Chemical characterization of Hymenocardia acida stem bark extract and modulation of selected enzymes in Kidney and Heart of Wistar rats
Main Article Content
Abstract
Hymenocardia acida tul leaf and stem bark are used in treatment of several diseases in Africa. We examined the chemical constituents of the stem bark extract and its effects on some antioxidant indices and esterases in Wistar rats. Hymenocardia acida stem bark extract (HASBE) was obtained by Soxhlet extraction using methanol, followed by Atomic Absorption Spectroscopy (AAS), Fourier-Transform Infrared (FT-IR) spectroscopy, ultraviolet (UV) spectroscopy, High-performance liquid chromatography (HPLC) and Gas Chromatography-Flame ionization detection (GC-FID). Forty-eight male Wistar rats were assigned into eight groups (6 rats each), and administered orally with normal saline (Control), 50, 100, 150, 200, 250, 300, 350 mg/kg of HASBE twice per week for eight weeks. The rats were sacrificed under chloroform anesthesia, and kidneys and heart were excised, and processed into homogenates. Superoxide dismutase (SOD), catalase, lipid peroxidation (LPO), glutathione peroxidase (GPx), acetylcholinesterase (AChE) and carboxylesterases (CES) were determined spectrophotometrically. The AAS of HASBE detected Cobalt, Copper, Zinc, Iron, Nickel, Chromium, Manganese and Magnesium. The FT-IR shows four peaks as 2961.4, 2926.0, 1056.7 and 1034.3 cm-1, while UV shows absorbance between 250 nm and 650 nm. The HPLC identified orientin, β-sitosterol, rutin and betulinic acid, while GC-FID identified rutin, orientin, stigmasterol, hymenocardine and homopterocarpin as prominent compounds. The SOD significantly (p < 0.05) reduced in kidneys, while catalase was elevated in kidney and heart, with an increase in LPO level only in heart, relative to controls. The GPx, AChE and CE activities in kidneys were increased by HASBE, whereas, CE activity was lowered in heart. This study has demonstrated that Hymenocardia acida stem bark extract majorly contains iron, nickel, orientin, rutin, stigmasterol, hymenocardine, β-sitosterol, homopterocarpin and betulinic acid, and could possibly modulate the activities of antioxidant and esterase enzymes in kidney and heart of Wistar rats.
Keywords:
Hymenocardia acida, elemental analysis, compound identification, enzyme activity
Article Details
How to Cite
ADELEKE, G. E. et al.
Chemical characterization of Hymenocardia acida stem bark extract and modulation of selected enzymes in Kidney and Heart of Wistar rats.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4288>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i9.4288.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Abu AH, Uchendu CN. Antifertility activity of aqueous ethanolic extract of Hymenocardia acida stem bark in female rats. Iranian Journal of Reproductive Med. 2011; 9(3): 217-222.
2. Tuenter E, Exarchou V, Baldѐ A, Cos P, Maes L, Apers S, Pieters L. Cyclopeptide alkaloids from Hymenocardia acida. Journal of natural products. 2016; 79(7): 1746-1751.
3. Keay RWJ. Trees of Nigeria. Clarendon Press Oxford, New York; 1989: 179-181.
4. Bum EN, Taiwe GS, Moto FCO, Ngoupaye GT, Vougat RRN, Sakoue VD, Gwa C, Ayissi ER., Dong C, Rakotonirina A, Rakotonirina SV. Antiepileptic medicinal plants used in traditional medicine to treat epilepsy. "Clinical and Genetic Aspects of Epilepsy", Zaid 4, Afawi (Ed.); 2011: 175-192.
5. Ibrahim H, Sani FS, Danladi BH, Ahmadu AA. Phytochemical and antisickling studies of the leaves of Hymenocardia acida Tul (Euphorbiaceae). Pakistan Journal of Biological Sciences. 2007; 10(5): 788-791s
6. Tor-Anyiin TA, Shimbe RY, Anyam JV. Phytochemical and medicinal activities of Hymenocardia acida Tul (Euphorbiaceae): A review. J.Nat. Prod.Plant Resour. 2013; 3: 11-16.
7. Ajao AA, Alimi AA, Olatunji OA, Balogun O.F, Saheed AS.. A synopsis of antipsychotic medicinal plants in Nigeria. Transactions of the Royal Society of South Africa. 2017; DOI: 10.1080/0035919X.2017.1386138
8. Orwa C, Mutua A, Kindt R, Jamnadass R, Anthony S. Agroforestree Database: A tree reference and selection guide version 4.0; 2009: (http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp)
9. Udeozo IP, Ejikeme CM, Eboatu AN, Kelle HI. An assay of some thermal characteristics, chemical and phytochemical constituents of Hymenocardia acida Timber. J.Appl.Sci. Environ.Manage. 2017; 21(5): 951-935.
10. Sofidiya MO, Odukoya OA, Afolayan AJ, Familoni OB.. Phenolic contents, antioxidant and antibacterial activities of Hymenocardia acida. Natural Product Research. 2009; 23(2): 168-177.
11. Olotu NP, Ibrahim H, Ilyas N, Ajima U, Olotu AI Phytochemical screening and analgesic studies of the root bark of Hymenocardia acida, Tul (Euphorbiaceae). International Journal of Drug Development and Research. 2011; 3(1): 219-223.
12. Oshomoh EO, Ndu M. (2013). Antimicrobialand antifungal activities of ethanol and aqueous cude extracts of Hymenocardia acida stem against selected dental caries pathogens. Pharmaconosy Journal.2013; 4(29): 55-60.
13. Adedokun O, Ntungwe EN, Viegas C, Ayinde BA, Barboni L, Maggi F, Saraiva, Rijo P, Fonte P. Enhanced anticancer activity of Hymenocardia acida stem bark extract loaded into PLGA nanoparticles. Pharmaceuticals (Basel). 2022; 15(5): 535.
14. Skovronsky D M, Lee VM.Y, Trojanowski JQ. Neurodegenerative diseases:new concepts of pathogenesis and their therapeutic implications. Annual Review of Pathology. 2006. 1, 151–170.
15. Usman AM, Danjuma NM, Ya’u J, Ahmad MM, Alhassan Z, Abubakar YM.Antidiarrhoeal potential of methanol extract of Hymenocardia acida Tul (Euphorbiaceae) in laboratory animals. Bulletin of the National Research Center. 2021; 45(1):118.
16. Koffi S, Soro TY, Begbin KE, Abizi G, Ahebe ME, Kouadio KJ, Zougrou NE, Kouakou, K. Acute and subchronic toxicities of the aqueous extract of the Hymenocardia acida (Euphorbiaceae) roots in rodents. European Journal of Medicinal Plants. 2022; 33(1): 39-48.
17. Lowry OH, Rosbrough NJ, Farr AL, et al. Protein measurement with the Folin- phenol reagent. J. Biol. Chem. 1951; 193: 265-275.
18. Mistra HP, Fridovich I. The generation of superoxide radical during the autoxidation of ferredoxin. J. Biol. Chem. 1979; 246: 6886-6890.
19. Aebi H. (1984). Catalase in-vitro. In: Packer L. Editor. Methods in Enzymology. Academic Press; pp . 121-126.
20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by Thiobarbituric acid reaction. Analytical Biochemistry. 1979; 95: 351-358.
21. Paglia, D.E. & Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab Clin. Med. 1967; 70:158-169.
22. Ellman G, Courtney KD, Andres V. Jr., Featherstone Y. A new and rapicolorimetric determination of acetylcholinesterase activity. Biohem. Pharmacol. 1961; 7: 88-95.
23. Nachmanshon D, Neumann E. In: Chemical and Molecular Basis of Nerve activity, Academic Press, New York. 1975.
24. Clement JG, Erhardt N. Serum Carboxylesterase activity in various strains of rats: sensitivity to inhibition by CBDP (2-O-cresyl 4H: 1::3:2-benzodioxaphosphorin-2-oxide). Arch. Toxicology. 1990; 64: 414416.
25. Evstatiev R, Gasche C. Iron sensing and signaling. Gut. 2012; 61(6): 933-953.
26. Murphy CJ, Oudit GY. Iron-overload cardiomyopathy: pathophysiology, diagnosis and treatment. J. Card. Fail. 2010; 16(11): 888-900.
27. Pennell DJ, Udelson JE, Arai AE. et al. American Heart Association Committee on Heart Failure and Transplantation of the Council on Cardiovascular Radiology and Imaging. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation. 2013; 128(3): 281-308.
28. Klip IT, Comin-Colet J, Voors AA. et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am. Heart J. 2013; 165: 575-582 e573.
29. Anker SD, Comin-Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J. et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N. Engl. J. Med. 2009; 361: 2436-2448.
30. Ponikowski P, van Veldhuisen DJ, Comin-Colet J. et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015; 36(11): 657-668.
31. Stangl GI, KirchgessnerM. Nickel deficiency alters liver lipid metabolism in rats. Journal of Nutrition. 1996; 126: 2466-2473.
32. Shriner RL, Hermann CKF, Morril TC, Curtin D, Fuson RC. The Systematic identification of organic compounds. John Wiley and Sons, Inc. (8th edition); 2004: Pp. 194-227.
33. Fessenden RJ, Fessenden JS. Organic chemistry (3 ed.). Brooks/Cole Publishing Company, Monterey, California; 1986.
34. Sun J, Yue Y, Tang F, Guo X. Simultaneous HPTLC analysis of flavonoids in the leaves of three different species of bamboo. Journal of Planar Chromatography - Modern TLC. 2010; 23(1): 40–45.
35. Pal D, Mishra P, Sachan N, Ghosh AK. Biological activities and medicinal properties of Cajanus cajan (L) Millsp. Journal of Advanced Pharmaceutical Technology and Research. 2011; 2(4): 207–214.
36. Lee SG, Ko H, Choi, EJ, Oh DR, Bae D, Choi C. Isolation and analytical method validation for phytochemicals of aqueous leaf extracts from Vaccinium bracteatum Thunb in Korea. Processes. 2021; 99(11): 1868.
37. Liu Z, Wang L, Li W, Huang Y, Xu ZC. Determination of orientin and vitexin in Trollius chinesis preparation by HPLC. China Journal of Chinese Materia Medica. 2004; 29(11): 1049-1051.
38. Wu LZ, Wu HF, Xu XD, Yang JS. Two new flavone C-glycosides from Trollius ledebouri. Chemical and Pharamceutical Bulletin. 2011; 59(11): 1393-1395.
39. Sar FB, Sarr M, Diallo MSY, Ngomi S, Gueye L, Samb A, Andriantsitohaina R, Lobstein A. Attenuation of allergic airways inflammation by an extract of Hymenocardia acida. Journal of Physiology and Pathophysiology. 2014; 5(3): 15-24.
40. Lam KY, Ling APK, Koh RY, Wong YP, Say YH. Cardioprotective effect of Orientin. Review on Medicinal Properties of Orientin. Adv. Pharmacol. Sci. 2016; 4104595:1-9.
41. Kalaiyarasu T, Karthi N, Kandakumar S, Mariyappan P, Mydhili G, Vanitha S, Manju, V. Orientin mitigates 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant and biotransforming bacterial enzyme alteration in experimental rats. Journal of Cancer Research and Therapeutics. 2018; 14(6): 1379-1388.
42. Ganeshpurkar A, Saluja Ak. The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal. 2017; 25(2): 149-164.
43. Park SE, Sapkota K, Choi IH, Kim MK, Kim YH, Kim KM, Kim KJ, Oh HN, Kim SJ, Kim S. Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p53 MAPK signaling. Neurochemical Research. 2014; 39(4): 707-718.
44. Yu XL, Li YN, Zhang H, Su YJ, Zhou WW, Zhang ZP, Wang SW, Xu PX, Wang YJ, Liu R.T. Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress. Food and Function. 2015; 6(10): 3296-3306.
45. Tuenter E, Bijttebier S, Foubert K, Breynaert A, Apers S, Hermans N, Pieters L. In Vitro and In Vivo Study of the Gastrointestinal Absorption and Metabolisation of Hymenocardine, a Cyclopeptide Alkaloid. Planta Med.2017; 83(09): 790-796.
46. Akinmoladun A, Olaleye MT, Komolafe K, Adetuyi A, Akindahunsi AA. Effects of homopterocarpin, an isoflavonoid from Pterocarpus erinaceus, on indices of liver injury and oxidative stress in acetaminophen-provoked hepatotoxicity. J Basic Clin Physiol Pharmacol. 2015; 26(6): 555-62.
47. Mpiana PT, Mudogo V, Kabangu YF, Tshibangu DST, Ngbolua KN, Atibu EK, Mangwala KP, Mbala MB, Makelele LK, Bokota MT. Antisickling activity and thermostability of anthocyanins extract from a Congolese plant, Hymenocardia acida (Hymenocardiaceae). International Journal of Pharmacology. 2009; 5(1):65-70.
48. Shimbe RY, Tor-Anyiin TA, Khan ME, Anyam, JV. B-Sitosterol from Hymenocardia acida root extract and its antimicrobial activity. Journal of chemical society of Nigeria. 2016; 41(1): 76-81.954.
49. Danladi S, Bisallah N, Lawal NB, Muhammad A, Alhassan AM. A Review on the phytochemical and Pharmacological activities of Hymenocardia acida Tul (Phyllantaceae). JCBR. 2021; 1(3): 1-13.
50. Adeleke GE, Adaramoye O.A. Modulatory role of Betulinic acid in N- Nitrosodimethylamine-induced hepatorenal toxicity in male rats. Hum and Expert Toxicol. 2016: 1-10.
51. Adeleke GE, Adaramoye OA. Betulinic acid protects against N-Nitrosodimethylamine-induced redox imbalance in testes of rats. Redox Report (Tailor and Francis group). 2017; 22(6):556-562.
52. Chen X, Guo C, Kong J. Oxidative stress in degenerative diseases. Neural in Regeneration Research. 2012; 7(5): 376-385.
53. Wadley AJ, van Zanten VJJ, Aldred S. The interactions of oxidative stress and inflammation with vascular dysfunction in ageing: the vascular health triad. Age (Dordr). 2013; 35: 705 – 718.
54. Phaniendra DBJ, Periyasamy L. Freeradicals: properties, sources, targets, and their implicationin various diseases. Ind. J. of Clin. Biochem. 2015; 30(1): 11-26.
55. Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J. Cell Biol. 2018; 217: 2291- 2298.
56. Anasaki Y, Ogwa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radical Biology and Medicine. 1994; 16(6): 845-850.
57. Al Enazi MM. Protective effects of combined therapy of rutin with silymarin on experimentally- induced diabetic neuropathy in rats. Pharmacology and Pharmacy. 2014 5(9): 876-889.
58. Kandemir FM, Ozkaraca M, Yildirim BA, Hanedan B, Kirbas A, Kilic K. Rutin attenuates gentamycin-induced renal damage by reducing oxidative stress, inflammation, apoptosis and autophagy in rats. Renal failure. 2015; 37(3): 518-525.
59. Oncu M, Gultekin F, Karaoz E, Altuntas T, Delibas N. Klorprifos Etil tarafindan olusturulan oksidatif hasarin sucan karacigerine etkileri. Turkiye Klinikleri. Journal of Medical Sciences. 2002; 22(1): 50-55.
60. Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M. Glutathione peroxidase family - an evolutionary overview. FEBS J. 2008; 275: 3959-3970.
61. Miranda-Diaz AG, Pazarin-Villasenor L, Yanowsky-Escatell FG, Andrade-Sierra J. Oxidative stress in diabetic nephropathy with early chronic kidney disease. Journal Diabetes Research, 2016: 7047238.
62. Soreq H, Seidman S. Acetylcholinesterase – new roles for an old actor. Nat. Rev. Neurosci. 2001; 2: 294-302.
63. Revuelta L, Piulachs MD, Bellés X, Castañera P., Ortego F, Díaz-Ruíz JR, Hernández-Crespo P, Tenllado F. RNAi of ace1 and ace2 in Blattella germanica reveals their differential contribution to acetylcholinesterase activity and sensitivity to insecticides. Insect Biochem Mol Biol.2009; 39: 913–919.
64. Lu Y, Park Y, Gao X, Zhang X, Yao J, Pang YP, Jiang H, Zhu KY. Cholinergic and non-cholinergic functions of two acetylcholinesterase genes revealed by gene-silencing in Tribolium castaneum. Sci Rep. 2012; 2:1–7.
65. Mondal P, Gupta V, Das G, Pradhan K, Khan J, Gharai PK, Ghosh, S. Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection. ACS Chem. Neurosci. 2018; 9: 2838–2848.
66. Ademosun AO, Oboh G, Bello F, Ayeni PO. Antioxidative properties and effect of quercetin and its glycosylated form (Rutin) on acetylcholinesterase and butyrylcholinesterase acticities,. J. Evid. Based Complementary Altern. Med. 2016; 21(4): NP11-17.
67. Holmes RS, Wright MW, Laulederkind SJF, Cox LA, Hosokawa M, Imai T, Ishibashi S, Lehner R, Miyazaki M, Perkins EJ, Potter PM, Redinbo MR, Robert J, Satoh T, Yamashita T, Yan B, Yokoi T, Zechner R, Maltais LJ. Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins. Mammalian Genome. 2010; 21 (9-10): 427-441
68. Laizure SC, Herring V, Hu Z, Witbrodt K, Parker RB. The Role of Human Carboxylesterases in Drug Metabolism: Have We Overlooked Their Importance? Pharmacotherapy. 2013; 33(2): 210-222.
69. Merali Z, Ross S, Pare G. The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug metabolism and drug interactions, 2014; 29(3): 143-151.
70. Crow JA, Middleton BL, Borazjani A, Hatfield MJ, Potter PM, Ross MK.Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochimica Et Biophysica Acta- Molecular and Cell Biology of Lipids. 2008; 1781(10): 643-654.
71. Kobayashi Y, Fukami T, Shimizu M, Nakajima M, Yokoi T. Contributions of Arylacetamide Deacetylase and Carboxylesterase 2 to Flutamide Hydrolysis in Human Liver. Drug Metabolism and Disposition. 2012; 40 (6): 1080-1084.
72. Zoua LW, Jina Q, Wanga DD, Qiana QK, Haoc DC, Gea GB, Yanga L. Carboxylesterase Inhibitors: An Update. Current Medicinal Chemistry. 2018; 25: 1-24
2. Tuenter E, Exarchou V, Baldѐ A, Cos P, Maes L, Apers S, Pieters L. Cyclopeptide alkaloids from Hymenocardia acida. Journal of natural products. 2016; 79(7): 1746-1751.
3. Keay RWJ. Trees of Nigeria. Clarendon Press Oxford, New York; 1989: 179-181.
4. Bum EN, Taiwe GS, Moto FCO, Ngoupaye GT, Vougat RRN, Sakoue VD, Gwa C, Ayissi ER., Dong C, Rakotonirina A, Rakotonirina SV. Antiepileptic medicinal plants used in traditional medicine to treat epilepsy. "Clinical and Genetic Aspects of Epilepsy", Zaid 4, Afawi (Ed.); 2011: 175-192.
5. Ibrahim H, Sani FS, Danladi BH, Ahmadu AA. Phytochemical and antisickling studies of the leaves of Hymenocardia acida Tul (Euphorbiaceae). Pakistan Journal of Biological Sciences. 2007; 10(5): 788-791s
6. Tor-Anyiin TA, Shimbe RY, Anyam JV. Phytochemical and medicinal activities of Hymenocardia acida Tul (Euphorbiaceae): A review. J.Nat. Prod.Plant Resour. 2013; 3: 11-16.
7. Ajao AA, Alimi AA, Olatunji OA, Balogun O.F, Saheed AS.. A synopsis of antipsychotic medicinal plants in Nigeria. Transactions of the Royal Society of South Africa. 2017; DOI: 10.1080/0035919X.2017.1386138
8. Orwa C, Mutua A, Kindt R, Jamnadass R, Anthony S. Agroforestree Database: A tree reference and selection guide version 4.0; 2009: (http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp)
9. Udeozo IP, Ejikeme CM, Eboatu AN, Kelle HI. An assay of some thermal characteristics, chemical and phytochemical constituents of Hymenocardia acida Timber. J.Appl.Sci. Environ.Manage. 2017; 21(5): 951-935.
10. Sofidiya MO, Odukoya OA, Afolayan AJ, Familoni OB.. Phenolic contents, antioxidant and antibacterial activities of Hymenocardia acida. Natural Product Research. 2009; 23(2): 168-177.
11. Olotu NP, Ibrahim H, Ilyas N, Ajima U, Olotu AI Phytochemical screening and analgesic studies of the root bark of Hymenocardia acida, Tul (Euphorbiaceae). International Journal of Drug Development and Research. 2011; 3(1): 219-223.
12. Oshomoh EO, Ndu M. (2013). Antimicrobialand antifungal activities of ethanol and aqueous cude extracts of Hymenocardia acida stem against selected dental caries pathogens. Pharmaconosy Journal.2013; 4(29): 55-60.
13. Adedokun O, Ntungwe EN, Viegas C, Ayinde BA, Barboni L, Maggi F, Saraiva, Rijo P, Fonte P. Enhanced anticancer activity of Hymenocardia acida stem bark extract loaded into PLGA nanoparticles. Pharmaceuticals (Basel). 2022; 15(5): 535.
14. Skovronsky D M, Lee VM.Y, Trojanowski JQ. Neurodegenerative diseases:new concepts of pathogenesis and their therapeutic implications. Annual Review of Pathology. 2006. 1, 151–170.
15. Usman AM, Danjuma NM, Ya’u J, Ahmad MM, Alhassan Z, Abubakar YM.Antidiarrhoeal potential of methanol extract of Hymenocardia acida Tul (Euphorbiaceae) in laboratory animals. Bulletin of the National Research Center. 2021; 45(1):118.
16. Koffi S, Soro TY, Begbin KE, Abizi G, Ahebe ME, Kouadio KJ, Zougrou NE, Kouakou, K. Acute and subchronic toxicities of the aqueous extract of the Hymenocardia acida (Euphorbiaceae) roots in rodents. European Journal of Medicinal Plants. 2022; 33(1): 39-48.
17. Lowry OH, Rosbrough NJ, Farr AL, et al. Protein measurement with the Folin- phenol reagent. J. Biol. Chem. 1951; 193: 265-275.
18. Mistra HP, Fridovich I. The generation of superoxide radical during the autoxidation of ferredoxin. J. Biol. Chem. 1979; 246: 6886-6890.
19. Aebi H. (1984). Catalase in-vitro. In: Packer L. Editor. Methods in Enzymology. Academic Press; pp . 121-126.
20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by Thiobarbituric acid reaction. Analytical Biochemistry. 1979; 95: 351-358.
21. Paglia, D.E. & Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab Clin. Med. 1967; 70:158-169.
22. Ellman G, Courtney KD, Andres V. Jr., Featherstone Y. A new and rapicolorimetric determination of acetylcholinesterase activity. Biohem. Pharmacol. 1961; 7: 88-95.
23. Nachmanshon D, Neumann E. In: Chemical and Molecular Basis of Nerve activity, Academic Press, New York. 1975.
24. Clement JG, Erhardt N. Serum Carboxylesterase activity in various strains of rats: sensitivity to inhibition by CBDP (2-O-cresyl 4H: 1::3:2-benzodioxaphosphorin-2-oxide). Arch. Toxicology. 1990; 64: 414416.
25. Evstatiev R, Gasche C. Iron sensing and signaling. Gut. 2012; 61(6): 933-953.
26. Murphy CJ, Oudit GY. Iron-overload cardiomyopathy: pathophysiology, diagnosis and treatment. J. Card. Fail. 2010; 16(11): 888-900.
27. Pennell DJ, Udelson JE, Arai AE. et al. American Heart Association Committee on Heart Failure and Transplantation of the Council on Cardiovascular Radiology and Imaging. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation. 2013; 128(3): 281-308.
28. Klip IT, Comin-Colet J, Voors AA. et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am. Heart J. 2013; 165: 575-582 e573.
29. Anker SD, Comin-Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J. et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N. Engl. J. Med. 2009; 361: 2436-2448.
30. Ponikowski P, van Veldhuisen DJ, Comin-Colet J. et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015; 36(11): 657-668.
31. Stangl GI, KirchgessnerM. Nickel deficiency alters liver lipid metabolism in rats. Journal of Nutrition. 1996; 126: 2466-2473.
32. Shriner RL, Hermann CKF, Morril TC, Curtin D, Fuson RC. The Systematic identification of organic compounds. John Wiley and Sons, Inc. (8th edition); 2004: Pp. 194-227.
33. Fessenden RJ, Fessenden JS. Organic chemistry (3 ed.). Brooks/Cole Publishing Company, Monterey, California; 1986.
34. Sun J, Yue Y, Tang F, Guo X. Simultaneous HPTLC analysis of flavonoids in the leaves of three different species of bamboo. Journal of Planar Chromatography - Modern TLC. 2010; 23(1): 40–45.
35. Pal D, Mishra P, Sachan N, Ghosh AK. Biological activities and medicinal properties of Cajanus cajan (L) Millsp. Journal of Advanced Pharmaceutical Technology and Research. 2011; 2(4): 207–214.
36. Lee SG, Ko H, Choi, EJ, Oh DR, Bae D, Choi C. Isolation and analytical method validation for phytochemicals of aqueous leaf extracts from Vaccinium bracteatum Thunb in Korea. Processes. 2021; 99(11): 1868.
37. Liu Z, Wang L, Li W, Huang Y, Xu ZC. Determination of orientin and vitexin in Trollius chinesis preparation by HPLC. China Journal of Chinese Materia Medica. 2004; 29(11): 1049-1051.
38. Wu LZ, Wu HF, Xu XD, Yang JS. Two new flavone C-glycosides from Trollius ledebouri. Chemical and Pharamceutical Bulletin. 2011; 59(11): 1393-1395.
39. Sar FB, Sarr M, Diallo MSY, Ngomi S, Gueye L, Samb A, Andriantsitohaina R, Lobstein A. Attenuation of allergic airways inflammation by an extract of Hymenocardia acida. Journal of Physiology and Pathophysiology. 2014; 5(3): 15-24.
40. Lam KY, Ling APK, Koh RY, Wong YP, Say YH. Cardioprotective effect of Orientin. Review on Medicinal Properties of Orientin. Adv. Pharmacol. Sci. 2016; 4104595:1-9.
41. Kalaiyarasu T, Karthi N, Kandakumar S, Mariyappan P, Mydhili G, Vanitha S, Manju, V. Orientin mitigates 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant and biotransforming bacterial enzyme alteration in experimental rats. Journal of Cancer Research and Therapeutics. 2018; 14(6): 1379-1388.
42. Ganeshpurkar A, Saluja Ak. The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal. 2017; 25(2): 149-164.
43. Park SE, Sapkota K, Choi IH, Kim MK, Kim YH, Kim KM, Kim KJ, Oh HN, Kim SJ, Kim S. Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p53 MAPK signaling. Neurochemical Research. 2014; 39(4): 707-718.
44. Yu XL, Li YN, Zhang H, Su YJ, Zhou WW, Zhang ZP, Wang SW, Xu PX, Wang YJ, Liu R.T. Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress. Food and Function. 2015; 6(10): 3296-3306.
45. Tuenter E, Bijttebier S, Foubert K, Breynaert A, Apers S, Hermans N, Pieters L. In Vitro and In Vivo Study of the Gastrointestinal Absorption and Metabolisation of Hymenocardine, a Cyclopeptide Alkaloid. Planta Med.2017; 83(09): 790-796.
46. Akinmoladun A, Olaleye MT, Komolafe K, Adetuyi A, Akindahunsi AA. Effects of homopterocarpin, an isoflavonoid from Pterocarpus erinaceus, on indices of liver injury and oxidative stress in acetaminophen-provoked hepatotoxicity. J Basic Clin Physiol Pharmacol. 2015; 26(6): 555-62.
47. Mpiana PT, Mudogo V, Kabangu YF, Tshibangu DST, Ngbolua KN, Atibu EK, Mangwala KP, Mbala MB, Makelele LK, Bokota MT. Antisickling activity and thermostability of anthocyanins extract from a Congolese plant, Hymenocardia acida (Hymenocardiaceae). International Journal of Pharmacology. 2009; 5(1):65-70.
48. Shimbe RY, Tor-Anyiin TA, Khan ME, Anyam, JV. B-Sitosterol from Hymenocardia acida root extract and its antimicrobial activity. Journal of chemical society of Nigeria. 2016; 41(1): 76-81.954.
49. Danladi S, Bisallah N, Lawal NB, Muhammad A, Alhassan AM. A Review on the phytochemical and Pharmacological activities of Hymenocardia acida Tul (Phyllantaceae). JCBR. 2021; 1(3): 1-13.
50. Adeleke GE, Adaramoye O.A. Modulatory role of Betulinic acid in N- Nitrosodimethylamine-induced hepatorenal toxicity in male rats. Hum and Expert Toxicol. 2016: 1-10.
51. Adeleke GE, Adaramoye OA. Betulinic acid protects against N-Nitrosodimethylamine-induced redox imbalance in testes of rats. Redox Report (Tailor and Francis group). 2017; 22(6):556-562.
52. Chen X, Guo C, Kong J. Oxidative stress in degenerative diseases. Neural in Regeneration Research. 2012; 7(5): 376-385.
53. Wadley AJ, van Zanten VJJ, Aldred S. The interactions of oxidative stress and inflammation with vascular dysfunction in ageing: the vascular health triad. Age (Dordr). 2013; 35: 705 – 718.
54. Phaniendra DBJ, Periyasamy L. Freeradicals: properties, sources, targets, and their implicationin various diseases. Ind. J. of Clin. Biochem. 2015; 30(1): 11-26.
55. Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J. Cell Biol. 2018; 217: 2291- 2298.
56. Anasaki Y, Ogwa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radical Biology and Medicine. 1994; 16(6): 845-850.
57. Al Enazi MM. Protective effects of combined therapy of rutin with silymarin on experimentally- induced diabetic neuropathy in rats. Pharmacology and Pharmacy. 2014 5(9): 876-889.
58. Kandemir FM, Ozkaraca M, Yildirim BA, Hanedan B, Kirbas A, Kilic K. Rutin attenuates gentamycin-induced renal damage by reducing oxidative stress, inflammation, apoptosis and autophagy in rats. Renal failure. 2015; 37(3): 518-525.
59. Oncu M, Gultekin F, Karaoz E, Altuntas T, Delibas N. Klorprifos Etil tarafindan olusturulan oksidatif hasarin sucan karacigerine etkileri. Turkiye Klinikleri. Journal of Medical Sciences. 2002; 22(1): 50-55.
60. Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M. Glutathione peroxidase family - an evolutionary overview. FEBS J. 2008; 275: 3959-3970.
61. Miranda-Diaz AG, Pazarin-Villasenor L, Yanowsky-Escatell FG, Andrade-Sierra J. Oxidative stress in diabetic nephropathy with early chronic kidney disease. Journal Diabetes Research, 2016: 7047238.
62. Soreq H, Seidman S. Acetylcholinesterase – new roles for an old actor. Nat. Rev. Neurosci. 2001; 2: 294-302.
63. Revuelta L, Piulachs MD, Bellés X, Castañera P., Ortego F, Díaz-Ruíz JR, Hernández-Crespo P, Tenllado F. RNAi of ace1 and ace2 in Blattella germanica reveals their differential contribution to acetylcholinesterase activity and sensitivity to insecticides. Insect Biochem Mol Biol.2009; 39: 913–919.
64. Lu Y, Park Y, Gao X, Zhang X, Yao J, Pang YP, Jiang H, Zhu KY. Cholinergic and non-cholinergic functions of two acetylcholinesterase genes revealed by gene-silencing in Tribolium castaneum. Sci Rep. 2012; 2:1–7.
65. Mondal P, Gupta V, Das G, Pradhan K, Khan J, Gharai PK, Ghosh, S. Peptide-Based Acetylcholinesterase Inhibitor Crosses the Blood-Brain Barrier and Promotes Neuroprotection. ACS Chem. Neurosci. 2018; 9: 2838–2848.
66. Ademosun AO, Oboh G, Bello F, Ayeni PO. Antioxidative properties and effect of quercetin and its glycosylated form (Rutin) on acetylcholinesterase and butyrylcholinesterase acticities,. J. Evid. Based Complementary Altern. Med. 2016; 21(4): NP11-17.
67. Holmes RS, Wright MW, Laulederkind SJF, Cox LA, Hosokawa M, Imai T, Ishibashi S, Lehner R, Miyazaki M, Perkins EJ, Potter PM, Redinbo MR, Robert J, Satoh T, Yamashita T, Yan B, Yokoi T, Zechner R, Maltais LJ. Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins. Mammalian Genome. 2010; 21 (9-10): 427-441
68. Laizure SC, Herring V, Hu Z, Witbrodt K, Parker RB. The Role of Human Carboxylesterases in Drug Metabolism: Have We Overlooked Their Importance? Pharmacotherapy. 2013; 33(2): 210-222.
69. Merali Z, Ross S, Pare G. The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug metabolism and drug interactions, 2014; 29(3): 143-151.
70. Crow JA, Middleton BL, Borazjani A, Hatfield MJ, Potter PM, Ross MK.Inhibition of carboxylesterase 1 is associated with cholesteryl ester retention in human THP-1 monocyte/macrophages. Biochimica Et Biophysica Acta- Molecular and Cell Biology of Lipids. 2008; 1781(10): 643-654.
71. Kobayashi Y, Fukami T, Shimizu M, Nakajima M, Yokoi T. Contributions of Arylacetamide Deacetylase and Carboxylesterase 2 to Flutamide Hydrolysis in Human Liver. Drug Metabolism and Disposition. 2012; 40 (6): 1080-1084.
72. Zoua LW, Jina Q, Wanga DD, Qiana QK, Haoc DC, Gea GB, Yanga L. Carboxylesterase Inhibitors: An Update. Current Medicinal Chemistry. 2018; 25: 1-24