Anti-inflammatory effects of açaí. Açaí improves anti-inflammatory status by directly reducing the synthesis of proinflammatory cytokines and expression of proinflammatory signaling pathways. Symbols and abbreviations: ↑: increase; ↓: decrease; Ca
: calcium; COX-2: cyclooxygenase-2; FMLP: N-formylmethionyl-leucyl-phenylalanine; IL-1β: interleukin-1β; IL-6: interleukin-6; IL-8: interleukin-8; IL-12: interleukin-12; NF-κB: nuclear factor-κB; iNOS: inflammatory nitric oxide synthase; PGs: prostaglandins; MAPK: mitogen-activated protein kinase; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-α.
4.3. Antinociceptive and Analgesic Activity
Pain can have a negative impact on quality of life, as well as the performance of daily activities. Currently, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are common pharmacological options of the treatment of pain. The anti-inflammatory, antihypertensive, antioxidant, and vasodilatory activities of açaí has resulted in the exploration of its value as an antinociceptive and analgesic agent [34][37][38][39][40][56,95,97,118,149]. According to Sudo et al. [37][95], the use of açaí seed extract reduced nociceptive responses to acute/inflammatory pain, including acetic acid-induced writhing, thermal hyperalgesia, and carrageenan-induced thermal hyperalgesia in mice. The antinociceptive responses to açaí were dose-dependent. Furthermore, açaí extract diminished the neurogenic and inflammatory phases resulting from intraplantar injections of formalin and prevented chronic pain, including mechanical allodynia and thermal hyperalgesia, induced by spinal nerve ligation. Açaí displayed noteworthy antinociceptive action through multiple pathways and, therefore, may be considered in the production of new analgesic therapeutics. Additionally, Marinho et al. [41][150] showed that extracts from açaí flowers and spikes have antinociceptive activity in rat models. The flower extract has significant peripheral activity, reducing the total number of abdominal contortions by up to 50% in an acetic acid-induced abdominal writhing pain model. Although none of the açaí extracts were able to change the analgesia indices in a hot plate pain model, higher dosages of açaí achieved positive spinal antinociceptive effects. Açaí may have potential as therapeutic in the treatment and management of pain.
4.4. Antimicrobial Activity
Due to growing antimicrobial resistance, the pharmaceutical field is constantly seeking new alternatives to oppose relevant pathogens. The high polyphenol content of açaí has been associated with antimicrobial activity
[42][60]. One study has investigated the effects of açaí oil (EOO) complex against
Escherichia coli, Pseudomonas aeruginosa,
Streptomyces aureus, and
Enterococcus faecalis [43][151]. EOO complexes containing β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD) were also investigated. Results showed a modulatory antibacterial response of EOO, EOO-β-CD, and EOO-HP-β-CD and revealed that EOO can successfully form inclusion complexes, especially with β-CD. Minimum inhibitory concentration (MIC) demonstrated that the inclusion complexes in EOO-β-CD and EOO-HP-β-CD exhibited antibacterial effects against Gram-positive and Gram-negative strains and were considerably more potent than pure EOO.
4.5. Antiulcer Activity
Gastric ulcers are one of the most common conditions afflicting humans. Current treatments for gastric ulcers include H2-receptor antagonists, M1-receptor blockers, and proton pump inhibitors. However, these drugs can be costly, have health-associated side effects, and result in relapse. For this reason, more efficacious and inexpensive therapeutics for gastric ulcers are in high demand.
4.6. Neuroprotective Activity
There are limited investigations examining the impact of açaí berry on cognitive function or brain health. The experiments available have established that açaí largely confers its neuroprotection through antioxidant and anti-inflammatory mechanisms, restoration of mitochondrial function, and inhibition of toxic protein aggregation
[44][45][46][47][152,153,154,155]. Antioxidants have a clear role in the neutralization of free radicals and, therefore, the protection of cells against oxidative damage caused by free radicals
[48][14]. Oxidative damage has been linked to the development of chronic illnesses and is the common cytopathology of many neurodegenerative diseases (NDDs)
[49][50][156,157]. Neuronal degradation and the development of NDDs are generally multifactorial processes incited by a genetics, aging, and environmental factors linked to the progression of oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, anomalous protein accumulation in brain tissues, and excitotoxicity
[47][51][52][72,148,155]. Data have shown that neurons unequipped for adequate response to oxidative stress undergo apoptotic or necrotic death
[53][69]. Thus, oxidative stress is a primary mechanism responsible for neuronal degradation. In comparison to other organs, the relative lack of antioxidant enzymes, abundance of readily oxidizable substances, and substantial oxygen requirements in the brain render it more susceptible to free radical damage
[51][72]. Hence, materials rich in antioxidants can afford neuroprotective effects against oxidative damage
[49][156].
Açaí juice has been shown to exhibit antidepressant actions similar to those of imipramine, which inhibits neuronal reuptake of norepinephrine and serotonin neurotransmitters. Currently, the similitude between these two substances and their antiaging and antidepressant effects is thought to be due to their roles in the prevention of lipid peroxidation and increase of telomerase reverse transcriptase mRNA expression
[49][50][51][54][72,156,157,158].
4.7. Antilipidemic Activity
Dyslipidemia is precipitated by disruptions in lipid metabolism that result in chronically elevated serum lipids and, therefore, increased predisposition to CVDs, obesity, atherogenic processes, diabetes, and metabolic syndrome (MetS)
[55][56][106,160]. Dietary unsaturated fats can reduce the risk of CVD. Several studies have shown that the consumption of açaí oil and its rich content of unsaturated fatty acids may benefit lipid profiles
[57][18]. Liz et al.
[58][159] investigated the effects of the daily consumption of 200 mL of açaí juice in adults and discovered increased levels of high-density lipoprotein cholesterol (HDL) in comparison to baseline levels. Moreover, Bem et al.
[59][113] demonstrated that açaí seed extract, in conjunction with exercise training, reduced total cholesterol levels by 81.2% in diabetic rats. In addition, Faria et al.
[60][105] examined the actions of açaí oil on hyperlipidemia induced by
Cocos nucifera L. saturated fat in rats. Although no alterations in triglycerides were noted, there were reductions in total cholesterol and low-density lipoprotein cholesterol (LDL). A treatment regimen of both açaí oil and simvastatin, a common anticholesterolemic drug, also prevented the formation of atheromatous plaques in the vascular endothelium of rats
[55][61][106,109].
Figure 810 shows an overview of antilipidemic effects of açaí.
![/media/item_content/202302/63f56916837aenutrients-15-00989-g010.png](/media/item_content/202302/63f56916837aenutrients-15-00989-g010.png)
Figure 810. Antidiabetic and antilipidemic effects of açaí. Açaí improves glycemic control and exerts antilipidemic effects via various mechanisms. Symbols and abbreviations: ↑, increase; ↓, decrease; GLP-1, glucagon-like peptide 1; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; LDL-R, low-density lipoprotein cholesterol receptor; Akt, protein kinase B; AMPK, 5′ adenosine monophosphate-activated protein kinase.
4.8. Hepatoprotective Activity
Globally, the most prevalent liver condition is nonalcoholic fatty liver disease (NAFLD)
[62][111]. NAFLD is an umbrella term for a variety of progressive illnesses, including steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Despite the multifactorial onset and progression of NAFLD, specific intracellular contributory factors, such as inflammation, oxidative stress, mitochondrial dysfunction, altered endoplasmic reticulum (ER) homeostasis, and apoptosis, have been identified
[63][115]. Therefore, the phenolic compounds of açaí are regarded as prospective therapeutic agents in the treatment of NAFLD due to their high antioxidant and anti-inflammatory capacities
[64][65][66][67][47,163,164,165]. The effects of filtered açaí pulp on the expression of paraoxonase (PON) activity in rats with NAFLD have also been investigated
[68][69][166,167]. Rats fed a high-fat diet supplemented with açaí displayed increased hepatic and serum PON-1 activity, decreased LDL oxidation, and upregulated expression of PON1 and APOA1, which encodes apolipoprotein A-I (ApoA-I), in the liver. Overall, the consumption of açaí pulp reduced liver damage, fat infiltration, and triglyceride content, suggesting its potential efficacy against hepatic steatosis and liver injuries
[70][114].
4.9. Antidiabetic Activity
Worldwide, T2DM is a serious public health crisis reaching epidemic proportions
[71][117]. Diabetes is a major cause of kidney failure, cardiovascular events, blindness, and lower limb amputation. T2DM is associated with an increased risk of morphological and metabolic modifications in vital organs such as the liver
[60][105]. In a study conducted with obese mice on a high-fat diet, Silva et al.
[72][108] revealed that the incorporation of 15% or 30% dietary açaí seed flour procured beneficial effects against insulin resistance. Furthermore, after 12 weeks of açaí intake, the animals presented lower serum glucose, insulin, and leptin concentrations. The reduction of lipogenesis induced by açaí seed flour consumption also prevented the development of hypertrophic obesity
[73][112].
4.10. Antihypertensive Activity
Cardiovascular risk factors such as hypertension, dyslipidemia, obesity, diabetes mellitus, and MetS promote endothelial injury due to oxidative stress
[74][120]. This endothelial dysfunction causes an imbalance in vasoconstriction and vasodilation, as well as increased proinflammatory factors and ROS. Oxidative stress, inflammation, and the renin-angiotensin system (RAS) contribute to the development of hypertension
[39][118]. The use of açaí seed extract can exhibit antihypertensive effects in mice fed a high-fat diet, as shown by Santos et al.
[66][67][68][164,165,166].
4.11. Cardioprotective Effects
CVDs are currently the leading cause of morbidity and mortality among adults. Although scientific progress has identified a spectrum of different risk factors for cardiovascular pathologies, the current state of prevention, and even treatment, of CVDs is suboptimal
[69][75][76][167,168,169]. Over the last few decades, the number of deaths and disability from CVDs has continued to increase, indicating the demand for alternative treatment options for the management and prevention of CVDs. For this reason, açaí has been investigated as a prospective cardiovascular therapeutic agent due to its various cardioprotective bioactive compounds.
Figure 911 illustrates the potential cardioprotective effects of açaí.
Figure 911. Potential actions of açaí against CVD and cardiovascular risk factors. Açaí improves cardiac function and decreases cardiac fibrosis, exerts vasodilatory effects, diminishes endothelial dysfunction, and ameliorates exercise resistance. Symbols and abbreviations: ↑: increase; ↓: decrease; eNOS: endothelial nitric oxide synthase; MMP: matrix metalloproteinase; NO: nitric oxide; NO–cGMP: nitric oxide cyclic guanosine monophosphate.
4.12. Renoprotective Effects
Chronic kidney disease (CKD) is a general term for a group of heterogenous disorders that affect kidney structure and function. Over time, considerable research has been conducted to properly define, classify, and treat CKD. Ultimately, data has indicated that prevention is the most effective way to avoid the development and progression of renal disorders
[76][77][169,170]. Because many patients with CKD present with pathology related to effects of oxidative stress and inflammation, açaí has emerged as a possible nutritional therapeutic strategy for the prevention and management of CKD.
4.13. Antineoplastic Activity
Over time, the global frequency of cancer, a group of diseases characterized by abnormal cell growth, has continued to increase. Therefore, cancer prevention has become a topic of paramount importance within the scientific field. The chemopreventive and anticarcinogenic potency of açaí has been linked to its ability to decrease the viability of cancer cells, as well as reduce the incidence of tumors and tumor cell proliferation
[45][78][79][80][81][82][76,130,153,171,172,173]. In a study performed by Silva et al.
[83][80], the antitumor effects of hydroalcoholic extracts from açaí bark, seed, and fruit was evaluated in vitro using cell lines derived from colorectal and breast adenocarcinomas (human Caco-2 and HT-29 colon adenocarcinoma cells and human MDA-MB-468 and MCF-7 mammary adenocarcinoma cells, respectfully). Results showed that the three extracts from various parts of the açaí plant significantly decreased cancer cell viability by increasing the presence and function of autophagic vacuoles. It was noted that all açaí extracts possessed significant polyphenol content. In another in vitro study, Silva et al.
[81][172] assessed the cytotoxic effects of the extracts of açaí seed, pulp, and fruit in MCF-7 breast cancer cell lines. Açaí seed extract not only reduced the viability of cancer cells via ROS production, but also demonstrated cytotoxic effects and prevented the formation of new cancerous colonies. Moreover, Martinez et al.
[84][174] studied A549 lung carcinoma cell lines treated with açaí seed extract and ascertained that the extract incited cell cycle arrest and increased apoptosis among cancer cells. Although the study lacked a comprehensive evaluation of proapoptotic pathways, the use of açaí extract was found to increase the percentage of cells in G0/G1 cycle phases and contributed to higher numbers of apoptotic cells in comparison to the untreated cells. These results revealed the potent antioxidant activity of açaí seed extract and its protective effects against cancer.
5. Toxicity and Safety
Marques et al.
[57][18] published the first cytotoxic, genotoxic, and antigenotoxic assessment of açaí fruit oil in human cell cultures. These authors showed that the acute treatments of EOO (2.5, 10, 100, 500, and 1000 µg/mL) demonstrated neither cytotoxic effects nor DNA damage in HepG2 and human lymphocytes. Moreover, samples from mammalian leukocytes did not suffer any genotoxic effects following the administration of 1% of açaí oil at doses of 30, 100, and 300 mg/kg for 14 days.
Additionally, Ribeiro et al.
[85][185] tested acute and subacute doses of açaí pulp in mice at 3.33, 10.0, and 16.67 g/kg and demonstrated that no genotoxic effects were induced by the açaí administration. To further illustrate this point, another study suggested the absence of toxic effects caused by açaí at acute doses up to 2000 mg/kg in animals (such as mice), which could be equated to the human consumption of 140 g of açaí at one time
[10].
However, Marques et al.
[86][186] used rat models to demonstrate that the oral administration of açaí oil at doses of 30, 100, and 300 mg/kg over a time period of 14 days resulted in altered thyroid cell follicular morphology and reduced size of follicular cells due to hypertrophy and unorganized growth. Interestingly, these doses of açaí oil also caused hepatocyte vacuolization, as well as a shift from eosinophilic to basophilic characteristics in the cells.
67. Conclusions, Limitations, and Future Perspectives
Açaí has medicinal properties and the economic potential for widespread use throughout the food and cosmetic industry. The fruit presents a rich phytochemical profile composed of phenolic compounds, quinones, terpenes, and norisoprenoids, all of which are related to its health-promoting and disease-preventing potential. In vitro and in vitro studies demonstrated that açaí possesses antioxidant and anti-inflammatory effects; exerts cardioprotective, gastroprotective, hepatoprotective, neuroprotective, and renoprotective activities; improves hyperinsulinemia and dyslipidemia; and shows antineoplastic actions. Additionally, açaí exerts antimicrobial and antiparasitic effects. Clinical trials have demonstrated that açaí protects against prostate cancer, MetS risk factors, and auditory dysfunctions. Moreover, its derivatives, such as berry extracts, whole fruit extracts, seed extracts, and phytochemically enriched extracts, have no hepatotoxicity, cardiotoxicity, or nephrotoxicity, strengthening its safety and health potential.