Search Results (45)

Obesity, marked by excessive fat accumulation, especially abdominal, is a global health concern with significant public impact. While obesity-associated chronic unresolved inflammation contributes to metabolic dysfunctions, acute inflammation supports healthy adipose tissue remodeling and expansion. Platelet-activating factor (PAF), a “primitive” signaling molecule, is among the key mediators involved in the acute phase of inflammation and in various pathophysiological processes. This article explores the role of PAF in fat accumulation and obesity by reviewing experimental data from cell cultures, animals, and humans. It proposes an emerging biochemical mechanism in an attempt to explain its dual role in the healthy and obese adipose tissue, including also data on PAF’s potential involvement in epigenetic mechanisms that may be linked to the “obesity memory”. Finally, it highlights the potential of natural PAF modulators in promoting functional adipose tissue, thermogenesis, and obesity prevention through a healthy lifestyle, including a Mediterranean diet rich in PAF weak agonists/PAF receptor antagonists and regular exercise, which help maintain controlled PAF levels. Conversely, in cases of obesity-related systemic inflammation with excessive PAF levels, potent PAF inhibitors like ginkgolide B and rupatadine may help mitigate metabolic dysfunctions with PAFR antagonists potentially enhancing their effects synergistically. Full article

Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation of neuronal structure, or loss of neuronal function, leading to a substantially reduced quality of life. They remain a significant focus of scientific and clinical interest due to their increasing medical and social importance. Most neurodegenerative diseases present intracellular protein aggregation or their extracellular deposition (plaques), such as α-synuclein in Parkinson’s disease and amyloid beta (Aβ)/tau aggregates in Alzheimer’s. Conventional treatments for neurodegenerative conditions incur high costs and are related to the development of several adverse effects. In addition, many patients are irresponsive to them. For these reasons, there is a growing tendency to find new therapeutic approaches to help patients. This review intends to investigate some phytocompounds’ effects on neurodegenerative diseases. These conditions are generally related to increased oxidative stress and inflammation, so phytocompounds can help prevent or treat neurodegenerative diseases. To achieve our aim to provide a critical assessment of the current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, and COCHRANE, seeking clinical trials that utilized phytochemicals against neurodegenerative conditions. A few clinical trials investigated the effects of phytocompounds in humans, and after screening, 13 clinical trials were ultimately included following PRISMA guidelines. These compounds include polyphenols (flavonoids such as luteolin and quercetin, phenolic acids such as rosmarinic acid, ferulic acid, and caffeic acid, and other polyphenols like resveratrol), alkaloids (such as berberine, huperzine A, and caffeine), and terpenoids (such as ginkgolides and limonene). The gathered evidence underscores that quercetin, caffeine, ginkgolides, and other phytochemicals are primarily anti-inflammatory, antioxidant, and neuroprotective, counteracting neuroinflammation, neuronal oxidation, and synaptic dysfunctions, which are crucial aspects of neurodegenerative disease intervention in various included conditions, such as Alzheimer’s and other dementias, depression, and neuropsychiatric disorders. In summary, they show that the use of these compounds is related to significant improvements in cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, and mood disorders. Full article

Determining hemicellulose (HM) degradation is crucial for evaluating the nutritional value of ruminant diets. Our previous study showed that oxalic acid (OA) regulates rumen fermentation. Building on this research, the present study examined the effects of OA supplementation in different hemicellulose diets on sheep rumen fermentation, microbial diversity, and metabolite production in vitro. Diets with low and high HM levels (10.3% and 17%, respectively) and supplemented with seven concentrations of OA (0, 2.5, 5, 10, 20, 40, 80 mg/kg DM) were evaluated. Tests were conducted under both low (HM10.3%) and high (HM17%) hemicellulose conditions; however, the addition of 10 mg/kg DM oxalic acid could have better effects under low hemicellulose (HM10.3%), with higher concentrations of acetic, propionic, and butyric acids, as well as total acids. A 2 × 2 factorial design was used to collect rumen fluid after 12 h of fermentation to analyze microbial populations and metabolites. OA supplementation at 10 mg/kg DM significantly increased the relative abundances of several bacterial genera, including Prevotella, Butyrivibrio, Ruminococcus, Sharpea, RFN20, Bulleidia, Olsenella, and Bifidobacterium (p < 0.05). A positive correlation was observed between Butyrivibrio and Sharpea and the production of isobutyric and isovaleric acids (p < 0.01), indicating that these bacteria play a role in volatile fatty acid (VFA) production. Furthermore, rumen metabolites involved in mineral absorption and lipid metabolism, including α-tocopherol, L-glutamic acid, and ginkgolide B, were upregulated. In summary, supplementation with oxalic acid in HM diets alters rumen fermentation, enhances nutrient digestibility, promotes microbial diversity, and influences metabolic pathways. Thus, OA supplementation should be tailored to specific dietary conditions for optimal effects. Full article

Ginkgo biloba extract (EGB) has been approved by the Food and Drug Administration in the United States for clinical studies on memory disorders. Ginkgolide B (GB) is the major terpene lactone component of EGB and is a specific and potent antagonist of platelet-activating factor (PAF). In a previous study, we reported the medium composition for the conversion of ginkgolides to GB by Coprinus comatus. In the present study, we applied the response surface methodology (RSM) to optimize the conversion conditions in a 20 L fermenter and applied HPLC-MS/MS, circular dichroism (CD) and infrared (IR) spectroscopy analyses, and nuclear magnetic resonance (NMR) to further confirm the sample structure. The optimal conversion conditions consisted of 12.7 L/min of ventilation, a 156 h conversion time, a 132 rpm rotating speed, a 0.04 MPa fermenter pressure, and a 27.8 °C conversion temperature. Under the optimal conditions, the GB conversion rate was 98.62%, and the GB content of the sample was higher than 98%. HPLC-MS/MS, CD, IR, and NMR analyses showed that the molecular formula of the sample was C₂₀H₂₄O₁₀ and the chemical structure of the sample was in good agreement with the standard GB. Our current study lays the groundwork for the industrial production of GB. Full article

Ginkgo biloba is an ancient plant that has survived up until the present day. Gingko biloba is a rich source of valuable secondary metabolites, particularly terpene trilactones (TTLs) such as ginkgolides and bilobalides, which are obtained from the leaves and seeds of the plant. TTLs have pharmacological properties, including anticancer, anti-dementia, antidepressant, antidiabetic, anti-inflammatory, anti-hypertensive, antiplatelet, immunomodulatory, and neuroprotective effects. However, ginkgo is a very-slow-growing tree that takes approximately 30 years to reach maturity. In addition, the accumulation of TTLs in these plants is affected by age, sex, and seasonal and geographical variations. Therefore, plant cell cultures have been established in ginkgo to produce TTLs. Extensive investigations have been conducted to optimize the culture media, growth regulators, nutrients, immobilization, elicitation, and precursor-feeding strategies for the production of TTLs in vitro. In addition, metabolic engineering and synthetic biology methods have been used for the heterologous production of TTLs. In this review, we present the research strategies applied to cell cultures for the production of TTLs. Full article

Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761^® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies. Full article

Ginkgo biloba L. leaves are rich in secondary metabolites with important medicinal values; to increase their contents, foliar spraying of micronutrients is a potential strategy. Zinc, a multifunctional element, has a significant impact on the content of secondary metabolites in other plants, but relevant research into ginkgo is still lacking. In our study, different spraying time and concentration strategies were used to investigate the effects of zinc sulfate (ZnSO₄) on physiological indicators and secondary metabolites of 2-year-old ginkgo. The results demonstrated that ZnSO₄ could increase the contents of hydrogen peroxide, abscisic acid, and free amino acids in ginkgo leaves. It also enhances the antioxidant enzyme activity of ginkgo leaves, decreases the content of plant auxin, and ultimately facilitates the accumulation of ginkgo terpene lactones (TTL). Spraying ZnSO₄ in June resulted in a more significant increase in the contents of TTL and flavonoids compared to spraying in August. After spraying 12 mmol/L ZnSO₄ in June, the contents of TTL and flavonoids in ginkgo leaves were significantly elevated by 35.95% and 24.30%, respectively, compared to those in the CK (p < 0.05). The contents of ginkgolide A, B, and C were notably increased by 45.93%, 46.56%, and 74.29%, respectively, compared to those in the CK (p < 0.05). Therefore, our study suggests that the optimal timing for spraying ZnSO₄ on ginkgo is in June, with a recommended concentration of 12 mmol/L. Our study provides a theoretical basis for the accumulation of secondary metabolites in ginkgo and guides the production of its leaf-utilization plantations. Full article

As a medicinal tree species, ginkgo (Ginkgo biloba L.) and terpene trilactones (TTLs) extracted from its leaves are the main pharmacologic activity constituents and important economic indicators of its value. The accumulation of TTLs is known to be affected by environmental stress, while the regulatory mechanism of environmental response mediated by microRNAs (miRNAs) at the post-transcriptional levels remains unclear. Here, we focused on grafted ginkgo grown in northwestern, southwestern, and eastern-central China and integrally analyzed RNA-seq and small RNA-seq high-throughput sequencing data as well as metabolomics data from leaf samples of ginkgo clones grown in natural environments. The content of bilobalide was highest among detected TTLs, and there was more than a twofold variation in the accumulation of bilobalide between growth conditions. Meanwhile, transcriptome analysis found significant differences in the expression of 19 TTL-related genes among ginkgo leaves from different environments. Small RNA sequencing and analysis showed that 62 of the 521 miRNAs identified were differentially expressed among different samples, especially the expression of miRN50, miR169h/i, and miR169e was susceptible to environmental changes. Further, we found that transcription factors (ERF, MYB, C3H, HD-ZIP, HSF, and NAC) and miRNAs (miR319e/f, miRN2, miRN54, miR157, miR185, and miRN188) could activate or inhibit the expression of TTL-related genes to participate in the regulation of terpene trilactones biosynthesis in ginkgo leaves by weighted gene co-regulatory network analysis. Our findings provide new insights into the understanding of the regulatory mechanism of TTL biosynthesis but also lay the foundation for ginkgo leaves’ medicinal value improvement under global change. Full article

Ischemic stroke (IS) is one of the leading causes of mortality worldwide. It is characterized by the partial or total occlusion of arteries that supply blood to the brain, leading to the death of brain cells. In recent years, natural bioactive compounds (NBCs) have shown properties that ameliorate the injury after IS and improve the patient’s outcome, which has proven to be a potential therapeutic strategy due to their neuroprotective effects. Hence, in the present study, we use both systems pharmacology and chemoinformatic analyses to identify which NBCs have the most potential to be used against IS in clinics. Our results identify that flavonoids and terpenoids are the most studied NBCs, and, mainly, salidrosides, ginkgolides A, B, C, and K, cordycepin, curcumin, baicalin, resveratrol, fucose, and cannabidiol, target the main pathological processes occurring in IS. However, the medicinal chemistry properties of such compounds demonstrate that only six fulfill such criteria. However, only cordycepin and salidroside possess properties as leader molecules, suggesting that these compounds may be considered in developing novel drugs against IS. Full article

Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A–C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress. Full article

The phytochemical profiles of extracts from closed, semi-opened and opened leaf buds and the summer leaves of Ginkgo biloba were studied. The extraction and purification of bilobalide and ginkgolides, using andrographolide as an internal standard, were optimised. The terpene trilactone concentrations increased with bud development, from 1.07 mg/g dry wt in closed buds to a maximum of 3.75 mg/g dry wt in summer leaves. The major terpene trilactone was bilobalide at all developmental stages. The concentration of flavonol aglycones in hydrolysed extracts was also analysed. The flavonol glycoside concentration increased from the closed bud stage (0.21 ± 0.01% dry wt) to the summer leaf stage (1.15 ± 0.01% dry wt). A linear correlation was observed between the terpene trilactone and flavonoid content during gingko leaf development. Full article

The reactive oxygen species (ROS) scavenging capacities of ginkgolides and bilobalide, which are the peculiar constituents of the extract of Ginkgo biloba, are investigated in silico (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Unlike other popular antioxidant natural substances, the carbon backbones of these compounds are entirely aliphatic and exclusively single C–C bonds are present. The selectivity for alkoxyl radicals via hydrogen-atom transfer (HAT) is assessed; importantly, the scavenging of peroxyl radicals is also possible from a peculiar site, here labeled C10 both for ginkgolides and bilobalide. The energetics are described in detail, and the analysis discloses that the studied compounds are powerful scavengers, with thermodynamic and kinetic properties similar to those of Trolox and melatonin, and that, in addition, they display selectivity for peroxyl radicals. These are all chemical-reactivity features contributing to the therapeutic action of the extract of G. biloba. Full article

Neurodegenerative diseases (NDs) affect the West due to the increase in life expectancy. Nervous cells accumulate oxidative damage, which is one of the factors that triggers and accelerates neurodegeneration. However, cells have mechanisms that scavenge reactive oxygen species (ROS) and alleviate oxidative stress (OS). Many of these endogenous antioxidant systems are regulated at the gene expression level by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). In the presence of prooxidant conditions, Nrf2 translocates to the nucleus and induces the transcription of genes containing ARE (antioxidant response element). In recent years, there has been an increase in the study of the Nrf2 pathway and the natural products that positively regulate it to reduce oxidative damage to the nervous system, both in in vitro models with neurons and microglia subjected to stress factors and in vivo models using mainly murine models. Quercetin, curcumin, anthocyanins, tea polyphenols, and other less studied phenolic compounds such as kaempferol, hesperetin, and icariin can also modulate Nrf2 by regulating several Nrf2 upstream activators. Another group of phytochemical compounds that upregulate this pathway are terpenoids, including monoterpenes (aucubin, catapol), diterpenes (ginkgolides), triterpenes (ginsenosides), and carotenoids (astaxanthin, lycopene). This review aims to update the knowledge on the influence of secondary metabolites of health interest on the activation of the Nrf2 pathway and their potential as treatments for NDs. Full article

Ginkgo biloba is a medicinal plant used in complementary and alternative medicines. Ginkgo biloba extracts contain many compounds with medical functions, of which the most critical is ginkgolide B (GB). The major role that GB plays is to function as an antagonist to the platelet-activating factor, which is one of the causes of thrombosis and cardiovascular diseases. Currently, GB is obtained mainly through extraction and purification from the leaves of Ginkgo biloba; however, the yield of GB is low. Alternatively, the immobilized cultivation of ginkgo calluses with biomaterial scaffolds and the addition of organic elicitors to activate the cell defense mechanisms were found to stimulate increases in GB production. The aim of this study was to use Ginkgo biloba calluses for immobilized cultures with different elicitors to find a more suitable method of ginkgolide B production via a recycling process. Full article

The work reveals the results of studying the content of biologically active substances in samples of extracts of Ginkgo biloba callus cultures. Callus cultures grown in vitro on liquid nutrient media were the objects of the study. Considering various factors affecting the yield of the target components during extraction, the volume fraction of the organic modifier in the extracting mixture, the temperature factor, and the exposure time were identified as the main ones. The maximum yield of extractive substances (target biologically active substances with a degree of extraction of at least 50%) from the samples of callus culture extracts was detected at a ratio of extragent of 70% ethanol, a temperature of 50 °C, and exposure time of 6 h. Flavonoids, such as luteolin, quercetin, isoramentin, kaempferol, and amentoflavone, were isolated in the extract samples. As a result of column chromatography, fractions of individual biologically active substances (bilobalide, ginkgolide A, B, and C) were determined. The proposed schemes are focused on preserving the nativity while ensuring maximum purification from associated (ballast) components. Sorbents (Sephadex LH-20, poly-amide, silica gel) were used in successive stages of chromatography with rechromatography. The degree of purity of individually isolated substances was at least 95%. Full article