Bioassay-Guided Isolated Compounds from Morinda officinalis Inhibit Alzheimer’s Disease Pathologies

Abstract

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, M. officinalis has not been evaluated in an AD bioassay. Therefore, M. officinalis extracts and fractions were tested for AD-related activity, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. A bioassay-guided approach led to isolation of 10 active compounds, eight anthraquinones (1–8), one coumarin (9), and one phytosterol (10), from n-hexane and ethyl acetate fractions of M. officinalis. The five anthraquinones (4–8) were stronger inhibitors of AChE than were other compounds. Compounds 3 and 9 were good inhibitors of BChE, and compounds 3 and 8 were good inhibitors of BACE1. Compounds 1–5 and 7–9 were more active than the positive control in inhibiting AGE formation. In addition, we first suggested a structure-activity relationship by which anthraquinones inhibit AChE and BACE1. Our findings demonstrate the preventive and therapeutic efficacy of M. officinalis for AD and its potential use as a natural alternative medicine.

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer’s Disease

“…Oligosaccharides from Radix Morindae Officinalis improve memory function of AD animal models (Yang et al, 2018). Isolated compounds from Radix Morindae Officinalis ameliorate AD (Lee et al, 2017). Other pharmacological studies have also demonstrated that extracts of Radix Morindae Officinalis have anti-Alzheimer’s, anti-fatigue, anti-aging, cardiovascular protective, anti-oxidative, immune-regulatory, and anti-inflammatory activities (Zhang et al, 2018).…”

Neuroprotective effects of Morinda officinalis How.: Anti-inflammatory and antioxidant roles in Alzheimer’s disease

“…Additionally, MO extract may also relieve AD symptoms through other mechanisms, including inhibition of acetylcholinesterase, butyrylcholinesterase, beta-site amyloid precursor protein cleaving enzyme 1, and advanced glycation end-products. These effects of MO extracts are exerted via anthraquinones, coumarin, and phytosterol, which have been isolated using a bioassay-guided approach; therefore, MO root extracts may have therapeutic effects as a natural medicine for treating AD ( Lee et al, 2017 ).…”

Selenium Nanoparticles Based on Morinda officinalis Polysaccharides: Characterization, Anti-Cancer Activities, and Immune-Enhancing Activities Evaluation In Vitro

“…Morinda officinalis radix, a geo-authentic crude drug of Guangdong province, is a widely-used traditional Chinese medicine. Morinda officinalis polysaccharide (MOP) is one of the foremost effective components with many pharmacological activities, such as antioxidation, anti-depression, anti-osteoporosis, immune system enhancement, and reproductive capacity enhancement [ 19 , 20 , 21 , 22 , 23 , 24 ]. Xu obtained a homogeneous MOP, and its molecular weight was 63 KDa.…”