Phyllanthin from Phyllanthus amarus protects the myocardium during pressure overload-induced cardiac hypertrophy by inhibiting the angiotensin-converting enzyme.
La filantina de la Phyllanthus amarus protegió el miocardio durante la hipertrofia cardíaca inducida por sobrecarga de presión mediante la inhibición de la enzima convertidora de angiotensina.
Palabras clave:
Enzima convertidora de angiotensina, estenosis aórtica, hipertrofia cardíaca, colágeno-I, Filantina, Phyllanthus amarus, sobrecarga de presión
Resumen
La cardiopatía isquémica es el resultado de la obstrucción del flujo sanguíneo del corazón y conduce al infarto de miocardio. Se ha demostrado que varios lignanos de origen herbario protegen contra la cardiotoxicidad. El presente estudio tuvo como objetivo evaluar el potencial de la filantina, identificada a partir de un extracto metanólico estandarizado de Phyllanthus amarus (PAME), contra la hipertrofia cardíaca inducida por sobrecarga de presión en ratas experimentales. El lignano se identificó en PAME mediante HPLC. La ligadura de la aorta abdominal indujo hipertrofia cardíaca en ratas Wistar (220-240 g). Luego se las trató con (n = 15, cada una) agua destilada (10 ml/kg, control de estenosis aórtica), lisinopril (15 mg/kg) o PAME (50, 100 y 200 mg/kg) durante 28 días. Los compuestos de lignano se identificaron utilizando espectros UV en PAME, y el análisis de HPLC mostró la presencia de filantina en un tiempo de retención de 25,30 con un área de 70,22%. El tratamiento con PAME (100 y 200 mg/kg) mejoró significativamente y de manera dosis-dependiente (p<0,01 y p<0,001) la elevación inducida por AS en los pesos cardíacos absolutos y relativos, aumentó los niveles de biomarcadores séricos y las alteraciones en las funciones electrocardiográficas y hemodinámicas. PAME inhibió eficazmente el estrés óxido- nitrosativo inducido por AS de manera dosis-dependiente (p<0,01 y p<0,001). La expresión de ARNm regulada al alza de la enzima convertidora de angiotensina cardíaca (ECA) y el colágeno-I también fueron inhibidos notablemente (p<0,01 y p<0,001) por PAME. PAME redujo significativamente (p<0,01 y p<0,001) las alteraciones inducidas por sobrecarga de presión en la histopatología cardíaca. En conclusión, la filantina identificada en P. amarus mejoró la hipertrofia cardíaca inducida por sobrecarga de presión al inhibir las vías de formación de la ECA y del colágeno-I para aliviar la hipertensión y la fibrosis. Estos hallazgos en conjunto sugieren que P. amarus ofrece una terapia prometedora para el manejo de las enfermedades cardíacas isquémicas.
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Visnagri A, Kandhare AD, Ghosh P, Bodhankar SL. Endothelin receptor blocker bosentan inhibits hypertensive cardiac fibrosis in pressure overload-induced cardiac hypertrophy in rats. Cardiovasc Endocrinol 2013;2:85-97.
Shivakumar V, Kandhare AD, Rajmane AR, Adil M, Ghosh P, Badgujar LB et al. Estimation of the long-term cardiovascular events using UKPDS Risk Engine in metabolic syndrome patients. Indian J Pharm Sci 2014;76:174-178.
Sreeniwas Kumar A, Sinha N. Cardiovascular disease in India: A 360 degree overview. Med J Armed Forces India 2020;76:1-3. https://doi.org/10.1016/j.mj afi.2019.12.005
Eide S, Feng Z-P. Implications of age-related changes in the blood-brain barrier for ischemic stroke and new treatment strategies. Advan Neurol 2022;1:1. https://doi.org/10.36922/an.v1i2.1
Katyal J, Joshi D, Kumar Gupta Y. Effects of losartan and enalapril on lithium-pilo carpine-induced status epilepticus, spontaneous convulsive seizures, and cardiac changes in rats. Advan Neurol 2023;2:0387. https://doi.org/10.36922/an.0387
Mao X, Wu LF, Guo HL, Chen WJ, Cui YP, Qi Q et al. The Genus Phyllanthus: An ethnopharmacological, phytochemical, and pharmacological review. Evid Based Complement Alternat Med 2016;2016:7584952. https://doi.org/10.1155/2016/7584952
Harikrishnan H, Jantan I, Haque MA, Kumolosasi E. Anti-inflammatory effects of hypophyllanthin and niranthin through downregulation of NF-κB/MAPKs/PI3K-Akt signaling pathways. Inflammation 2018; 41:984-995.
Bose Mazumdar Ghosh A, Banerjee A, Chattopadhyay S. An insight into the potent medicinal plant Phyllanthus amarus Schum. and Thonn. The Nucleus 2022;65:437-472.
Karuna R, Bharathi VG, Reddy SS, Ramesh B, Saralakumari D. Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin-induced diabetic rats. Indian J Pharmacol 2011;43:414-418. https://doi. org/10.4103/0253-7613.83112
Putakala M, Gujjala S, Nukala S, Bongu SBR, Chintakunta N, Desireddy S. Cardioprotective effect of Phyllanthus amarus against high fructose diet induced myocardial and aortic stress in rat model. Bio-med Pharmacother 2017;95:1359-1368. https://doi.org/10.1016/j.biopha.2017. 09.054
Wu W, Li Y, Jiao Z, Zhang L, Wang X, Qin R. Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-alpha, and IL’s. Immunopharmacol Immunotoxicol 2019;41:55-67. https://doi.org/10.1080/08923973.2018.1545788
Kandhare AD, Ghosh P, Ghule AE, Zambare GN, Bodhankar SL. Protective effect of Phyllanthus amarus by modulation of endogenous biomarkers and DNA damage in acetic acid induced ulcerative colitis: Role of phyllanthin and hypophyllanthin. Apollo Medicine 2013;10:87-97.
Ghule AE, Kandhare AD, Jadhav SS, Zanwar AA, Bodhankar SL. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis. Int Immunopharmacol 2015;28:751-763. https://doi.org/10.1016/j.intimp.2015. 08.005
Liu J, Han XC, Wang D, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL et al. Elucidation of molecular mechanism involved in nephroprotective potential of naringin in fthylene glycol-induced urolithiasis in experimental uninephrectomized hypertensive rats. Lat Am J Pharm 2020;39:991-999.
Mukherjee AA, Kandhare AD, Bodhankar SL. Elucidation of protective efficacy of Pentahydroxy flavone isolated from Madhuca indica against arsenite-induced cardiomyopathy: Role of Nrf-2, PPAR- gamma, c-fos and c-jun. Environ Toxicol Pharmacol 2017;56:172-185. https://doi. org/10.1016/j.etap.2017.08.027
Tambewagh UU, Kandhare AD, Honmore VS, Kadam PP, Khedkar VM, Bodhankar SL et al. Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea: Role of COX-2 inhibition. Int Immunopharmacol 2017;52:110-118. https://doi. org/10.1016/j.intimp.2017.09.001
Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and prognostic biomarkers for myocardial infarction. Front Cardiovasc Med 2020;7:617277. https://doi.org/10. 3389/fcvm.2020.617277
Kandhare AD, Bandyopadhyay D, Thakurdesai PA. Low molecular weight galactomannans-based standardized fenugreek seed extract ameliorates high-fat diet-induced obesity in mice via modulation of FASn, IL -6, leptin, and TRIP-Br2. RSC Adv 2018;8:32401-32416. https://doi.org/10.1039/c8ra05204b
Edem E. Relationship between alkaline phosphatase and impaired coronary flow in patients with ST-segment elevated myocardial infarction. J Int Med Res 2018;46:3918-3927. https://doi.org/10.1177/0300060518785544
Adil M, Kandhare AD, Ghosh P, Venkata S, Raygude KS, Bodhankar SL. Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1. Ren Fail 2016;38:1007-1020. https://doi.org/10.3109/0886022X.2016.1163998
Cui J, Wang G, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL. Neuroprotective effect of naringin, a flavone glycoside in quinolinic acid-induced neurotoxicity: Possible role of PPAR-gamma, Bax/Bcl-2, and caspase-3. Food Chem Toxicol 2018;121:95-108. https://doi.org/10.1016/j.fct.2018.08.028
Thakkar H, Eerla R, Gangakhedkar S, Shah RP. Exploring unexplored biomarkers of oxidative distress and their use. Adv Redox Res 2021;3:100020. https://doi.org/10.1016/j.arres.2021.100020
Honmore VS, Kandhare AD, Kadam PP, Khedkar VM, Sarkar D, Bodhankar SL et al. Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory, antioxidant and molecular docking studies. Int Immunopharmacol 2016;33:8-17. https://doi.org/10.1016/j.intimp.2016.01.024
Visnagri A, Adil M, Kandhare AD, Bodhankar SL. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J Pharm Bioallied Sci 2015;7:121-127. https://doi.org/10.4103/0975-7406.154437
Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI et al. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-κB-mediated pathway. Biomed Res Int 2020;2020.
Allocati N, Masulli M, Di Ilio C, Federici L. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases. Oncogenesis 2018;7:8. https://doi.org/10.1038/ s41389-017-0025-3
Kandhare AD, Bodhankar SL, Singh V, Mohan V, Thakurdesai PA. Anti-asthmatic effects of type-A procyanidine polyphenols from cinnamon bark in ovalbumin-induced airway hyperresponsiveness in laboratory animals. Biomed Aging Pathol 2013;3:23-30.
Ketkar S, Rathore A, Kandhare A, Lohidasan S, Bodhankar S, Paradkar A et al. Alleviating exercise-induced muscular stress using neat and processed bee pollen: oxidative markers, mitochondrial enzymes, and myostatin expression in rats. Integr Med Res 2015;4:147-160. https://doi.org/10.1016/j.imr.2015.02.003
Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim) 2018;12:88-93.
Osmakov DI, Kalinovskii AP, Belozerova OA, Andreev YA, Kozlov SA. Lignans as pharmacological agents in disorders related to oxidative stress and inflammation: Chemical Synthesis Approaches and Biological Activities. Int J Mol Sci 2022;23. https://doi.org/10.3390/ijms23116031
Karuna R, Reddy SS, Baskar R, Saralakumari D. Antioxidant potential of aqueous extract of Phyllanthus amarus in rats. Indian J Pharmacol 2009;41:64-67. https://doi.org/10.4103/0253-7613.51342
Kumar KB, Kuttan R. Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine 2005;12:494-500. https://doi.org/10.1016/j.phymed.2004.03.009
Cai W, Zhang Z, Huang Y, Sun H, Qiu L. Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats. Exp Ther Med 2018;15:924-932. https://doi.org/10.3892/etm.2017.5442
Borghi C, Omboni S. Angiotensin-converting enzyme inhibition: beyond blood pressure control-The role of Zofenopril. Adv Ther 2020;37:4068-4085. https://doi.org/10.1007/s12325-020-01455-2
Giani JF, Veiras LC, Shen JZY, Bernstein EA, Cao D, Okwan-Duodu D et al. Novel roles of the renal angiotensin converting enzyme. Mol Cell Endocrinol 2021;529:111257. https://doi.org/10.1016/j.mce.2021.111257
Dostal DE, Baker KM. The cardiac renin-angiotensin system: conceptual, or a regulator of cardiac function? Circ Res 1999;85:643-650. https://doi.org/10.1161/01.res.85.7.643
Welch WJ. The pathophysiology of renin release in renovascular hypertension. Semin Nephrol 2000;20:394-401.
Raveinal R. The effect of natural immune-modulator (Phyllanti herb extract) administration on cellular immune response of patients with pulmonary tuberculosis. Padang: University of Andalas 2003.
Amin Z. The effect of Phyllanthus extract as an additional treatment in tuberculosis patients with minimal and moderately advanced radiological lesion. Diss, University of Indonesia, Jakarta 2005.
Halim H, Saleh K. The effectiveness of Phyllanthus niruri extract in the management of pulmonary tuberculosis. Dexa Media 2005;18:103-107.
Pramayanti I, Paraton H, Ma’at S. Comparison of success rate of vaginal candidiasis treatment between ketokonazole and combination of ketoconazole Phyllanthus niruri extract. Dexa Media 2005;18:97-102.
Nishiura JL, Campos AH, Boim MA, Heilberg IP, Schor N. Phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients. Urol Res 2004;32:362-366. https://doi. org/10.1007/s00240-004-0432-8
Micali S, Sighinolfi MC, Celia A, De Stefani S, Grande M, Cicero A et al. Can Phyllanthus niruri affect the efficacy of extra-corporeal shock wave lithotripsy for renal stones? A randomized, prospective, long term study. J Urol 2006;176:1020-1022.
Narendranathan M, Remla A, Mini PC, Satheesh P. A trial of Phyllanthus amarus in acute viral hepatitis. Trop Gastroenterol 1999;20:164-166.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet 1988;2:764-766. https://doi.org/10.1016/s0140-6736(88)92416-6
Shivakumar V, Kandhare AD, Rajmane AR, Adil M, Ghosh P, Badgujar LB et al. Estimation of the long-term cardiovascular events using UKPDS Risk Engine in metabolic syndrome patients. Indian J Pharm Sci 2014;76:174-178.
Sreeniwas Kumar A, Sinha N. Cardiovascular disease in India: A 360 degree overview. Med J Armed Forces India 2020;76:1-3. https://doi.org/10.1016/j.mj afi.2019.12.005
Eide S, Feng Z-P. Implications of age-related changes in the blood-brain barrier for ischemic stroke and new treatment strategies. Advan Neurol 2022;1:1. https://doi.org/10.36922/an.v1i2.1
Katyal J, Joshi D, Kumar Gupta Y. Effects of losartan and enalapril on lithium-pilo carpine-induced status epilepticus, spontaneous convulsive seizures, and cardiac changes in rats. Advan Neurol 2023;2:0387. https://doi.org/10.36922/an.0387
Mao X, Wu LF, Guo HL, Chen WJ, Cui YP, Qi Q et al. The Genus Phyllanthus: An ethnopharmacological, phytochemical, and pharmacological review. Evid Based Complement Alternat Med 2016;2016:7584952. https://doi.org/10.1155/2016/7584952
Harikrishnan H, Jantan I, Haque MA, Kumolosasi E. Anti-inflammatory effects of hypophyllanthin and niranthin through downregulation of NF-κB/MAPKs/PI3K-Akt signaling pathways. Inflammation 2018; 41:984-995.
Bose Mazumdar Ghosh A, Banerjee A, Chattopadhyay S. An insight into the potent medicinal plant Phyllanthus amarus Schum. and Thonn. The Nucleus 2022;65:437-472.
Karuna R, Bharathi VG, Reddy SS, Ramesh B, Saralakumari D. Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin-induced diabetic rats. Indian J Pharmacol 2011;43:414-418. https://doi. org/10.4103/0253-7613.83112
Putakala M, Gujjala S, Nukala S, Bongu SBR, Chintakunta N, Desireddy S. Cardioprotective effect of Phyllanthus amarus against high fructose diet induced myocardial and aortic stress in rat model. Bio-med Pharmacother 2017;95:1359-1368. https://doi.org/10.1016/j.biopha.2017. 09.054
Wu W, Li Y, Jiao Z, Zhang L, Wang X, Qin R. Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-alpha, and IL’s. Immunopharmacol Immunotoxicol 2019;41:55-67. https://doi.org/10.1080/08923973.2018.1545788
Kandhare AD, Ghosh P, Ghule AE, Zambare GN, Bodhankar SL. Protective effect of Phyllanthus amarus by modulation of endogenous biomarkers and DNA damage in acetic acid induced ulcerative colitis: Role of phyllanthin and hypophyllanthin. Apollo Medicine 2013;10:87-97.
Ghule AE, Kandhare AD, Jadhav SS, Zanwar AA, Bodhankar SL. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis. Int Immunopharmacol 2015;28:751-763. https://doi.org/10.1016/j.intimp.2015. 08.005
Liu J, Han XC, Wang D, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL et al. Elucidation of molecular mechanism involved in nephroprotective potential of naringin in fthylene glycol-induced urolithiasis in experimental uninephrectomized hypertensive rats. Lat Am J Pharm 2020;39:991-999.
Mukherjee AA, Kandhare AD, Bodhankar SL. Elucidation of protective efficacy of Pentahydroxy flavone isolated from Madhuca indica against arsenite-induced cardiomyopathy: Role of Nrf-2, PPAR- gamma, c-fos and c-jun. Environ Toxicol Pharmacol 2017;56:172-185. https://doi. org/10.1016/j.etap.2017.08.027
Tambewagh UU, Kandhare AD, Honmore VS, Kadam PP, Khedkar VM, Bodhankar SL et al. Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea: Role of COX-2 inhibition. Int Immunopharmacol 2017;52:110-118. https://doi. org/10.1016/j.intimp.2017.09.001
Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and prognostic biomarkers for myocardial infarction. Front Cardiovasc Med 2020;7:617277. https://doi.org/10. 3389/fcvm.2020.617277
Kandhare AD, Bandyopadhyay D, Thakurdesai PA. Low molecular weight galactomannans-based standardized fenugreek seed extract ameliorates high-fat diet-induced obesity in mice via modulation of FASn, IL -6, leptin, and TRIP-Br2. RSC Adv 2018;8:32401-32416. https://doi.org/10.1039/c8ra05204b
Edem E. Relationship between alkaline phosphatase and impaired coronary flow in patients with ST-segment elevated myocardial infarction. J Int Med Res 2018;46:3918-3927. https://doi.org/10.1177/0300060518785544
Adil M, Kandhare AD, Ghosh P, Venkata S, Raygude KS, Bodhankar SL. Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1. Ren Fail 2016;38:1007-1020. https://doi.org/10.3109/0886022X.2016.1163998
Cui J, Wang G, Kandhare AD, Mukherjee-Kandhare AA, Bodhankar SL. Neuroprotective effect of naringin, a flavone glycoside in quinolinic acid-induced neurotoxicity: Possible role of PPAR-gamma, Bax/Bcl-2, and caspase-3. Food Chem Toxicol 2018;121:95-108. https://doi.org/10.1016/j.fct.2018.08.028
Thakkar H, Eerla R, Gangakhedkar S, Shah RP. Exploring unexplored biomarkers of oxidative distress and their use. Adv Redox Res 2021;3:100020. https://doi.org/10.1016/j.arres.2021.100020
Honmore VS, Kandhare AD, Kadam PP, Khedkar VM, Sarkar D, Bodhankar SL et al. Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti-inflammatory, antioxidant and molecular docking studies. Int Immunopharmacol 2016;33:8-17. https://doi.org/10.1016/j.intimp.2016.01.024
Visnagri A, Adil M, Kandhare AD, Bodhankar SL. Effect of naringin on hemodynamic changes and left ventricular function in renal artery occluded renovascular hypertension in rats. J Pharm Bioallied Sci 2015;7:121-127. https://doi.org/10.4103/0975-7406.154437
Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI et al. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-κB-mediated pathway. Biomed Res Int 2020;2020.
Allocati N, Masulli M, Di Ilio C, Federici L. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases. Oncogenesis 2018;7:8. https://doi.org/10.1038/ s41389-017-0025-3
Kandhare AD, Bodhankar SL, Singh V, Mohan V, Thakurdesai PA. Anti-asthmatic effects of type-A procyanidine polyphenols from cinnamon bark in ovalbumin-induced airway hyperresponsiveness in laboratory animals. Biomed Aging Pathol 2013;3:23-30.
Ketkar S, Rathore A, Kandhare A, Lohidasan S, Bodhankar S, Paradkar A et al. Alleviating exercise-induced muscular stress using neat and processed bee pollen: oxidative markers, mitochondrial enzymes, and myostatin expression in rats. Integr Med Res 2015;4:147-160. https://doi.org/10.1016/j.imr.2015.02.003
Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim) 2018;12:88-93.
Osmakov DI, Kalinovskii AP, Belozerova OA, Andreev YA, Kozlov SA. Lignans as pharmacological agents in disorders related to oxidative stress and inflammation: Chemical Synthesis Approaches and Biological Activities. Int J Mol Sci 2022;23. https://doi.org/10.3390/ijms23116031
Karuna R, Reddy SS, Baskar R, Saralakumari D. Antioxidant potential of aqueous extract of Phyllanthus amarus in rats. Indian J Pharmacol 2009;41:64-67. https://doi.org/10.4103/0253-7613.51342
Kumar KB, Kuttan R. Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine 2005;12:494-500. https://doi.org/10.1016/j.phymed.2004.03.009
Cai W, Zhang Z, Huang Y, Sun H, Qiu L. Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats. Exp Ther Med 2018;15:924-932. https://doi.org/10.3892/etm.2017.5442
Borghi C, Omboni S. Angiotensin-converting enzyme inhibition: beyond blood pressure control-The role of Zofenopril. Adv Ther 2020;37:4068-4085. https://doi.org/10.1007/s12325-020-01455-2
Giani JF, Veiras LC, Shen JZY, Bernstein EA, Cao D, Okwan-Duodu D et al. Novel roles of the renal angiotensin converting enzyme. Mol Cell Endocrinol 2021;529:111257. https://doi.org/10.1016/j.mce.2021.111257
Dostal DE, Baker KM. The cardiac renin-angiotensin system: conceptual, or a regulator of cardiac function? Circ Res 1999;85:643-650. https://doi.org/10.1161/01.res.85.7.643
Welch WJ. The pathophysiology of renin release in renovascular hypertension. Semin Nephrol 2000;20:394-401.
Raveinal R. The effect of natural immune-modulator (Phyllanti herb extract) administration on cellular immune response of patients with pulmonary tuberculosis. Padang: University of Andalas 2003.
Amin Z. The effect of Phyllanthus extract as an additional treatment in tuberculosis patients with minimal and moderately advanced radiological lesion. Diss, University of Indonesia, Jakarta 2005.
Halim H, Saleh K. The effectiveness of Phyllanthus niruri extract in the management of pulmonary tuberculosis. Dexa Media 2005;18:103-107.
Pramayanti I, Paraton H, Ma’at S. Comparison of success rate of vaginal candidiasis treatment between ketokonazole and combination of ketoconazole Phyllanthus niruri extract. Dexa Media 2005;18:97-102.
Nishiura JL, Campos AH, Boim MA, Heilberg IP, Schor N. Phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients. Urol Res 2004;32:362-366. https://doi. org/10.1007/s00240-004-0432-8
Micali S, Sighinolfi MC, Celia A, De Stefani S, Grande M, Cicero A et al. Can Phyllanthus niruri affect the efficacy of extra-corporeal shock wave lithotripsy for renal stones? A randomized, prospective, long term study. J Urol 2006;176:1020-1022.
Narendranathan M, Remla A, Mini PC, Satheesh P. A trial of Phyllanthus amarus in acute viral hepatitis. Trop Gastroenterol 1999;20:164-166.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet 1988;2:764-766. https://doi.org/10.1016/s0140-6736(88)92416-6
Publicado
2025-03-06
Cómo citar
Zhu, C., Liu, Z., & Gai, Y. (2025). Phyllanthin from Phyllanthus amarus protects the myocardium during pressure overload-induced cardiac hypertrophy by inhibiting the angiotensin-converting enzyme.: La filantina de la Phyllanthus amarus protegió el miocardio durante la hipertrofia cardíaca inducida por sobrecarga de presión mediante la inhibición de la enzima convertidora de angiotensina. Investigación Clínica, 66(1), 63-77. https://doi.org/10.54817/IC.v66n1a06
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