Nutraceuticals, Volume 3, Issue 3 (September 2023) – 11 articles

In the United States (US), tianeptine is sold as a dietary supplement under the trade name Tianaa™. Tianeptine is a synthetic drug prescribed by physicians as an antidepressant in parts of Europe, Asia and South America. The drug is not permitted for use by physicians in the US, because it is a μ-opioid receptor agonist with a propensity for severe addiction. As the incidence of Tianaa™-related opioid addiction across the southern US escalates, the current study aimed to quantify tianeptine in over-the-counter Tianaa™ White, Red, and Green products. The results of this investigation measured tianeptine levels between 3.1 and 10.9 mg per 531 mg capsules. Tianaa™ White capsules consistently contained the least tianeptine, while Green had the most. The close inspection of Tianaa™ products showed that capsule mass varied by as much as 16% from label claim, and the amount of tianeptine per capsule varied by as much as 35% from the average measured amount for each product. Tianaa™ Red contains kava leaf extract, which led to the identification of four kavapyrone components by mass spectrometry. The data presented provide insight into tianeptine quantity and capsule mass variation for Tianaa™ supplements sold to customers naive to the risk of addiction. Full article

Carotenoids represent a large group of well-known substances, mainly due to their nature as pigments and their beneficial effects on human health. These compounds are found naturally in microorganisms and plants but are not produced by humans, who must consume them through their diet. However, the mere intake of foods containing even large quantities of carotenoids is insufficient to guarantee their optimum absorption and, therefore, the desired beneficial effects. Due to their physicochemical characteristics, carotenoids are poorly stable and mostly insoluble in polar solvents like water. The conservation and improvement of their properties have become crucial objectives for the nutraceutical and functional food sector. Increasingly innovative delivery systems are being tested and developed. In this context, chitosan, a polysaccharide derived from the deacetylation of chitin, available in the exoskeleton of crustaceans and insects and the cell wall of some fungi and marine microalgae, has proved to be highly advantageous. In this review, we summarize the main characteristics of carotenoids, their benefits on human health, and their bioaccessibility and bioavailability for humans. We analyze the most recent carotenoid delivery systems, focusing on the potential of chitosan in preserving and enhancing the beneficial effects of these valuable pigments. Full article

Herbal infusions (HI) are a popular type of beverage known for their potential health benefits due to the extraction of phytochemicals and bioactive compounds. The Mediterranean Diet (MD) is a well-known dietary pattern with beneficial effects on health, and Psychological Resilience (PsyR) is a key indicator of mental health and human well-being. The aim of this cross-sectional study was to explore the relationship between HI and the MD, as well as their association with PsyR. The study included 398 healthy adults from Greece who participated voluntarily in an online research survey. The results indicated that 45.9% of participants consumed HI more than twice per week. There was a statistically significant association between the weekly consumption of HI and the Mediterranean Diet Adherence Screener (14-MEDAS), which identified HI consumption as a prognostic factor of high adherence to the MD. Additionally, HI consumption was significantly associated with PsyR. St John’s wort, green tea, and Greek mountain tea were associated with higher levels of PsyR. Greek mountain tea was also associated with a healthful and sustainable lifestyle. These findings suggest that HI are an integral part of the Mediterranean Diet, and their consumption is associated with PsyR. Promoting the consumption of HI such as Greek mountain tea and other herbs could be an effective way to promote healthy lifestyle behaviors and sustainable practices. Further randomized control trials are needed to confirm the results of this study. Full article

The stimulation of melanogenesis by novel natural products is desirable for cosmetic applications such as skin tanning, anti-greying, and clinical use for treating vitiligo and leukoderma disorders. Microphthalmia transcription factor (MITF) is a central transcription factor that controls the expression of tyrosinase, which is a key enzyme responsible for catalyzing the rate-limiting processes of melanin production. Tetrahydrocurcuminoids (THCr), which mostly consist of tetrahydrocurcumin (THC), are a colorless bioactive mixture derived from curcuminoids that are extracted from the Curcuma longa plant. THCr has been reported to exhibit superior properties, including antioxidant and anti-inflammatory effects. Our previous study reported the greater melanogenesis-stimulating effects of purified THC, compared to hexahydrocurcumin (HHC) or octahydrocurcumin (OHC). Curowhite™ (CW) is a proprietary extract that consists of 25% hydrogenated curcuminoids (mixture of THCr, hexahydrocurcuminoids, and octahydrocurcuminoids) encapsulated in a β-cyclodextrin (βCyD) excipient. The encapsulation of THCr in a suitable excipient, such as the widely popular cyclodextrins, helps to enhance the stability, solubility, and bioavailability of the THCr. CW is marketed as a nutraceutical with GRAS status and is safe when administered orally, as shown in vivo studies. However, the impact of CW on melanogenesis remains unexplored. Herein, the impact of CW on melanogenesis were investigated using B16F10 and MNT-1 cells. Our findings show that CW is markedly cytotoxic to B16F10 cells without affecting the cellular melanin content. However, in MNT-1 cells, CW significantly stimulated intracellular melanin content over the concentration range (20–60 µg/mL) with increased dendrite formation while being nontoxic to MNT-1 cells or HaCaT cells after a 5-day treatment. Examination of the effects of the excipient βCyD on cytotoxicity and melanogenesis confirmed that the excipient had no contribution to the biological impacts that were found to be exclusively attributable to the encapsulated mixture (THCr). The mechanisms of CW’s promelanogenic effects in MNT-1 cells were found to be related, at least in part, to an increase in tyrosinase and MITF protein levels, as CW did not alter tyrosinase activity in MNT-1 cells. Moreover, CW exhibited antioxidant activity as obtained through DPPH radical scavenging assay. Together, the findings of this pilot study indicate that CW might hold an exciting avenue as a pro-pigmenting nutraceutical for treating hypopigmentation disorders, the detailed mechanisms of which warrant further exploration. Moreover, future investigations are necessary to examine CW’s effects on melanogenesis in normal human melanocytes and in vivo studies. Full article

Vitamin D is a pleiotropic hormone that plays a vital role in regulating bone growth, maintaining calcium and phosphate homeostasis, modulating immune function, and a wide range of other pleiotrophic actions in humans, which have increased the attention for its clinical applications. Despite its importance, vitamin D deficiency is prevalent worldwide and is related to a range of pathophysiological conditions, including an increased risk of osteoporosis and chronic and autoimmune diseases. The recommended daily doses of vitamin D vary depending on genetics, age, sex, and health status, with specific doses recommended for infants, children, adults, and those at increased risk of deficiency or specific health conditions. Maintaining adequate vitamin D levels is essential for optimal health, and together with sun exposure, appropriate supplementation strategies can help achieve this goal. Vitamin D supplementation is commonly used to maintain adequate levels, and the optimal administration strategy, such as a daily dose vs. a bolus, is still being investigated. This review aims to understand vitamin D physiology and the impact of relevant vitamin D polymorphisms and to evaluate the role of a daily dose versus a bolus in maintaining optimal vitamin D levels and clinical health outcomes. It also provides suggested clinical guidelines for clinicians based on the most recent scientific evidence. Full article

To promote the rational use of Inonotus obliquus (chaga) from Eastern Canada, a mushroom consumed in infusion as a health drink, the extraction of its constituents was investigated. The extraction was carried out with water or ethanol at room temperature or by heating as well as following exposure to ultrasound. The extracts of the four seasons obtained with the four extraction methods were compared for their contents in carbon, nitrogen (N), sulfur (S), potassium (K), betulin, betulinic acid, potassium, flavonoids, and polyphenols. The antiradical effect as well as the photoprotective effects of all extracts were also investigated. The results show that there is no difference between the quantities extracted from the extracts of the 4 seasons. The results show a significant difference between the mass of the extracts obtained with water and ethanol. Betulinic acid was found to be more abundant in the extracts obtained with water while betulin was more abundant in the extracts obtained with ethanol. The mushroom and the extracts had high C contents, but low N and S contents, typical of protein-poor and carbohydrate-rich materials. Extracts were particularly rich in potassium, five times more than bananas. Heating favors the extraction of polyphenols and flavonoids. The aqueous extracts of chaga harvested in winter had the highest antiradical capacity. With a Sun Protection Factor (SPF) higher than 30 in the UVB wavelength, chaga extracts might be used as sunscreen. Extracts obtained with water had the highest SPF in general. The analysis of this mushroom further highlights this local product that deserves more attention for its potential benefits as a functional food/nutraceutical product. In addition to its nutritional values, this mushroom can also be used for its cosmetic qualities as it can be used as a sunscreen. Full article

The augmentation of adipocytes in the adipose tissues brings disordered pathophysiological conditions, including type 2 diabetes, hyperlipidemia, hypertension, cardiovascular disease, and cancer. The phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) prevents oxidative stress as radical scavenging in cells. However, the role of the disorder as a pharmacologic factor has been poorly understood. This study elucidates the regulatory effects of DHMBA on adipogenesis in mouse 3T3-L1 adipocytes in vitro. The 3T3-L1 preadipocytes were cultured in DMEM containing 10% calf fetal serum in the presence of DHMBA. Culturing with DHMBA repressed the growth of 3T3-L1 preadipocytes cultured in a medium without differentiation factors. Interestingly, when 3T3-L1 preadipocytes were cultured in a medium including differentiation factors containing insulin, DHMBA did not affect the number of cells with the differentiation process of adipogenesis. Culturing with DHMBA (1, 10, or 100 μM) inhibited lipid accumulation in adipocytes and repressed adipogenesis in 3T3-L1 cells. The potent inhibitory effects of DHMBA on adipogenesis were seen at the later stage of culture. Adipogenesis was inhibited by the presence of wortmannin, PD98059, or Bay 11-7082, which are inhibitors of pathways related to insulin signaling pathway. Notably, the suppressive effects of DHMBA on adipogenesis were expressed by the presence of these inhibitors. DHMBA treatment declined the levels of PPARy and C/EBPα related to preadipocyte differentiation and PI3 kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR implicated in the insulin signaling pathway, leading to adipogenesis promotion. Thus, DHMBA may inhibit adipogenesis via regulating diverse signaling pathways, providing a new strategy for the therapy of obesity. Full article

Natural phytochemicals (PCs) are responsible for the taste, colour, and aroma of many edible plants. Cohort studies have linked higher intake to a reduced risk of chronic degenerative diseases and premature ageing. The ability of foods rich in PCs, such as phytanthocyanins, apigenin, flavonols, flavonoids, bioflavonoids, gallic acid, ellagic acid, quercetin, and ellagitannins, to support physical activity has also been highlighted in a number of published pre-clinical and prospective clinical studies. This literature mostly emphasises the ability of PCs to enhance the adaptive upregulation of antioxidant enzymes (AEs), which reduces exercise-associated oxidative stress, but there are several other mechanisms of benefit that this narrative review addresses. These mechanisms include; protecting joints and tendons from physical trauma during exercise; mitigating delayed-onset muscle symptoms (DOMS) and muscle damage; improving muscle and tissue oxygenation during training; cultivating a healthy gut microbiome hence lowering excess inflammation; cutting the incidence of upper respiratory tract viral infections which disrupt training programmes; and helping to restore circadian rhythm which improves sleep recovery and reduces daytime fatigue, which in turn elevates mood and motivation to train. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease showing an exponential increase in its prevalence all over the world. High blood glucose level is one of the main clinical signs of the disease. Although several classes of drugs are available for treatment, their prolonged use and adverse effects behoove the use of alternative medicine. Plant-derived natural products have multifaceted beneficial roles in human pathophysiology. Plant metabolites like tannins, organic acids, polyphenols, terpenes, and flavonoids show multiple mechanisms of action against diabetes. The fruits of Emblica officinalis (EOF), also known as Indian gooseberry (amla), contain several phytochemicals, potentially having anti-diabetic activity. Hydrolyzable tannins are the major bioactive components of the amla fruit, the most abundant hydrolyzable tannin being β-glucogallin. The present review summarizes the mechanism of action and clinical evidence for the beneficial effects of EOF on T2DM and its associated complications. Full article

Even with its endemic transition, the COVID-19 pandemic remains a public health threat, particularly in the light of emerging variants of concern (VoCs) and the need for pandemic preparedness in the future. In November 2021, the SARS-CoV-2 VoC Omicron emerged and its subvariants BA.1, BA.2 and BA.5 became predominant. Although the protease inhibitor Paxlovid^® and the polymerase inhibitors Molnupiravir and Remdesivir were approved as specific antiviral treatment options for COVID-19 patients in the early stages after infection, effective prophylactically acting substances without adverse effects are not available yet. In a recent study, we demonstrated that iota-carrageenan, a sulfated polysaccharide extracted from red seaweed, efficiently inhibits the replication of the SARS-CoV-2 Wuhan Type and the VoCs Alpha, Beta, Gamma and Delta. Now, we extended this study by investigating the antiviral effects of iota-, lambda- and kappa-carrageenans on the VoC Omicron subvariants BA.1, BA.2 and BA.5. Using a VoC Omicron BA.1 spike pseudotyped murine leukemia virus (BA.1 MLV_OMVLP) as well as patient-derived SARS-CoV-2 Omicron isolates BA.1, BA.2 and BA.5 (SARS-CoV-2_{OM BA.1}, SARS-CoV-2_{OM BA.2} and SARS-CoV-2_{OM BA.5}), we demonstrate that iota-carrageenan exhibits similar antiviral activity against all analyzed Omicron subvariants. As with other VoCs shown before, the biologically inert iota-carrageenan was more efficient than kappa- and lambda-carrageenan. Altogether, these results confirm that, independent of the current and potential future variants, the physical barrier provided by iota-carrageenan might be applicable for prophylaxis and early treatment of SARS-CoV-2 infections. Full article

Plants with therapeutic potential are a rich resource for the inhabitants of a country, with Romania among them, having a diverse flora not only from plants but also from fungi. New trends in biopharmaceuticals are also addressed in studies related to topical administration, representing a great advantage; research has determined biological activities in vivo and in vitro. This study aimed to present the main active compounds from extracts of Lactarius piperatus, Centaurea cyanus, and Ribes rubrum. In vitro (DPPH scavenging activity and reducing power) and in vivo activities were determined. A survey of hydrating cosmetic products and the completion of a patch test (in vivo test) under dermatological control were realized to confirm the skin compatibility of the product in a panel of human subjects after a single application. The cosmetic product did not induce allergic reactions, erythema, irritation, or itching. This study showed that the extracts incorporated in the formulation of the face cream had a nutricosmetic effect. The research demonstrated a result of increasing skin elasticity and an anti-inflammatory effect following direct application to the skin of volunteers. The product offered in vitro/in vivo protection against the action of free radicals; it was effective in reducing the side effects of exposure to the action of blue light. Full article