Improvement of butyrylcholinesterase enzyme inhibition and medicinal properties of extracts of Aristotelia serrata leaves by ultrasound extraction
Graphical abstract
Introduction
Neurodegeneration is characterized by gradual loss of neurons which leads to memory impairment (Dubey and Chinnathambi, 2019). Among all types of neuronal disorders in the elderly population, Alzheimer’s Disease (AD) is the most common disease. The disease is highly associated with age, with 3% of patients belonging to 65–74 age group, 18.7% of patients are between 75–84, while as high as 47.2% of patients are above 85 years old (Markesbery, 1997). With the ageing society, it is estimated that the global prevalence of dementia will increase from 24.3 million in 2005 to 81.1 million in 2040 (Ma et al., 2019). AD is the third main cause of death behind cardiovascular and cancer in developed countries (Huang et al., 2016). Although it is known that AD is caused by genetic and other environmental factors, the pathogenesis and mechanism behind AD remains unclear. One of the pathological features proposed includes the formation of amyloid plaques, neurofibrillary tangles, oxidative stress, and neuroinflammation. The main treatments for AD patients are cholinesterase inhibitors such as donepezil, galantamine and rivastigmine. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are the two brain enzymes targeted by these drugs. Initially AChE enzyme inhibitors were employed to treat patients. It was later demonstrated that changes in the levels of BChE enzyme are also associated with the progression of AD, especially in later stages of the disease (Farlow, 2002). As AD progresses, AChE levels decrease while BChE becomes the predominant cholinesterase in the brain. Hence, the inhibition of BChE activity may retard the formation of senile plaques (Schelterns and Feldman, 2003). It is believed that specific BChE inhibitors should improve the condition of patients with advanced AD, with fewer side effects (Giacobini, 2001; Greig et al., 2001; Pajk et al., 2020).
Aristotelia serrata, also known as wineberry or makomako, is a small tree found throughout the south island and lower north island of New Zealand (Saxton, 2008). The A. serrata leaves have been medicinally used as a decoction or infusion for treatment of burns, sore eyes, and rheumatism (Brooker and Cooper, 1961). Several chemical compounds have been identified from the roots, stems, and leaves of A. serrata: major alkaloid aristoteline and some minor alkaloids of aristoserratine, aristotelinone, serratenone, makomakine, aristoserratenine, aristomakine, serratoline, isohobartine, aristomakinine, isosorelline, and tasmanine (Saxton, 2008). Interestingly, screening studies with this plant revealed that 1000 μg/mL of methanol and ethyl acetate extracts from Aristotelia serrata leaves presented > 90% inhibition of BChE enzyme activity (Majid and Silva, 2020). Since most of the AChE inhibitors are known to contain nitrogen (Orhan et al., 2004), the high BChE inhibitory activity A. serrata extract may also be related to its rich nitrogen alkaloidal content.
Extraction is the first step in the separation of medically active portions from plant matrices (Tiwari et al., 2011). The ideal extraction method must be sustainable, economically viable, and must be performed as efficiently as possible (Apel et al., 2020). Ultrasound assisted extraction (UAE) treatment has been known to increase extraction efficiency of bioactive compounds such as alkaloids from various plant materials (Hossain et al., 2014; Rambo et al., 2019). The sonication facilitates higher recoveries of bioactive compounds from plant materials as a result of the cavitation phenomena, mechanical agitation and thermology (Chakraborty et al., 2020). Increased yield of extraction, higher extraction rate/quicker extraction, and the use of clean, green solvent with improved performance are other advantages of ultrasound extraction. The optimization of the extraction process conditions leads to maximum efficacy of extraction. Response surface methodology (RSM) is a statistical method for developing, improving and optimizing processes involving several variables (Liu et al., 2000; Chakraborty et al., 2020). The rationale behind RSM application is to reduce the number of experiment trials needed for the study of multiple variables, which is not possible using the conventional one factor at a time optimization method. RSM also generates useful mathematical models to predict responses for different extraction conditions. The main objective of this study was to use RSM to estimate the optimal conditions of UAE parameters acoustic power density (A), extraction time (t) and ethanol concentration (E) to obtain the highest BChE inhibition, antioxidant activity (expressed as DPPH radical scavenging activity, RSA), and yield. Mathematical models for prediction of BChE inhibition, DPPH RSA, and extraction yield as a function of extraction parameters were also generated and validated. The specific objectives were: 1. To select the best solvent and appropriate range of extraction parameters to extract anti-butyrylcholinesterase (BChE) compounds from A. serrata leaves; 2. To study the effect of acoustic power density, extraction time, and ethanol concentration on BChE inhibition using response surface methodology; 3. To experimentally validate the optimum extraction conditions; 4. To determine the IC50 concentrations for BChE inhibition and DPPH RSA of the optimized extracts.
Section snippets
Plant materials and chemicals
Dried Aristotelia serrata leaves were purchased from a local plant supplier “Kiwi Plants Ltd”, Wellington, New Zealand (https://www.kiwiplants.co.nz). The material was ground into fine particles using a grinder and sifted through a 0.25 mm sieve to obtain a uniform particle size. The material was then vacuum-sealed and stored in a dark condition at room temperature until use in the extraction experiments (Adewusi and Steenkamp, 2011).
Methanol and ethyl acetate were of chromatography grade and
Results and discussion
Section 3.1 presents the results of single factor experiments. Based on these results a fixed temperature of 50 °C was selected for RSM study presented in Section 3.2, as the temperature of extraction had a minor effect on BChE inhibition between 50 and 70 °C (Fig. 3). Appropriate ranges were chosen for the other extraction variables: A 0.13−0.65 W/mL, t 1−20 min, and E 20–80 % (Section 3.2). In Section 3.3, the experimental validation of the optimal conditions predicted by the RSM models is
Conclusion
This study demonstrates that ultrasound assisted extraction was an effective and reliable method for extraction of anti-BChE and antioxidant related compounds from Aristotelia serrata leaves. The quadratic models obtained through RSM were adequate to describe the effect of A, t, and E on BChE inhibition, DPPH RSA, and extraction yield. The parameters investigated were found to have individual and combined effects for all the responses. Studies involving the chemical analysis of extracts
Conflict of interest
The authors confirm there is no conflict of interest.
Acknowledgements
PhD Scholarship by Ministry of Higher Education Malaysia, Government of Malaysia is acknowledged. The authors acknowledge “The Biocide ToolBox for New Zealand Manufacturing Exporters”, funded by the New Zealand Ministry of Business, Innovation and Employment. Fred Allen (Kiwi Plants Ltd, New Zealand) for supply of plant material.
References (40)
- et al.
In vitro screening for acetylcholinesterase inhibition and antioxidant activity of medicinal plants from southern Africa
Asian Pac. J. Trop. Med.
(2011) - et al.
Potential for the use of ultrasound in the extraction of antioxidants from Rosmarinus officinalis for the food and pharmaceutical industry
Ultrason. Sonochem.
(2004) - et al.
Antioxidant capacity and phenolic content of selected tropical fruits from Malaysia, extracted with different solvents
Food Chem.
(2009) - et al.
Screening the effect of different extraction methods (ultrasound-assisted extraction and solid–liquid extraction) on the recovery of glycoalkaloids from potato peels: optimisation of the extraction conditions using chemometric tools
Food Bioprod. Process.
(2020) - et al.
Optimization of ultrasound-assisted extraction (UAE) process for the recovery of bioactive compounds from bitter gourd using response surface methodology (RSM)
Food Bioprod. Process.
(2020) - et al.
Optimization of ultrasonic extraction process of polysaccharides from Ornithogalum caudatum Ait and evaluation of its biological activities
Ultrason. Sonochem.
(2012) - et al.
Optimization of extraction conditions of antioxidant phenolic compounds from mashua (Tropaeolum tuberosum Ruíz & Pavón) tubers
Sep. Purif. Technol.
(2007) - et al.
Brahmi (Bacopa monnieri): an ayurvedic herb against the Alzheimer’s disease
Arch. Biochem. Biophys.
(2019) - et al.
Optimization of ultrasound-assisted extraction of polyphenols from spruce wood bark
Ultrasonics Sonochem.
(2015) - et al.
Ultrasonic extraction of steroidal alkaloids from potato peel waste
Ultrason. Sonochem.
(2014)
The effect of ethyl acetate extract from persimmon leaves on Alzheimer’s disease and its underlying mechanism
Phytomedicine
Oxidative stress hypothesis in Alzheimer’s disease
Free Radic. Biol. Med.
Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some Turkish medicinal plants
J. Ethnopharmacol.
Solvent selection for efficient extraction of bioactive compounds from grape pomace
Ind. Crops Prod.
Box–Behnken experimental design for extraction optimization of alkaloids from Erythrina verna Vell. trunk barks and LC Method Validation
Ind. Crops Prod.
A new lupene triterpenetriol and anticholinesterase activity of Salvia sclareoides
Fitoterapia
Non-toxic Salvia sclareoides Brot. extracts as a source of functional food ingredients: phenolic profile, antioxidant activity and prion binding properties
Food Chem.
Optimization of olive leaf extract obtained by ultrasound-assisted extraction with response surface methodology
Ultrason. Sonochem.
Optimization of ultrasonic-assisted extraction of natural antioxidants from rice bran using response surface methodology
Ultrason. Sonochem.
Optimization of ultrasonic-assisted extraction of pomegranate (Punica granatum L.) seed oil
Ultrason. Sonochem.
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