Background In recent times, research has highlighted the bioactive roles played by non-extractable polyphenols (NEP) in human health, especially from by-products of grains, fruits and vegetables. Most studies have reported on the total phenol content of samples without adequate attention paid to a major class of polyphenols referred to as NEP. This limits the scope of polyphenol studies and the extent of NEP incorporation into medicines, nutraceuticals, cosmetic and foods among other applications. Scope and approach This review introduces NEP and gives an update on recent advances in free and bound polyphenol extraction from plant by-products. Owing to the fact that most researchers are already familiar with the extraction of free polyphenols, this review emphasizes the extraction of NEP and provides a basis for the selection of appropriate techniques and applications for different plant by-product sources. It also presents suggestions for future studies into NEP extraction efficiency from complex plant sources using alternative physical approaches. Key findings and conclusions NEP from by-products have high potential for use in industry, especially in pharmaceutical, nutraceutical and cosmetic applications. To ascertain the total phenol content of extracts, both free and bound phenols must be accounted for with special attention directed at appropriate sample pretreatment and extract hydrolysis. Higher bioactive properties of NEP, coupled with their cheaper by-product sources makes them economically viable and medicinally potent. Also, structure-function relationships and the possibility to use physical means such as slow-freezing-thawing to increase hydrolytic yield of NEP is recommended.

Latest developments in polyphenol recovery and purification from plant by-products: A review

Coffee is one of the most widely consumed beverages worldwide. It is usually identified as a stimulant because of a high content of caffeine. However, caffeine is not the only coffee bioactive component. The coffee beverage is in fact a mixture of a number of bioactive compounds such as polyphenols, especially chlorogenic acids (in green beans) and caffeic acid (in roasted coffee beans), alkaloids (caffeine and trigonelline), and the diterpenes (cafestol and kahweol). Extensive research shows that coffee consumption appears to have beneficial effects on human health. Regular coffee intake may protect from many chronic disorders, including cardiovascular disease, type 2 diabetes, obesity, and some types of cancer. Importantly, coffee consumption seems to be also correlated with a decreased risk of developing some neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and dementia. Regular coffee intake may also reduce the risk of stroke. The mechanism underlying these effects is, however, still poorly understood. This review summarizes the current knowledge on the neuroprotective potential of the main bioactive coffee components, i.e., caffeine, chlorogenic acid, caffeic acid, trigonelline, kahweol, and cafestol. Data from both in vitro and in vivo preclinical experiments, including their potential therapeutic applications, are reviewed and discussed. Epidemiological studies and clinical reports on this matter are also described. Moreover, potential molecular mechanism(s) by which coffee bioactive components may provide neuroprotection are reviewed.

Neuroprotective Effects of Coffee Bioactive Compounds: A Review.

Tangerine, banana and pomegranate peels valorisation for sustainable environment: A review.

Background Citrus fruits are appreciated worldwide owing to their high nutritional importance. Its industrial processing generates several underexploited by-products which are generally disposed into environment or are used as animal feed. Therefore, their proper disposal and management has become a major concern globally. Nevertheless, these by-products contain abundant quantities of high-value compounds having numerous health benefits and industrial applications. Therefore, valorization of citrus by-products can be considered as an alluring choice to enhance the value of citrus processing chain by recovery and subsequent applications of bioactive compounds. Scope and approach Considering the presence of several bioactive compounds in citrus by-products allied with extensive opportunity of industrial applications, this review describes an updated overview of scientific literature regarding conventional and current sustainable strategies adopted for the management of citrus by-products. In addition, the emerging applications of bioactive compounds extracted from citrus by-products in food, pharmaceutical, and cosmetic sectors along with development of environmentally sustainable materials have been discussed. Key findings and conclusions: Fruit and vegetable by-products, generated especially from citrus processing industries can be considered as lucrative resource having several bioactive compounds with functional properties and potential industrial applications. Therefore, the extraction of these compounds for the complete recycle/reuse of citrus by-products can be considered as a roadmap towards an advanced and circular economy. However, a multidisciplinary approach is required for the complete understanding of these processes, which can allow researchers to achieve the concept of zero-waste economy and sustainable society.

Unraveling the scientific perspectives of citrus by-products utilization: Progress towards circular economy

The therapeutic effect of phenolics on neurodegenerative diseases has been attributed to their potent antioxidant properties. In the present study, the neuroprotective activities of vanillin and vanillic acid were investigated in Fe2+- induced oxidative toxicity in brain tissues by investigating their therapeutic effects on oxidative imbalance, cholinergic and nucleotide-hydrolyzing enzymes activities, dysregulated metabolic pathways. Their cytotoxicity was investigated in hippocampal neuronal cell lines (HT22). The reduced glutathione level, SOD and catalase activities were ameliorated in tissues treated with the phenolics, with concomitant depletion of malondialdehyde and nitric oxide levels. They inhibited acetylcholinesterase and butyrylcholinesterase activities, while concomitantly elevated ATPase activity. Treatment with vanillin led to restoration of oxidative-depleted metabolites and reactivation of the pentose phosphate and purine metabolism pathways, with concomitant activation of pathways for histidine and selenoamino metabolisms. While vanillic acid restored and reactivated oxidative-depleted metabolites and pathways but did not activate any additional pathway. Both phenolics portrayed good binding affinity for catalase, with vanillic acid having the higher binding energy of −7.0 kcal/mol. Both phenolics were not cytotoxic on HT22 cells, and their toxicity class were predicted to be 4. Only vanillin was predicted to be permeable across the blood brain barrier (BBB). These results insinuate that vanillin and vanillic acid confer a neuroprotective effect on oxidative brain damage, when vanillin being the most potent.

Vanillin and vanillic acid modulate antioxidant defense system via amelioration of metabolic complications linked to Fe2+-induced brain tissues damage

Caffeine and caffeic acid are two bioactive compounds that are present in plant foods and are major constituent of coffee, cocoa, tea, cola drinks and chocolate. Although not structurally related, caffeine and caffeic acid has been reported to elicit neuroprotective properties. However, their different proportional distribution in food sources and possible effect of such interactions are not often taken into consideration. Therefore, in this study, we investigated the effect of caffeine, caffeic acid and their various combinations on activities of some enzymes [acetylcholinesterase (AChE), monoamine oxidase (MAO) ecto-nucleoside triphosphate diphosphohydrolase (E-NTPase), ecto-51-nucleotidase (E-NTDase) and Na+/K+ ATPase relevant to neurodegeneration in vitro in rat brain. The stock concentration of caffeine and caffiec acid and their various proportional combinations were prepared and their interactions with the activities of these enzymes were assessed (in vitro) in different brain structures. The Fe2+ and Cu2+ chelating abilities of the samples were also investigated. The results revealed that caffeine, caffeic acid and their various combinations exhibited inhibitory effect on activities of AChE, MAO, E-NTPase and E-NTDase, but stimulatory effect on Na+/K+ ATPase activity. The combinations also exhibited Fe2+ and Cu2+ chelating abilities. Considering the various combinations, a higher caffeine to caffeic acid ratio produced significantly highest enzyme modulatory effects; these were significantly lower to the effect of caffeine alone but significantly higher than the effect of caffeic acid alone. These findings may provide new insight into the effect of proportional combination of these bioactive compounds as obtained in many foods especially with respect to their neuroprotective effects.

Effect of caffeine, caffeic acid and their various combinations on enzymes of cholinergic, monoaminergic and purinergic systems critical to neurodegeneration in rat brain-In vitro.

Citrus peels, which are an environmental menace in many developing countries have been in use in folk medicine for the management of some degenerative conditions, though there was limited information on the mechanism of such medicinal properties. These medicinal properties also promote the peels as functional foods; since they are generally regarded as safe and are consumed in some countries in forms of candies, wines, infusions and additives. Studies on the mechanisms for the antioxidant, anti-diabetic, cardioprotective, neuroprotective and anticancer activities of the peels have established the intereaction with some key enzymes relevant to the management of such diseases. The phenolic compounds and volatile compounds which have been linked with the biological activities of the peels have been characterized. This review looks at the bioactive compounds of citrus peels and the mechanisms for the biological activities of the peels.

From folk medicine to functional food: a review on the bioactive components and pharmacological properties of citrus peels

Caffeine (CA) and caffeic acid (CAF) are two bioactive phytochemicals found richly distributed in many plant foods such as coffee in different proportions. CA, an alkaloid, is adjudged world’s most consumed food bioactive substance, while CAF is a common phenolic acid in plants. With reports of potential cardiomodulatory properties of CA and CAF, we sought to investigate if proportional combinations of CA and CAF could influence the antihypertensive properties of each compounds by assessing their effect on activities of enzymes [angiotensin-1 converting enzyme (ACE), acetylcholinesterase, arginase, monoamine oxidase, phosphodiesterase-5 (PDE-5)] relevant to hypertension in vitro. Aqueous solutions of 1 mg/ml CAF and CA was prepared; thereafter, two combinations (C1 and C2) were prepared, where C1 is 5CA: 1CAF and C2 is 10CA: 1CAF. These samples were subsequently used for various enzyme assays. Results showed that C1 and C2 exhibited synergistic effects by eliciting significantly higher (P   0.05) from that of standard drugs Lisinopril and Sildenafil respectively. Also, both combinations exhibited higher antioxidant properties compared to CA and CAF. Hence, results presented in this paper support that combinations of CA and CAF as often found in plant foods exhibit improved antioxidant properties and enhanced inhibitory effects on critical enzymes relevant to hypertension, which, could be essential for the management of hypertension.

Effect of combinations of caffeine and caffeic acid on key enzymes linked to hypertension (in vitro)

Nigella sativa, a core dietary supplement and food additive in folklore is one of the most broadly studied seed plants in the global nutraceutical sector. Malaria infection impairs the ability of principal cells of the immune system to trigger an efficient inflammatory and immune response. Ninety-six mice, weighing 20-25 g, were grouped into 12 consisting of 8 animals each. The mice were infected with standard inoculum of the strain NK65 Plasmodium berghei (chloroquine sensitive) and the percentage parasitemia suppression were evaluated. The individual effect of black seed supplemented diet and its combinatory effect with chloroquine (CQ) were investigated on reactive oxygen species (ROS), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione-S-transferase (GST), serum immunoglobulins (IgG and IgM), and the hematological parameters (hemoglobin, packed cell volume, and red blood cell count) in P. berghei infected mice. The inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin (IL-6 and IL-10), as well as IgG and IgM were assayed in the serum. The mice temperature and behavioral changes were observed. Infected mice treated with the dietary supplementation of black seed with a percentage inclusion (2.5%, 5%, 10%) showed significantly decreased parasitemia and ROS levels (p < 0.05) compared with the untreated mice. The result demonstrated a significant suppression in the pro-inflammatory cytokines (TNF-α, IL-6) levels and a notable elevation in the anti-inflammatory cytokine (IL-10), antioxidant markers as well as the immunoglobulin levels of the P. berghei-infected mice treated with black seed. The study revealed that black seed enhanced host antioxidant status, modulated inflammatory and immune response by regulating some inflammatory cytokines and immunomodulatory mediators. PRACTICAL APPLICATIONS: Black seed (Nigella sativa) has been a dietary supplement and natural remedy for many centuries. Inflammatory and immune diseases are the most notable cause of mortality in the world and more than 50% of deaths have been attributed to it. However, there is paucity of information on the effect of N. sativa on anti-inflammatory and immunomodulatory ability during malaria infection. The result suggests that N. sativa produced antioxidant, anti-inflammatory, and immunomodulatory effect in Plasmodium berghei-infected mice via the participation of glutathione antioxidant system, serum antibodies, and some inflammatory cytokines. 

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Opeyemi O. Adeoyo

Papers

Effect of caffeine, caffeic acid and their various combinations on enzymes of cholinergic, monoaminergic and purinergic systems critical to neurodegeneration in rat brain-In vitro.

From folk medicine to functional food: a review on the bioactive components and pharmacological properties of citrus peels

Effect of combinations of caffeine and caffeic acid on key enzymes linked to hypertension (in vitro)

Effect of black seeds ( <i>Nigella sativa</i> ) on inflammatory and immunomodulatory markers in <i>Plasmodium berghei</i> <scp>‐infected</scp> mice