Potential Challenges of the Extraction of Carotenoids and Fatty Acids from Pequi (Caryocar brasiliense) Oil.

Pequi is a natural source of bioactive compounds with wide versatility for fresh or processed fruit consumption, but it is still little explored economically. Functional foods are the subject of diverse scientific research since, in addition to being nourishing, they contain bioactive compounds capable of promoting several benefits to the human body. Pequi is a fruit species native to the Brazilian Cerrado, which is rich in oil and has components with a high nutritional value, such as unsaturated fatty acids (omega-3, omega-6, EPA, and DHA), antioxidants (carotenoids and phenolic compounds), and vitamins. Therefore, the present narrative review aims to compile and critically evaluate the methods used to extract oil from the pulp and almonds of pequi and describes the carotenoid separation from the oil because carotenoids are natural pigments of great interest in the pharmaceutical and food industries. It is emphasized that the main challenges linked to bioactive compound extraction are their susceptibility to degradation in the processing and storage stages of pequi and its derived products.

Studying the Predictive Effects of Bacterial Carotenoids in the Treatment of Endometriosis Using Virtual Screening Methods

Background: Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. Cytokines appear to play vital roles in the development and progression of endometriosis and associated infertility. Tumor necrosis factoralpha (TNF-alpha) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. TNF- alpha plays an important role in endometrial physiology as well as during early implantation. In addition, this cytokine has a considerable pathophysiological function in diseases such as menorrhagia, endometriosis, or infertility due to its regulatory impact on proliferation, differentiation, and angiogenesis in the human endometrium. In women with endometriosis, TNF-alpha levels increases in peritoneal fluid and serum significantly. In the present study, we focused on finding novel small molecules that can directly block TNFalpha- hTNFR1 (human TNF receptor 1) interaction. Method(s): In this regard, TNF-alpha inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-alpha-hTNFR1 interaction with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. Result(s): A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties, and they all met Lipinski's rule of five. Among them, sorgomol, strigol, and orobanchol had the most favorable DELTAG with the best pharmacokinetics properties and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. It was shown that sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with the lowest RMSD and RMSF. Conclusion(s): Our results showed that sorgomol was the most appropriate candidate as a TNF-alpha inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-alpha which plays an important role in the inflammation of endometriosis.

Diet and Lifestyle Guidelines for Immunomodulation with Reference to Corona Virus Pandemic: A Scientific Statement of the International College of Nutrition

The immune system is comprised of lymph glands, lymph nodes, thymus gland, spleen, bone marrow, lymphocytes, and molecules such as antibodies and cytokines. It has a vast array of functionally different cells such as T and B lymphocytes, macrophages, neutrophils and mast cells. The ontogenesis of the immune system is comprised of the innate immune cells and the adaptive immune cells, where innate immune cells are the first defense mechanisms to respond to pathogenic environmental factors. There are multiple components of the adaptive immune cells, including immunoglobulins (Igs), T-cell receptors (TCR), and major histocompatibility complex (MHC) responsible for adaptive immunity. However, many elements of both the innate and adaptive immune systems are conserved in our bodies. The adaptive immunity is a type of immunity that develops when a person’s immune cells respond to a pathogen such as microorganism or vaccination. Environmental factors such as pathogenic bacteria or viruses, solar exposure, age, exercise, stress, diet, sleep quality and air pollutants can influence the immune system. There may be marked decline in the immune function due to attack of COVID-19. Most patients with mild COVID-19 develop an appropriate immune response that culminates with viral clearance. However, severe disease manifestations have been linked to lymphopenia and immune hyper-responsiveness leading to cytokine storm. It has been observed that in COVID-19, alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immune-paralysis. Western diets are known to have adverse effects on the immune function. However, Mediterranean-type diets rich in short-and long-chain polyunsaturated fatty acids (PUFA), vegetables, nuts and fruits, dairy products and fish and red wine, due to high content of vitamins, minerals and flavonoids may be useful in boosting immunity. Moderate physical activity may also cause an extensive increase in numerous and varied lipid super-pathway metabolites, including oxidized derivatives called oxylipins. Emerging evidence suggests that dietary supplements containing flavonoids, carotenoids, coenzyme Q10 (CoQ10), vitamins, minerals and antioxidants modulate gene and protein expression and thereby modify endogenous metabolic pathways, and consequently enhance the immunity. Mediterranean-type diet and multiple bioactive nutrients, fatty acids, amino acids, vitamins and minerals as well as moderate physical activity may be crucial for enhancing immunomodulation.

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro.

The marine carotenoids fucoxanthin and siphonaxanthin are powerful antioxidants that are attracting focused attention to identify a variety of health benefits and industry applications. In this study, the binding energy of these carotenoids with the SARS-CoV-2 Spike-glycoprotein was predicted by molecular docking simulation, and their inhibitory activity was confirmed with SARS-CoV-2 pseudovirus on HEK293 cells overexpressing angiotensin-converting enzyme 2 (ACE2). Siphonaxanthin from Codium fragile showed significant antiviral activity with an IC50 of 87.4 µM against SARS-CoV-2 pseudovirus entry, while fucoxanthin from Undaria pinnatifida sporophyll did not. The acute toxicities were predicted to be relatively low, and pharmacokinetic predictions indicate GI absorption. Although further studies are needed to elucidate the inhibition of viral infection by siphonaxanthin, these results provide useful information in the application of these marine carotenoids for the treatment and prevention of COVID-19.

Extraction of Carotenoids from Tomato Pomace via Water-Induced Hydrocolloidal Complexation.

Agro-industrial waste is a largely untapped natural resource of bioactive compounds including carotenoids and pectin. However, conventional solvent extraction involves the excessive use of organic solvents, costly equipment, and tedious operation. These limitations of conventional extraction methods could be prospectively overcome by the carotenoid-pectin hydrocolloidal complexation. The complexation of lycopene and pectin was efficiently promoted in an aqueous environment, resulting in the colloidal complexes that can be subsequently recovered by sedimentation or centrifugation. In this study, the potential of carotenoid-pectin complexation on tomato pomace containing carotenoids and pectin was evaluated. Tomato pomace is a rich source of lycopene, ß-carotene as well as pectin, making it suitable as the raw material for the carotenoid extraction. The extraction of carotenoid and pectin from tomato pomace was optimized using response surface methodology. The maximum recovery was 9.43 mg carotenoid fractions/100 g tomato pomace, while the purity of carotenoid-rich fractions was 92%. The antioxidant capacity of carotenoids extracted from the complexation method was found to be higher than that from the solvent extraction method. Moreover, extraction yield and antioxidant capacity of carotenoid obtained from the carotenoid-pectin complexation were comparable to that from solvent extraction. The carotenoid-pectin complexation is a promising green approach to valorize agro by-products for the extraction of valuable carotenoids.

Findings in redox biology: From H2O2 to oxidative stress.

My interest in biological chemistry proceeded from enzymology in vitro to the study of physiological chemistry in vivo Investigating biological redox reactions, I identified hydrogen peroxide (H2O2) as a normal constituent of aerobic life in eukaryotic cells. This finding led to developments that recognized the essential role of H2O2 in metabolic redox control. Further research included studies on GSH, toxicological aspects (the concept of "redox cycling"), biochemical pharmacology (ebselen), nutritional biochemistry and micronutrients (selenium, carotenoids, flavonoids), and the concept of "oxidative stress." Today, we recognize that oxidative stress is two-sided. It has its positive side in physiology and health in redox signaling, "oxidative eustress," whereas at higher intensity, there is damage to biomolecules with potentially deleterious outcome in pathophysiology and disease, "oxidative distress." Reflecting on these developments, it is gratifying to witness the enormous progress in redox biology brought about by the science community in recent years.

COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome.

This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic acid-dependent component" and "retinoic acid non-dependent component". If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called "Endogenous Retinoic Acid Theory". Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called "retinoic acid depletion syndrome". COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases.