The Standardized Extract of Centella asiatica and Its Fractions Exert Antioxidative and Anti-Neuroinflammatory Effects on Microglial Cells and Regulate the Nrf2/HO-1 Signaling Pathway

Issue title: Pro-Oxidants and Antioxidants in Alzheimer’s Disease

Guest editors: Pravat K. Mandal

Article type: Research Article

Authors: Hambali, Aqilah^a | Jusril, Nor Atiqah^b | Md Hashim, Nur Fariesha^c | Abd Manan, Nizar^a | Adam, Siti Khadijah^a | Mehat, Muhammad Zulfadli^a | Adenan, Mohd Ilham^d | Stanslas, Johnson^e | Abdul Hamid, Hafizah^{a; *}

Affiliations: [a] Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia | [b] Faculty of Bioresources and Food Industry, Universiti Sultan Zainal Abidin, Besut, Terengganu, Malaysia | [c] Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia | [d] Universiti Teknologi MARA, Cawangan Pahang, Bandar Tun Abdul Razak, Jengka, Pahang, Malaysia | [e] Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

Correspondence: [*] Correspondence to: Hafizah Abdul Hamid, PhD, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Tel.: +603 9769 2353; E-mail: [email protected].

Abstract: Background:Neuroinflammation and oxidative stress can aggravate the progression of Alzheimer’s disease (AD). Centella asiatica has been traditionally consumed for memory and cognition. The triterpenes (asiaticoside, madecassoside, asiatic acid, madecassic acid) have been standardized in the ethanolic extract of Centella asiatica (SECA). The bioactivity of the triterpenes in different solvent polarities of SECA is still unknown. Objective:In this study, the antioxidative and anti-neuroinflammatory effects of SECA and its fractions were explored on lipopolysaccharides (LPS)-induced microglial cells. Methods:HPLC measured the four triterpenes in SECA and its fractions. SECA and its fractions were tested for cytotoxicity on microglial cells using MTT assay. NO, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and MDA (lipid peroxidation) produced by LPS-induced microglial cells were measured by colorimetric assays and ELISA. Nrf2 and HO-1 protein expressions were measured using western blotting. Results:The SECA and its fractions were non-toxic to BV2 microglial cells at tested concentrations. The levels of NO, TNF-α, IL-6, ROS, and lipid peroxidation in LPS-induced BV2 microglial cells were significantly reduced (p < 0.001) by SECA and its fractions. SECA and some of its fractions can activate the Nrf2/HO-1 signaling pathway by significantly enhancing (p < 0.05) the Nrf2 and HO-1 protein expressions. Conclusions:This study suggests that the inhibitory activity of SECA and its fractions on pro-inflammatory and oxidative stress events may be the result of the activation of antioxidant defense systems. The potential of SECA and its fractions in reducing neuroinflammation and oxidative stress can be further studied as a potential therapeutic strategy for AD.

Keywords: Alzheimer’s disease, Centella asiatica , HO-1, neuroinflammation, Nrf2, oxidative stress

DOI: 10.3233/JAD-230875

Journal: Journal of Alzheimer's Disease, vol. 99, no. s1, pp. S119-S138, 2024