Abstract
The current study aims to identify the phytochemical constituents of Guilandina bonduc L. aqueous seed extract to evaluate their antioxidant potential through in vitro and in vivo toxicity models in female wistar albino rats. Phytochemical screening and in vitro antioxidant activities of G. bonduc aqueous seed extract (GBASE), were evaluated using 2, 2-diphenyl-1-picrylhydrazyl radical (DPPH) and hydroxyl radical along with the estimation of total phenolic and flavonoid contents. Three different doses (100, 200 and 300 mg/kg) were used for the proposed study to evaluate the efficacy against Letrozole induced PCOS in rats. Renal toxicity and hepatotoxicity were evaluated by quantifying the serum levels of Kidney Function Test (KFT) and Liver Function Test (LFT). Histopathologic changes of kidney and liver were also evaluated. In vitro studies revealed that G. bonduc seed extracts strongly scavenging the DPPH with an IC50 value of 276.95 μg/ml and hydroxyl scavenging radical with an IC50 value of 296.34 μg/ml. Our phytochemical evaluation reveals the presence of phenolic compounds (2.834 ± 0.09 mg of gallic acid equivalent/g dried extract) and flavonoids (0.905 ± 0.01 mg of catechol equivalents/g dried extract) content. In vivo activity was evaluated in rats as an PCOS model, when compared to control and vehicle group, a normal arrangement of the hepatocyte sheath and central vein was observed. The letrozole induced by PCOS groups also exhibited no remarkable changes in hepatic histology but a minor irregularity in hepatocyte arrangement was observed. In the treatment group, the histopathological evaluation of the kidneys showed a prevalent control-like morphology with a sufficient mobile structure and a standard atrophy free glomerulus. Moreover, the treated animals showed significant changes in their liver and kidney weights. The biochemical evaluation shows elevated levels of serum AST and it indicates harm to the liver due to necrosis, inflammation, or bruising, indicating ill health. The aqueous seed extracts of 200 mg/kg exhibited a significant response compare favorably to that of the standard drug treated group (PCOS + Pioglitazone) which also had substantially reduced KFT and LFT levels in their serum when compared to the PCOS induced group. Herbal medications strengthen the immune system and help regulate the menstrual cycle. The results suggest that G. bonduc L. could be considered as an important candidate for its possible role in the treatment of PCOS and for the future drug discoveries.
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References
Ainsworth EA, Gillespie KM (2007) Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin–Ciocalteu reagent. Nat Protoc 2(4):875–877
Alahmadi AA, Alahmadi BA, Wahman LF, El-Shitany NA (2021) Chamomile flower extract ameliorates biochemical and histological kidney dysfunction associated with polycystic ovary syndrome. Saudi Pharm J 11:6158–6166
Al-Amoudi WM (2012) Biochemical and histological effects of clomiphene citrate on liver of female albino rat. J Am Sci 8(5):646–651
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
Amini L, Tehranian N, Movahedin M, Ramezani Tehrani F, Ziaee S (2015) Antioxidants and management of polycystic ovary syndrome in Iran: a systematic review of clinical trials. Iran J Reprod Med 13:1–8
Ansil PN, Nitha A, Prabha SP, Wills PJ, Jazaira V, Latha MS (2011) Protective effect of Amorphophallus campanulatus (Roxb.) Blume.tuber against thioacetamide induced oxidative stress in rats. Asian Pac J Trop Med 4:870–877
Ayala A, Munoz MF, Arguelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360–438
Aydin M, Oktar S, Ozkan OV, Alcin E, Ozturk OH, Nacar A (2011) Letrozole induces hepatotoxicity without causing oxidative stress the protective effect of melatonin. Gynecol Endocrinol 27:209–215
Ayyadurai T, Thiruppathi SK, Shanmugam A, Diana RKB (2021) Effect of aqueous seed extract of Caesalpinia bonduc (L.) Roxb., on hormonal assay and lipid profile in induced Polycystic Ovary Syndrome albino female rats. Int J Bot Stud 6(3):139–146
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, Androgen Excess S (2006) Positions statement criteria for defining polycystic ovary syndrome as a predominantly hyper androgenic syndrome an Androgen Excess Society guideline. J Clin Endo Crinol Metab 91:4237–4245
Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (2005) GenBank. Nucleic Acids Res 33:34–38
Billah MM, Islam R, Khatun H, Parvin S, Islam E, Islam SA, Mia AA (2013) Antibacterial, antidiarrhoeal and cytotoxic activities of methanol extract and its fractions of Caesalpinia bonducella (L.) Roxb leaves. BMC Complement Altern Med 13:101
Brinda P, Sasikala P, Purushothaman K (1981) Pharmacognostic studies on Merugankizhangu. Bull Med Ethno Bot Res 3:84–96
Chatgilialoglu C, Neill P (2001) Free radicals associated with DNA damage. Exp Gerontol 36:1459–1471
Chauhan P, Sharma H, Kumar U, Mayachari A, Sangli G, Singh S (2020) Protective effects of Glycyrrhizaglabra supplementation against methotrexate-induced hepato-renal damage in rats An experimental approach. J Ethno Pharmacol 263:113–209
Chryssanthi DG, Dedes PG, Karamanos NK, Lamari CP, FN, (2011) Crocetin inhibits invasiveness of MDA-MB-231 breast cancer cells via downregulation of matrix metalloproteinases. Planta Med 77:146–151
Da Silva RC, Miranda WL, Chacra AR, Dib SA (2007) Insulin resistance, beta-cell function, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus. J Diabetes Complicat 21:84–92
Deepika ML, Nalini S, Maruthi G, Ramchander V, Ranjith K, Latha KP, Rani VU, Jahan P (2014) Analysis of oxidative stress status through MN test and serum MDA levels in PCOS women. Pak J BiolSci 17:574–577
Farzadi L, Khaki A, Ghasemzadeh A, Asl Z, Ahamadi S, Ashteani HA (2013) Effect of Allium Cepa seeds ethanolic extract, on Serum total antioxidant in experimental induced poly cystic ovarian (PCO) rats. Life Sci 10:97–102
Femi-olabisi FJ, Faokunla O, Agboola AO, Olorunyolemi IM (2020) Biochemical and toxicological evaluations of aqueous extract of Parquetina nigrescens (Afzel.) leaves on mifepristone-induced polycystic ovarian syndrome in rats. J Drug Deliv Ther 10(2-s):94–101
Ferreira ICFR, Baptista P, Vilas-Boas M, Barros L (2007) Free-radical scavenging capacity and reducing power of wild edible mushrooms from northeast Portugal Individual cap and stipe activity. Food Chem 100:1511–1516
Flora SJ (2007) Role of free radicals and antioxidants in health and disease. Cell Mol Biol (noisy-Le-Grand) 53:1–2
Fujii J, Iuchi Y, Okada F (2005) Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol 3:43
Gaur RL, Sahoo MK, Dixit S, Fatma N, Rastogi S, Kulshreshtha DK, Chatterjee RK, Murthy PK (2008) Antifilarial activity of Caesalpinia bonducella against experimental filarial infections. Indian J Med Res 128:65–70
Gautam A, Jhade D, Ahirwar D, Sujane M, Sharma GN (2010) Pharmacognostic evaluation of toonaciliata bark. J Adv Pharm Technol Res 1:216–220
Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7:219–231
Gozukara IO, Gozukara KH, Kucur SK, Karakilic EU, Keskin H, Akdeniz D, Aksoy AN, Carlioglu A (2015) Association of glomerular filtration rate with inflammation in polycystic ovary syndrome. Int J Fertil Steril 9:176–182
Gupta M, Mazumder UK, Kumar RS (2003) Hepatoprotective effect and antioxidant role of Caesalpinia bonducella on paracetamol-induced hepatic damage in rats. Nat Prod Sci 9:186–191
Gupta M, Mazumder UK, Sambath Kumar R, Sivakumar T, Gomathi P, Rajeshwar Y (2008) Antioxidant defense system induced by a methanol extract of Caesalpinia bonducella in RAT LIVER. Pharm Biol 43:411–419
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Hajibabaei M, Singer GA, Hebert PD, Hickey DA (2007) DNA barcoding how it complements taxonomy, molecular phylogenetics and population genetics. Trends Genet 23:167–172
Hall T (1999) Bio Edit a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98
Hassan N, Rashad M, Elleithy E, Sabry Z, Ali G, Elmosalamy S (2022) L- Carnitine alleviates hepatic and renal mitochondrial-dependent apoptotic progression induced by letrozole in female rats through modulation of Nrf-2, Cyt c and CASP-3 signaling. Drug Chem Toxicol 17:1–2
Iqbal E, Salim KA, Lim LBL (2015) Phytochemical screening total phenolics and antioxidant activities of bark and leaf extracts of Goniothalamus velutinus (Airy Shaw) from Brunei Darussalam. J King Saud Univ Sci 27:224–232
Jang M, Lee MJ, Lee JM, Bae CS, Kim SH, Ryu JH, Cho IH (2014) Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats. PLoS ONE 9:87623
Jaradat N, Hussen F, Al Ali A, Alniss H, Dweikat M (2015) Phytoconstituents free radical scavenging potential total phenols and total flavonoids assessments for violet horned poppy from Jerusalem mountains. J Mater Environ Sci 6:2958–2966
Kafali H, Iriadam M, Ozardali I, Demir N (2004) Letrozole-induced polycystic ovaries in the rat a new model for cystic ovarian disease. Arch Med Res 35:103–108
Karuppanapandian T, Moon JC, Kim C, Manoharan K, Kim W (2011) Reactive oxygen species in plants their generation signal transduction and scavenging mechanisms. Aust J Crop Sci 5:709–725
Liu F, Ng TB (2000) Antioxidative and free radical scavenging activities of selected medicinal herbs. Life Sci 66:725–735
Liu J, Zhang D (2012) The role of oxidative stress in the pathogenesis of polycystic ovary syndrome. Sichuan Da XueXueBao Yi Xue Ban 43:187–190
Liu T, Li X, Ning Z, Qi S, Gao H (2021) Two new cassane-type diterpenoids from the seed kernels of Caesalpinia bonduc (Linn.) Roxb, their anti-inflammatory activity. Nat Prod Res 1–8
Lobo RA, Carmina E (2000) The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med 132:989–993
Loew D, Kaszkin M (2002) Approaching the problem of bioequivalence of herbal medicinal products. Phytother Res 16:705–711
Manneras L, Cajander S, Holmang A, Seleskovic Z, Lystig T, Lonn M, Stener-Victorin E (2007) A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 148:3781–3791
Marcondes F, Bianchi F, Tanno A (2002) Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 62:609–614
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Meir S, Kanner J, Akiri BS (2002) Determination and involvement of aqueous reducing compounds in oxidative defense systems of various senescing leaves. J Agric Food Chem 43:1813–1819
Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175
Mohan PK, Adarsh Krishna TP, Senthil Kumar T, Ranjitha Kumari BD (2021) Pharmaco-chemical profiling of Desmodium gangeticum (L.) DC. with special reference to soil chemistry. Future J Pharm Sci 7(1):1–11
Mouffouk C, Hambaba L, Haba H, Mouffouk S, Bensouici C, Hachemi M, Khadraoui H (2018) Acute toxicity and in vivo anti-inflammatory effects and in vitro antioxidant and anti-arthritic potential of Scabiosa Stellata. Orient Pharm Exp Med 18(4):335–348
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Oki T, Masuda M, Furuta S, Nishiba Y, Terahara N, Suda I (2002) Involvement of anthocyanins and other phenolic compounds in radical-scavenging activity of purple-fleshed sweet potato cultivars. J Food Sci 67:1752–1756
Ozsoy N, Can A, Yanardag R, Akev N (2008) Antioxidant activity of Smilax excelsa L. leaf extracts. Food Chem 110:571–583
Paccola C, Resende C, Stumpp T, Miraglia S, Cipriano I (2018) The rat estrous cycle revisited: a quantitative and qualitative analysis. Anim Reprod 10:677–683
Pandey S (2015) Preliminary phytochemical screening and in vitro antibacterial activity of Bauhinia variegata Linn. against human pathogens. Asian Pac J Trop Dis 5:123–129
Park JA, Park BJ, Kim AH, Park SY, Paek KY (2015) Airlift bioreactor system and nitrogen sources for biomass and antioxidant compound production from in vitro culture of Vitis flexuosa plantlets. Hortic Environ Biotechnol 56:358–365
Parthasarathy R, Nivethetha M, Brindha P (2007) Hepatoprotective activity of Caesalpinia bonducella seeds on paracetamol induced hepatotoxicity in male albino rats. Indian Drugs 44:401–404
Pasquali R, Stener-Victorin E, Yildiz BO, Duleba AJ, Hoeger Mason H, Homburg R, Hickey T, Franks S, Tapanainen JS, Balen A, Abbott DH, Diamanti-Kandarakis E, Legro RS (2011) PCOS forum research in polycystic ovary syndrome today and tomorrow. Clin Endocrinol (oxf) 74:424–433
Ramakrishnan M, Antony Ceasar S, Duraipandiyan V, Vinod KK, Kalpana K, Al-Dhabi NA, Ignacimuthu S (2016) Tracing QTLs for leaf blast resistance and agronomic performance of finger millet (Eleusine coracana (L.) Gaertn) genotypes through association mapping and in silico comparative genomics analyses. PLoS ONE 11:0159264
Rosenfield RL, Ehrmann DA (2016) The Pathogenesis of Polycystic Ovary Syndrome (PCOS) the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 37:467–520
Sabuncu T, Vural H, Harma M, Harma M (2001) Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem 34:407–413
Saghai-Maroof MA, Soliman KM, Jorgensen RA, Allard RW (1984) Ribosomal DNA spacer-length polymorphisms in barley: Mendelian inheritance, chromosomal location and population dynamics. Proc Natl Acad Sci U S A 81:8014–8018
Salisbury TB, Marcinkiewicz JL (2002) In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-penta chloro dibenzofuran reduces growth and disrupts reproductive parameters in female rats. Biol Reprod 66:1621–1626
Sambath R, Kumar K, Asok K, Venkateswara M (2010) Hepatoprotective and antioxidant effects of Caesalpinia bonducella on carbon tetrachloride-induced liver injury in rats. Int Res J Plant Sci 1:062–068
Sarkar R, Hazra B, Mandal N (2012) Hepatoprotective potential of Caesalpinia crista against iron-overload-induced liver toxicity in mice. Evid Based Complement Altern Med 2012:896341
Senthilkumar N, Badami S, Dongre SH, Bhojraj S (2008) Antioxidant and hepatoprotective activity of the methanol extract of Careyaar borea bark in Ehrlich ascites carcinoma-bearing mice. J Nat Med 62:336–339
Serra Bonvehí J, Soliva Torrentó M, Centelles Lorente E (2001) Evaluation of polyphenolic and flavonoid compounds in honeybee-collected pollen produced in Spain. J Agric Food Chem 49(4):1848–1853
Sharma US, Kumar A (2011) In vitro antioxidant activity of Rubuselli pticus fruits. J Adv Pharm Technol Res 2:47–50
Shaw LJ, BaireyMerz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, Kelsey SF, Kip KE, Cooper-Dehoff RM, Johnson BD, Vaccarino V, Reis SE, Bittner V, Hodgson TK, Rogers W, Pepine CJ (2008) Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival results from the National Institutes of Health—National Heart Lung and Blood Institute sponsored Women’s Ischemia Syndrome Evaluation. J Clin Endocrinol Metab 93:1276–1284
Shelar P, Mandavkar Y, Khedkar A, Thorat M, Raje V (2014) Review on pharmacology and phytochemistry of Caesalpinia bondu. Int J Curr Pharm 4:1309
Shukla S, Mehta A, Mehta P, Vyas SP, Shukla S, Bajpai VK (2010) Studies on anti-inflammatory, antipyretic and analgesic properties of Caesalpinia bonducella F. seed oil in experimental animal models. Food Chem Toxicol 48:61–64
Siddhuraju P, Becker K (2007) The antioxidant and free radical scavenging activities of processed cowpea (Vignaun guiculata (L.) Walp.) seed extracts. Food Chem 101:10–19
Silva BA, Ferreres F, Malva JO, Dias ACP (2005) Phytochemical and antioxidant characterization of Hypericum perforatum alcoholic extracts. Food Chem 90:157–167
Sindete M, Rharass T, Gbankoto A, Yemoa A, Ganfon H, Adjagba M, Ribou AC (2021) A comparative study of Caesalpinia bonduc (L.) Roxb. root extracts on sexual behaviour in male Wistar rats. Andrologia 53(7):14072
Singh V, Raghav PK (2012) Review on pharmacological properties of Caesalpinia bonduc L. Int J Med Arom Plants 2:514–530
Sinha D, Roy S, Roy M (2010) Antioxidant potential of tea reduces arsenite induced oxidative stress in Swiss albino mice. Food Chem Toxicol 48:1032–1039
Siriwardhana N, Lee KW, Jeon YJ, Kim SH, Haw JW (2016) Antioxidant activity of Hizikia fusiformis on reactive oxygen species scavenging and lipid peroxidation inhibition. Food Sci Technol Int 9:339–346
Soares JR, Dinis TC, Cunha AP, Almeida LM (1997) Antioxidant activities of some extracts of Thymus zygis. Free Radic Res 26:469–478
Srivastava RP, Saxena G, Singh L, Singh A, Verma PC, Kaur G (2022) Interspecific and intraspecific analysis of Selinum spp. collected from Indian Himalayas using DNA barcoding. J Genet Eng Biotechnol 20(1):1–12
Sun T, Powers JR, Tang J (2007) Evaluation of the antioxidant activity of asparagus, broccoli and their juices. Food Chem 105:101–106
Sundararajan B, Mahendran G, Thamaraiselvi R, Kumari BDR (2016) Biological activities of synthesized silver nanoparticles from Cardiospermum halicacabum L. B. Mater Sci 39:423–431
Suriyakala U, Gayathiri R, Sankar Ganesh D, Kokilavani P, Sukirtha R, Ramachandran R, Kamalakkannan S, Achiraman S (2016) Modulating role of pheromonal cues from oestrus-specific urine on 3-methylcholanthrene-induced male reproductive toxicity. Andrologia 48:745–753
Teede H, Deeks A, Moran L (2010) Polycystic ovary syndrome a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 8:41
Thapa BR, Walia A (2007) Liver function tests and their interpretation. Indian J Pediatr 74:663–671
Thirumurugan A, Kumar TS, Kumari BR (2020) Influence of plant growth regulators on plant regeneration from epicotyl and hypocotyl explants of Caesalpinia bonduc (L.) Roxb—an ethnomedical plant. J Appl Hortic 22(1):80–84
Tu WC, Ding LF, Peng LY, Song LD, Wu XD, Zha QS (2022) Cassane diterpenoids from the seeds of Caesalpinia bonduc and their nitric oxide production and α-glucosidase inhibitory activities. Phytochem 193:112–973
Wang L, Xu Z (2006) Effects of arsenic (As III) on lipid peroxidation, glutathione content and antioxidant enzymes in growing pigs. Asian-Australas J Anim Sci 19:727–733
Wattoo JI, Saleem MZ, Shahzad MS, Arif A, Hameed A, Saleem MA (2016) DNA barcoding: amplification and sequence analysis of rbcl and matK genome regions in three divergent plant species. Adv Life Sci 4:03–07
White R (2005) Legume web [Internet] version 10.01. Cardiff University, School of Computer Sciences, Cardiff
Wright ES, Yilmaz LS, Noguera DR (2012) Decipher, a search-based approach to chimera identification for 16S rRNA sequences. Appl Environ Microbiol 78:717–725
Yildirim A, Oktay M, Bilaloğlu V (2001) The antioxidant activity of the leaves of Cydonia vulgaris. Turk J Med Sci 31:23–27
Acknowledgements
The corresponding author wants to thank the University Grants Commission for funding the BSR Faculty Fellowship under Grant Number F.18-1/2011 (BSR). The first author wishes to express gratitude to the Indian Council of Medical Research (ICMR). New Delhi, (SRF) fellowship support file number RBMH/FW/2020/5. The authors also thank DST—Purse (Phase 2), DST—FIST, UGC—SAP support to Department of Botany, Bharathidasan University, Tiruchirappalli-24, Tamil Nadu, India.
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ATM conceived the research, assisted in its design, execution, and analysis, as well as data interpretation and manuscript writing. AKM and PKM helped with the implementation of the experiment as well as the manuscript revision. TSK and SA assisted in the design of the experiments and provided valuable feedback on the manuscript. BDRK was involved in the study's design, planning, data processing, and interpretation, as well as proofreading the manuscript. The manuscript was written by both contributors, who also provided feedback. The final manuscript has been read by all writers and authorized.
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Ayyadurai Thirumurugan has no conflict of interest. Anil Kumar Moola has no conflict of interest. Prasobh K. Mohan has no conflict of interest. Thiruppathi Senthil Kumar has no conflict of interest. Shanmugam Achiraman has no conflict of interest. Bollipo Diana Ranjitha Kumari has no conflict of interest.
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Ayyadurai, T., Moola, A.K., Mohan, P.K. et al. Ameliorative effects of Guilandina bonduc L. aqueous seed extract on letrozole induced polycystic ovary syndrome in female wistar albino rats. ADV TRADIT MED (ADTM) 22, 885–903 (2022). https://doi.org/10.1007/s13596-022-00652-4
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DOI: https://doi.org/10.1007/s13596-022-00652-4