Elsevier

Food and Bioproducts Processing

Volume 124, November 2020, Pages 445-454
Food and Bioproducts Processing

Improvement of butyrylcholinesterase enzyme inhibition and medicinal properties of extracts of Aristotelia serrata leaves by ultrasound extraction

https://doi.org/10.1016/j.fbp.2020.10.004Get rights and content

Highlights

  • The yield of the optimized Aristotelia serrata extract increased 13 percentage points.

  • Optimized plant extract was 2.5 times more inhibitory of BChE Alzheimer enzyme.

  • Optimized extract was 2 times more antioxidant than the ascorbic acid reference.

  • A. serrata extract is a potential complement for Alzheimer’s Disease medicines.

Abstract

Aristotelia serrata, wineberry, or makomako, is a small deciduous fast-growing shrub of New Zealand that produces a berry. In this study leaf extracts were produced using ultrasound technology. Alzheimer’s Disease is a progressive mental deterioration related with ageing and senility, in which approved drugs for treatment inhibit butyrylcholinesterase (BChE), an enzyme present in the human brain. The ultrasound assisted extraction of natural anti-butyrylcholinesterase and antioxidants from this plant, and the yield of extraction were optimized using response surface methodology. The effect of acoustic power density (0.13–0.65 W/mL), time (1–20 min), and ethanol concentration (20–80%) on BChE inhibition, antioxidant activity, and extraction yield was determined, the optimum extraction conditions being 0.53 W/mL, 17.12 min and 74% ethanol. The optimized extracts were produced to experimentally validate the predicted responses. The IC50 concentrations were experimentally determined (26.2 μg/mL for BChE, 5.5 μg/mL for radical scavenging activity). A. serrata leaf extracts have potential to be used as complements to medicines traditionally used for memory dysfunction.

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)

Cited by (8)

  • Principles of sonication and its equipment in the food industry

    2023, Non-thermal Food Processing Operations: Unit Operations and Processing Equipment in the Food Industry
  • Performance of corrosion inhibitor extracted from enzymatic hydrolysate of waste Platanus acerifolia leaves

    2022, Journal of Industrial and Engineering Chemistry
    Citation Excerpt :

    Interestingly, when the concentration exceeded 10 mg/g, the extraction yield did not increase significantly with the complex-enzyme concentration. This indicated that the excessive complex enzyme aggregation might make the solution viscous, which was not conducive to enzymatic hydrolysis [30–32]. To avoid enzyme overuse, the complex-enzyme concentration of 10 mg/g was chosen as a center value for the next test part where the extraction yield could reach a maximal value of 26 mg/g.

  • Kanuka bush leaves for Alzheimer's disease: Improved inhibition of β-secretase enzyme, antioxidant capacity and yield of extracts by ultrasound assisted extraction

    2021, Food and Bioproducts Processing
    Citation Excerpt :

    Among these modern techniques, ultrasound assisted extraction (UAE) is a promising and widely used method for extraction of bioactive compounds from various plant materials (Mahindrakar and Rathod, 2020; Zhang et al., 2019). UAE is also very popular industrially as is it inexpensive, simple, easily scaled up, and offers efficient alternative as it requires less extraction time and lower solvent consumption (Mahindrakar and Rathod, 2020; Majid and Silva, 2020b, 2020c; Saifullah et al., 2020; Zhang et al., 2019). In addition, UAE does not require the high temperatures that are often associated with conventional extraction methods, which can degrade thermolabile bioactive compounds of the extract.

View all citing articles on Scopus
View full text