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Ashwagandha root extract attenuates inflammation in Oleic acid induced-ALI/ARDS rat model via inhibition of ACE and MAPK signaling pathways

Year 2023, Volume: 10 Issue: 1, 196 - 202, 28.01.2023
https://doi.org/10.30910/turkjans.1209593

Abstract

Ashwagandha (Withania somniferous) is one of the most important plants of folk medicine and is widely used to treat various diseases. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are defined as a respiratory failure that abruptly develops due to hypoxemia with alveolar injury secondary to intense inflammation. The present study was focused on evaluating the activity of Ashwagandha against Oleic Acid-Induced ALI/ARDS in a rat model. For this purpose, the animals were divided into the following three groups: Control, Oleic acid (50 μl kg−1, i.v. injection), Ashwagandha (500 mg/kg, orally) + Oleic acid. Ashwagandha was given daily for two weeks before a single dose of the Oleic acid. 24 hours after the last application, all the group animals were sacrificed by sevoflurane, and their lung was evaluated. The levels of Mitogen-activated protein kinases (MAPK), and the activities of myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD), total oxidant status (TOS), and angiotensin-converting enzyme (ACE) were determined in lung tissues by ELISA. Compared with the model group, there was a significantly improving in the levels of MAPK, MPO, and TOS in the Ashwagandha administration group. Moreover, Ashwagandha markedly increased the activities of GSH and SOD, and decreased the activity of ACE. Therefore, Ashwagandha may be used as a potential natural resource for mitigating acute lung injury caused by Oleic acid.

References

  • Akella, A., Sharma, P., Pandey, R., Deshpande, S.B. 2014. Characterization of oleic acid-induced acute respiratory distress syndrome model in rat. Indian Journal of Experimental Biology, 52: 712-719.
  • Ale, Y., Sharma, S., Chaudhary, A., Singh, A. 2021. A Review on Therapeutic Use of Withania Somnifera (Ashwagandha). Annals of the Romanian Society for Cell Biology, 25(7): 577-585.
  • Anand, U., Jacobo-Herrera, N., Altemimi, A., Lakhssassi, N. 2019. A comprehensive review on medicinal plants as antimicrobial therapeutics: potential avenues of biocompatible drug discovery. Metabolites, 9(11): 258.
  • Birla, H., Keswani, C., Rai, S. N., Singh, S. S., Zahra, W., Dilnashin, H., Rathore, A. S., Singh, S. P. 2019. Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice. Behavioral and Brain Functions, 15(1): 1-9.
  • Brieger, K., Schiavone, S., Miller, F. J., Krause, K. H. 2012. Reactive oxygen species: from health to disease. Swiss medical weekly, 142: w13659.
  • Daneshvar, M., Heidari-Soureshjani, R., Zakerimoghadam, M., Mortezanasab, M., Aloweiwi, W. 2021. Withania somnifera and COVID-19: Current evidence and future prospective. Future Natural Products, 7(1): 24-47.
  • Elhadidy, M. E., Sawie, H. G., Meguid, N. A., Khadrawy, Y. A. 2018. Protective effect of ashwagandha (Withania somnifera) against neurotoxicity induced by aluminum chloride in rats. Asian Pacific Journal of Tropical Biomedicine, 8(1): 59.
  • Gonçalves-de-Albuquerque, C. F., Silva, A. R., Burth, P., Castro-Faria, M. V., Castro-Faria-Neto, H. C. 2016. Oleic Acid and Lung Injury. In Handbook of lipids in human function, AOCS Press, 605-634.
  • Imai, Y., Kuba, K., Penninger, J. M. 2008. The discovery of angiotensin‐converting enzyme 2 and its role in acute lung injury in mice. Experimental physiology, 93(5): 543-548.
  • Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, Leong-Poi, H., Crackower, M.A., Fukamizu, A., Hui, C., Hein, L., Uhlig, S., Slutsky, A.S., Jiang, C., Penninger, J. M. 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436(7047): 112-116.
  • Ito, K., Mizutani, A., Kira, S., Mori, M., Iwasaka, H., Noguchi, T. 2005. Effect of Ulinastatin, a human urinary trypsin inhibitor, on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes. Injury, 36(3):387-394.
  • Kashyap, V. K., Dhasmana, A., Yallapu, M. M., Chauhan, S. C., Jaggi, M. 2020. Withania somnifera as a potential future drug molecule for COVID-19. Future Drug Discovery, 2(4): FDD50.
  • Kaur, G., Singh, N., Samuel, S.S., Bora, H.K., Sharma, S., Pachauri, S.D., Dwivedi, A. K., Siddiqui, H.H., Hanif, K. 2015. Withania somnifera shows a protective effect in monocrotaline-induced pulmonary hypertension. Pharmaceutical Biology, 53(1): 147-157.
  • Khan, M. A., Subramaneyaan, M., Arora, V. K., Banerjee, B. D., Ahmed, R. S. 2015. Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats. Journal of Complementary and Integrative Medicine, 12(2): 117-125.
  • Mishra, A. K., Kumar, S. P. 2021. Phytochemical Analysis of Ashwagandha (Withania Somnifera) and its Role on Covid-19–A Qualitative Review. AYUSHDHARA, 8(3): 3362-3370.
  • Nile, S. H., Liang, Y., Wang, Z., Zheng, J., Sun, C., Nile, A., Patel, G., Kai, G. 2021. Chemical composition, cytotoxic and pro-inflammatory enzyme inhibitory properties of Withania somnifera (L.) Dunal root extracts. South African Journal of Botany, 151: 46-52.
  • Oktyabrsky, O.N., Smirnova, G.V. 2007. Redox regulation of cellular functions. Biochemistry (Mosc), 72:132–145.
  • Paul, S., Chakraborty, S., Anand, U., Dey, S., Nandy, S., Ghorai, M., Saha, S.C., Patil, M.K., Kandimalla, R., Proćków, J., Dey, A. 2021. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomedicine & Pharmacotherapy, 143: 112175. Qiu, H., Wu, J., Hong, L., Luo, Y., Song, Q., Chen, D. 2020. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: An observational cohort study. Lancet Infectious Diseases, 20(6): 689-696.
  • Raghavendran, K., Napolitano, L. M. 2011. ALI and ARDS: challenges and advances. Critical care clinics, 27(3): 429–437.
  • Sabina, E. P., Rasool, M., Vedi, M., Navaneethan, D., Ravichander, M., Parthasarthy, P. O. O. R. N. I. M. A., Thella, S. R. 2013. Hepatoprotective and antioxidant potential of Withania somnifera against paracetamol-induced liver damage in rats. International Journal of Pharmacy and Pharmaceutical Sciences, 5(2): 648-651.
  • Sankar, S. R., Manivasagam, T., Krishnamurti, A., Ramanathan, M. 2007. The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: An analysis of behavioral and biochemical varibles. Cellular & Molecular Biology Letters, 12(4): 473-481.
  • Shree, P., Mishra, P., Selvaraj, C., Singh, S. K., Chaube, R., Garg, N., Tripathi, Y. B. 2022. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants–Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi)–a molecular docking study. Journal of Biomolecular Structure and Dynamics, 40(1): 190-203.
  • Singh, D. J. 2015. Ayurvedic Treatment of Chronic obstructive pulmonary disease (COPD). https://www.ayurtimes.com/ayurvedic-treatment-of-chronic-obstructive-pulmonary-disease-copd/ Singh, P., Salman, K. A., Shameem, M., Warsi, M. S. 2022. Withania sominifera as add-on therapy for COPD patients: A randomized, placebo-controlled, double-blind study. Frontiers in Pharmacology, 13: 1-16.
  • Singh, S., Nath, R., Pal, R., Mehrotra, A., Singh, P.K., Dixit, R. K., Singh, S., Kumar, R. 2019. The Role of Withania somnifera (Ashwagandha) and Omega-3 Fatty Acids on TNF-α and Joint Inflammation in an Animal Model of Rheumatoid Arthritis. Journal of Clinical & Diagnostic Research, 13(4): 1-5.
  • Tayman, C., Çakır, U., Akduman, H., Karabulut, Ş., Çağlayan, M. 2021. The therapeutic effect of Apocynin against hyperoxy and Inflammation-Induced lung injury. International Immunopharmacology, 101: 108190.
  • Tong, X., Zhang, H., Timmermann, B. N. 2011. Chlorinated Withanolides from Withania somnifera. Phytochemistry Letters, 4(4): 411–414.
  • Tripathi, M. K., Singh, P., Sharma, S., Singh, T. P., Ethayathulla, A. S., Kaur, P. 2021. Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor. Journal of Biomolecular Structure and Dynamics, 39(15): 5668-5681.
  • Valavanidis, A., Vlachogianni, T., Fiotakis, K., Loridas, S. 2013. Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. International Journal of Environmental Research and Public Health, 10(9): 3886-3907.
  • Wang, Y., Wu, H., Niu, W., Chen, J., Liu, M., Sun, X., Li, Z. 2018. Tanshinone IIA attenuates paraquat induced acute lung injury by modulating angiotensin converting enzyme 2/angiotensin (1 7) in rats. Molecular Medicine Reports, 18(3), 2955-2962.
  • Zambon, M., Vincent, J. L. 2008. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest, 133(5): 1120-1127.
  • Zhang, L. P., Zhao, Y., Liu, G. J., Yang, D. G., Dong, Y. H., Zhou, L. H. 2017. Glabridin attenuates lipopolysaccharide-induced acute lung injury by inhibiting p38MAPK/ERK signaling pathway. Oncotarget, 8(12): 18935.
  • Zhang, Y., Zhang, Y., Xing, J., Zhang, Y., Xing, J., Ai, T., Wen, T., Guan, L., Zhao, J. 2007. Protection of echinacoside against acute lung injury caused by oleic acid in rats. Free radical research, 41(7): 798-805.

Ashwagandha kök ekstresi, ACE ve MAPK sinyal yollarının inhibisyonu yoluyla Oleik asit kaynaklı ALI/ARDS sıçan modelinde inflamasyonu hafifletir

Year 2023, Volume: 10 Issue: 1, 196 - 202, 28.01.2023
https://doi.org/10.30910/turkjans.1209593

Abstract

Ashwagandha (Withania somniferous), halk hekimliğinin en önemli bitkilerinden biridir ve çeşitli hastalıkları tedavi etmek için yaygın olarak kullanılmaktadır. Akut akciğer hasarı (AAH) ve akut solunum sıkıntısı sendromu (ASSS), yoğun inflamasyona sekonder alveoler hasar ile birlikte hipoksemiye bağlı olarak ani gelişen solunum yetmezliği olarak tanımlanır. Mevcut çalışma, Ashwagandha'nın Oleik Asit kaynaklı AAH/ASSS'na karşı aktivitesini sıçan modelinde değerlendirmeye odaklanmıştır. Bu amaçla hayvanlar, aşağıdaki üç gruba ayrılmıştır: Kontrol, Oleik asit (50 µl kg-1, i.v. enjeksiyon), Ashwagandha (500 mg/kg, oral) + Oleik asit. Ashwagandha, tek Oleik asit dozundan önce iki hafta boyunca günlük olarak verilmiştir. Son uygulamadan 24 saat sonra gruptaki tüm hayvanlar sevofluran ile sakrifiye edilerek akciğerleri değerlendirilmiştir. Mitojenle-etkinleşen protein kinazlar (MAPK)’ın seviyeleri ve miyeloperoksidaz (MPO), glutatyon (GSH), süperoksit dismutaz (SOD), total oksidan durum (TOS) ve anjiyotensin dönüştürücü enzim (ACE) aktiviteleri akciğer dokularıda ELISA ile belirlenmiştir. Model grubu ile karşılaştırıldığında, Ashwagandha uygulanan grupta MAPK, MPO ve TOS seviyelerinde önemli bir düzelme olmuştur. Ayrıca Ashwagandha, GSH ve SOD aktivitelerini önemli ölçüde arttırırken, ACE aktivitesini azaltmıştır. Bu nedenle Ashwagandha, Oleik asitin neden olduğu akut akciğer hasarını hafifletmek için potansiyel bir doğal kaynak olarak kullanılabilir.

References

  • Akella, A., Sharma, P., Pandey, R., Deshpande, S.B. 2014. Characterization of oleic acid-induced acute respiratory distress syndrome model in rat. Indian Journal of Experimental Biology, 52: 712-719.
  • Ale, Y., Sharma, S., Chaudhary, A., Singh, A. 2021. A Review on Therapeutic Use of Withania Somnifera (Ashwagandha). Annals of the Romanian Society for Cell Biology, 25(7): 577-585.
  • Anand, U., Jacobo-Herrera, N., Altemimi, A., Lakhssassi, N. 2019. A comprehensive review on medicinal plants as antimicrobial therapeutics: potential avenues of biocompatible drug discovery. Metabolites, 9(11): 258.
  • Birla, H., Keswani, C., Rai, S. N., Singh, S. S., Zahra, W., Dilnashin, H., Rathore, A. S., Singh, S. P. 2019. Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice. Behavioral and Brain Functions, 15(1): 1-9.
  • Brieger, K., Schiavone, S., Miller, F. J., Krause, K. H. 2012. Reactive oxygen species: from health to disease. Swiss medical weekly, 142: w13659.
  • Daneshvar, M., Heidari-Soureshjani, R., Zakerimoghadam, M., Mortezanasab, M., Aloweiwi, W. 2021. Withania somnifera and COVID-19: Current evidence and future prospective. Future Natural Products, 7(1): 24-47.
  • Elhadidy, M. E., Sawie, H. G., Meguid, N. A., Khadrawy, Y. A. 2018. Protective effect of ashwagandha (Withania somnifera) against neurotoxicity induced by aluminum chloride in rats. Asian Pacific Journal of Tropical Biomedicine, 8(1): 59.
  • Gonçalves-de-Albuquerque, C. F., Silva, A. R., Burth, P., Castro-Faria, M. V., Castro-Faria-Neto, H. C. 2016. Oleic Acid and Lung Injury. In Handbook of lipids in human function, AOCS Press, 605-634.
  • Imai, Y., Kuba, K., Penninger, J. M. 2008. The discovery of angiotensin‐converting enzyme 2 and its role in acute lung injury in mice. Experimental physiology, 93(5): 543-548.
  • Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, Leong-Poi, H., Crackower, M.A., Fukamizu, A., Hui, C., Hein, L., Uhlig, S., Slutsky, A.S., Jiang, C., Penninger, J. M. 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436(7047): 112-116.
  • Ito, K., Mizutani, A., Kira, S., Mori, M., Iwasaka, H., Noguchi, T. 2005. Effect of Ulinastatin, a human urinary trypsin inhibitor, on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes. Injury, 36(3):387-394.
  • Kashyap, V. K., Dhasmana, A., Yallapu, M. M., Chauhan, S. C., Jaggi, M. 2020. Withania somnifera as a potential future drug molecule for COVID-19. Future Drug Discovery, 2(4): FDD50.
  • Kaur, G., Singh, N., Samuel, S.S., Bora, H.K., Sharma, S., Pachauri, S.D., Dwivedi, A. K., Siddiqui, H.H., Hanif, K. 2015. Withania somnifera shows a protective effect in monocrotaline-induced pulmonary hypertension. Pharmaceutical Biology, 53(1): 147-157.
  • Khan, M. A., Subramaneyaan, M., Arora, V. K., Banerjee, B. D., Ahmed, R. S. 2015. Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats. Journal of Complementary and Integrative Medicine, 12(2): 117-125.
  • Mishra, A. K., Kumar, S. P. 2021. Phytochemical Analysis of Ashwagandha (Withania Somnifera) and its Role on Covid-19–A Qualitative Review. AYUSHDHARA, 8(3): 3362-3370.
  • Nile, S. H., Liang, Y., Wang, Z., Zheng, J., Sun, C., Nile, A., Patel, G., Kai, G. 2021. Chemical composition, cytotoxic and pro-inflammatory enzyme inhibitory properties of Withania somnifera (L.) Dunal root extracts. South African Journal of Botany, 151: 46-52.
  • Oktyabrsky, O.N., Smirnova, G.V. 2007. Redox regulation of cellular functions. Biochemistry (Mosc), 72:132–145.
  • Paul, S., Chakraborty, S., Anand, U., Dey, S., Nandy, S., Ghorai, M., Saha, S.C., Patil, M.K., Kandimalla, R., Proćków, J., Dey, A. 2021. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomedicine & Pharmacotherapy, 143: 112175. Qiu, H., Wu, J., Hong, L., Luo, Y., Song, Q., Chen, D. 2020. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: An observational cohort study. Lancet Infectious Diseases, 20(6): 689-696.
  • Raghavendran, K., Napolitano, L. M. 2011. ALI and ARDS: challenges and advances. Critical care clinics, 27(3): 429–437.
  • Sabina, E. P., Rasool, M., Vedi, M., Navaneethan, D., Ravichander, M., Parthasarthy, P. O. O. R. N. I. M. A., Thella, S. R. 2013. Hepatoprotective and antioxidant potential of Withania somnifera against paracetamol-induced liver damage in rats. International Journal of Pharmacy and Pharmaceutical Sciences, 5(2): 648-651.
  • Sankar, S. R., Manivasagam, T., Krishnamurti, A., Ramanathan, M. 2007. The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: An analysis of behavioral and biochemical varibles. Cellular & Molecular Biology Letters, 12(4): 473-481.
  • Shree, P., Mishra, P., Selvaraj, C., Singh, S. K., Chaube, R., Garg, N., Tripathi, Y. B. 2022. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants–Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi)–a molecular docking study. Journal of Biomolecular Structure and Dynamics, 40(1): 190-203.
  • Singh, D. J. 2015. Ayurvedic Treatment of Chronic obstructive pulmonary disease (COPD). https://www.ayurtimes.com/ayurvedic-treatment-of-chronic-obstructive-pulmonary-disease-copd/ Singh, P., Salman, K. A., Shameem, M., Warsi, M. S. 2022. Withania sominifera as add-on therapy for COPD patients: A randomized, placebo-controlled, double-blind study. Frontiers in Pharmacology, 13: 1-16.
  • Singh, S., Nath, R., Pal, R., Mehrotra, A., Singh, P.K., Dixit, R. K., Singh, S., Kumar, R. 2019. The Role of Withania somnifera (Ashwagandha) and Omega-3 Fatty Acids on TNF-α and Joint Inflammation in an Animal Model of Rheumatoid Arthritis. Journal of Clinical & Diagnostic Research, 13(4): 1-5.
  • Tayman, C., Çakır, U., Akduman, H., Karabulut, Ş., Çağlayan, M. 2021. The therapeutic effect of Apocynin against hyperoxy and Inflammation-Induced lung injury. International Immunopharmacology, 101: 108190.
  • Tong, X., Zhang, H., Timmermann, B. N. 2011. Chlorinated Withanolides from Withania somnifera. Phytochemistry Letters, 4(4): 411–414.
  • Tripathi, M. K., Singh, P., Sharma, S., Singh, T. P., Ethayathulla, A. S., Kaur, P. 2021. Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor. Journal of Biomolecular Structure and Dynamics, 39(15): 5668-5681.
  • Valavanidis, A., Vlachogianni, T., Fiotakis, K., Loridas, S. 2013. Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. International Journal of Environmental Research and Public Health, 10(9): 3886-3907.
  • Wang, Y., Wu, H., Niu, W., Chen, J., Liu, M., Sun, X., Li, Z. 2018. Tanshinone IIA attenuates paraquat induced acute lung injury by modulating angiotensin converting enzyme 2/angiotensin (1 7) in rats. Molecular Medicine Reports, 18(3), 2955-2962.
  • Zambon, M., Vincent, J. L. 2008. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest, 133(5): 1120-1127.
  • Zhang, L. P., Zhao, Y., Liu, G. J., Yang, D. G., Dong, Y. H., Zhou, L. H. 2017. Glabridin attenuates lipopolysaccharide-induced acute lung injury by inhibiting p38MAPK/ERK signaling pathway. Oncotarget, 8(12): 18935.
  • Zhang, Y., Zhang, Y., Xing, J., Zhang, Y., Xing, J., Ai, T., Wen, T., Guan, L., Zhao, J. 2007. Protection of echinacoside against acute lung injury caused by oleic acid in rats. Free radical research, 41(7): 798-805.
There are 32 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Kubra Koc 0000-0001-6208-165X

Publication Date January 28, 2023
Submission Date November 24, 2022
Published in Issue Year 2023 Volume: 10 Issue: 1

Cite

APA Koc, K. (2023). Ashwagandha root extract attenuates inflammation in Oleic acid induced-ALI/ARDS rat model via inhibition of ACE and MAPK signaling pathways. Türk Tarım Ve Doğa Bilimleri Dergisi, 10(1), 196-202. https://doi.org/10.30910/turkjans.1209593