Yıl 2022,
, 146 - 161, 02.01.2023
Pranob Jyoti Bharali
Sushanta Kumar Bordoloi
Swarnamoni Das
Kingshuk Lahon
Kaynakça
- Ramadori, G., Moriconi, F., Malik, I., and Dudas J., (2008). Physiology and pathophysiology of liver inflammation, damage and repair. Journal of Physiology and Pharmacology, Aug;59 Suppl 1:107-117. PMID: 18802219.
- Mansour, H.H., Hafez, H.F., and Fahmy, N.M., (2006). Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats. Journal of Biochemistry and Molecular Biology, Nov 30,39(6),656-661. doi: 10.5483/bmbrep.2006.39.6.656. PMID: 17129399.
- Camini, FC., and Costa, DC., (2020). Silymarin: not just another antioxidant. Journal of Basic and Clinical Physiology and Pharmacology, 2020 Mar 5,31(4)/j/jbcpp.2020.31.issue-4/jbcpp-2019-0206/jbcpp-2019-0206.xml. doi: 10.1515/jbcpp-2019-0206. PMID: 32134732.
- Polyak, SJ., Ferenci, P., and Pawlotsky, JM., (2013). Hepatoprotective and antiviral functions of silymarin components in hepatitis C virus infection. Hepatology, 57(3),1262-1271. doi: 10.1002/hep.26179. PMID: 23213025; PMCID: PMC3594650.
- Bedi, O., Bijjem, KRV., Kumar, P., and Gauttam, V., (2016). Herbal Induced Hepatoprotection and Hepatotoxicity: A Critical Review. Indian Journal of Physiology and Pharmacology,60(1),6-21. PMID: 29953177.
- Ilyas, U., Katare, DP., Aeri V., and Naseef, PP., (2016). A Review on Hepatoprotective and Immunomodulatory Herbal Plants. Pharmacognosy Reviews,10(19),66-70. doi: 10.4103/0973-7847.176544. PMID: 27041876; PMCID: PMC4791991.
- Kumar, VS., and Navaratnam, V., (2013). Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pacific Journal of Tropical Biomedicine,3(7),505-514. https://doi:10.1016/S2221-1691(13)60105-7
- Islas, JF., Acosta, E., G-Buentello, Z., Delgado-Gallegos, JL., Moreno-Trevino MG., and Escalante B., et al (2020). An overview of Neem (Azadirachta indica) and its potential impact on health. Journal of Functional Foods, 74, 104171 https://doi.org/10.1016/j.jff.2020.104171
- National Research Council (U.S.), Board on Science and Technology for International Development (1992). Neem: A Tree for Solving global Problems. In: Report of an Ad Hoc Panel of the Board on Science and Technology for International Development, National Research Council, The National Academies Press, Washington, DC, USA,1-152 https://doi.org/10.17226/1924
- Biswas, K., Chattopadhyay, I., Banerjee, RK., and Bandopadhyay, U.,(2002). Biological activities and medicinal properties of neem (Azadirachta indica), Current Science,82(11),1336-1345
- Rahmani, AH., Almatroudi, A., Alrumaihi, F., and Khan, AA., (2018). Pharmacological and therapeutic potential of neem (Azadirachta indica), Pharmacognosy Reviews,8(12),250-255
- Kharwar, RN., Sharma, VK., Mishra, A., Kumar, J., Singh, DK., Verma, SK., and Gond, SK., et. al (2020). Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms, Planta Medica, Sep,86(13-14),906-940. doi: 10.1055/a-1107-9370. Epub 2020 Mar 3. PMID: 32126583.
- Subapriya, R., and Nagini, S.,(2005). Medicinal properties of neem leaves: a review, Current medicinal chemistry. Anti-cancer agents, Mar,5(2),149-6. doi: 10.2174/1568011053174828. PMID: 15777222.
- Brahmachari. G.,(2004). Neem--an omnipotent plant: a retrospection, ChemBioChem, Apr, 2,5(4),408-421. doi: 10.1002/cbic.200300749. PMID: 15185362.
- Kaushik, N., Revuru, B., and Kusari, S.,(2020). Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms, Planta Medica, Sep 86(13-14),906-940. doi: 10.1055/a-1107-9370. Epub 2020 Mar 3. PMID: 32126583.
- Gupta, SC., Prasad, S., Tyagi, AK., Kunnumakkara, AB., and Aggarwal, BB.,(2017). Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis, Phytomedicine, Oct 15,34,14-20. doi: 10.1016/j.phymed.2017.07.001. Epub 2017 Jul 3. PMID: 28899496.
- Alzohairy, MA., (2016). Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment. Evidence Based Complementary and Alternative Medicine,2016:7382506. doi: 10.1155/2016/7382506. Epub 2016 Mar 1. PMID: 27034694; PMCID: PMC4791507.
- Khanna, N., Goswami, M., Sen, P., and Ray, A., (1995). Antinociceptive action of Azadirachta indica (neem) in mice: possible mechanisms involved. Indian Journal of Experimental Biology,Nov,33(11),848-850.PMID: 8786160.
- Chattopadhyay, RR., Chattopadhyay, RN., and Maitra, SK.,(1997). Possible mechanism of anti-inflammatory activity of Azadirachta indica leaf extract, Indian Journal of Pharmacology,27(2),99-100.
- Alam, A., Haldar, S., Thulasiram, HV., Kumar, R., Goyal, M., and Iqbal, MS., et al (2012). Novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor. Journal of Biological Chemistry,287(29):24844-24861
- Thoh, M., Babajan, B., Raghavendra, PB., Sureshkumar, C., and Manna, SK.,(2011). Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses. Journal of Biological Chemistry,286(6),4690-4702.
- Pingali, U., Ali, MA., Gundagani, S., and Nutalapati, C.,(2020). Evaluation of the Effect of an Aqueous Extract of Azadirachta indica (Neem) Leaves and Twigs on Glycemic Control, Endothelial Dysfunction and Systemic Inflammation in Subjects with Type 2 Diabetes Mellitus - A Randomized, Double-Blind, Placebo-Controlled Clinical Study, Diabetes Metabolic Syndrome and Obesity, Nov 17,13,4401-4412. doi: 10.2147/DMSO.S274378. PMID: 33244247; PMCID: PMC7683773.
- Ponnusamy, S., Haldar, S., Mulani, F., Zinjarde, S., Thulasiram, H., and RaviKumar, A.,(2015). Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents, PLoS One, Oct 15,10(10):e0140113. doi: 10.1371/journal.pone.0140113. PMID: 26469405; PMCID: PMC4607367.
- Bopanna, KN., Kanan, J., Gadgil, S., Balarman, R., and Rathod, SP.,(1997). Antidiabetic and antihyperlipidemic effects of neem seed kernel powder on alloxan diabetic rabbits. Indian Journal of Pharmacology,29(3):162-167
- Mukherjee, A., and Sengupta, S.,(2013). Characterization of nimbidiol as a potent intestinal disaccharidase and glucoamylase inhibitor present in Azadirachta indica (neem) useful for the treatment of diabetes, Journal of Enzyme Inhibition and Medicinal Chemistry,Oct,28(5):900-10. doi: 10.3109/14756366.2012.694877. Epub 2012 Jul 18. PMID: 22803678.
- Yarmohammadi, F., Mehri, S., Najafi, N., Salar Amoli, S., and Hosseinzadeh, H.,(2021). The protective effect of Azadirachta indica (neem) against metabolic syndrome: A review. Iran Journal of Basic Medical Sciences,Mar;24(3),280-292. doi: 10.22038/ijbms.2021.48965.11218. PMID: 33995939; PMCID: PMC8087850.
- Sen, P., Mediratta, PK., and Ray, A.,(1992). Immunostimulant activities of A.indica. Indian Journal of Experimental Biology,33: 1170-1195.
- Yadav, DY., Bharitkar, YP., Chatterjee, K., Ghosh, M., Mondal, NB., and Swarnakar, S.,(2016). Importance of Neem leaf: An insight into its role in combating diseases. Indian Journal of Experimental Biology,54,708-718
- Sarah, R., Tabassum, B., Idrees, N., and Hussain MK..,(2019). Bio-active Compounds Isolated from Neem Tree and Their Applications. In: Akhtar M, Swamy M, Sinniah U. (eds.) Natural Bio-active Compounds. Springer, Singapore,509-528 https://doi.org/10.1007/978-981-13-7154-7_17
- Quelemes, PV., Perfeito, ML., Guimarães, MA., dos Santos, RC., Lima, DF., and Nascimento, C., et. al (2015). Effect of neem (Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms, Journal of Ethnopharmacology, Dec 4,175,287-294. doi: 10.1016/j.jep.2015.09.026. Epub 2015 Sep 25. PMID: 26408045.
- Lu, XF., Lin, PC., Zi, JC., and Fan, XN.,(2019). [Limonoids from seeds of Azadirachta indica and their antibacterial activity], Zhongguo Zhong Yao Za Zhi,Nov,44(22),4864-4873. Chinese. doi: 10.19540/j.cnki.cjcmm.20190813.202. PMID: 31872594.
- Singh, AK., Sharma, RK., Sharma, V., Singh, T., Kumar, R., and Kumari, D.,(2017). Isolation, morphological identification and in vitro antibacterial activity of endophytic bacteria isolated from Azadirachta indica (neem) leaves. Veterinary World, May,10(5),510-516. doi: 10.14202/vetworld.2017.510-516. Epub 2017 May 11. PMID: 28620254; PMCID: PMC5465764.
- Thakurta, P., Bhowmik, P., Mukherjee. S., Hajra, TK., Patra, A., and Bag, PK.,(2007). Antibacterial, antisecretory and antihemorrhagic activity of Azadirachta indica used to treat cholera and diarrhea in India. Journal of Ethnopharmacology, May 22;111(3):607-612. doi: 10.1016/j.jep.2007.01.022. Epub 2007 Jan 21. PMID: 17314018.
- Ahmad, A., Javed, MR., Rao, AQ., and Husnain, T.,(2016).Designing and screening of universal drug from neem (Azadirachta indica) and standard drug chemicals against influenza virus nucleoprotein. BMC Complementary and Alternative Medicine Dec 16,16(1),519. doi: 10.1186/s12906-016-1469-2. PMID: 27986088; PMCID: PMC5162082.
- Faccin-Galhardi, LC., Yamamoto, KA., Ray, S., Ray, B., Carvalho Linhares, RE., and Nozawa C.,(2012).The in vitro antiviral property of Azadirachta indica polysaccharides for poliovirus. Journal of Ethnopharmacology, Jun 26,142(1),86-90. doi: 10.1016/j.jep.2012.04.018. PMID: 22855945.
- Tiwari, V., Darmani, NA., Yue, BY., and Shukla, D.,(2010).In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type-1 infection. Phytotherapy Research, Aug,24(8),1132-1140. doi: 10.1002/ptr.3085. PMID: 20041417; PMCID: PMC3767196.
- Natarajan, V., Venugopal, PV., and Menon, T.,(2003).Effect of Azadirachta indica (neem) on the growth pattern of dermatophytes. Indian Journal of Medical Microbiology, Apr-Jun,21(2),98-101. PMID: 17642990.
- Chianese, G., Yerbanga, SR., Lucantoni, L., Habluetzel, A., Basilico, N., and Taramelli, D., et al,(2010).Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica. Journal of Natural Products,Aug 27,73(8),1448-1452. doi: 10.1021/np100325q. PMID: 20669933.
- Batabyal, L., Sharma, P., Mohan, L., Maurya, P,, and Srivastava, CN.,(2009).Relative toxicity of neem fruit, bitter gourd, and castor seed extracts against the larvae of filaria vector, Culex quinquefasciatus (Say). Parasitology Research, Oct,105(5),1205-1210. doi: 10.1007/s00436-009-1541-7. Epub 2009 Jun 27. PMID: 19562373.
- Patel, SM., Nagulapalli Venkata, KC., Bhattacharyya, P., Sethi, G., Bishayee, A.,(2016).Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. Seminars in Cancer Biology,Oct;40-41,100-115. doi: 10.1016/j.semcancer.2016.03.002. Epub 2016 Mar 24. PMID: 27019417.
- Iman, M., Taheri, M., and Bahari, Z., (2021). The anti-cancer properties of neem (Azadirachta indica) through its antioxidant activity in the liver; its pharmaceutics and toxic dosage forms; a literature review. Journal of Complementary and Integrative Medicine, May 10. doi: 10.1515/jcim-2021-0009. Epub ahead of print. PMID: 33964199.
- Sarkar, S., Singh, RP., and Bhattacharya, G.,(2021).Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: an update on molecular approach, 3 Biotech, Apr,11(4),178. doi: 10.1007/s13205-021-02745-4. Epub 2021 Mar 20. PMID: 33927969; PMCID: PMC7981372.
- Saleem, S., Muhammad, G., Hussain, MA., and Bukhari, SNA.,(2018). A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica, Phytotherapy Research,Jul,32(7),1241-1272. doi: 10.1002/ptr.6076. Epub 2018 Apr 19. PMID: 29671907.
- Sujarwo, W., Keim, AP., Caneva, G., Toniolo, C., and Nicoletti, M.,(2016). Ethnobotanical uses of neem (Azadirachta indica A.Juss.; Meliaceae) leaves in Bali (Indonesia) and the Indian subcontinent in relation with historical background and phytochemical properties, Journal of Ethnopharmacology, Aug 2,189,186-193. doi: 10.1016/j.jep.2016.05.014. Epub 2016 May 10. PMID: 27178630.
- Maity, P., Biswas, K., Chattopadhyay, I., Banerjee, RK., and Bandyopadhyay, U.,(2009).The use of neem for controlling gastric hyperacidity and ulcer, Phytotherapy Research, Jun,23(6),747-755. doi: 10.1002/ptr.2721. PMID: 19140119.
- Dorababu, M., Joshi, MC., Bhawani, G., Kumar, MM., and Chaturvedi, A., and Goel, RK.,(2006). Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and diffensive gastric mucosal factors in rats. Indian Journal of Physiology and Pharmacology,Jul-Sep,50(3),241-249. PMID: 17193895.
- Bandyopadhyay, U., Biswas, K., Sengupta, A., Moitra, P., Dutta, P., and Sarkar, D., et. al, (2004).Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer, Life Sciences, Oct 29,75(24),2867-2878. doi: 10.1016/j.lfs.2004.04.050. PMID: 15454339.
- Maity, P., Biswas K., Chattopadhyay, I., Banerjee, RK., and Bandyopadhyay, U.,(2009). The use of neem for controlling gastric hyperacidity and ulcer, Phytotherapy Research, Jun, 23(6),747-755. doi: 10.1002/ptr.2721. PMID: 19140119.
- Khillare, B., and Shrivastav, TG.,(2003). Spermicidal activity of Azadirachta indica (neem) leaf extract,Contraception, Sep,68(3),225-229. doi: 10.1016/s0010-7824(03)00165-3. PMID: 14561544.
- Chaube, SK., Shrivastav, TG., Tiwari, M., Prasad, S., Tripathi, A., and Pandey, AK.,(2014). Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals, SpringerPlus, Aug 26,3,464. doi: 10.1186/2193-1801-3-464. PMID: 25197620; PMCID: PMC4155053.
- Hummel, HE., Langner, SS., Leithold, G., Schmutterer, H.,(2014). NEEM: UNUSUALLY VERSATILE PLANT GENUS AZADIRACHTA WITH MANY USEFUL AND SO FAR INSUFFICIENTLY EXPLOITED PROPERTIES FOR AGRICULTURE, MEDICINE, AND INDUSTRY. Communications in Agricultural Applications and Biological Sciences,79(2),211-228. PMID: 26084100.
- Handa, SS., Sharma, A., and Chakraborti, KK., (1986). Natural products and plants as liver protecting drugs, Fitoterapia,57,307-352
- Chattopadhyay, RR., Sarkar, SK., Ganguly, S., Banerjee, RN., Basu, TK., and Mukherjee, A. Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats, Indian Journal of Experimental Biology, Aug,30(8),738-740. PMID: 1459654.
- Mukherjee, PK., Bhakta, T., Saha, BP., Pal, S., Pal, M., and Das, AA.,(1994). Protective effect of fraction of Azadirachta indica leaf extract on carbon tetrachloride induced hepatotoxicity, Ancient Science of Life, Jul,14(1-2),71-76. PMID: 22556679; PMCID: PMC3336499.
- Nahed, AM.,(1996). Effect of azadirachta indica NEEM extract on paracetamol induced hepatotoxicity, Assiut Medical Journal,20(2),137-154 | IMEMR | ID: emr-40412
- Bhanwra, S., Singh, J., and Khosla, P.,(2000). Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats, Indian Journal of Physiology and Pharmacology,Jan,44(1),64-68. PMID: 10919097.
- Kale, BP., Kothekar, MA., Tayade, HP., Jaju, JB., and Mateenuddin, M.,(2003). Effect of aqueous extract of Azadirachta indica leaves on hepatotoxicity induced by antitubercular drugs in rats, Indian Journal of Pharmacology,35,177‑180.
- Yanpallewar, SU., Sen, S., Tapas, S., Kumar, M., Raju, SS, and Acharya, SB. Effect of Azadirachta indica on paracetamol-induced hepatic damage in albino rats, Phytomedicine,10(5),391-396. doi: 10.1078/0944-7113-00230. PMID: 12834004.
- Kalaivani, T., Meignanam, E., Premkumar, N., Siva, R., Vijayakumar, V., and Rajasekaran, C., et al. Studies on hepatoprotective properties of leaf extracts of Azadirachta indica A. Juss (Meliaceae),Ethobotanicalleaflets,13,165-170
- Ezz-Din, D., Gabry, MS., and Farrag, ARH., and Abdel Moneim, AE.,(2011). Physiological and histological impact of Azadirachta indica (neem) leaves extract in a rat model of cisplatin-induced hepato and nephrotoxicity. Journal of Medical Plants Research, 5(23),5499-5506 http://www.academicjournals.org/JMPR
- Akinola, OB., Omotoso, GO., Akinola, OS., Dosumu, OO., and Adewoye, ET.,(2011). Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats. Zhong Xi Yi Jie He Xue Bao, Dec,9(12),1373-1379. doi: 10.3736/jcim20111215. PMID: 22152778.
- Dkhil, MA., Al-Quraishy, S., Aref, AM., Othman, MS., El-Deib KM., and Abdel Moneim, AE.,(2013). The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats. Oxidative Medicine and Cellular Longevity,2013:741817. doi: 10.1155/2013/741817. Epub 2013 Dec 4. PMID: 24369490; PMCID: PMC3867870.
- Essien, NA., Iwara, IA., Mgbeje, BAI., Igile, GO., Egbung, GE., and Ebong, PE.,(2013). Lipid profile and hepatoprotective effects of combined leaf extracts of Azadirachta indica (Neem) and Peristrophe bycaliculata in Alloxan-induced diabetic rats, International Journal of Phytomedicine 5:159-162.
- Johnson, M., Olufunmilayo, LA., Anthony, DO., and Olusoji., EO.,(2013). Hepatoprotective Effect of Ethanolic Leaf Extract of Vernonia amygdalina and Azadirachta indica against Acetaminophen-Induced Hepatotoxicity in Sprague-Dawley Male Albino Rats, American Journal of Pharmacological Sciences,3(3),79-86 Available online at http://pubs.sciepub.com/ajps/3/3/5 DOI:10.12691/ajps-3-3-5
- Koul, A., Mohan, V., Bharati, S.,(2014). Azadirachta indica mitigates DMBA-induced hepatotoxicity: a biochemical and radiometric study. Indian Journal of Biochemistry and Biophysics, Feb,51(1),37-45. PMID: 24791415.
- Baligar, NS., Aladakatti, RH., Ahmed, M., and Hiremath, MB.,(2014). Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats. Canadian Journal of Physiology and Pharmacology Apr,92(4),267-277. doi: 10.1139/cjpp-2013-0449. Epub 2014 Jan 9. PMID: 24708208.
- Baligar, NS., Aladakatti, RH., Ahmed, M., and Hiremath, MB.,(2014). Evaluation of acute toxicity of neem active constituent, nimbolide and its hepatoprotective activity against acute dose of carbon tetrachloride treated albino rats. International Journal of Pharmaceutical Sciences and Research, 5(8), 3455-3466. doi: 10.13040/IJPSR.0975-8232.5(8).3455-66
- Kesarkar, R., Sangar, V., Oza, G., Sawant, T., Kothari, S., and Sharon, M.,(2014). Synthesis, characterization and hepatoprotective activity of Neem gold nanoparticles for improved efficacy and sustained drug release profile of Azidothymidine, International Journal of Pharmaceutical Sciences Review and Research,26(2),117-122
- Abdel, Moneim AE., Othman, MS., and Aref, AM.,(2014).Azadirachta indica attenuates cisplatin-induced nephrotoxicity and oxidative stress. Biomedical Research International,2014,647131. doi: 10.1155/2014/647131. Epub 2014 Aug 3. PMID: 25162019; PMCID: PMC4137610.
- Aslam, F., Jamil, S., and Aslam, MA., (2016). Antihepatotoxic activity of Gemmotherapeutically treated Neem and alcoholic extract of Neem in albino rats. Pakistan Journal of Medical and Health Sciences,10(1),68-76
- Chavan, T., Ghadge, A., Karandikar, M., Pandit, V., Ranjekar, P., and Kulkarni, O., et. al (2017). Hepatoprotective Activity of Satwa, an Ayurvedic Formulation, Against Alcohol-induced Liver Injury in Rats, Alternative Therapies in Health and Medicine, Jul,23(4),34-40. PMID: 28646813.
- Idu, M., Ovuakpurie-Uvo, O., and Okojie, S.,(2017). Protective effects of neem (Azadirachta indica A. Juss) seed oil on carbon tetrachloride-induced hepatotoxicity in Wistar rats. Journal of Medicinal Plants for Economic Development, Published Online: 22 Aug,doi:https://doi.org/10.4102/jomped.v1i1.6 https://hdl.handle.net/10520/EJC-a87b303b6
- Nwobodo, EI., Nwosu, DC., Ogbodo, SO., Ugwuene, FO., Ihim, AC., and Ani, NO.,(2018). Effects of Azadirachta indica leaf aqueous extract on the antioxidant enzymes in paracetamol-induced hepatotoxicity in Wistar rats, International Journal of Biological and Chemical Sciences,12(1),1-10 DOIhttps://dx.doi.org/10.4314/ijbcs.v12i1.1
- Althaiban MA.,(2019). Evaluation of hepatopotective activity of Neem extract in Rifampin induced acute hepatic failure in rats. International Journal of Pharmaceutical Research and Allied Sciences,8(3),29-36
- Sani, I., Umar, RA., Hassan, SW., Faruq, UZ., Bello, F., and Aminu, H., et al. (2020). Hepatoprotective Effect of Azadirachta indica Leaf Fractionated Extracts against Snake Venom Toxicity on Albino Rats, Saudi Journal of Biomedical Research,5(6),112-117 DOI: 10.36348/sjbr.2020.v05i06.004
- Seriana, I., Akmal, M., Darusman, D., Wahyuni, S., Khairan, K., and Sugito, S., (2021). Neem Leaf (Azadirachta indica A. Juss) Ethanolic Extract on the Liver and Kidney Function of Rats, Hindawi The Scientific World Journal 2021,Article ID 7970424, 7 pages https://doi.org/10.1155/2021/7970424
- Committee for the purpose of control and supervision of experimental animals,(2018). In: Compendium of CPCSEA, New Delhi: Ministry of Environment, Forests and Climate Change, Animal Welfare Division, Govt. of India, 202 p. Available from http://cpcsea.nic.in/WriteReadData/userfiles/file/Compendium%20of%20CPCSEA.pdf, Accessed 20th August 2021
- Reinhold, JG., (1953). Biuret method. In: Reiner M, editor. Standard Methods of Clinical Chemistry. Ann Arbor: Academic Press, Inc;Vol. 1, p. 88.
- GORNALL, AG., BARDAWILL, CJ., and DAVID, MM.,(1949).Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry Feb,177(2),751-766. PMID: 18110453.
- King, EJ., Abul-Fadl, MAM., and Walker, PG.,(1951). King-Armstrong phosphatase estimation by the determination of liberated phosphate, Journal of Clinical Pathology,4,85.
- Reitman, S., and Frankel, S.,(1957). Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transminases. American Journal of Clinical Pathology,28(1),56-63. doi: 10.1093/ajcp/28.1.56. PMID: 13458125.
- Ann Preece.,(1972). In: Manual for histologic technicians,3rd ed.,Boston: Little, Brown and Company
- Haque, E., Mandal, I., Pal, S., and Baral, R.,(2006). Prophylactic Dose of Neem (Azadirachta indica) Leaf Preparation Restricting Murine Tumor Growth is Nontoxic, Hematostimulatory and Immunostimulatory, Immunopharmacology and Immunotoxicology,28,33-50 https://doi.org/10.1080/08923970600623632
- Mallick, A., Ghosh, S., Banerjee, S., Majumder, S., Das, A., and Mondal, B., et. al, (2013). Neem leaf glycoprotein is nontoxic to physiological functions of Swiss mice and Sprague Dawley rats: histological, biochemical and immunological perspectives, International Immunopharmacology, Jan,15(1),73-83. doi: 10.1016/j.intimp.2012.11.006. Epub 2012 Nov 21. PMID: 23178577.
- Suhendro., Susraini, AAAN., Saputra, H., and Sriwidyani, NP.,(2018). Oral administration of neem (Azadirachta indica A. Juss) leaf extract increases Cyclin D1 expression in hepatocyte regeneration in acetaminophen-induced hepatotoxic wistar rats, Bali Medical Journal,7(1),12-16 DOI:10.15562/bmj.v7i1.700
- Kim, WR., Flamm, SL., Di Bisceglie, AM., and Bodenheimer, HC.,(2008). Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease, Hepatology, Apr,47(4),1363-1370. doi: 10.1002/hep.22109. PMID: 18366115.
- Giannini, EG., Testa, R., and Savarino, V.,(2005). Liver enzyme alteration: a guide for clinicians, Canadian Medical Association Journal,172(3),367-379.
- Rotermund, HM., Schreiber, G., Maeno, H., Weinssen, U., and Weigand, K.,(1970). The ratio of albumin synthesis to total protein synthesis in normal rat liver, in host liver, and in Morris hepatoma 9121,Cancer Research, 30: 2139-2146.
- Landel, AM., Hammond, WG., and Meguid, MM.,(1985). Aspects of amino acid and protein metabolism in cancer - bearing states,Cancer,55: 230-237.
- Teloh HA., (1978). Serum proteins in hepatic disease, Annals of Clinical & Laboratory Science,8(2),127-129
- Amacher, DE.,(1998). Serum transaminase elevations as indicators of hepatic injury following the administration of drugs, Regulatory Toxicology and Pharmacology,27,119-130.
- Raucy, JL., Lasker, JM., Lieber, CS., and Black, M.,(1989). Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2, Archives of Biochemistry and Biophysics, Jun,271(2),270-283. doi: 10.1016/0003-9861(89)90278-6. PMID: 2729995.
- James, LP., Mayeux, PR., and Hinson, JA.,(2003). Acetaminophen-induced hepatotoxicity. Drug Metabolism and Disposition, 31,1499 -1506.
- Moore, M., Thor, H., Moore, G., Nelson, S., Moldeus, P., and Orrenius, S.,(1985). The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+, Journal of Biologocal Chemistry,260:13035-13040.
- Jollow, DJ., Mitchell, JR., Potter, WZ., Davis, DC., Gillette, JR., and Brodie, BB.,(1973). Acetaminophen induced hepatic necrosis. II. Role of covalent binding in vivo, Journal of Pharmacology and Experimental Therapeutics,187:195-202.
- Tiwari, BK., and Khosa, RL.,(2010). Hepatoprotective and antioxidant effect of Sphaeranthus indicus against acetaminophen–induced hepatotoxicity in rats,The Internet Journal of Tropical Medicine,6,1540-2681.
- Tirmenstein, MA., and Nelson, SD.,(1990). Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides. Journal of Biological Chemistry, Feb 25,265(6),3059-3065. PMID: 2303440.
- Bailey, B., Amre, DK., and Gaudreault, P., (2003). Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Critical Care Medicine,31,299-305.
- Lee, WM.,(2004). Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology,4,6-9.
- Potter, DW., and Hinson, JA.,(1986). Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH, Molecular Pharmacology Jul,30(1),33-41. PMID: 3724743.
- Bridger S., Henderson, K., Glucksman, E., Ellis, AJ., Henry, JA., and Williams, R., (1998). Deaths from low dose paracetamol poisoning, British Medical Journal, Jun 6,316(7146),1724-1725. doi: 10.1136/bmj.316.7146.1724. PMID: 9614027; PMCID: PMC1113277.
- Zimmerman, HJ., Maddrey, WC.,(1995). Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure,Hepatology,Sep,22(3),767-773. Erratum in: Hepatology 1995 Dec;22(6):1898. PMID: 7657281.
- Gujral, JS., Knight, TR., Farhood, A., Bajt, ML., and Jaeschke, H., (2002). Mode of Cell Death after Acetaminophen Overdose in Mice:Apoptosis or Oncotic Necrosis?,Toxicological Sciences,67:322-328
- Dehmlow, C., Erhard, J., and de Groot, H.,(1996). Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin, Hepatology,23,749-754.
- Jeong, DH., Lee, GP., Jeong, WI., Do, SH., Yang, HJ., and Yuan DW, et al. (2005). Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl4- induced hepatic fibrosis, World Journal of Gastroenterology,11:1141-1148
- Kokate, C., Purohit, A.P., and Gokhale, S.B.,(2010). In: Pharmacognosy, 10th ed., New Delhi: Nirali Prakashan,p.28-29.
- Hossain, MA., Al-Toubi, WAS., Weli, AM., Al-Riyami, QA., and Al-Sabahi, JN.,(2013).Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem, Journal of. Taibah University Sciences,7(4),181-188.
- Chattopadhyay, RR.,(2003). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II, Journal of Ethnopharmacology,Dec;89(2-3),217-219. doi: 10.1016/j.jep.2003.08.006. PMID: 14611885.
- Chattopadhyay, RR., and Bandopadhyay, M., (2005). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract against paracetamol induced hepatic damage in rats: Part III, Indian Journal of Pharmacology, 37(3),184-185
- Sithisarn, P., Supabphol, R., and Gritsanapan, W.,(2005). Antioxidant activity of Siamese neem tree (VP1209). Journal of Ethnopharmacology,99,109‑112.
- Manikandan, P., Anandan, R., and Nagini, S.,(2009). Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and protective effects against H2O2-induced oxidative damage to pBR322 DNA and red blood cells. Journal of Agriculture and Food Chemistry, 57(15),6990-6996.
- Al-Hashemi, ZSS., and Hossain, MA.,(2016). Biological activities of different neem leaf crude extracts used locally in Ayurvedic medicine. Pacific Science Review A: Natural Science and Engineering,18,128-131 http://dx.doi.org/10.1016/j.psra.2016.09.013
- Priyadarsini, RV., Manikandan, P., Kumar, GH., and Nagini, S.,(2009). The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radical Research,43,492.
- Schumacher, M., Cerella, C., Reuter, S., Dicato, M., and Diederich, M.,(2011). Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway, Genes and Nutrition,6,149.
- Hwang, SJ., Kim, YW., Park, Y., Lee, HJ., Kim, KW., (2014). Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflammation Research,63,81.
Effect of chronic administration of aqueous extract of Neem (Azadirachta indica) leaves on Paracetamol-induced hepatotoxicity in Wistar albino rats
Yıl 2022,
, 146 - 161, 02.01.2023
Pranob Jyoti Bharali
Sushanta Kumar Bordoloi
Swarnamoni Das
Kingshuk Lahon
Öz
Hepatoprotective drugs are not available for use in modern medicine and different parts of medicinal plants like Neem (Azadirachta indica) are used as hepatoprotectants in traditional medicine. Although there are scientific reports of its hepatoprotective activity on acute administration, we found only one study which had evaluated its hepatoprotective effect on chronic administration. Objectives: To evaluate the effect of chronic oral administration of Neem on paracetamol-induced hepatotoxicity in Wistar rats. Methods: We randomly assigned 72 male and female Wistar albino rats to four groups of 18 animals each and orally administered Distilled water 5ml/kg body weight/day to Groups A (Normal control) and B (Experimental control), 500 mg/kg aqueous Neem leaf extract (Test) to Group C and Silymarin suspension (Standard) 100mg/kg/day to Group D for 30 days. On the 8th day, we induced hepatotoxicity with Paracetamol 2g/kg body weight single dose to groups B, C and D. We performed liver function tests, recorded liver weights and examined liver histology of six rats from each group on 10th, 20th and 30th days. Results: We observed significant difference (P<0.05) in Mean ± SEM values of serum bilirubin, ALP, AST, ALT, liver weights, total protein and albumin: globulin in Group B compared to Group A, whereas these changes were significantly less in groups C and D compared to B. Histopathological examination of liver showed hepatic necrosis on 10th day in Groups B, C and D, but on 20th and 30th day in Group B and on 10th day in Groups C and D, we observed decrease in sinusoidal congestion and cloudy swelling along with small areas of regenerative changes. All abnormal histological changes decreased by the 30th day. Conclusion: Thus, aqueous extract of Azadirachta indica leaves shows hepatoprotective activity on chronic oral administration in Wistar rats.
Destekleyen Kurum
Assam Medical College, Dibrugarh, Assam, India
Teşekkür
1. Dibrugarh University, Dibrugarh Assam, India for financial support (dissertation grant) for the study.
2. Dr. Jibon Gogoi, Vice Principal, Institute of Pharmacy and faculty and postgraduates of the department of Pharmacology, Assam Medical College & Hospital, Dibrugarh, Assam, India
3. Laboratory technicians of the departments of Pathology and Biochemistry
4. Laboratory attendants of the Central Animal House and the department of Pharmacology for animal care and handling
Kaynakça
- Ramadori, G., Moriconi, F., Malik, I., and Dudas J., (2008). Physiology and pathophysiology of liver inflammation, damage and repair. Journal of Physiology and Pharmacology, Aug;59 Suppl 1:107-117. PMID: 18802219.
- Mansour, H.H., Hafez, H.F., and Fahmy, N.M., (2006). Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats. Journal of Biochemistry and Molecular Biology, Nov 30,39(6),656-661. doi: 10.5483/bmbrep.2006.39.6.656. PMID: 17129399.
- Camini, FC., and Costa, DC., (2020). Silymarin: not just another antioxidant. Journal of Basic and Clinical Physiology and Pharmacology, 2020 Mar 5,31(4)/j/jbcpp.2020.31.issue-4/jbcpp-2019-0206/jbcpp-2019-0206.xml. doi: 10.1515/jbcpp-2019-0206. PMID: 32134732.
- Polyak, SJ., Ferenci, P., and Pawlotsky, JM., (2013). Hepatoprotective and antiviral functions of silymarin components in hepatitis C virus infection. Hepatology, 57(3),1262-1271. doi: 10.1002/hep.26179. PMID: 23213025; PMCID: PMC3594650.
- Bedi, O., Bijjem, KRV., Kumar, P., and Gauttam, V., (2016). Herbal Induced Hepatoprotection and Hepatotoxicity: A Critical Review. Indian Journal of Physiology and Pharmacology,60(1),6-21. PMID: 29953177.
- Ilyas, U., Katare, DP., Aeri V., and Naseef, PP., (2016). A Review on Hepatoprotective and Immunomodulatory Herbal Plants. Pharmacognosy Reviews,10(19),66-70. doi: 10.4103/0973-7847.176544. PMID: 27041876; PMCID: PMC4791991.
- Kumar, VS., and Navaratnam, V., (2013). Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pacific Journal of Tropical Biomedicine,3(7),505-514. https://doi:10.1016/S2221-1691(13)60105-7
- Islas, JF., Acosta, E., G-Buentello, Z., Delgado-Gallegos, JL., Moreno-Trevino MG., and Escalante B., et al (2020). An overview of Neem (Azadirachta indica) and its potential impact on health. Journal of Functional Foods, 74, 104171 https://doi.org/10.1016/j.jff.2020.104171
- National Research Council (U.S.), Board on Science and Technology for International Development (1992). Neem: A Tree for Solving global Problems. In: Report of an Ad Hoc Panel of the Board on Science and Technology for International Development, National Research Council, The National Academies Press, Washington, DC, USA,1-152 https://doi.org/10.17226/1924
- Biswas, K., Chattopadhyay, I., Banerjee, RK., and Bandopadhyay, U.,(2002). Biological activities and medicinal properties of neem (Azadirachta indica), Current Science,82(11),1336-1345
- Rahmani, AH., Almatroudi, A., Alrumaihi, F., and Khan, AA., (2018). Pharmacological and therapeutic potential of neem (Azadirachta indica), Pharmacognosy Reviews,8(12),250-255
- Kharwar, RN., Sharma, VK., Mishra, A., Kumar, J., Singh, DK., Verma, SK., and Gond, SK., et. al (2020). Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms, Planta Medica, Sep,86(13-14),906-940. doi: 10.1055/a-1107-9370. Epub 2020 Mar 3. PMID: 32126583.
- Subapriya, R., and Nagini, S.,(2005). Medicinal properties of neem leaves: a review, Current medicinal chemistry. Anti-cancer agents, Mar,5(2),149-6. doi: 10.2174/1568011053174828. PMID: 15777222.
- Brahmachari. G.,(2004). Neem--an omnipotent plant: a retrospection, ChemBioChem, Apr, 2,5(4),408-421. doi: 10.1002/cbic.200300749. PMID: 15185362.
- Kaushik, N., Revuru, B., and Kusari, S.,(2020). Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms, Planta Medica, Sep 86(13-14),906-940. doi: 10.1055/a-1107-9370. Epub 2020 Mar 3. PMID: 32126583.
- Gupta, SC., Prasad, S., Tyagi, AK., Kunnumakkara, AB., and Aggarwal, BB.,(2017). Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis, Phytomedicine, Oct 15,34,14-20. doi: 10.1016/j.phymed.2017.07.001. Epub 2017 Jul 3. PMID: 28899496.
- Alzohairy, MA., (2016). Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment. Evidence Based Complementary and Alternative Medicine,2016:7382506. doi: 10.1155/2016/7382506. Epub 2016 Mar 1. PMID: 27034694; PMCID: PMC4791507.
- Khanna, N., Goswami, M., Sen, P., and Ray, A., (1995). Antinociceptive action of Azadirachta indica (neem) in mice: possible mechanisms involved. Indian Journal of Experimental Biology,Nov,33(11),848-850.PMID: 8786160.
- Chattopadhyay, RR., Chattopadhyay, RN., and Maitra, SK.,(1997). Possible mechanism of anti-inflammatory activity of Azadirachta indica leaf extract, Indian Journal of Pharmacology,27(2),99-100.
- Alam, A., Haldar, S., Thulasiram, HV., Kumar, R., Goyal, M., and Iqbal, MS., et al (2012). Novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor. Journal of Biological Chemistry,287(29):24844-24861
- Thoh, M., Babajan, B., Raghavendra, PB., Sureshkumar, C., and Manna, SK.,(2011). Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses. Journal of Biological Chemistry,286(6),4690-4702.
- Pingali, U., Ali, MA., Gundagani, S., and Nutalapati, C.,(2020). Evaluation of the Effect of an Aqueous Extract of Azadirachta indica (Neem) Leaves and Twigs on Glycemic Control, Endothelial Dysfunction and Systemic Inflammation in Subjects with Type 2 Diabetes Mellitus - A Randomized, Double-Blind, Placebo-Controlled Clinical Study, Diabetes Metabolic Syndrome and Obesity, Nov 17,13,4401-4412. doi: 10.2147/DMSO.S274378. PMID: 33244247; PMCID: PMC7683773.
- Ponnusamy, S., Haldar, S., Mulani, F., Zinjarde, S., Thulasiram, H., and RaviKumar, A.,(2015). Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents, PLoS One, Oct 15,10(10):e0140113. doi: 10.1371/journal.pone.0140113. PMID: 26469405; PMCID: PMC4607367.
- Bopanna, KN., Kanan, J., Gadgil, S., Balarman, R., and Rathod, SP.,(1997). Antidiabetic and antihyperlipidemic effects of neem seed kernel powder on alloxan diabetic rabbits. Indian Journal of Pharmacology,29(3):162-167
- Mukherjee, A., and Sengupta, S.,(2013). Characterization of nimbidiol as a potent intestinal disaccharidase and glucoamylase inhibitor present in Azadirachta indica (neem) useful for the treatment of diabetes, Journal of Enzyme Inhibition and Medicinal Chemistry,Oct,28(5):900-10. doi: 10.3109/14756366.2012.694877. Epub 2012 Jul 18. PMID: 22803678.
- Yarmohammadi, F., Mehri, S., Najafi, N., Salar Amoli, S., and Hosseinzadeh, H.,(2021). The protective effect of Azadirachta indica (neem) against metabolic syndrome: A review. Iran Journal of Basic Medical Sciences,Mar;24(3),280-292. doi: 10.22038/ijbms.2021.48965.11218. PMID: 33995939; PMCID: PMC8087850.
- Sen, P., Mediratta, PK., and Ray, A.,(1992). Immunostimulant activities of A.indica. Indian Journal of Experimental Biology,33: 1170-1195.
- Yadav, DY., Bharitkar, YP., Chatterjee, K., Ghosh, M., Mondal, NB., and Swarnakar, S.,(2016). Importance of Neem leaf: An insight into its role in combating diseases. Indian Journal of Experimental Biology,54,708-718
- Sarah, R., Tabassum, B., Idrees, N., and Hussain MK..,(2019). Bio-active Compounds Isolated from Neem Tree and Their Applications. In: Akhtar M, Swamy M, Sinniah U. (eds.) Natural Bio-active Compounds. Springer, Singapore,509-528 https://doi.org/10.1007/978-981-13-7154-7_17
- Quelemes, PV., Perfeito, ML., Guimarães, MA., dos Santos, RC., Lima, DF., and Nascimento, C., et. al (2015). Effect of neem (Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms, Journal of Ethnopharmacology, Dec 4,175,287-294. doi: 10.1016/j.jep.2015.09.026. Epub 2015 Sep 25. PMID: 26408045.
- Lu, XF., Lin, PC., Zi, JC., and Fan, XN.,(2019). [Limonoids from seeds of Azadirachta indica and their antibacterial activity], Zhongguo Zhong Yao Za Zhi,Nov,44(22),4864-4873. Chinese. doi: 10.19540/j.cnki.cjcmm.20190813.202. PMID: 31872594.
- Singh, AK., Sharma, RK., Sharma, V., Singh, T., Kumar, R., and Kumari, D.,(2017). Isolation, morphological identification and in vitro antibacterial activity of endophytic bacteria isolated from Azadirachta indica (neem) leaves. Veterinary World, May,10(5),510-516. doi: 10.14202/vetworld.2017.510-516. Epub 2017 May 11. PMID: 28620254; PMCID: PMC5465764.
- Thakurta, P., Bhowmik, P., Mukherjee. S., Hajra, TK., Patra, A., and Bag, PK.,(2007). Antibacterial, antisecretory and antihemorrhagic activity of Azadirachta indica used to treat cholera and diarrhea in India. Journal of Ethnopharmacology, May 22;111(3):607-612. doi: 10.1016/j.jep.2007.01.022. Epub 2007 Jan 21. PMID: 17314018.
- Ahmad, A., Javed, MR., Rao, AQ., and Husnain, T.,(2016).Designing and screening of universal drug from neem (Azadirachta indica) and standard drug chemicals against influenza virus nucleoprotein. BMC Complementary and Alternative Medicine Dec 16,16(1),519. doi: 10.1186/s12906-016-1469-2. PMID: 27986088; PMCID: PMC5162082.
- Faccin-Galhardi, LC., Yamamoto, KA., Ray, S., Ray, B., Carvalho Linhares, RE., and Nozawa C.,(2012).The in vitro antiviral property of Azadirachta indica polysaccharides for poliovirus. Journal of Ethnopharmacology, Jun 26,142(1),86-90. doi: 10.1016/j.jep.2012.04.018. PMID: 22855945.
- Tiwari, V., Darmani, NA., Yue, BY., and Shukla, D.,(2010).In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type-1 infection. Phytotherapy Research, Aug,24(8),1132-1140. doi: 10.1002/ptr.3085. PMID: 20041417; PMCID: PMC3767196.
- Natarajan, V., Venugopal, PV., and Menon, T.,(2003).Effect of Azadirachta indica (neem) on the growth pattern of dermatophytes. Indian Journal of Medical Microbiology, Apr-Jun,21(2),98-101. PMID: 17642990.
- Chianese, G., Yerbanga, SR., Lucantoni, L., Habluetzel, A., Basilico, N., and Taramelli, D., et al,(2010).Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica. Journal of Natural Products,Aug 27,73(8),1448-1452. doi: 10.1021/np100325q. PMID: 20669933.
- Batabyal, L., Sharma, P., Mohan, L., Maurya, P,, and Srivastava, CN.,(2009).Relative toxicity of neem fruit, bitter gourd, and castor seed extracts against the larvae of filaria vector, Culex quinquefasciatus (Say). Parasitology Research, Oct,105(5),1205-1210. doi: 10.1007/s00436-009-1541-7. Epub 2009 Jun 27. PMID: 19562373.
- Patel, SM., Nagulapalli Venkata, KC., Bhattacharyya, P., Sethi, G., Bishayee, A.,(2016).Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. Seminars in Cancer Biology,Oct;40-41,100-115. doi: 10.1016/j.semcancer.2016.03.002. Epub 2016 Mar 24. PMID: 27019417.
- Iman, M., Taheri, M., and Bahari, Z., (2021). The anti-cancer properties of neem (Azadirachta indica) through its antioxidant activity in the liver; its pharmaceutics and toxic dosage forms; a literature review. Journal of Complementary and Integrative Medicine, May 10. doi: 10.1515/jcim-2021-0009. Epub ahead of print. PMID: 33964199.
- Sarkar, S., Singh, RP., and Bhattacharya, G.,(2021).Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: an update on molecular approach, 3 Biotech, Apr,11(4),178. doi: 10.1007/s13205-021-02745-4. Epub 2021 Mar 20. PMID: 33927969; PMCID: PMC7981372.
- Saleem, S., Muhammad, G., Hussain, MA., and Bukhari, SNA.,(2018). A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica, Phytotherapy Research,Jul,32(7),1241-1272. doi: 10.1002/ptr.6076. Epub 2018 Apr 19. PMID: 29671907.
- Sujarwo, W., Keim, AP., Caneva, G., Toniolo, C., and Nicoletti, M.,(2016). Ethnobotanical uses of neem (Azadirachta indica A.Juss.; Meliaceae) leaves in Bali (Indonesia) and the Indian subcontinent in relation with historical background and phytochemical properties, Journal of Ethnopharmacology, Aug 2,189,186-193. doi: 10.1016/j.jep.2016.05.014. Epub 2016 May 10. PMID: 27178630.
- Maity, P., Biswas, K., Chattopadhyay, I., Banerjee, RK., and Bandyopadhyay, U.,(2009).The use of neem for controlling gastric hyperacidity and ulcer, Phytotherapy Research, Jun,23(6),747-755. doi: 10.1002/ptr.2721. PMID: 19140119.
- Dorababu, M., Joshi, MC., Bhawani, G., Kumar, MM., and Chaturvedi, A., and Goel, RK.,(2006). Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and diffensive gastric mucosal factors in rats. Indian Journal of Physiology and Pharmacology,Jul-Sep,50(3),241-249. PMID: 17193895.
- Bandyopadhyay, U., Biswas, K., Sengupta, A., Moitra, P., Dutta, P., and Sarkar, D., et. al, (2004).Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer, Life Sciences, Oct 29,75(24),2867-2878. doi: 10.1016/j.lfs.2004.04.050. PMID: 15454339.
- Maity, P., Biswas K., Chattopadhyay, I., Banerjee, RK., and Bandyopadhyay, U.,(2009). The use of neem for controlling gastric hyperacidity and ulcer, Phytotherapy Research, Jun, 23(6),747-755. doi: 10.1002/ptr.2721. PMID: 19140119.
- Khillare, B., and Shrivastav, TG.,(2003). Spermicidal activity of Azadirachta indica (neem) leaf extract,Contraception, Sep,68(3),225-229. doi: 10.1016/s0010-7824(03)00165-3. PMID: 14561544.
- Chaube, SK., Shrivastav, TG., Tiwari, M., Prasad, S., Tripathi, A., and Pandey, AK.,(2014). Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals, SpringerPlus, Aug 26,3,464. doi: 10.1186/2193-1801-3-464. PMID: 25197620; PMCID: PMC4155053.
- Hummel, HE., Langner, SS., Leithold, G., Schmutterer, H.,(2014). NEEM: UNUSUALLY VERSATILE PLANT GENUS AZADIRACHTA WITH MANY USEFUL AND SO FAR INSUFFICIENTLY EXPLOITED PROPERTIES FOR AGRICULTURE, MEDICINE, AND INDUSTRY. Communications in Agricultural Applications and Biological Sciences,79(2),211-228. PMID: 26084100.
- Handa, SS., Sharma, A., and Chakraborti, KK., (1986). Natural products and plants as liver protecting drugs, Fitoterapia,57,307-352
- Chattopadhyay, RR., Sarkar, SK., Ganguly, S., Banerjee, RN., Basu, TK., and Mukherjee, A. Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats, Indian Journal of Experimental Biology, Aug,30(8),738-740. PMID: 1459654.
- Mukherjee, PK., Bhakta, T., Saha, BP., Pal, S., Pal, M., and Das, AA.,(1994). Protective effect of fraction of Azadirachta indica leaf extract on carbon tetrachloride induced hepatotoxicity, Ancient Science of Life, Jul,14(1-2),71-76. PMID: 22556679; PMCID: PMC3336499.
- Nahed, AM.,(1996). Effect of azadirachta indica NEEM extract on paracetamol induced hepatotoxicity, Assiut Medical Journal,20(2),137-154 | IMEMR | ID: emr-40412
- Bhanwra, S., Singh, J., and Khosla, P.,(2000). Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats, Indian Journal of Physiology and Pharmacology,Jan,44(1),64-68. PMID: 10919097.
- Kale, BP., Kothekar, MA., Tayade, HP., Jaju, JB., and Mateenuddin, M.,(2003). Effect of aqueous extract of Azadirachta indica leaves on hepatotoxicity induced by antitubercular drugs in rats, Indian Journal of Pharmacology,35,177‑180.
- Yanpallewar, SU., Sen, S., Tapas, S., Kumar, M., Raju, SS, and Acharya, SB. Effect of Azadirachta indica on paracetamol-induced hepatic damage in albino rats, Phytomedicine,10(5),391-396. doi: 10.1078/0944-7113-00230. PMID: 12834004.
- Kalaivani, T., Meignanam, E., Premkumar, N., Siva, R., Vijayakumar, V., and Rajasekaran, C., et al. Studies on hepatoprotective properties of leaf extracts of Azadirachta indica A. Juss (Meliaceae),Ethobotanicalleaflets,13,165-170
- Ezz-Din, D., Gabry, MS., and Farrag, ARH., and Abdel Moneim, AE.,(2011). Physiological and histological impact of Azadirachta indica (neem) leaves extract in a rat model of cisplatin-induced hepato and nephrotoxicity. Journal of Medical Plants Research, 5(23),5499-5506 http://www.academicjournals.org/JMPR
- Akinola, OB., Omotoso, GO., Akinola, OS., Dosumu, OO., and Adewoye, ET.,(2011). Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats. Zhong Xi Yi Jie He Xue Bao, Dec,9(12),1373-1379. doi: 10.3736/jcim20111215. PMID: 22152778.
- Dkhil, MA., Al-Quraishy, S., Aref, AM., Othman, MS., El-Deib KM., and Abdel Moneim, AE.,(2013). The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats. Oxidative Medicine and Cellular Longevity,2013:741817. doi: 10.1155/2013/741817. Epub 2013 Dec 4. PMID: 24369490; PMCID: PMC3867870.
- Essien, NA., Iwara, IA., Mgbeje, BAI., Igile, GO., Egbung, GE., and Ebong, PE.,(2013). Lipid profile and hepatoprotective effects of combined leaf extracts of Azadirachta indica (Neem) and Peristrophe bycaliculata in Alloxan-induced diabetic rats, International Journal of Phytomedicine 5:159-162.
- Johnson, M., Olufunmilayo, LA., Anthony, DO., and Olusoji., EO.,(2013). Hepatoprotective Effect of Ethanolic Leaf Extract of Vernonia amygdalina and Azadirachta indica against Acetaminophen-Induced Hepatotoxicity in Sprague-Dawley Male Albino Rats, American Journal of Pharmacological Sciences,3(3),79-86 Available online at http://pubs.sciepub.com/ajps/3/3/5 DOI:10.12691/ajps-3-3-5
- Koul, A., Mohan, V., Bharati, S.,(2014). Azadirachta indica mitigates DMBA-induced hepatotoxicity: a biochemical and radiometric study. Indian Journal of Biochemistry and Biophysics, Feb,51(1),37-45. PMID: 24791415.
- Baligar, NS., Aladakatti, RH., Ahmed, M., and Hiremath, MB.,(2014). Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats. Canadian Journal of Physiology and Pharmacology Apr,92(4),267-277. doi: 10.1139/cjpp-2013-0449. Epub 2014 Jan 9. PMID: 24708208.
- Baligar, NS., Aladakatti, RH., Ahmed, M., and Hiremath, MB.,(2014). Evaluation of acute toxicity of neem active constituent, nimbolide and its hepatoprotective activity against acute dose of carbon tetrachloride treated albino rats. International Journal of Pharmaceutical Sciences and Research, 5(8), 3455-3466. doi: 10.13040/IJPSR.0975-8232.5(8).3455-66
- Kesarkar, R., Sangar, V., Oza, G., Sawant, T., Kothari, S., and Sharon, M.,(2014). Synthesis, characterization and hepatoprotective activity of Neem gold nanoparticles for improved efficacy and sustained drug release profile of Azidothymidine, International Journal of Pharmaceutical Sciences Review and Research,26(2),117-122
- Abdel, Moneim AE., Othman, MS., and Aref, AM.,(2014).Azadirachta indica attenuates cisplatin-induced nephrotoxicity and oxidative stress. Biomedical Research International,2014,647131. doi: 10.1155/2014/647131. Epub 2014 Aug 3. PMID: 25162019; PMCID: PMC4137610.
- Aslam, F., Jamil, S., and Aslam, MA., (2016). Antihepatotoxic activity of Gemmotherapeutically treated Neem and alcoholic extract of Neem in albino rats. Pakistan Journal of Medical and Health Sciences,10(1),68-76
- Chavan, T., Ghadge, A., Karandikar, M., Pandit, V., Ranjekar, P., and Kulkarni, O., et. al (2017). Hepatoprotective Activity of Satwa, an Ayurvedic Formulation, Against Alcohol-induced Liver Injury in Rats, Alternative Therapies in Health and Medicine, Jul,23(4),34-40. PMID: 28646813.
- Idu, M., Ovuakpurie-Uvo, O., and Okojie, S.,(2017). Protective effects of neem (Azadirachta indica A. Juss) seed oil on carbon tetrachloride-induced hepatotoxicity in Wistar rats. Journal of Medicinal Plants for Economic Development, Published Online: 22 Aug,doi:https://doi.org/10.4102/jomped.v1i1.6 https://hdl.handle.net/10520/EJC-a87b303b6
- Nwobodo, EI., Nwosu, DC., Ogbodo, SO., Ugwuene, FO., Ihim, AC., and Ani, NO.,(2018). Effects of Azadirachta indica leaf aqueous extract on the antioxidant enzymes in paracetamol-induced hepatotoxicity in Wistar rats, International Journal of Biological and Chemical Sciences,12(1),1-10 DOIhttps://dx.doi.org/10.4314/ijbcs.v12i1.1
- Althaiban MA.,(2019). Evaluation of hepatopotective activity of Neem extract in Rifampin induced acute hepatic failure in rats. International Journal of Pharmaceutical Research and Allied Sciences,8(3),29-36
- Sani, I., Umar, RA., Hassan, SW., Faruq, UZ., Bello, F., and Aminu, H., et al. (2020). Hepatoprotective Effect of Azadirachta indica Leaf Fractionated Extracts against Snake Venom Toxicity on Albino Rats, Saudi Journal of Biomedical Research,5(6),112-117 DOI: 10.36348/sjbr.2020.v05i06.004
- Seriana, I., Akmal, M., Darusman, D., Wahyuni, S., Khairan, K., and Sugito, S., (2021). Neem Leaf (Azadirachta indica A. Juss) Ethanolic Extract on the Liver and Kidney Function of Rats, Hindawi The Scientific World Journal 2021,Article ID 7970424, 7 pages https://doi.org/10.1155/2021/7970424
- Committee for the purpose of control and supervision of experimental animals,(2018). In: Compendium of CPCSEA, New Delhi: Ministry of Environment, Forests and Climate Change, Animal Welfare Division, Govt. of India, 202 p. Available from http://cpcsea.nic.in/WriteReadData/userfiles/file/Compendium%20of%20CPCSEA.pdf, Accessed 20th August 2021
- Reinhold, JG., (1953). Biuret method. In: Reiner M, editor. Standard Methods of Clinical Chemistry. Ann Arbor: Academic Press, Inc;Vol. 1, p. 88.
- GORNALL, AG., BARDAWILL, CJ., and DAVID, MM.,(1949).Determination of serum proteins by means of the biuret reaction. Journal of Biological Chemistry Feb,177(2),751-766. PMID: 18110453.
- King, EJ., Abul-Fadl, MAM., and Walker, PG.,(1951). King-Armstrong phosphatase estimation by the determination of liberated phosphate, Journal of Clinical Pathology,4,85.
- Reitman, S., and Frankel, S.,(1957). Colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transminases. American Journal of Clinical Pathology,28(1),56-63. doi: 10.1093/ajcp/28.1.56. PMID: 13458125.
- Ann Preece.,(1972). In: Manual for histologic technicians,3rd ed.,Boston: Little, Brown and Company
- Haque, E., Mandal, I., Pal, S., and Baral, R.,(2006). Prophylactic Dose of Neem (Azadirachta indica) Leaf Preparation Restricting Murine Tumor Growth is Nontoxic, Hematostimulatory and Immunostimulatory, Immunopharmacology and Immunotoxicology,28,33-50 https://doi.org/10.1080/08923970600623632
- Mallick, A., Ghosh, S., Banerjee, S., Majumder, S., Das, A., and Mondal, B., et. al, (2013). Neem leaf glycoprotein is nontoxic to physiological functions of Swiss mice and Sprague Dawley rats: histological, biochemical and immunological perspectives, International Immunopharmacology, Jan,15(1),73-83. doi: 10.1016/j.intimp.2012.11.006. Epub 2012 Nov 21. PMID: 23178577.
- Suhendro., Susraini, AAAN., Saputra, H., and Sriwidyani, NP.,(2018). Oral administration of neem (Azadirachta indica A. Juss) leaf extract increases Cyclin D1 expression in hepatocyte regeneration in acetaminophen-induced hepatotoxic wistar rats, Bali Medical Journal,7(1),12-16 DOI:10.15562/bmj.v7i1.700
- Kim, WR., Flamm, SL., Di Bisceglie, AM., and Bodenheimer, HC.,(2008). Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease, Hepatology, Apr,47(4),1363-1370. doi: 10.1002/hep.22109. PMID: 18366115.
- Giannini, EG., Testa, R., and Savarino, V.,(2005). Liver enzyme alteration: a guide for clinicians, Canadian Medical Association Journal,172(3),367-379.
- Rotermund, HM., Schreiber, G., Maeno, H., Weinssen, U., and Weigand, K.,(1970). The ratio of albumin synthesis to total protein synthesis in normal rat liver, in host liver, and in Morris hepatoma 9121,Cancer Research, 30: 2139-2146.
- Landel, AM., Hammond, WG., and Meguid, MM.,(1985). Aspects of amino acid and protein metabolism in cancer - bearing states,Cancer,55: 230-237.
- Teloh HA., (1978). Serum proteins in hepatic disease, Annals of Clinical & Laboratory Science,8(2),127-129
- Amacher, DE.,(1998). Serum transaminase elevations as indicators of hepatic injury following the administration of drugs, Regulatory Toxicology and Pharmacology,27,119-130.
- Raucy, JL., Lasker, JM., Lieber, CS., and Black, M.,(1989). Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2, Archives of Biochemistry and Biophysics, Jun,271(2),270-283. doi: 10.1016/0003-9861(89)90278-6. PMID: 2729995.
- James, LP., Mayeux, PR., and Hinson, JA.,(2003). Acetaminophen-induced hepatotoxicity. Drug Metabolism and Disposition, 31,1499 -1506.
- Moore, M., Thor, H., Moore, G., Nelson, S., Moldeus, P., and Orrenius, S.,(1985). The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+, Journal of Biologocal Chemistry,260:13035-13040.
- Jollow, DJ., Mitchell, JR., Potter, WZ., Davis, DC., Gillette, JR., and Brodie, BB.,(1973). Acetaminophen induced hepatic necrosis. II. Role of covalent binding in vivo, Journal of Pharmacology and Experimental Therapeutics,187:195-202.
- Tiwari, BK., and Khosa, RL.,(2010). Hepatoprotective and antioxidant effect of Sphaeranthus indicus against acetaminophen–induced hepatotoxicity in rats,The Internet Journal of Tropical Medicine,6,1540-2681.
- Tirmenstein, MA., and Nelson, SD.,(1990). Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides. Journal of Biological Chemistry, Feb 25,265(6),3059-3065. PMID: 2303440.
- Bailey, B., Amre, DK., and Gaudreault, P., (2003). Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Critical Care Medicine,31,299-305.
- Lee, WM.,(2004). Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology,4,6-9.
- Potter, DW., and Hinson, JA.,(1986). Reactions of N-acetyl-p-benzoquinone imine with reduced glutathione, acetaminophen, and NADPH, Molecular Pharmacology Jul,30(1),33-41. PMID: 3724743.
- Bridger S., Henderson, K., Glucksman, E., Ellis, AJ., Henry, JA., and Williams, R., (1998). Deaths from low dose paracetamol poisoning, British Medical Journal, Jun 6,316(7146),1724-1725. doi: 10.1136/bmj.316.7146.1724. PMID: 9614027; PMCID: PMC1113277.
- Zimmerman, HJ., Maddrey, WC.,(1995). Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure,Hepatology,Sep,22(3),767-773. Erratum in: Hepatology 1995 Dec;22(6):1898. PMID: 7657281.
- Gujral, JS., Knight, TR., Farhood, A., Bajt, ML., and Jaeschke, H., (2002). Mode of Cell Death after Acetaminophen Overdose in Mice:Apoptosis or Oncotic Necrosis?,Toxicological Sciences,67:322-328
- Dehmlow, C., Erhard, J., and de Groot, H.,(1996). Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin, Hepatology,23,749-754.
- Jeong, DH., Lee, GP., Jeong, WI., Do, SH., Yang, HJ., and Yuan DW, et al. (2005). Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl4- induced hepatic fibrosis, World Journal of Gastroenterology,11:1141-1148
- Kokate, C., Purohit, A.P., and Gokhale, S.B.,(2010). In: Pharmacognosy, 10th ed., New Delhi: Nirali Prakashan,p.28-29.
- Hossain, MA., Al-Toubi, WAS., Weli, AM., Al-Riyami, QA., and Al-Sabahi, JN.,(2013).Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem, Journal of. Taibah University Sciences,7(4),181-188.
- Chattopadhyay, RR.,(2003). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II, Journal of Ethnopharmacology,Dec;89(2-3),217-219. doi: 10.1016/j.jep.2003.08.006. PMID: 14611885.
- Chattopadhyay, RR., and Bandopadhyay, M., (2005). Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract against paracetamol induced hepatic damage in rats: Part III, Indian Journal of Pharmacology, 37(3),184-185
- Sithisarn, P., Supabphol, R., and Gritsanapan, W.,(2005). Antioxidant activity of Siamese neem tree (VP1209). Journal of Ethnopharmacology,99,109‑112.
- Manikandan, P., Anandan, R., and Nagini, S.,(2009). Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and protective effects against H2O2-induced oxidative damage to pBR322 DNA and red blood cells. Journal of Agriculture and Food Chemistry, 57(15),6990-6996.
- Al-Hashemi, ZSS., and Hossain, MA.,(2016). Biological activities of different neem leaf crude extracts used locally in Ayurvedic medicine. Pacific Science Review A: Natural Science and Engineering,18,128-131 http://dx.doi.org/10.1016/j.psra.2016.09.013
- Priyadarsini, RV., Manikandan, P., Kumar, GH., and Nagini, S.,(2009). The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis. Free Radical Research,43,492.
- Schumacher, M., Cerella, C., Reuter, S., Dicato, M., and Diederich, M.,(2011). Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway, Genes and Nutrition,6,149.
- Hwang, SJ., Kim, YW., Park, Y., Lee, HJ., Kim, KW., (2014). Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflammation Research,63,81.