eid A, Jaradat N, Elmarzugi N. A Review of chemical constituents and traditional usage of Neem plant (Azadirachta Indica). (PMPJ). 2017 May 25; 2: 75–81. |
| [38] | Mohammad A. Alzohairy. Therapeutic Role of Azadirachta indica (Neem) and their Active Constituents in Disease Prevention and Treatment. Evidence-Based Alternative and Complementary Medicine. 2016 Mar 1; |
| [39] | Usman H, Abdulrahman F, Usman A. Qualitative Phytochemical Screening and In Vitro Antimicrobial Effects of Methanol Stem Bark Extract of Ficus Thonningii (Moraceae). Afr J Tradit Complement Altern Med. 2009 May 7; 6 (3): 289–95. |
| [40] | Prashanth G. K., Krishnaiah G. M. Chemical composition of the leaves of Azadirachta indica Linn (Neem). International Journal of Advancement in Engineering Technology, Management & Applied Science (IJAETMAS). 2014 Oct; 1 (5): 21–31. |
| [41] | Chen X-Y, Chen H-M, Liu Y-H, Zhang Z-B, Zheng Y-F, Su Z-Q, et al. The gastroprotective effect of pogostone from Pogostemonis Herba against indomethacin-induced gastric ulcer in rats. Exp Biol Med. 2016 Jan; 241 (2): 193–204. |
| [42] | OECD/OCDE. OECD guideline for testing of chemicals [Internet]. OECD/OCDE; 2001. Available from: https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd_gl420.pdf. |
| [43] | Nde DB, Emmanuel Ngu A, Immaculate Natang M. Physical properties of neem (Azadirachtaindicaa. juss) fruits, nuts and kernels. Sky Journal of Food Science. 2013 Dec; 2 (8): 014–23. |
| [44] | Adinortey MB, Ansah C, Galyuon I, Nyarko A. In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents [Internet]. Ulcers. 2013 [cited 2018 Feb 23]. Available from: https://www.hindawi.com/journals/ulcers/2013/796405/. |
| [45] | Dash SP, Dixit S, Sahoo S. Phytochemical and Biochemical Characterizations from Leaf Extracts from Azadirachta Indica: An Important Medicinal Plant. Biochem Anal Biochem [Internet]. 2017 Jun 12 [cited 2018 Mar 21]; 6 (2). Available from: https://www.omicsonline.org/open-access/phytochemical-and-biochemical-characterizations-from-leaf-extracts-fromazadirachta-indica-an-important-medicinal-plant-2161-1009-1000323.php?aid=90323. |
APA Style
Tembe Fokunang Estella, Ndi Sirri Akwen, Njinkio Borgia Nono, Tsabang Nole, Ndikum Valentin Nchafor, et al. (2019). Investigation of Toxicity and Systemic Exposure of Bioactive Compounds of Aqueous Leaf Extract of Azadirachta indica A. Juss (Meliaceae) on Wistar Rats. Journal of Drug Design and Medicinal Chemistry, 5(1), 10-17. https://doi.org/10.11648/j.jddmc.20190501.12
ACS Style
Tembe Fokunang Estella; Ndi Sirri Akwen; Njinkio Borgia Nono; Tsabang Nole; Ndikum Valentin Nchafor, et al. Investigation of Toxicity and Systemic Exposure of Bioactive Compounds of Aqueous Leaf Extract of Azadirachta indica A. Juss (Meliaceae) on Wistar Rats. J. Drug Des. Med. Chem. 2019, 5(1), 10-17. doi: 10.11648/j.jddmc.20190501.12
AMA Style
Tembe Fokunang Estella, Ndi Sirri Akwen, Njinkio Borgia Nono, Tsabang Nole, Ndikum Valentin Nchafor, et al. Investigation of Toxicity and Systemic Exposure of Bioactive Compounds of Aqueous Leaf Extract of Azadirachta indica A. Juss (Meliaceae) on Wistar Rats. J Drug Des Med Chem. 2019;5(1):10-17. doi: 10.11648/j.jddmc.20190501.12
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Download@article{10.11648/j.jddmc.20190501.12,
author = {Tembe Fokunang Estella and Ndi Sirri Akwen and Njinkio Borgia Nono and Tsabang Nole and Ndikum Valentin Nchafor and Ngameni Bathelemy and Nguefack Tsague Georges and Charles Fokunang and Ngadjui Bonaventure Tchaleu},
title = {Investigation of Toxicity and Systemic Exposure of Bioactive Compounds of Aqueous Leaf Extract of Azadirachta indica A. Juss (Meliaceae) on Wistar Rats},
journal = {Journal of Drug Design and Medicinal Chemistry},
volume = {5},
number = {1},
pages = {10-17},
doi = {10.11648/j.jddmc.20190501.12},
url = {https://doi.org/10.11648/j.jddmc.20190501.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20190501.12},
abstract = {Conventional medications used to treat ulcers are not easily accessible to remote areas, costly and not without side effects, thus causing many patients residing in rural areas to resort to herbal means of treatment. World Health Organization records that at least 80% of the world’s population depends on herbal medicinal products. Herbal therapy is the belief that it will promote healthier living. Azadirachta indica is a tree extensively spread in the Northern parts and sparsely distributed in the Northwest Region of Cameroon, used as a remedy for several pathologies, amongst which we have gastric ulcers which is our area of interest. The objective of this study was to evaluate the acute oral toxicity (420 OECD guidelines), systemic exposure and biochemical parameters of toxicity of Azadirachta indica. A. Juss on Wistar rats. Various biochemical parameters such as the: MDA, Catalase, Glutathione, Pepsin, SOD, ASAT, ALAT, Creatinine, XO, and total proteins, were quantified. The acute oral toxicity was of 2000 mg/Kg single dose and compared to a control group which was administered tap water. The administration of 2000 mg/Kg was well tolerated and no death was recorded throughout the fourteen days of observation. No toxic effects were recorded in the organs, implying that at the dose of 2000 mg/Kg, Azadirachta indica was safe. Azadirachta indica aqueous leaf extract contains active metabolites coumarins, catechic tannins, polyphenols, tannins, flavonoids and phlobotannins that were bioavailable in systemic circulation. Showed bioavailability at the tested doses (12.5, 25 and 50 mg/Kg), with the presence of phytochemicals being dose dependent. A clean toxicity profile, with just a slight increase in the level of creatinine.},
year = {2019}
}
TY - JOUR T1 - Investigation of Toxicity and Systemic Exposure of Bioactive Compounds of Aqueous Leaf Extract of Azadirachta indica A. Juss (Meliaceae) on Wistar Rats AU - Tembe Fokunang Estella AU - Ndi Sirri Akwen AU - Njinkio Borgia Nono AU - Tsabang Nole AU - Ndikum Valentin Nchafor AU - Ngameni Bathelemy AU - Nguefack Tsague Georges AU - Charles Fokunang AU - Ngadjui Bonaventure Tchaleu Y1 - 2019/06/24 PY - 2019 N1 - https://doi.org/10.11648/j.jddmc.20190501.12 DO - 10.11648/j.jddmc.20190501.12 T2 - Journal of Drug Design and Medicinal Chemistry JF - Journal of Drug Design and Medicinal Chemistry JO - Journal of Drug Design and Medicinal Chemistry SP - 10 EP - 17 PB - Science Publishing Group SN - 2472-3576 UR - https://doi.org/10.11648/j.jddmc.20190501.12 AB - Conventional medications used to treat ulcers are not easily accessible to remote areas, costly and not without side effects, thus causing many patients residing in rural areas to resort to herbal means of treatment. World Health Organization records that at least 80% of the world’s population depends on herbal medicinal products. Herbal therapy is the belief that it will promote healthier living. Azadirachta indica is a tree extensively spread in the Northern parts and sparsely distributed in the Northwest Region of Cameroon, used as a remedy for several pathologies, amongst which we have gastric ulcers which is our area of interest. The objective of this study was to evaluate the acute oral toxicity (420 OECD guidelines), systemic exposure and biochemical parameters of toxicity of Azadirachta indica. A. Juss on Wistar rats. Various biochemical parameters such as the: MDA, Catalase, Glutathione, Pepsin, SOD, ASAT, ALAT, Creatinine, XO, and total proteins, were quantified. The acute oral toxicity was of 2000 mg/Kg single dose and compared to a control group which was administered tap water. The administration of 2000 mg/Kg was well tolerated and no death was recorded throughout the fourteen days of observation. No toxic effects were recorded in the organs, implying that at the dose of 2000 mg/Kg, Azadirachta indica was safe. Azadirachta indica aqueous leaf extract contains active metabolites coumarins, catechic tannins, polyphenols, tannins, flavonoids and phlobotannins that were bioavailable in systemic circulation. Showed bioavailability at the tested doses (12.5, 25 and 50 mg/Kg), with the presence of phytochemicals being dose dependent. A clean toxicity profile, with just a slight increase in the level of creatinine. VL - 5 IS - 1 ER -
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