Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammat
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Inflammopharmacology
ORIGINAL ARTICLE
Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type‑2 diabetes Nelli Giribabu1 · Kamarulzaman Karim1 · Eswar Kumar Kilari2 · Srinivasa Rao Nelli3 · Naguib Salleh1 Received: 23 October 2019 / Accepted: 10 June 2020 © Springer Nature Switzerland AG 2020
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 N rf2, 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 N a+/K+, Mg2+, and C a2+-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. Keywords Centella asiatica · Cerebrum · Oxidative stress · Inflammation · Apoptosis · Diabetes mellitus
Introduction Diabetes mellitus (DM) is known to adversely affect the brain where neurochemical, neurophysiological, metabolic, and structural alterations have been reported (Mijnhout et al. 2006). Consequently, these changes could lead to diabetic encephalopathy (DE), a condition that is associated with brain dysfunction and atrophy (Seaquist 2015). Cognitive * Naguib Salleh [email protected]; [email protected] 1
Department of Physiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
2
Pharmacology Division, A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh 530 003, India
3
Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50‑370 Wroclaw, Poland
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