Search Results (160)

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, and its dysregulation is implicated in HF pathophysiology. Traditional Chinese Medicine (TCM) has been investigated in HF management, but a systematic synthesis of preclinical evidence on TCM-mediated AMPK modulation is lacking. Methods: PubMed and Web of Science were searched from January 2020 to December 2025 using a comprehensive strategy combining terms for AMPK, HF, and TCM. Studies were included if they were original research investigating TCM-derived compounds or formulas in HF models and reporting AMPK modulation. Study quality and evidence levels were assessed using predefined criteria. The review was conducted in accordance with PRISMA 2020 guidelines. Results: Of 243 records identified, 56 studies met the inclusion criteria (7 from database search and 49 from manual screening). Direct evidence for AMPK-dependent cardioprotection was limited. Cinnamaldehyde and paeoniflorin showed the most rigorous validation with confirmed target engagement and loss-of-function rescue. Berberine, crocin, ginsenoside Rb1, and honokiol demonstrated pathway-specific effects validated by pharmacological or genetic approaches. Most complex herbal formulas provided correlative evidence only, with Fuyu Decoction being a notable exception where AMPK agonist EX229 confirmed pathway involvement. Conclusions: Current evidence for TCM-mediated AMPK modulation in HF remains predominantly preliminary and correlative. Future research should prioritize causality validation using genetic models and human-relevant systems. Full article

Crocus sativus L. (saffron), a sterile geophyte of the Iridaceae family, has been traditionally used in culinary and medicinal practices and is currently gaining attention as a source of pharmacologically active metabolites. The main bioactive compounds (BACs) of saffron, crocin, crocetin, picrocrocin, and safranal, are associated with a wide range of biological activities, including anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, antiproliferative, and antidiabetic properties, among others. This review aims to comprehensively and critically summarize the preclinical and clinical evidence for saffron-derived BACs in the context of the most prevalent non-communicable diseases. A literature search of the main scientific databases was conducted to identify peer-reviewed articles on neurodegenerative disorders, cancer, cardiovascular diseases, and diabetes mellitus, with additional topics on ethnopharmacology, phytochemistry, safety, and toxicity. The mechanistic findings include anti-inflammatory, immunomodulatory, antioxidant, antiproliferative, and neuroprotective effects, mediated by activation of the Nrf2 pathway and inhibition of NF-κB. Eligibility criteria were applied, excluding publications focused primarily on food, cosmetics, or technological applications, to prioritize mechanistic and therapeutic endpoints. The findings suggest that BACs from saffron extracts have promising disease-modifying properties and symptom-relieving actions, especially in the case of neurologic disorders, mild cognitive impairment, and some models of metabolic and oncological diseases. Nevertheless, the current variability in study design, dosage, standardization of plant extracts, and sample size limits a conclusive clinical application. More carefully designed studies with a representative number of cases and well-defined plant preparations are needed to validate efficacy, establish structure-activity relationships, and define the prevention and therapeutic potential of saffron in evidence-based pharmacotherapy. Full article

Ram semen is highly susceptible to cold shock, which induces irreversible damage to the integrity and fluidity of membranes. Chilled semen is commonly used within 24 h of collection. However, while its storage at 5 °C extends semen lifespan, it is often accompanied by quality deterioration due to accumulation of reactive oxygen species (ROS). This study evaluated the potential of crocin, a carotenoid with antioxidant properties, to improve the quality of chilled ram semen stored at 5 °C for up to three days in a soybean lecithin–based extender supplemented with two crocin concentrations (0.5 and 1 mM). Sperm motility, viability, glutathione levels, the expression of proteins involved in the heat stress response (HSR), and apoptosis were assessed at 24 h intervals. Crocin preserved motility (up to Day 1), viability (up to Day 2,) and kinematic parameters (up to Day 3). In addition, crocin enhanced intracellular glutathione and Hsp70 levels and inhibited apoptotic levels dose-dependently, indicating the antioxidant and cytoprotective role of crocin. Despite 0.5 mM being effective up to Day 1, 1 mM crocin augmented antioxidant capacity, modulated stress response mechanisms, and preserved sperm quality during chilled storage up to Day 3, highlighting its potential as a valuable additive of ram semen extenders. Full article

Saffron (Crocus sativus L.) is widely cultivated for the spice obtained from the stigmas, while the remaining floral biomass is discarded as biowaste. Accessing the phytochemical composition of these residues could enable their valorization as a low-cost and sustainable resource for nutraceutical applications. In this context, a quantitative ¹H NMR-based metabolite profiling approach, complemented by HPLC-DAD and LC-MS, was employed to comprehensively characterize saffron biowaste. A total of 40 metabolites were identified and quantified by NMR, including amino acids (611.1 ± 36.5 mg/100 g FW), carbohydrates (2801.4 ± 33.7 mg/100 g FW), lipids (702.7 ± 28.2 mg/100 g FW), and saffron-specific compounds such as crocin (596.6 ± 21.5 mg/100 g FW), picrocrocin (1126.3 ± 18.9 mg/100 g FW), safranal (398.4 ± 14.8 mg/100 g FW), and crocetin (13.4 ± 0.4 mg/100 g FW). Targeted fractionation further allowed the identification of kaempferol 3-O-sophoroside (15.44 ± 0.61% w/w in dry ethanolic extract) and 3-hydroxy-γ-butyrolactone. Overall, the results highlight the rich metabolite composition of saffron production waste and support its potential reuse as a valuable source of functional ingredients within a circular economy framework. Full article

In traditional Chinese medicine (TCM), Gardeniae Fructus is classified as a “cold” herb, a property that is increasingly explained by modern research showing that it can alleviate related disorders through modulation of the central nervous and endocrine systems, energy metabolism, and gut microbiota. This study aimed to elucidate the material foundation and biological mechanisms underlying its cold property. Chemical components of Gardeniae Fructus were separated via multi-stage extraction and characterized by GC-MS and LC-MS, yielding four distinct fractions: aliphatic, iridoid, crocin, and polysaccharide. In a rat model of heat syndrome induced by levothyroxine sodium, administration of the total extract or individual fractions over 15 days modulated central nervous, endocrine, and energy metabolism indicators, with the iridoid, crocin, and polysaccharide fractions demonstrating significant cold properties. Gut microbiota analysis revealed that the total extract, polysaccharide, and iridoid fractions notably reshaped microbial structure, reducing Firmicutes and Lactobacillus abundance. These findings indicate that the iridoid, crocin, and polysaccharide fractions may be key material bases for the cold property of Gardeniae Fructus, with the iridoid fraction exhibiting the strongest effect. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Among the diverse pathological features of AD, amyloid beta (Aβ) aggregation and neuroinflammation are recognized as central and interlinked mechanisms driving disease progression. This review focuses specifically on these two processes and highlights current pharmacological limitations in modifying disease pathology. Natural products such as curcumin, resveratrol, Ginkgo biloba, epigallocatechin gallate (EGCG), crocin, ashwagandha, and cannabidiol (CBD) have shown promising activity in modulating Aβ aggregation and neuroinflammatory pathways, offering multi-target neuroprotective effects in preclinical studies. However, their therapeutic application remains hindered by poor solubility, instability, rapid metabolism, and limited blood–brain barrier (BBB) permeability. To overcome these barriers, nanotechnology-based drug delivery systems—including polymeric nanoparticles, niosomes, solid lipid nanoparticles, and chitosan-based carriers—have emerged as effective strategies to enhance brain targeting, bioavailability, and pharmacological efficacy. We summarize the mechanistic insights and nanomedicine approaches related to these bioactives and discuss their potential in developing future disease-modifying therapies. By focusing on Aβ aggregation and neuroinflammation, this review provides a targeted perspective on the evolving role of natural compounds and nanocarriers in AD treatment. Full article

Crocosmia is a genus of bulbous, perennial plants from the Iridaceae family whose characteristic red to orange pigmentation suggests the presence of anthocyanins, flavonoids, and carotenoids—secondary metabolites often associated with antioxidant activity. This study aimed to characterize and compare the major pigment-related metabolites in two Crocosmia varieties (Crocosmia masoniorum “Lucifer” and Crocosmia aurea) through chromatographic (HPLC-DAD) and spectrophotometric analyses (UV-Vis), using Crocus sativus L. flowers as a reference matrix. Successfully, the major crocin trans-4-GG, the flavonol kaempferol-3-O-β-sophoroside, and the anthocyanin delphinidin-3-O-β-glucoside were quantified in Crocosmia flowers. Additional metabolites absent in Crocus sativus L. were also identified and quantified. Both Crocosmia varieties exhibited higher antioxidant capacity than Crocus sativus L. flowers, highlighting their potential for future applications in pharmaceutical, nutraceutical, or functional ingredient development. Full article

Background: Population aging increases susceptibility to cognitive decline, anxiety, and metabolic dysregulation, yet safe and effective interventions remain limited. Saffron (Crocus sativus L.) has been traditionally used to enhance mood and cognition, and its main metabolites, crocins and safranal, exert neuroprotective, anxiolytic, and metabolic effects. However, variability in extract composition and frequent adulteration hinder reproducibility. Objectives: To clarify the efficacy of genuine saffron preparations in aging, we investigated a saffron extract standardized for safranal and crocin content (SSE). Methods: Safranal bioavailability was first characterized in rats, followed by an evaluation of behavioral, neuroendocrine, and metabolic outcomes after 35 days of oral SSE administration (25 or 200 mg/kg/day) in 25-month-old male C57BL/6 mice. Behavioral performance was assessed using open field and novel object recognition tests, while molecular analyses targeted neuropeptides in the hypothalamus and amygdala, hippocampal plasticity markers, cortical inflammatory proteins, and hepatic lipid metabolism genes. Results: SSE administration induced a rapid but transient increase in the plasma’s safranal, confirming its bioavailability. In aged mice, the low dose prevented age-related weight loss and modulated hepatic lipid metabolism, whereas the high dose reduced anxiety-like behavior and improved recognition memory. The anxiolytic effects are consistent with elevated hypothalamic Npy, an anxiolytic peptide, reduced amygdalar Crh, a key mediator of stress and anxiety, and decreased hypothalamic Hcrt, an arousal modulator. The improvement in memory is associated with modulation of the cortical and hippocampal inflammatory and endocannabinoid proteins involved in neural plasticity. Conclusions: These findings highlight content-standardized saffron extracts as a promising multi-target nutraceuticals for healthy aging. Full article

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

Neurodegeneration—driven by oxidative stress, chronic inflammation, and protein aggregation—underlies disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and stroke. Current pharmacological treatments are largely symptomatic and do not restore lost neural circuitry, motivating regenerative approaches. Mesenchymal stem cells (MSCs) provide neurotrophic and immunomodulatory benefits and can support synaptic repair, yet robust conversion into mature, electrophysiologically functional neurons remain challenging and often depends on complex inducer cocktails with translational limitations. Crocin, a saffron-derived carotenoid, is reported to enhance neurogenesis and neuroprotection in preclinical models through pathways including Wnt/β-catenin, Notch1, CREB/BDNF, and modulation of GSK-3β, while reducing apoptosis and inflammatory signaling. Here, we synthesize evidence supporting crocin’s neuroprotective and proneurogenic activity and propose a testable hypothesis that crocin-based or crocin-modified formulations could be evaluated as adjuncts to guide MSC neuronal lineage commitment. Importantly, direct evidence that crocin alone can drive MSC trans-differentiation into fully functional neurons is currently insufficient; future work should define functional benchmarks (electrophysiology, synaptogenesis, and phenotypic stability) and rigorously validate safety, dosing, and delivery strategies for neuroregenerative translation. Full article

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut–brain axis dysregulation. Despite advances in anti-amyloid therapeutics, current interventions provide only modest symptomatic relief and face limitations in accessibility, cost, and long-term efficacy. Plant-derived bioactive compounds, rooted in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine, have gained increasing attention as multi-target therapeutic agents due to their pleiotropic actions, relative safety, and ability to cross the blood–brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides (Withania somnifera), curcumin (Curcuma longa), ginkgolides and bilobalide (Ginkgo biloba), bacosides (Bacopa monnieri), ginsenosides (Panax ginseng), crocin/safranal (Crocus sativus), epigallocatechin-3-gallate (Camellia sinensis), rosmarinic acid (Salvia officinalis, Melissa officinalis), and asiaticosides (Centella asiatica). These compounds exert neuroprotective effects by inhibiting Aβ aggregation, reducing tau phosphorylation, scavenging reactive oxygen species, attenuating NF-κB-mediated inflammation, modulating cholinergic signaling, enhancing synaptic plasticity via brain-derived neurotrophic factor/cAMP response element-binding protein (BDNF/CREB) activation, and regulating gut microbiota. Multi-target approach analyses underscore their synergistic potential in targeting interconnected AD pathways. However, translation remains hindered by poor oral bioavailability, rapid metabolism, and variability in clinical outcomes. Advances in delivery platforms, including liposomes, bilosomes, solid lipid nanoparticles, and nanostructured lipid carriers, are improving stability, blood–brain penetration, and therapeutic efficacy in preclinical models. Collectively, plant-derived phytochemicals serve as promising, affordable, and multi-modal candidates for reshaping AD management, bridging traditional knowledge with modern therapeutic innovation. Full article

Saffron (Crocus sativus L.), known as the world’s most valuable spice, has long been appreciated for its culinary, medicinal, and cultural significance. In recent years, increasing scientific attention has been directed toward its unique phytochemical profile and wide-ranging therapeutic potential. This review provides a comprehensive synthesis of current evidence regarding saffron’s chemical composition, molecular mechanisms of action, pharmacological activities, and safety aspects. The stigmas of saffron contain a rich array of bioactive constituents, notably crocin, crocetin, picrocrocin, and safranal, which collectively contribute to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, hepatoprotective, neuroprotective, anti-obesity, antidiabetic, and anticancer properties. Evidence from in vitro and in vivo models, as well as clinical studies, suggests that saffron primarily exerts its beneficial effects through the modulation of oxidative stress, apoptosis, autophagy, lipid metabolism, and the regulation of key molecular pathways, including the NF-κB, PI3K/Akt/mTOR, and Nrf2/HO-1 pathways. Furthermore, recent advances in nanotechnology-based formulations have demonstrated improved bioavailability and enhanced therapeutic efficacy, thereby opening up promising avenues for clinical applications. While saffron is generally regarded as safe, challenges remain concerning its high cost, limited availability, and variability in quality due to geographic and environmental factors. Collectively, the accumulated body of evidence highlights saffron as a promising natural agent for the prevention and management of chronic diseases. However, further translational and large-scale clinical investigations are needed to fully establish its therapeutic value and optimize its integration into modern pharmacological and nutraceutical strategies. Full article

Background/Objectives: Dyslipidemia is a global health concern. It refers to increased blood levels of LDL-C, triglycerides, and total cholesterol, accompanied by decreased blood HDL-C levels. Many pharmacological and non-pharmacological approaches have been designed to improve dyslipidemia management. However, nutritional therapies have gained more attention due to their antioxidant and anti-inflammatory properties. In this scenario, the carotenoid crocin stands out as a prominent anti-dyslipidemia phytochemical. Its unique structure permits lipid-lowering effects via various mechanisms, including the enhancement of lipid breakdown, reduction in lipid formation, bolstering of antioxidant defenses to diminish lipid toxicity, and decreased absorption of dietary fats. However, no recent systematic review or meta-analysis has addressed its anti-dyslipidemia effects with statistical power. Therefore, we aim to fill this gap with our current meta-analysis, as well as dose and time–response assessments. Methods: PubMed, SpringerLink, ScienceDirect, Cochrane, and Google Scholar databases were searched, and PRISMA guidelines were followed. Ten studies comprising eleven results were included. Results: Crocin did not improve LDL-C (0.2120, 95% CI: −0.0799 to 0.5040), HDL-C (−0.1937, 95% CI: −0.4896 to 0.1022), triglyceride (−0.2063, 95% CI: −0.5764 to 0.1638), or total cholesterol (0.1528, 95% CI: −0.1074 to 0.4129). The dose–response or time–response was also not statistically significant. Conclusions: More clinical studies with robust designs must be conducted to thoroughly assess crocin’s effectiveness in modulating lipid levels with the utmost care. Full article

Saffron (Crocus sativus L.) is one of the most valued spices worldwide, rich in bioactive apocarotenoids such as crocins, picrocrocin, and safranal, which display antioxidant, neuroprotective, and anticancer properties. Saffron’s chemical composition is critical for its therapeutic efficacy and a combination of components appears essential to reach the best protection and increase tissue resilience, so stigmas were subjected to hydroalcoholic extraction followed by purification via solid-phase extraction to enriched crocin and picrocrocin fractions. The extracts were included in liposomes to enhance their bioavailability and gastrointestinal absorption by oral administration while protecting them in the harsh gastric environment, increasing their permeation and sustaining their release in the gastrointestinal tract. Liposomes were prepared by the reverse-phase evaporation method using saturated or unsaturated lipids extracted from soy. Encapsulation efficiency was determined by HPLC monitoring of trans-4GG crocin, cis-4GG crocin, and picrocrocin. The results indicate that liposomes show greater encapsulation capacity for hydrophilic apocarotenoids such as crocins (≈90% for cis-4GG, ≈50% for trans-4GG crocin) with respect to picrocrocins (<20%). These findings support the application of liposomal carriers to improve the stability, shelf-life, and potential bioavailability of saffron’s bioactive properties for nutraceutical, pharmaceutical, and functional food applications. Full article

Crocins are high-value apocarotenoid pigments with broad applications in pharmaceuticals, foods, and personal-care products, and they exhibit diverse bioactivities, including antioxidant, antidepressant, and antidementia effects. In this study, we achieved the heterologous biosynthesis of crocins in Solanum lycopersicum L. by introducing the GjCCD4a, GjALDH2C3, GjUGT74F8 and GjUGT94E13 of Gardenia jasminoides J.Ellis to the binary expression vector via in-fusion technology and self-cleaving 2A peptides. Following Agrobacterium-mediated transformation, the engineered tomato plants predominantly produced main active ingredient crocin I, which accounted for 97–99% of the total crocins. The transgenic fruits displayed mixed red-and-golden colouration. These results highlight S. lycopersicum as a promising chassis for crocin I biosynthesis, helping to address supply constraints and enabling colour-trait breeding through synthetic biology. Full article