Analysis of Multiple Causes of Death: A Review of Methods and Practices.

BACKGROUND: Research and reporting of mortality indicators typically focus on a single underlying cause of death selected from multiple causes recorded on a death certificate. The need to incorporate the multiple causes in mortality statistics-reflecting increasing multimorbidity and complex causation patterns-is recognized internationally. This review aims to identify and appraise relevant analytical methods and practices related to multiple causes. METHODS: We searched Medline, PubMed, Scopus, and Web of Science from their incept ion to December 2020 without language restrictions, supplemented by consultation with international experts. Eligible articles analyzed multiple causes of death from death certificates. The process identified 4,080 items of which we reviewed 434 full-text articles. RESULTS: Most articles we reviewed (76%, n = 332) were published since 2001. The majority of articles examined mortality by "any- mention" of the cause of death (87%, n = 377) and assessed pairwise combinations of causes (57%, n = 245). Since 2001, applications of methods emerged to group deaths based on common cause patterns using, for example, cluster analysis (2%, n = 9), and application of multiple-cause weights to re-evaluate mortality burden (1%, n = 5). We describe multiple-cause methods applied to specific research objectives for approaches emerging recently. CONCLUSION: This review confirms rapidly increasing international interest in the analysis of multiple causes of death and provides the most comprehensive overview, to our knowledge, of methods and practices to date. Available multiple-cause methods are diverse but suit a range of research objectives. With greater availability of data and technology, these could be further developed and applied across a range of settings.

Quantifying cause-related mortality in Australia, incorporating multiple causes: observed patterns, trends and practical considerations.

BACKGROUND: Mortality statistics using a single underlying cause of death (UC) are key health indicators. Rising multimorbidity and chronic disease mean that deaths increasingly involve multiple conditions. However, additional causes reported on death certificates are rarely integrated into mortality indicators, partly due to complexities in data and methods. This study aimed to assess trends and patterns in cause-related mortality in Australia, integrating multiple causes (MC) of death. METHODS: Deaths (n = 1 773 399) in Australia (2006-17) were mapped to 136 ICD-10-based groups and MC indicators applied. Age-standardized cause-related rates (deaths/100 000) based on the UC (ASRUC) were compared with rates based on any mention of the cause (ASRAM) using rate ratios (RR = ASRAM/ASRUC) and to rates based on weighting multiple contributing causes (ASRW). RESULTS: Deaths involved on average 3.4 causes in 2017; the percentage with >4 causes increased from 20.9 (2006) to 24.4 (2017). Ischaemic heart disease (ASRUC = 73.3, ASRAM = 135.8, ASRW = 63.5), dementia (ASRUC = 51.1, ASRAM = 98.1, ASRW = 52.1) and cerebrovascular diseases (ASRUC = 39.9, ASRAM = 76.7, ASRW = 33.5) ranked as leading causes by all methods. Causes with high RR included hypertension (ASRUC = 2.2, RR = 35.5), atrial fibrillation (ASRUC = 8.0, RR = 6.5) and diabetes (ASRUC = 18.5, RR = 3.5); the corresponding ASRW were 12.5, 12.6 and 24.0, respectively. Renal failure, atrial fibrillation and hypertension ranked among the 10 leading causes by ASRAM and ASRW but not by ASRUC. Practical considerations in working with MC data are discussed. CONCLUSIONS: Despite the similarities in leading causes under the three methods, with integration of MC several preventable diseases emerged as leading causes. MC analyses offer a richer additional perspective for population health monitoring and policy development.

Observed and predicted premature mortality in Australia due to non-communicable diseases: a population-based study examining progress towards the WHO 25X25 goal.

BACKGROUND: The World Health Organization's (WHO) 25X25 goal aims for a 25% relative reduction in premature death due to four non-communicable diseases (NCD4)-cancer, cardiovascular disease, chronic respiratory diseases and diabetes-by 2025 compared to 2010. This study aimed to quantify the premature mortality in the Australian population due to NCD4, quantify the variation in mortality rates by age and sex, predict the premature mortality due to NCD4 in 2025 and evaluate the progress towards the WHO 25X25 goal. METHODS: A population-based study using cause-specific mortality data of all deaths which occurred in Australia from 2010 to 2016 and registered up to 2017, for adults aged 30-69 years, was conducted. Age-specific and age-standardised mortality rates (ASMR) and probability of death for NCD4 were calculated for each year. ASMRs in 2016 were calculated for men and women. Deaths and the probability of death in 2025 were predicted using Poisson regression based on data from 2006 to 2016. To assess the progress against the WHO 25X25 goal, the relative reduction in the probability of death from NCD4 conditions in 2025 compared to 2010 was calculated. RESULTS: ASMRs for NCD4 decreased from 2010 to 2016, except for diabetes which increased on average by 2.5% per year. Across sociodemographic factors, ASMRs were highest in males and increased with age. The projected probability of premature death in 2025 was 7.36%, equivalent to a relative reduction of 25.16% compared to 2010 levels. CONCLUSIONS: Premature mortality due to cancer, cardiovascular disease, respiratory diseases and diabetes declined in Australia from 2010 to 2016. This trend is consistent across age groups and by sex, and higher mortality rates were observed in males and at older ages. Nationally, if the current trends continue, we estimate that Australia will achieve a 25.16% relative reduction in premature deaths due to NCD4 in 2025 compared to 2010, signifying substantial progress towards the WHO 25X25 goal. Concerted efforts will need to continue to meet the 25X25 goal, especially in the context of the COVID-19 pandemic.

Phenolic-rich feijoa extracts from flesh, peel and whole fruit activate apoptosis pathways in the LNCaP cell line.

This study aimed to explore the potential anticancer activity of phenolic-rich feijoa extracts from the flesh, peel, and whole fruit on the human prostate cancer cell line (LNCaP). Results showed that feijoa extracts had cancer-specific anti-proliferative activity on the LNCaP cell line. The anticancer activity of feijoa extracts was shown through activation of the caspase-dependent apoptosis pathway based on the increase of sub-G1 phase in the cell cycle, the decrease of mitochondrial membrane potential, as well as the elevated caspase 3, 8, and 9 activity in the treated LNCaP cells. The anti-cancer activity of feijoa extracts could be attributed to the high total phenolic contents (0.14-0.37 mg GAE/mg dw) and, in particular, the high ellagic acid content (2.662-9.119 µg/mg dw). The successful activation of the caspase-dependent apoptosis pathway indicates that phenolic-rich feijoa extracts have a good potential to be utilized as a functional ingredient in foods and nutraceuticals.

Education-related inequalities in cause-specific mortality: first estimates for Australia using individual-level linked census and mortality data.

BACKGROUND: Socioeconomic inequalities in mortality are evident in all high-income countries, and ongoing monitoring is recommended using linked census-mortality data. Using such data, we provide the first estimates of education-related inequalities in cause-specific mortality in Australia, suitable for international comparisons. METHODS: We used Australian Census (2016) linked to 13 months of Death Registrations (2016-17). We estimated relative rates (RR) and rate differences (RD, per 100 000 person-years), comparing rates in low (no qualifications) and intermediate (secondary school) with high (tertiary) education for individual causes of death (among those aged 25-84 years) and grouped according to preventability (25-74 years), separately by sex and age group, adjusting for age, using negative binomial regression. RESULTS: Among 13.9 M people contributing 14 452 732 person-years, 84 743 deaths occurred. All-cause mortality rates among men and women aged 25-84 years with low education were 2.76 [95% confidence interval (CI): 2.61-2.91] and 2.13 (2.01-2.26) times the rates of those with high education, respectively. We observed inequalities in most causes of death in each age-sex group. Among men aged 25-44 years, relative and absolute inequalities were largest for injuries, e.g. transport accidents [RR = 10.1 (5.4-18.7), RD = 21.2 (14.5-27.9)]). Among those aged 45-64 years, inequalities were greatest for chronic diseases, e.g. lung cancer [men RR = 6.6 (4.9-8.9), RD = 57.7 (49.7-65.8)] and ischaemic heart disease [women RR = 5.8 (3.7-9.1), RD = 20.2 (15.8-24.6)], with similar patterns for people aged 65-84 years. When grouped according to preventability, inequalities were large for causes amenable to behaviour change and medical intervention for all ages and causes amenable to injury prevention among young men. CONCLUSIONS: Australian education-related inequalities in mortality are substantial, generally higher than international estimates, and related to preventability. Findings highlight opportunities to reduce them and the potential to improve the health of the population.

Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (- 10.06%, p = 0.0057), former-ADT (- 12.77%, p = 0.0239), and in PCa controls group (- 16.73, p = 0.0022); and OPG levels in chronic ADT (- 8.28%, p = 0.003) and PCa controls group (- 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

Tangerine tomatoes: origin, biochemistry, potential health benefits and future prospects.

BACKGROUND: Tomatoes and lycopene have been associated with the prevention of chronic diseases. Tetra-cis lycopene from tangerine tomatoes has been reported to be more bioavailable than the all-trans isomer found in red tomatoes. Therefore, tangerine tomatoes might contain superior health benefits compared to those of red tomatoes. SCOPE AND APPROACH: This review focuses on the origin, biochemistry, nutritional composition, and potential health benefits of tangerine tomatoes, as well as their comparison with those of the red and high-ß-carotene varieties. Information gathered from numerous studies on tomatoes, as well as conflicting perspectives, have been summarized to provide an unbiased review. KEY FINDINGS AND CONCLUSION: The origin of tangerine tomatoes is disputable, but they were reportedly present from as early as 1934. The carotenoid biosynthesis pathway underlying the accumulation of tetra-cis lycopene in tangerine tomatoes has been well defined. However, the nutritional composition of tangerine tomatoes is not currently publicly available. The carotenoid composition of tangerine tomatoes is unique not only because of the presence of tetra-cis lycopene, but also due to the relatively high content of phytoene, phytofluene, ζ-carotene, and neurosporene relative to other tomato varieties. Although a few in vitro and in vivo studies have shown promising results, further studies are required to validate the health benefits of tangerine tomatoes. Furthermore, published data regarding the potential health benefits of tangerine tomatoes on cardiovascular and bone health is currently lacking even though red tomatoes have shown promise in these areas.

Characterisation of Extracts and Anti-Cancer Activities of Fomitopsis pinicola.

Fomitopsis pinicola (Sw. Karst) is a common bracket fungus, with a woody texture. It is found predominantly in coniferous forests in temperate regions throughout Europe and Asia. Fomitopsis pinicola has been extensively used for medicinal purposes, particularly in Chinese and Korean traditional medicine. In this mini-review, the anti-cancer characteristics of F. pinicola extracts were investigated. In vitro experiments revealed the pro-apoptotic, anti-oxidant and anti-inflammatory properties of extracts, whilst two of three in vivo studies reported an inhibition of tumour growth and prolonged survival. Only studies wherein fungal specimens were sourced from Europe or Asia were included in this review, as samples sourced as F. pinicola from North America were probably not F. pinicola, but a different species. Although not one of the most revered fungal species, F. pinicola has been used as a medicinal fungus for centuries, as well as consumed as a health food supplement. To date, the results from only three in vivo studies, investigating anti-cancer properties, have been published. Further studies, using comprehensively identified specimens, are required to fully elucidate the anti-cancer properties of F. pinicola extracts.

Characterization of phenolic compounds and aroma active compounds in feijoa juice from four New Zealand grown cultivars by LC-MS and HS-SPME-GC-O-MS.

The phenolic compounds and aroma active compounds in feijoa (Acca sellowiana (O.Berg) Burret) juice from four New Zealand grown cultivars (Apollo, Unique, Opal Star, and Wiki Tu) were investigated. A high total phenolic content (maximum 1.89 mg GAE/mL juice) and significant antioxidant activities (maximum 14.66 mM Trolox/mL juice) were determined in feijoa juices. A total of 7 phenolic compounds from the screening of 29 standards were identified and quantified by LC-MS, with procyanidin B1 (209.78-511.07 µg/mL) and (+)-catechin (121.80-472.75 µg/mL) being the most abundant. Procyanidin B2 and quercetin-3-galactoside were reported in feijoa samples for the first time. The volatile compounds in feijoa juice were identified by HS-SPME-GC-MS, and 17 of the 63 identified compounds were not previously reported in feijoa samples. A total of 25 aroma active compounds were further identified by the olfactory test, and the esters and terpenes were the dominant compounds contributing to the aroma of feijoa juice. Methyl benzoate showed the characteristic "feijoa-like" aroma with a concentration of 13.62-52.62 µg/g juice. The aroma profile of feijoa juice from the four selected cultivars was established, and the "fruity" and "green, grassy & herbal" notes were the predominant attributes. Among the four selected cultivars, the Unique cultivar had the highest total phenolic content and antioxidant activities, while the Wiki Tu was the most aroma intensive. This study, first report on the phenolics and aroma compounds in feijoa juice with comparison of four cultivars, could be fundamental and essential to natural fruit juice industry and feijoa fruit investigation, as well as provided scientific evidence to local feijoa market and growers regarding cultivar selection.

Anticancer Characteristics of Fomitopsis pinicola Extract in a Xenograft Mouse Model-a Preliminary Study.

Introduction: Medicinal mushrooms have been used for the treatment of diseases and general promotion of health for many centuries. Recent pharmacological research into medicinal mushrooms has identified various therapeutic properties, with applications in modern medicine.Aim: To evaluate the anti-cancer activities of Fomitopsis pinicola (F. pinicola) alcoholic extract in an in vivo setting.Methods: The anti-tumour effect of the F. pinicola extract was tested in a xenograft immune-compromised Rag-1 mouse model. This was followed by RT-PCR and metabolomics analyses.Results: There were no observable differences in tumor growth between treated and non-treated groups. The bioactive components were not detected in the mouse plasma or the tumor site.Conclusions: The extract was poorly absorbed; this is likely due to the timing of treatment, dosage levels and modifications made to the extract where the alcohol-based solvent was replaced with water. This, in combination with fractionation studies which identified most anti-cancer compounds to be hydrophobic, largely explained the lack of anti-cancer activities in vivo.

Characterization of the bioactivities of an ethanol extract and some of its constituents from the New Zealand native mushroom Hericium novae-zealandiae.

In this study, we investigated the potential bioactivities of an ethanol extract of Hericium novae-zealandiae and four of its constituents, namely hericenone C, hericene B, ergosterol and ergosterol peroxide. The proliferation of three prostate cancer cell lines, namely DU145, LNCaP and PC3, was evaluated after treatment with the extract and constituents. It was found that both the ethanol extract and ergosterol peroxide possess anti-proliferative activities to the three prostate cancer cell lines. Ergosterol peroxide was considered likely to be one of the major compounds responsible for the anti-proliferative effect of the ethanol extract. Subsequently, the results of RT-qPCR assay showed two possible mechanisms for these anti-proliferative activities. One is apoptosis, supported by the up-regulation of CASP3, CASP8, CASP9, and an increase in the ratio of Bax/Bcl2. The other is anti-inflammation, indicated by the down-regulation of IL6 and up-regulation of IL24. The ethanol extract also exhibited antioxidant and AChE inhibitory (though weak) activities. However, none of the four compounds were found to account for these latter two activities. This is the first report of the bioactivities, and the corresponding active ingredients of lipophilic constituents from H. novae-zealandiae.

The Mediterranean Diet and Breast Cancer: A Personalised Approach.

There have been many original and review articles summarizing the impact of nutrition and diet on breast cancer risk. However, very few consider the implication of genetic background and the effect of personalised nutrition on the risk and prognosis of breast cancer. A literature search was performed using the following databases: MEDLINE (Ovid), PubMed, Scopus and EMBASE (Ovid). The ensuing search terms were selected: genomics, nutrigenomics, breast cancer, breast neoplasms, cancer, nutrigenetics, diet-gene interaction, and Mediterranean, nutrition, polyphenols and diet. In this review, we discuss the Mediterranean-style diet and associated nutrients, evidence of benefit, impact on gene expression and evidence of interactions with genotype and how this interaction can modify breast cancer risk and progression. In addition, the impact of nutrients commonly associated with a Mediterranean-style diet, on breast cancer treatment, and synergistic effects are mentioned when modified by genotype. Some evidence exists around the benefit of a gene-based personalised diet based on a Mediterranean-style dietary pattern, but further evidence in the form of clinical trials is required before such an approach can be comprehensively implemented.

Comprehensive Approaches to Improving Nutrition: Future Prospects.

When it comes to nutrition, nearly everyone has an opinion. In the past, nutrition was considered to be an individual's responsibility, however, more recently governments have been expected (by some) to share that responsibility by helping to ensure that marketing is responsible, and that food chains offer healthy meal choices in addition to their standard fare, for example. In some countries, governments have gone as far as to remove tax from unprocessed foods or to introduce taxes, such as that imposed on sugary soft drinks in the UK, Mexico, France and Norway. Following on from the sugar tax, chocolate might be next! Is this the answer to our burgeoning calorie intake and increasing poor nutritional status, or is there another approach? In this narrative we will focus on some of the approaches taken by communities and governments to address excess calorie intake and improve nutritional status, as well as some of the conflicts of interest and challenges faced with implementation. It is clear that in order to achieve meaningful change in the quality of nutritional intake and to reduce the long-term prevalence of obesity, a comprehensive approach is required wherein governments and communities work in genuine partnership. To take no or little action will doom much of today's youth to a poor quality of life in later years, and a shorter life expectancy than their grandparents.

Pancreatic Cancer Cachexia: The Role of Nutritional Interventions.

Pancreatic cancer is a cancer with one of the highest mortality rates and many pancreatic cancer patients present with cachexia at diagnosis. The definition of cancer cachexia is not consistently applied in the clinic or across studies. In general, it is "defined as a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass with or without loss of fat mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment." Many regard cancer cachexia as being resistant to dietary interventions. Cachexia is associated with a negative impact on survival and quality of life. In this article, we outline some of the mechanisms of pancreatic cancer cachexia and discuss nutritional interventions to support the management of pancreatic cancer cachexia. Cachexia is driven by a combination of reduced appetite leading to reduced calorie intake, increased metabolism, and systemic inflammation driven by a combination of host cytokines and tumour derived factors. The ketogenic diet showed promising results, but these are yet to be confirmed in human clinical trials over the long-term. L-carnitine supplementation showed improved quality of life and an increase in lean body mass. As a first step towards preventing and managing pancreatic cancer cachexia, nutritional support should be provided through counselling and the provision of oral nutritional supplements to prevent and minimise loss of lean body mass.

Screening of In Vitro Health Benefits of Tangerine Tomatoes.

Tomatoes have been associated with various health benefits, including the prevention of chronic diseases. The cis-isomers of lycopene occurring in tangerine tomatoes were, through clinical trials, proven to be more bioavailable than the all-trans lycopene found in red tomatoes. Nonetheless, scientific evidence regarding the bioactivities of the tangerine tomatoes is lacking. In this article, the antioxidant, anticancer, and anti-inflammatory properties of extracts prepared from four different tomato varieties, namely Alfred, Olga's Round Golden Chicken Egg, Golden Green, and Golden Eye, were investigated. While the antioxidant capacities of the extracts were measured through the ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, their anti-proliferative properties in prostate cancer cell lines were examined through the Sulforhodamine-B (SRB) assay. The anti-inflammatory activities of the extracts were assessed through the toll-like receptor (TLR)2, TLR4, and nucleotide-binding oligomerization domain containing protein 2 (NOD2)-mediated inflammatory pathways. Our results show that the tangerine tomatoes had lower IC50 values in both the anticancer and anti-inflammatory assays compared to the red tomatoes. Specifically, the half-maximal inhibitory concentration (IC50) values of the tangerine tomatoes in LNCaP cells were approximately two to three fold lower than the red tomato (IC50: 14.46, 5.62, and 8.08 mg dry tomato equivalent/mL from Alfred hexane-acetone, Olga's Round Golden Chicken Egg hexane, and Golden Green hexane, respectively). These findings indicate that the tangerine varieties, Olga's Round Golden Chicken Egg and Golden Green, possess greater potential to be used in conjunction with treatment and for the prevention of cancer and inflammatory-related diseases than the Alfred (red) and Golden Eye (high beta-carotene) varieties.

Assessment of In Vitro Bioactivities of Polysaccharides Isolated from Hericium Novae-Zealandiae.

The objective of this study was to investigate the potential effect of the polysaccharides isolated from Hericium novae-zealandiae, a native New Zealand fungus, on the in vitro proliferation of prostate cancer cell lines, gene expression, acetylcholinesterase (AChE) activity, and oxidation. One water-soluble and two alkali-soluble polysaccharide fractions were isolated from H. novae-zealandiae. The proliferation of the prostate cancer cell lines DU145, LNCaP, and PC3 was evaluated following treatment with these polysaccharide fractions. It was found that the polysaccharides possess anti-proliferative activity on LNCaP and PC3 cells, with a 50% growth inhibition (IC50) value as low as 0.61 mg/mL in LNCaP. Subsequently, it was determined through via RT-qPCR assay that apoptosis was one of the possible mechanisms responsible for the anti-proliferative activity in LNCaP. This was supported by the up-regulation of CASP3, CASP8, and CASP9. An alternative, discovered in PC3, was revealed to be anti-inflammation, which was hinted at by the down-regulation of IL6 and up-regulation of IL24. The polysaccharides also exhibited antioxidant and weak AChE inhibitory activities. This is the first report on the potential health benefits of polysaccharides prepared from the New Zealand fungus, H. novae-zealandiae.

Compositional Analysis and Aroma Evaluation of Feijoa Essential Oils from New Zealand Grown Cultivars.

Feijoa is an aromatic fruit and the essential oil from feijoa peel could be a valuable by-product in the juicing industry. An initial comparison of the essential oil extraction methods, steam-distillation and hydro-distillation, was conducted. The volatile compounds in the essential oils from four feijoa cultivars were identified and semi-quantified by GC-MS and the aroma active compounds in each essential oil were characterized using SPME-GC-O-MS. Hydro-distillation, with a material to water ratio of 1:4 and an extraction time of 90 min, was the optimized extraction method for feijoa essential oil. The Wiki Tu cultivar produced the highest essential oil yield among the four selected cultivars. A total of 160 compounds were detected, among which 90 compounds were reported for the first time in feijoa essential oils. Terpenes and esters were dominant compounds in feijoa essential oil composition and were also major contributors to feijoa essential oil aroma. Key aroma active compounds in feijoa essential oils were α-terpineol, ethyl benzoate, (Z)-3-hexenyl hexanoate, linalool, (E)-geraniol, 2-undecanone, 3-octanone, α-cubebene, and germacrene D. This is the first report on the optimization of the extraction method and the establishment of the aroma profile of feijoa essential oils, with a comparison of four New Zealand grown cultivars.

Extraction Optimization, Antioxidant Capacity and Phenolic Profiling of Extracts from Flesh, Peel and Whole Fruit of New Zealand Grown Feijoa Cultivars.

Feijoa fruit is becoming increasingly popular, yet limited studies have focused on the antioxidant capacity and phenolic profiling of its extracts. In this research, optimization of phenolic extraction from feijoa flesh, peel, and whole fruit from four New Zealand grown cultivars was conducted using orthogonal design. Antioxidant activities of the extracts were assessed, followed by phenolic profiling by a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. For feijoa flesh and whole fruit, the extraction was optimized using 70% ethanol, material to solvent ratio of 1:30, at extraction temperature of 50 °C for 30 min. For feijoa peel, extraction at 50 °C for 60 min using 50% ethanol with a material to solvent ratio of 1:30 were the optimized conditions. Results showed feijoa peel had higher total phenolic content (TPC) and antioxidant activities than the flesh and whole fruit. Overall, the Unique cultivar had a relatively higher TPC and antioxidant activity than the other cultivars tested. A total of 15 phenolic compounds were identified, and seven of them were reported for the first time in feijoa fruit. This is the first systematic investigation on the extraction method, phenolic content, antioxidant activity and phenolic profile of feijoa emphasis on comparison of sample types and cultivars.

Screening of Cytotoxicity and Anti-Inflammatory Properties of Feijoa Extracts Using Genetically Modified Cell Models Targeting TLR2, TLR4 and NOD2 Pathways, and the Implication for Inflammatory Bowel Disease.

Feijoa has been increasingly studied in the recent decade, while investigations into its bioactivities including anti-inflammatory activity are lacking. In this article, the cytotoxicity and anti-inflammatory properties of feijoa extracts, from flesh, peel and whole fruit, from four cultivars namely APOLLO, UNIQUE, OPAL STAR and WIKI TU are presented. Three inflammatory pathways, Toll-like receptor 2 (TLR2), TLR4 and nucleotide-binding oligomerization domain-containing protein 2 (NOD2), were investigated using genetically modified cell models namely HEK-Blue™ hTLR2, HEK-Blue™ hTLR4, NOD2-WT and NOD2-G908R. Results show that feijoa peel extract induced higher cytotoxicity than flesh and whole fruit extracts, and the APOLLO cultivar was the most anti-inflammatory among the four tested cultivars. The anti-inflammatory activity of feijoa flesh was detected only through the TLR2 pathway, and the activity of feijoa peel and whole fruit was evident mainly through the TLR2 and NOD2 pathways. Most notably, feijoa anti-inflammatory activity was superior to ibuprofen particularly through the TLR2 pathway, with significantly lower secreted embryonic alkaline phosphatase IC50 concentrations (7.88, 12.81, 30.84 and 442.90 µg/mL for APOLLO flesh, peel, whole fruit extract and ibuprofen respectively). These findings indicate that feijoa has great potential to be used in the treatment and prevention of inflammation-related diseases including inflammatory bowel disease.