Abstract
The present study reports the effect of different seasons on polyphenol content and antioxidant potential of ethanolic, methanolic, ethyl acetate, and aqueous extracts of leaves, stems, and roots of Premna integrifolia. Ethyl acetate extract of leaves (EAEPI) collected in the rainy season showed potent antioxidant activity with highest total phenol (74.33 ± 2.26 µg/mg, gallic acid equivalent), and flavonoid (98.83 ± 0.26 µg/mg, rutin equivalent) content. Therefore, EAEPI extract was subjected to characterization by UHPLC-Q-TOF-MS/MS and GC–MS analysis for the identification of active constituents. UHPLC-Q-TOF-MS/MS analysis in + ve ion mode revealed the presence of eight polyphenolic compounds namely quercetin-3-D-xyloside, kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin-3-Oglucoside, luteolin-3′,7-di-O-glucoside, eriodictyol-7-O-glucoside, syringetin-3-O-galactoside, petunidin-3-O-beta-glucopyranoside and vitexin-2″-O-rhamnoside. GC–MS analysis confirmed the presence of 26 compounds with six major compounds viz; citronellol, phytol acetate, campesterol, squalene, stigmasterol, and hexadecanoic acid. These compounds are reported for the first time from P. integrifolia except phytol and stigmasterol. Our previous study validates the hepatoprotective potential of P. integrifolia but there was no idea about the bioactive compound responsible for the activity. So, in present work, the major compounds identified in spectrometry analysis were subjected to in silico docking against an important liver enzyme alanine amino transaminase to confirm its hepatoprotective properties. Docking analysis validates the presence of two hepatoprotective lead compounds stigmasterol, and campesterol, which satisfy the drug-likeness criteria with good absorption, distribution, metabolism, and toxicity properties. Thus, present work gives a clear insight about the influence of season on the total polyphenolic constituent in different plant parts of P. integrifolia, their antioxidant potential and preclinical evaluation of hepatoprotective lead compounds.
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Abbreviations
- EAEPI:
-
Ethyl acetate extract of Premna integrifolia
- DPPH:
-
2,2-Diphenyl-1-picrylhydrazyl
- NBT:
-
Nitro blue tetrazolium
- TBARS:
-
Thiobarbituric acid-reactive species
- TPC:
-
Total phenolic content
- TFC:
-
Total flavonoid content
- ALT:
-
Alanine aminotransaminase
- ADMET:
-
Absorption, Distribution, Metabolism, Excretion, Toxicity
References
Adeosun CB, Olaseinde S, Opeifa A, Atolani O (2013) Essential oil from the stem bark of Cordia sebestena scavenges free radicals. JACME 3:138–141
Agnihotri VK, Elsohly HN, Khan SI, Jacob MR, Joshi VC, Smillie T, Khan IA, Walker LA (2008) Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity. Phytochem Lett 1:89–93
Awika JM, Rooney LW, Wu X, Prior RL, Cisneros-Zevallos L (2003) Screening methods to measure antioxidant activity of sorghum (Sorghum bicolor) and sorghum products. J Agric Food Chem 51:6657–6662
Bonanome A, Grundy SM (1988) Effect of dietary stearic acid on plasma cholesterol and lipoprotein levels. N Engl J Med 318:1244–1248
Bose LV, George K, Iyer RS, Deepa T (2012) Identification of novel cardiac principle in the roots of Premna serratifolia L. J Pharm Res 5:3261–3264
Bottje W, Erf G, Bersi T, Wang S, Barnes D, Beers K (1997) Effect of dietary dl-alphatocopherol on tissue alpha-and gamma-tocopherol and pulmonary hypertension syndrome (ascites) in broilers. Poult Sci 76:1506–1512
Buonocore G, Perrone S, Tataranno ML (2010) Oxygen toxicity: chemistry and biology of reactive oxygen species. Seminars in fetal and neonatal medicine, vol 4. Elsevier, Amsterdam, pp 186–190
Chang C-C, Yang M-H, Wen H-M, Chern J-C (2002) Estimation of total flavonoid content in Propolis by two complementary colorimetric methods. J Food Drug Anal 10:178–182
Chaves N, Escudero JC, Gutierrez-Merino C (1997) Role of ecological variables in the seasonal variation of flavonoid content of Cistus ladanifer exudate. J Chem Ecol 23:579–603
Chiswick ML, Johnson M, Woodhall C, Gowland M, Davies J, Toner N, Sims DG (1983) Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies. Br Med J (Clin Res Ed) 287:81–84
Choi JM, Lee EO, Lee HJ, Kim KH, Ahn KS, Shim BS, Kim NI, Song MC, Baek NI, Kim SH (2007) Identification of campesterol from Chrysanthemum coronarium L. and its antiangiogenic activities. Phytother Res 21:954–959
Choi J-H, Kim D-W, Yun N, Choi J-S, Islam MN, Kim Y-S, Lee S-M (2011) Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J Nat Prod 74:1055–1060
Christie PJ, Alfenito MR, Walbot V (1994) Impact of low-temperature stress on general phenylpropanoid and anthocyanin pathways: enhancement of transcript abundance and anthocyanin pigmentation in maize seedlings. Planta 194:541–549
Desai K, Wei H, Lamartiniere C (1996) The preventive and therapeutic potential of the squalene-containing compound, Roidex, on tumor promotion and regression. Cancer Lett 101:93–96
Do Nascimento NC, Fett-Neto AG (2010) Plant secondary metabolism and challenges in modifying its operation an overview. Plant secondary metabolism engineering. Springer, New York, pp 1–13
Fokum FD, Shahidullah M, Jorgensen E, Binns H (2017) Prevalence and elimination of childhood lead poisoning in Illinois, 1996–2012. Applied demography and public health in the 21st century. Springer, New Yoek, pp 221–236
Ganaie H, Ali M, Ganai B, Kaur J, Ahmad M (2016) GC–MS analysis and evaluation of mutagenic and antimutagenic activity of ethyl acetate extract of Ajuga bracteosa wall ex. Benth: an endemic medicinal plant of Kashmir Himalaya, India. J Clin Toxicol 6:0495–2161
Ghosh T, Maity TK, Singh J (2011) Evaluation of antitumor activity of stigmasterol, a constituent isolated from Bacopa monnieri Linn aerial parts against Ehrlich Ascites Carcinoma in mice. Orient Pharm Exp Med 11:41–49
Gokani RH, Lahiri SK, Santani DD, Shah MB (2011) Evaluation of anti-inflammatory and antioxidant activity of Premna integrifolia root. J Complement Integr Med. https://doi.org/10.2202/1553-3840.1216
Gómez-Alonso S, Collins VJ, Vauzour D, Rodríguez-Mateos A, Corona G, Spencer JP (2012) Inhibition of colon adenocarcinoma cell proliferation by flavonols is linked to a G2/M cell cycle block and reduction in cyclin D1 expression. Food Chem 130:493–500
Gopal RH, Purushothaman K (1984) Effect of plant isolates on coagulation of blood: an in vitro study. Bull Med Ethnobot Res 5:171–177
Group AP (2009) An update of the Angiosperm phylogeny group classification for the orders and families of flowering plants: APG III. Bot J Linn Soc 161:105–121
Halliwell B, Aeschbach R, Löliger J, Aruoma O (1995) The characterization of antioxidants. Food Chem Toxicol 33:601–617
Harada H, Yamashita U, Kurihara H, Fukushi E, Kawabata J, Kamei Y (2002) Antitumoractivity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer Res 22:2587–2590
Henry GE, Momin RA, Nair MG, Dewitt DL (2002) Antioxidant and cyclooxygenase activities of fatty acids found in food. J Agric Food Chem 50:2231–2234
Hu Q, Zhang DD, Wang L, Lou H, Ren D (2012) Eriodictyol-7-O-glucoside, a novel Nrf2 activator, confers protection against cisplatin-induced toxicity. Food Chem Toxicol 50:1927–1932
Idan SA, Al-Marzoqi AH, Hameed IH (2015) Spectral analysis and anti-bacterial activity of methanolic fruit extract of Citrullus colocynthis using gas chromatography-mass spectrometry. Afr J Biotech 14:3131–3158
Igarashi K, Mikami T, Takahashi Y, Sato H (2008) Comparison of the preventive activity of isorhamnetin glycosides from atsumi-kabu (red turnip, Brassica campestris L.) Leaves on carbon tetrachloride-induced liver Injury in mice. Biosci Biotechnol Biochem 72:856–860
Jananie R, Priya V, Vijayalakshmi K (2011) Determination of bioactive components of Cynodon dactylon by GC-MS analysis. N Y Sci J 4:1–5
Kähkönen MP, Heinonen M (2003) Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 51:628–633
Ko T-F, Weng Y-M, Chiou RY-Y (2002) Squalene content and antioxidant activity of Terminalia catappa leaves and seeds. J Agric Food Chem 50:5343–5348
Lajubutu B, Pinney R, Roberts M, Odelola H, Oso B (1995) Antibacterial activity of diosquinone and plumbagin from the root of Diospyros mespiliformis (Hostch) (Ebenaceae). Phytother Res 9:346–350
Leonetti C, Biroccio A, Gabellini C, Scarsella M, Maresca V, Flori E, Bove L, Pace A, Toppacciaro A, Zupi G (2003) α-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. Int J Cancer 104:243–250
Leung YH, Liu RH (2000) Trans-10, cis-12-conjugated linoleic acid isomer exhibits stronger oxyradical scavenging capacity than cis-9, trans-11-conjugated linoleic acid isomer. J Agric Food Chem 48:5469–5475
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3–25
López-Lázaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9:31–59
Majumder R, Akter S, Naim Z, Al-Amin M, Alam MB (2014) Antioxidant and anti-diabetic activities of the methanolic extract of Premna integrifolia bark. Adv Biol Res 8:29–36
Malhi Y, Nobre AD, Grace J, Kruijt B, Pereira MG, Culf A, Scott S (1998) Carbon dioxidetransfer over a Central Amazonian rain forest. J Geophys Res Atmos 103:31593–31612
Mcdonald S, Prenzler PD, Antolovich M, Robards K (2001) Phenolic content and antioxidantactivity of olive extracts. Food Chem 73:73–84
Mckillop IH, Schrum LW (2005) Alcohol and liver cancer. Alcohol 35:195–203
Mishra AK, Upadhyay R, Chaurasia JK, Tiwari KN (2016) Comparative antioxidant study in different flower extracts of Nyctanthes arbor-tristis (L.)(Oleaceae): an important medicinal plant. Braz J Bot 39:813–820
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J Comput Chem 30:2785–2791
Muthukumaran P, Salomi S, Umamaheshwari R (2013) In vitro antioxidant activity of Premna serratifolia Linn. Asian J Res Pharm Sci 3:15–18
Ogunlesi M, Okiei W, Ofor E, Osibote AE (2009) Analysis of the essential oil from the dried leaves of Euphorbia hirta Linn (Euphorbiaceae), a potential medication for asthma. Afr J Biotech 8:7042–7050
Okeleye BI, Mkwetshana NT, Ndip RN (2013) Evaluation of the antibacterial and antifungal potential of Peltophorum africanum: toxicological effect on human chang liver cell line. Sci World J. https://doi.org/10.1155/2013/878735
Pandey MP (2016) Carpesterol-A novel phytosterol obtained from the plants of the family solanaceae with evaluation of antineoplastic activity. J Med Pharm Allied Sci 1:1–10
Pasqualini V, Robles C, Garzino S, Greff S, Bousquet-Mélou A, Bonin G (2003) Phenolic compounds content in Pinus halepensis Mill. Needles: a bioindicator of air pollution. Chemosphere 52:239–248
Patel MJ, Patel J (2012) Evaluation of the anti-hyperlipidaemic activity of Premna integrifolia on nicotine induced hyperlipidaemia in rats. Int J Pharm Biosci 3:226–232
Poongulali S, Sundararaman M (2016) Antimycobacterial, anticandidal and antioxidant properties of Terminalia catappa and analysis of their bioactive chemicals. Int J Pharm Biol Sci 6:69–83
Rajab MS, Cantrell CL, Franzblau SG, Fischer NH (1998) Antimycobacterial activity of (E)-phytol and derivatives: a preliminary structure-activity study. Planta Med 64:2–4
Rajendran R, Krishnakumar E (2010) Anti-arthritic activity of Premna serratifolia Linn., wood against adjuvant induced arthritis. Avicenna J Med Biotechnol 2:101–106
Rajendran R, Basha NS, Ruby S (2009) Evaluation of in vitro Antioxidant Activity of stembark and stem-wood of Premna serratifolia Lin., (Verbenaceae). Phytochemistry 1:11–14
Saeed MA, Sabir A (2001) Antibacterial activity of Caesalpinia bonducella seeds. Fitoterapia 72:807–809
Safarpour S, Givianrad M, Beheshti P (2012) Detection and determination of antioxidant compounds of seed oil of capparis spinosa l. In iran
Selvam TN, Venkatakrishnan V, Damodar KS, Elumalai P (2012) Antioxidant and tumor cell suppression potential of Premna serratifolia Linn leaf. Toxicol Int 19:31
Sermakkani M, Thangapandian V (2012) GC-MS analysis of Cassia italica leaf methanol extract. Asian J Pharm Clin Res 5:90–94
Shin E, Hong H, Park J, Oh Y, Jung J, Lee Y (2016) Characterization of Staphylococcus aureus faecal isolates associated with food-borne disease in Korea. J Appl Microbiol 121:277–286
Singh C, Prakash C, Tiwari KN, Mishra SK, Kumar V (2018) Premna integrifolia ameliorates cyclophosphamide-induced hepatotoxicity by modulation of oxidative stress and apoptosis. Biomed Pharmacother 107:634–643
Singh C, Prakash C, Mishra P, Tiwari KN, Mishra SK, More RS, Kumar V, Singh J (2019) Hepatoprotective efficacy of Premna integrifolia L. leaves against aflatoxin B1-induced toxicity in mice. Toxicon 166:88–100
Sivakrishnan S, Muthu AK (2014) Evaluation of hepatoprotective activity of squalene isolated from Albizia procera against paracetamol induced hepatotoxicity on Wistar rats. World J Pharm Pharm Sci 3:1351–1362
Tiwari S, Mishra S, Misra DR, Upadhyay R (2016) Identification of new bioactive compounds from fruit of Abutilon indicum through GCMS analysis. Biol Forum 8:548–554
Upadhyay R, Tiwari KN (2018) Phyllanthus fraternus a potent natural antioxidant as pharmaceutical supplement. Res J Biotech 13:55–62
Upadhyay R, Chaurasia JK, Tiwari KN, Singh K (2014) Antioxidant property of aerial parts and root of Phyllanthus fraternus Webster, an important medicinal plant. Sci World J. https://doi.org/10.1155/2014/692392
Wang L, Yang Z, Wang S, Wang S, Liu J (2011) Antioxidant and antibacterial activities of Camptotheca acuminate D. Seed oil. Afr J Microbiol Res 5:5854–5862
Wang Y, Tang C, Zhang H (2015) Hepatoprotective effects of kaempferol 3-O-rutinoside and kaempferol 3-O-glucoside from Carthamus tinctorius L. On ccl4-induced oxidative liver injury in mice. J Food Drug Anal 23:310–317
Wu Y-B, Zheng L-J, Wu J-G, Chen T-Q, Yi J, Wu J-Z (2012) Antioxidant activities of extract and fractions from Receptaculum nelumbinis and related flavonol glycosides. Int J Mol Sci 13:7163–7173
Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Chen X, Hou T, Cao D (2021) ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 49:5–14
Yoshida Y, Niki E (2003) Antioxidant effects of phytosterol and its components. J Nutr Sci Vitaminol 49:277–280
Yosr Z, Imen BHY, Rym J, Chokri M, Mohamed B (2018) Sex-related differences in essential oil composition, phenol contents and antioxidant activity of aerial parts in Pistacia lentiscus L. During seasons. Ind Crops Prod 121:151–159
Yulia R, Christyaningsih J, Kristina EM, Soegiono NK (2016) The antioxidant compounds in methanol extract of glycine max l. merr detam i and ii varieties by kinetic maceration method
Zhuang SR, Chen SL, Tsai JH, Huang CC, Wu TC, Liu WS, Tseng HC, Lee HS, Huang MC, Shane GT (2009) Effect of citronellol and the Chinese medical herb complex on cellular immunity of cancer patients receiving chemotherapy/radiotherapy. Phytother Res Int J Devoted Pharmacol Toxicol Eval Nat Prod Deriv 23:785–790
Acknowledgements
Authors CS and KNT would like to acknowledge University Grants Commission (UGC), Government of India, for financial assistance. Author KNT thankfully acknowledges to BHU Varanasi for providing financial assistance through incentive Grant under IoE scheme (6031) for research. Advance Instrumentation Research Facility (AIRF), Jawaharlal Nehru University, New Delhi acknowledged for providing GC-MS and UPLC/MS-MS facility.
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CS designed the study, conducted the experiment, performs the analysis and wrote the paper. KNT supervisor of this study designed the study and reviewed drafts of the manuscript. RU performed the analysis and reviewed the final draft.
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Singh, C., Upadhyay, R. & Tiwari, K.N. Comparative analysis of the seasonal influence on polyphenolic content, antioxidant capacity, identification of bioactive constituents and hepatoprotective biomarkers by in silico docking analysis in Premna integrifolia L.. Physiol Mol Biol Plants 28, 223–249 (2022). https://doi.org/10.1007/s12298-021-01120-0
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DOI: https://doi.org/10.1007/s12298-021-01120-0