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Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes

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Abstract

Centella asiatica is claimed to have a neuroprotective effect; however, its ability to protect the cerebrum against damage in diabetes has never been identified. The aims were to identify the possibility that C. asiatica ameliorates inflammation, oxidative stress, and apoptosis in the cerebrum in diabetes. C. asiatica leave aqueous extract (C. asiatica) (50, 100, and 200 mg/kg/b.w.) were given to diabetic rats for 28 days. Changes in rats’ body weight, food and water intakes, and insulin and FBG levels were monitored. Following sacrificed, cerebrum was harvested and subjected for histological, biochemical, and molecular biological analyses. The results revealed treatment with C. asiatica was able to ameliorate the loss in body weight, the increase in food and water intakes, the decrease in insulin, and the increase in FBG levels in diabetic rats. Additionally, histopathological changes in the cerebrum and levels of p38, ERK, JNK, cytosolic Nrf2, Keap-1, LPO, RAGE, and AGE levels decreased; however, PI3K, AKT, IR, IRS, GLUT-1, nuclear Nrf2, Nqo-1, Ho-1, and anti-oxidative enzymes (SOD, CAT, and GPx) levels increased in diabetic rats receiving C. asiatica. Furthermore, C. asiatica treatment also caused cerebral inflammation and apoptosis to decrease as indicated by decreased inflammatory markers (cytosolic NF-κB p65, p-Ikkβ, Ikkβ, iNOS, COX-2, TNF-α, IL-6, and IL-1β), decreased pro-apoptosis markers (Casp-3, 9, and Bax), but increased anti-apoptosis marker, Bcl-2. Activity level of Na+/K+, Mg2+, and Ca2+-ATPases in the cerebrum also increased by C. asiatica treatment. Conclusions: C. asiatica treatment helps to prevent cerebral damage and maintain near normal cerebral function in diabetes.

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Acknowledgements

This research is funded by AICTE RPS project Grant No. A.V. (3)/AICTE-RPS/2014, India.

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  1. Department of Physiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Nelli Giribabu, Kamarulzaman Karim & Naguib Salleh

  2. Pharmacology Division, A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, 530 003, India

    Eswar Kumar Kilari

  3. Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland

    Srinivasa Rao Nelli

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Authors participated in the design: NG and NS. Interpretation of the studies and analysis of the data: NG, KK, EK, and NS. Materials: NS. Analyzed LCMS/MS findings: SRN. Drafted the manuscript: NG and NS. Critical evaluation and finalizing the manuscript content: NS.

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Giribabu, N., Karim, K., Kilari, E.K. et al. Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes. Inflammopharmacol 28, 1599–1622 (2020). https://doi.org/10.1007/s10787-020-00733-3

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