{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:07:17Z","timestamp":1772608037604,"version":"3.50.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Manipal Academy of Higher Education, Manipal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["3 Biotech"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proteins of the macroglobulin family are prime targets of venom enzymes in snake bite. A massive reduction in the active concentration of these multifunctional proteins in snake bite, makes the living system vulnerable to dysregulation. This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of <jats:italic>Andrographis paniculata<\/jats:italic> (MAP) and their combination in rescuing human alpha 2-macroglobulin (A2MG) and its homologues in rat plasma, from inactivation by <jats:italic>Naja naja<\/jats:italic> (N.N) venom enzymes. In-vitro experiments were conducted with heparinized human plasma and in-vivo experiments with female Wistar rats. Along with appropriate controls, there were 3 test groups in in-vitro and 8 test groups in in-vivo experiments. The in-vitro test groups were exposed to N.N venom for zero, 30 or 90\u00a0min prior to incubation with ASV or MAP or reduced ASV supplemented with MAP and incubated for 16\u00a0h at 37\u00a0\u00b0C. Chymotrypsin-bound esterase (CTBE) activity of A2MG was estimated. Rats were administered the venom intramuscularly and treated with ASV\/MAP\/ASV\u2009+\u2009MAP. CTBE activity of macroglobulin homologues was measured on day 1, 7 and 14. Survival of animals was noted. In human plasma, addition of ASV or MAP or ASV\u2009+\u2009MAP prevented loss of A2MG activity maximally to the extent of 88\u2013100% (<jats:italic>p<\/jats:italic>\u2009=\u20090.001). In rats, reduced concentration of ASV supplemented with MAP showed complete rescue of macroglobulin homologues and 90% survival. The compulsive evidence from this study, underscores the merits of using this multipronged strategy in rescuing the macroglobulins and improving survival in envenomation due to N.N.<\/jats:p>","DOI":"10.1007\/s13205-022-03379-w","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T06:02:57Z","timestamp":1664949777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Augmented rescue of macroglobulins by supplementation of anti-snake venom with methanolic extract of Andrographis paniculata in Naja naja envenomation"],"prefix":"10.1007","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-5807","authenticated-orcid":false,"given":"Akshatha G.","family":"Nayak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-6746","authenticated-orcid":false,"given":"P. Ashwini","family":"Aithal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-3954","authenticated-orcid":false,"given":"Nitesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-1855","authenticated-orcid":false,"given":"Smita","family":"Shenoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-0736","authenticated-orcid":false,"given":"Maya","family":"Roche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"issue":"10","key":"3379_CR1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/S0041-0101(98)00076-2","volume":"36","author":"MI Alam","year":"1998","unstructured":"Alam MI, Gomes A (1998) Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant `sarsaparilla\u2019 (Hemidesmus indicus R. Br.). Toxicon 36(10):1423\u20131431. https:\/\/doi.org\/10.1016\/S0041-0101(98)00076-2","journal-title":"Toxicon"},{"key":"3379_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-019-1790-9","author":"R Amos Samkumar","year":"2019","unstructured":"Amos Samkumar R, Premnath D, Raj DP (2019) Strategy for early callus induction and identification of anti-snake venom triterpenoids from plant extracts and suspension culture of Euphorbia hirta L. 3 Biotech. https:\/\/doi.org\/10.1007\/s13205-019-1790-9","journal-title":"3 Biotech"},{"issue":"8","key":"3379_CR3","doi-asserted-by":"publisher","first-page":"4968","DOI":"10.4049\/jimmunol.166.8.4968","volume":"166","author":"RJ Binder","year":"2001","unstructured":"Binder RJ, Karimeddini D, Srivastava PK (2001) Adjuvanticity of \u03b1 2 -macroglobulin, an independent ligand for the heat shock protein receptor CD91. J Immunol 166(8):4968\u20134972. https:\/\/doi.org\/10.4049\/jimmunol.166.8.4968","journal-title":"J Immunol"},{"issue":"2","key":"3379_CR4","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1530\/eje.0.1390224","volume":"139","author":"G Birkenmeier","year":"1998","unstructured":"Birkenmeier G et al (1998) Human leptin forms complexes with \u03b12-macroglobulin which are recognized by the \u03b12-macroglobulin receptor\/low density lipoprotein receptor-related protein. Eur J Endocrinol 139(2):224\u2013230. https:\/\/doi.org\/10.1530\/eje.0.1390224","journal-title":"Eur J Endocrinol"},{"key":"3379_CR5","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/153045","author":"BMA Carvalho","year":"2013","unstructured":"Carvalho BMA et al (2013) Snake venom PLA2s inhibitors isolated from Brazilian plants: Synthetic and natural molecules. BioMed Res Int. https:\/\/doi.org\/10.1155\/2013\/153045","journal-title":"BioMed Res Int"},{"issue":"3","key":"3379_CR6","doi-asserted-by":"publisher","first-page":"605","DOI":"10.15517\/rbt.v47i3.19215","volume":"47","author":"O Castro","year":"1999","unstructured":"Castro O et al (1999) Neutralizaci\u00f3n del efecto hemorr\u00e1gico inducido por veneno de Bothrops asper (Serpentes: Viperidae) por extractos de plantas tropicales. Rev Biol Trop 47(3):605\u2013615. https:\/\/doi.org\/10.15517\/rbt.v47i3.19215","journal-title":"Rev Biol Trop"},{"key":"3379_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.toxicon.2017.06.005","volume":"135","author":"M Choudhury","year":"2017","unstructured":"Choudhury M et al (2017) Comparison of proteomic profiles of the venoms of two of the \u201cBig Four\u201d snakes of India, the Indian cobra (Naja naja) and the common krait (Bungarus caeruleus), and analyses of their toxins. Toxicon 135:33\u201342. https:\/\/doi.org\/10.1016\/j.toxicon.2017.06.005","journal-title":"Toxicon"},{"key":"3379_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21101350","author":"E Coriolano de Oliveira","year":"2016","unstructured":"Coriolano de Oliveira E et al (2016) Protective effect of the plant extracts of erythroxylum sp. against toxic effects induced by the venom of lachesis muta snake. Molecules. https:\/\/doi.org\/10.3390\/molecules21101350","journal-title":"Molecules"},{"issue":"5","key":"3379_CR9","doi-asserted-by":"publisher","first-page":"535","DOI":"10.2174\/1381612822666151125001751","volume":"22","author":"A Dar","year":"2016","unstructured":"Dar A et al (2016) Unique medicinal properties of withania somnifera: phytochemical constituents and protein component. Curr Pharm Des 22(5):535\u2013540. https:\/\/doi.org\/10.2174\/1381612822666151125001751","journal-title":"Curr Pharm Des"},{"issue":"08","key":"3379_CR10","doi-asserted-by":"publisher","first-page":"15176","DOI":"10.15680\/ijirset.2014.0308016","volume":"03","author":"P Das","year":"2014","unstructured":"Das P, Srivastav AK (2014) Phytochemical extraction and characterization of the leaves of andrographis paniculata for its anti-bacterial, anti-oxidant, anti-pyretic and anti-diabetic activity. Int J Innov Res Sci Eng Technol 03(08):15176\u201315184. https:\/\/doi.org\/10.15680\/ijirset.2014.0308016","journal-title":"Int J Innov Res Sci Eng Technol"},{"issue":"3","key":"3379_CR11","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1111\/bcp.12739","volume":"81","author":"HJAJA de Silva","year":"2016","unstructured":"de Silva HJAJA, Ryan NM, de Silva HJAJ (2016) \u2018Adverse reactions to snake antivenom, and their prevention and treatment. Br J Clin Pharmacol 81(3):446\u2013452. https:\/\/doi.org\/10.1111\/bcp.12739","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"3379_CR12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jyp.2013.02.003","volume":"5","author":"RP Deshpande","year":"2013","unstructured":"Deshpande RP et al (2013) Adverse drug reaction profile of anti-snake venom in a rural tertiary care teaching hospital. J Young Pharm 5(2):41\u201345. https:\/\/doi.org\/10.1016\/j.jyp.2013.02.003","journal-title":"J Young Pharm"},{"issue":"1","key":"3379_CR13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/2231-0738.106973","volume":"3","author":"YN Dey","year":"2013","unstructured":"Dey YN, Kumari S, Sarada Ota NS (2013) Phytopharmacological review of Andrographis paniculata (Burm. f). Int J Nutr Pharmacol Neurol Dis 3(1):3\u201310","journal-title":"Int J Nutr Pharmacol Neurol Dis"},{"issue":"19","key":"3379_CR14","doi-asserted-by":"publisher","first-page":"11428","DOI":"10.1016\/s0021-9258(18)60482-x","volume":"264","author":"JJ Enghild","year":"1989","unstructured":"Enghild JJ et al (1989) Proteinase binding and inhibition by the monomeric \u03b1-macroglobulin rat \u03b11-inhibitor-3. J Biol Chem 264(19):11428\u201311435. https:\/\/doi.org\/10.1016\/s0021-9258(18)60482-x","journal-title":"J Biol Chem"},{"issue":"2","key":"3379_CR15","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.toxicon.2003.11.012","volume":"43","author":"T Escalante","year":"2004","unstructured":"Escalante T et al (2004) Bothrops asper metalloproteinase BaP1 is inhibited by \u03b1 2-macroglobulin and mouse serum and does not induce systemic hemorrhage or coagulopathy. Toxicon 43(2):213\u2013217. https:\/\/doi.org\/10.1016\/j.toxicon.2003.11.012","journal-title":"Toxicon"},{"issue":"2\u20133","key":"3379_CR16","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0167-4838(84)90114-6","volume":"784","author":"HJ Evans","year":"1984","unstructured":"Evans HJ, Guthrie VH (1984) Proteolytic activities of cobra venoms based on inactivation of \u03b12-macroglobulin. Biochim Biophys Acta Protein Struct Mol 784(2\u20133):97\u2013101. https:\/\/doi.org\/10.1016\/0167-4838(84)90114-6","journal-title":"Biochim Biophys Acta Protein Struct Mol"},{"issue":"17","key":"3379_CR17","doi-asserted-by":"publisher","first-page":"5700","DOI":"10.1073\/pnas.82.17.5700","volume":"82","author":"SR Feldman","year":"1985","unstructured":"Feldman SR, Gonias SL, Pizzo SV (1985) Model of \u03b12-macroglobulin structure and function. Proc Natl Acad Sci USA 82(17):5700\u20135704. https:\/\/doi.org\/10.1073\/pnas.82.17.5700","journal-title":"Proc Natl Acad Sci USA"},{"key":"3379_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ghir.2005.11.001","volume-title":"Physiology and pathophysiology of growth hormone-binding protein: methodological and clinical aspects. Growth Hormone and IGF Research","author":"S Fisker","year":"2006","unstructured":"Fisker S (2006) Physiology and pathophysiology of growth hormone-binding protein: methodological and clinical aspects. Growth Hormone and IGF Research. Livingstone, Churchill, pp 1\u201328. https:\/\/doi.org\/10.1016\/j.ghir.2005.11.001"},{"key":"3379_CR19","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.toxrep.2014.08.012","volume":"1","author":"K Gopi","year":"2014","unstructured":"Gopi K, Renu K, Jayaraman G (2014) Inhibition of Naja naja venom enzymes by the methanolic extract of Leucas aspera and its chemical profile by GC-MS. Toxicol Rep 1:667\u2013673. https:\/\/doi.org\/10.1016\/j.toxrep.2014.08.012","journal-title":"Toxicol Rep"},{"key":"3379_CR20","unstructured":"Gopi K et al (2011) The neutralization effect of methanol extract of Andrographis paniculata on Indian cobra Naja naja snake venom. J Pharm Res 4(4): 1010\u20131012. Available at: http:\/\/jprsolutions.info."},{"issue":"1","key":"3379_CR21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s42826-019-0014-0","volume":"35","author":"R Ito","year":"2019","unstructured":"Ito R, Kuribayashi T (2019) Correlation between synthesis of \u03b12-macroglobulin as acute phase protein and degree of hepatopathy in rats. Lab Anim Res 35(1):4\u20139. https:\/\/doi.org\/10.1186\/s42826-019-0014-0","journal-title":"Lab Anim Res"},{"issue":"3","key":"3379_CR22","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/0304-4165(94)90172-4","volume":"1200","author":"AS Kamiguti","year":"1994","unstructured":"Kamiguti AS et al (1994) Ineffectiveness of the inhibition of the main haemorrhagic metalloproteinase from Bothrops jararaca venom by its only plasma inhibitor, \u03b12-macroglobulin. BBA General Subjects 1200(3):307\u2013314. https:\/\/doi.org\/10.1016\/0304-4165(94)90172-4","journal-title":"BBA General Subjects"},{"issue":"1","key":"3379_CR23","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/s0021-9258(19)75946-8","volume":"262","author":"K Lonberg-Holm","year":"1987","unstructured":"Lonberg-Holm K et al (1987) Three high molecular weight protease inhibitors of rat plasma. Isolation, characterization, and acute phase changes. J Biol Chem 262(1):438\u2013445. https:\/\/doi.org\/10.1016\/s0021-9258(19)75946-8","journal-title":"J Biol Chem"},{"issue":"1","key":"3379_CR24","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/s0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry OH et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265\u2013275. https:\/\/doi.org\/10.1016\/s0021-9258(19)52451-6","journal-title":"J Biol Chem"},{"issue":"6","key":"3379_CR25","first-page":"212","volume":"4","author":"M SK, M","year":"2013","unstructured":"M SK, M (2013) Andographis paniculata and its bioactive phytochemical constiturents for oxidative damage: a systemic review. Pharmacophore 4(6):212\u2013229","journal-title":"Pharmacophore"},{"issue":"4","key":"3379_CR26","first-page":"76","volume":"2","author":"S Meenatchisundaram","year":"2009","unstructured":"Meenatchisundaram S (2009) Studies on antivenom activity of Andrographis paniculata and Aristolochia indica plant extracts against Daboia russelli venom by in vivo and in vitro methods. J Sci Technol 2(4):76\u201379","journal-title":"J Sci Technol"},{"issue":"2","key":"3379_CR27","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1271\/bbb.70540","volume":"72","author":"N Morine","year":"2008","unstructured":"Morine N et al (2008) The occurrence of HR1b in the venom of the snake Okinawa habu (Protobothrops flavoviridis). Biosci Biotechnol Biochem 72(2):591\u2013594. https:\/\/doi.org\/10.1271\/bbb.70540","journal-title":"Biosci Biotechnol Biochem"},{"issue":"12","key":"3379_CR28","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.1016\/J.FCT.2011.09.026","volume":"49","author":"R Nagalekshmi","year":"2011","unstructured":"Nagalekshmi R et al (2011) Hepatoprotective activity of Andrographis paniculata and Swertia chirayita. Food Chem Toxicol 49(12):3367\u20133373. https:\/\/doi.org\/10.1016\/J.FCT.2011.09.026","journal-title":"Food Chem Toxicol"},{"issue":"1","key":"3379_CR29","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/s10620-007-9849-6","volume":"53","author":"S Nancey","year":"2008","unstructured":"Nancey S et al (2008) Serum interleukin-6, soluble interleukin-6 receptor and Crohn\u2019s disease activity. Dig Dis Sci 53(1):242\u2013247. https:\/\/doi.org\/10.1007\/s10620-007-9849-6","journal-title":"Dig Dis Sci"},{"key":"3379_CR30","doi-asserted-by":"publisher","first-page":"3946","DOI":"10.3389\/fimmu.2020.603569","volume":"11","author":"N Naseraldeen","year":"2021","unstructured":"Naseraldeen N et al (2021) The role of alpha 2 macroglobulin in igg-aggregation and chronic activation of the complement system in patients with chronic lymphocytic leukemia. Front Immunol 11:3946. https:\/\/doi.org\/10.3389\/fimmu.2020.603569","journal-title":"Front Immunol"},{"key":"3379_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112480","author":"AG Nayak","year":"2020","unstructured":"Nayak AG et al (2020a) Can the methanolic extract of Andrographis paniculata be used as a supplement to anti-snake venom to normalize hemostatic parameters: a thromboelastographic study. J Ethnopharmacol. https:\/\/doi.org\/10.1016\/j.jep.2019.112480","journal-title":"J Ethnopharmacol"},{"issue":"11","key":"3379_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13205-020-02462-4","volume":"10","author":"AG Nayak","year":"2020","unstructured":"Nayak AG et al (2020b) Anti-snake venom and methanolic extract of Andrographis paniculata: a multipronged strategy to neutralize Naja naja venom acetylcholinesterase and hyaluronidase. 3 Biotech 10(11):1\u201312. https:\/\/doi.org\/10.1007\/s13205-020-02462-4","journal-title":"3 Biotech"},{"key":"3379_CR33","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-021-02766-z","author":"AG Nayak","year":"2021","unstructured":"Nayak AG et al (2021) Evaluation of the merit of the methanolic extract of Andrographis paniculata to supplement anti-snake venom in reversing secondary hemostatic abnormalities induced by Naja naja venom. 3 Biotech. https:\/\/doi.org\/10.1007\/s13205-021-02766-z","journal-title":"3 Biotech"},{"issue":"3","key":"3379_CR34","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S2222-1808(14)60509-0","volume":"4","author":"A Okhuarobo","year":"2014","unstructured":"Okhuarobo A et al (2014) Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis 4(3):213\u2013222. https:\/\/doi.org\/10.1016\/S2222-1808(14)60509-0","journal-title":"Asian Pac J Trop Dis"},{"key":"3379_CR35","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/B978-1-4832-2845-7.50012-8","volume-title":"evaluation of drug activities","author":"GE Paget","year":"1964","unstructured":"Paget GE, Barnes JM (1964) Toxicity tests in evaluation of drug activities pharmacometrics. evaluation of drug activities. Elsevier, Amsterdam, pp 135\u2013166"},{"issue":"2","key":"3379_CR36","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4103\/0971-6580.97194","volume":"19","author":"YKG Peshin","year":"2012","unstructured":"Peshin YKG, SS, (2012) Do herbal medicines have potential for managing snake bite envenomation? Y. Toxicol Int 19(2):89\u201399. https:\/\/doi.org\/10.4103\/0971-6580.97194","journal-title":"Toxicol Int"},{"key":"3379_CR37","doi-asserted-by":"publisher","unstructured":"Peslova G et al (2009) Hepcidin, the hormone of iron metabolism, is bound specifically to-2-macroglobulin in blood. doi: https:\/\/doi.org\/10.1182\/blood-2009-01-201590.","DOI":"10.1182\/blood-2009-01-201590"},{"issue":"3","key":"3379_CR38","doi-asserted-by":"publisher","first-page":"270","DOI":"10.4103\/0253-7613.157117","volume":"47","author":"SM Pore","year":"2015","unstructured":"Pore SM et al (2015) A retrospective study of use of polyvalent anti-snake venom and risk factors for mortality from snake bite in a tertiary care setting. Indian J Pharmacol 47(3):270. https:\/\/doi.org\/10.4103\/0253-7613.157117","journal-title":"Indian J Pharmacol"},{"issue":"2","key":"3379_CR39","doi-asserted-by":"publisher","first-page":"198","DOI":"10.4103\/0976-9668.92326","volume":"2","author":"SJ Premendran","year":"2011","unstructured":"Premendran SJ et al (2011) Anti-cobra venom activity of plant Andrographis paniculata and its comparison with polyvalent anti-snake venom. J Nat Sci Biol Med 2(2):198\u2013204. https:\/\/doi.org\/10.4103\/0976-9668.92326","journal-title":"J Nat Sci Biol Med"},{"issue":"3","key":"3379_CR40","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/0006-2944(84)90042-5","volume":"32","author":"NR Rao","year":"1984","unstructured":"Rao NR, Bhat PG, Pattabiraman TN (1984) Estimation of serum \u03b12-macroglobulin based on the esterolytic activity of bound \u03b1-chymotrypsin. Biochem Med 32(3):357\u2013363. https:\/\/doi.org\/10.1016\/0006-2944(84)90042-5","journal-title":"Biochem Med"},{"key":"3379_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24266","author":"AH RehmanAA","year":"2013","unstructured":"RehmanAA AH, Khan FH (2013) Alpha-2-macroglobulin: a physiological guardian. J Cell Physiol. https:\/\/doi.org\/10.1002\/jcp.24266","journal-title":"J Cell Physiol"},{"issue":"2","key":"3379_CR42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/BF02703369","volume":"15","author":"M Roche","year":"1990","unstructured":"Roche M, Pattabiraman TN (1990) Effect of king cobra venom on \u03b12-macroglobulin and proteases in human blood plasma. J Biosci 15(2):59\u201366. https:\/\/doi.org\/10.1007\/BF02703369","journal-title":"J Biosci"},{"issue":"3","key":"3379_CR43","doi-asserted-by":"publisher","first-page":"207","DOI":"10.7897\/2230-8407.050344","volume":"5","author":"RS A, S K, P C, S Gnaniah","year":"2014","unstructured":"RS A, S K, P C, S Gnaniah (2014) Isolation, purification and characterization of active compound from Andrographis paniculata L and Phyllanthus amarus L and testing the antivenom activity of the di-herbal extract by invitro and invivo studies. Int Res J Pharm 5(3):207\u2013211. https:\/\/doi.org\/10.7897\/2230-8407.050344","journal-title":"Int Res J Pharm"},{"issue":"16","key":"3379_CR44","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.2174\/1381612824666180223172854","volume":"24","author":"SL Saavedra","year":"2018","unstructured":"Saavedra SL et al (2018) Natural snake venom inhibitors and their pharmaceutical uses: challenges and possibilities. Curr Pharm Des 24(16):1737\u20131747. https:\/\/doi.org\/10.2174\/1381612824666180223172854","journal-title":"Curr Pharm Des"},{"issue":"1","key":"3379_CR45","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1080\/08923970600626007","volume":"28","author":"K Sheeja","year":"2006","unstructured":"Sheeja K, Shihab PK, Kuttan G (2006) Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata nees. Immunopharmacol Immunotoxicol 28(1):129\u2013140. https:\/\/doi.org\/10.1080\/08923970600626007","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"1","key":"3379_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/13813455.2015.1115525","volume":"122","author":"T Siddiqui","year":"2016","unstructured":"Siddiqui T et al (2016) Reactive oxygen species and anti-proteinases. Arch Physiol Biochem 122(1):1\u20137. https:\/\/doi.org\/10.3109\/13813455.2015.1115525","journal-title":"Arch Physiol Biochem"},{"issue":"12","key":"3379_CR47","first-page":"1036","volume":"4","author":"A Sivakumar","year":"2015","unstructured":"Sivakumar A, Manikandan A (2015) Andrographis paniculata leaf extracts as potential Naja naja anti-snake venom. World J Pharm Pharmac Sci 4(12):1036\u20131050","journal-title":"World J Pharm Pharmac Sci"},{"issue":"1","key":"3379_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2041731412442668","volume":"3","author":"LA Solchaga","year":"2012","unstructured":"Solchaga LA et al (2012) Safety of recombinant human platelet-derived growth factor-BB in Augment\u00ae bone graft. J Tissue Eng 3(1):1\u20136. https:\/\/doi.org\/10.1177\/2041731412442668","journal-title":"J Tissue Eng"},{"issue":"2","key":"3379_CR49","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0885-4505(88)90079-5","volume":"39","author":"S Sujatha","year":"1988","unstructured":"Sujatha S, Jacob RT, Pattabiraman TN (1988) Effect of cobra and viper venoms on \u03b12-macroglobulin activity in human, bovine, and goat sera. Biochem Med Metab Biol 39(2):217\u2013225. https:\/\/doi.org\/10.1016\/0885-4505(88)90079-5","journal-title":"Biochem Med Metab Biol"},{"key":"3379_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.803244","author":"J Vandooren","year":"2021","unstructured":"Vandooren J, Itoh Y (2021) Alpha-2-macroglobulin in inflammation, immunity and infections. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2021.803244","journal-title":"Front Immunol"},{"key":"3379_CR51","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.ijbiomac.2020.03.055","volume":"153","author":"DE Vivas-Ruiz","year":"2020","unstructured":"Vivas-Ruiz DE et al (2020) Fibrinogen-clotting enzyme, pictobin, from Bothrops pictus snake venom. Structural and functional characterization. Int J Biol Macromol 153:779\u2013795. https:\/\/doi.org\/10.1016\/j.ijbiomac.2020.03.055","journal-title":"Int J Biol Macromol"}],"container-title":["3 Biotech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13205-022-03379-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13205-022-03379-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13205-022-03379-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T14:14:01Z","timestamp":1666793641000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13205-022-03379-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["3379"],"URL":"https:\/\/doi.org\/10.1007\/s13205-022-03379-w","relation":{},"ISSN":["2190-572X","2190-5738"],"issn-type":[{"value":"2190-572X","type":"print"},{"value":"2190-5738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]},"assertion":[{"value":"29 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest in the publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"310"}}