Cytochrome P450 (CYP450) enzymes are the most important phase I drug-metabolizing enzymes in humans, and regulation of their activity is directly related to drug efficacy and safety. As herbal medicines gain worldwide popularity, their concurrent use with drugs has become more common. The effect of phytochemicals from herbal sources on CYP450 activity is a critical factor contributing to clinical drug interactions. When CYP450 activity is inhibited, it is easy to cause the accumulation of substrate drugs and cause toxic side effects, or the formation of toxic intermediates due to altered metabolic pathways, which seriously threaten the medication safety of patients. However, only a limited number of herbs have been evaluated for their impact on CYP450 enzyme activity, and data on the inhibitory effects of key CYP450 isoforms involved in drug metabolism remain scarce. Particularly noteworthy is the lack of research on the mechanisms of herb-drug interactions (HDIs) and the constituents of compound herbs, which impedes comprehensive identification and evaluation of potential clinical risks. This paper provides a systematic summary of CYP450 phytochemical inhibitors such as alkaloids, quinones, flavonoids, terpenoids, and coumarins in herbal medicine. In addition to the common CYP450 isoforms (e.g., CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), this review also focuses on some less frequently studied isoforms, including CYP1B1, CYP7A1, CYP8B1, CYP17A1, and CYP19A1. Through an in-depth analysis of the current research limitations, this study proposes targeted directions for technological innovation and research standardization, thereby providing a scientific basis for addressing the research gap in HDIs and herb-herb interactions (HHIs) and formulating strategies for the rational use of herbs and standards for safety evaluation.
Ganoderma lucidum, a revered medicinal mushroom with a rich history in traditional East Asian medicine, has garnered significant scientific attention for its diverse pharmacological properties. This comprehensive review synthesises recent advancements in understanding the phytochemistry, biological activities and therapeutic applications of G. lucidum . We delve into the intricate composition of its bioactive compounds, including polysaccharides, triterpenoids, sterols and phenolic compounds, elucidating their mechanisms of action in immunomodulation, anti-inflammatory responses, antioxidant defence, hepatoprotection and anticancer potential. Furthermore, this review examines emerging applications in nanotechnology, where G. lucidum extracts are utilised for the green synthesis of nanoparticles and as components in advanced drug delivery systems, antimicrobial nanomaterials and biosensors. We also discuss its expanding role in nutraceuticals, functional foods and cosmeceuticals, highlighting its anti-aging, skin-brightening and calming properties. Finally, the safety profile and toxicological evaluations of G. lucidum are critically assessed, alongside its growing economic significance. This review underscores the immense therapeutic potential of G. lucidum as a natural resource for modern medicine and biotechnology, while also identifying key challenges and future directions for research to facilitate its broader clinical and industrial translation.
The gut-lung axis constitutes a dynamic, multidirectional communication platform between the gastrointestinal and respiratory tracts. Its complexity arises from the integrated crosstalk among the microbiota, immune system, and redox homeostasis, collectively influencing disease susceptibility and progression. The gut microbiota directly impacts pulmonary inflammation through immune modulation and oxidative stress regulation. Conversely, disturbances in lung homeostasis, including shifts in the local microbiota, can in turn reshape gut microbial communities, establishing a bidirectional feedback loop. Polyphenols, a class of bioactive compounds abundant in plant-based foods, have emerged as key modulators of this bidirectional network. The primary objective of this review is to systematically synthesize current knowledge on the mechanisms by which polyphenols orchestrate gut-lung axis. We critically examine how they modulate gut and lung microbiota, redox homeostasis, and immune responses, thereby impacting the progression of respiratory and gastrointestinal diseases. This review aims to highlights the translational significance of polyphenols as dietary components and therapeutic candidates, while identifying key knowledge gaps, such as dose optimization and combination strategies, to guide future research aimed at harnessing the gut-lung axis for disease prevention and treatment.
Lung cancer remains an aggressive and highly prevalent disease worldwide, causing an estimated 1.8 million deaths in 2022 and becoming a leading cause of cancer-related mortality. Resistance to current therapies necessitates novel approaches that target the tumour immune microenvironment (TIME), which is crucial for disease progression. Studies suggest that certain phytochemicals can enhance antitumour immunity by modulating the TIME. This systematic review aimed to elucidate and synthesise the mechanisms by which phytochemicals exert antitumour immunomodulatory effects in lung cancer and to assess their therapeutic potential and translational challenges. We comprehensively reviewed the literature from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) until December 2025. Phytochemical mechanisms were analysed and classified based on their chemical structures and specific targets within the TIME. Phytochemicals effectively reprogrammed the immunosuppressive TIME using multi-target strategies. Key actions include the inhibition of immunosuppressive cells-such as myeloid-derived suppressor cells (MDSCs), Treg cells, and M2-polarised macrophages (e.g., via STAT3 downregulation by dihydroisotanshinone I)-activation of effector cells (e.g., NK cells, CD8+ T cells, and M1 macrophages), and the reversal of T helper cell drift (e.g., panaxan and aesculetin). This multipronged modulation offers superior efficacy by enhancing CD8+ T cell responses and overcoming functional exhaustion. This review validates the significant potential of phytochemicals as novel multi-target therapeutic agents for TIME-targeted therapy in lung cancer. Future research should prioritise addressing pharmacological challenges to accelerate rational clinical integration.
The use of medicinal products derived from cannabis and its synthetic analogues has grown in recent years for various health conditions, which led to an increase in systematic reviews (SR) on the topic. The objective of this overview was to identify, synthesize, and critically appraise the evidence from SR on the benefits and harms of cannabis derivatives when used for therapeutic purposes in different health conditions. A comprehensive search was conducted to identify all relevant SR in Embase, Epistemonikos, MEDLINE, and Cochrane Database of Systematic Reviews. The inclusion criteria was SR assessing the effects of cannabis and its derivatives for any clinical condition that included only randomized controlled trials. A structured selection and extraction process was performed by two independent researchers. The methodological quality of the included SR was assessed using AMSTAR-2. This overview included 102 SR, 68.6% of which were of critically low quality and 17.6% were of high quality. There is low to moderate certainty of evidence of benefits from these interventions for ulcerative colitis, chronic non-cancer pain, Crohn's disease, multiple sclerosis, and post-chemotherapy nausea and vomiting. The results point to a lack of benefits for sleep disorders, chronic cancer pain refractory to opioids, pain related to radiotherapy, and pain in people receiving palliative care. For other conditions, the certainty of the evidence was very low or not assessed. This overview opens a broad and complex field for the development of primary studies to evaluate the effects of cannabinoids as primary or adjunctive therapy for different health conditions and reinforces the importance of safety assessment. Decision-makers and guideline developers can be guided by the results summarized in this overview. However, when making formal recommendations, it is essential to consider the quality of the SR and the certainty of the evidence identified for each outcome.
Atherosclerosis and its complications significantly affect human health globally. The etiology of atherosclerosis is multifaceted, with current research focusing on abnormalities in lipid metabolism, immune cell activation, inflammation, and epithelial damage. Currently, highly effective preventive and therapeutic strategies for atherosclerosis remain lacking. Recent reports have indicated the anti-atherosclerotic effects of medicinal herbs from the Araliaceae family, including Panax ginseng C. A. Mey., Panax notoginseng, Panax quinquefolius L., and Panax japonicus. The pharmacological effects of these herbs on atherosclerosis include lipid metabolism, immune cell activation, inflammation, oxidative stress, endothelial function, cell proliferation and migration, angiogenesis, apoptosis, autophagy, and gut microbiota homeostasis. This review aims to comprehensively elucidate, summarize, and update the protective effects and underlying mechanisms of Araliaceae herbs against atherosclerosis.
Liver diseases such as viral hepatitis, fatty liver disease, autoimmune and genetic disorders, drug-induced liver injury, hepatocellular carcinoma, and cirrhosis represent a major global health burden, while current pharmacotherapies remain limited by suboptimal efficacy, adverse effects, and poor accessibility. Ethnopharmacological use of medicinal plants offers a rich resource for discovering novel hepatoprotective agents, particularly secondary metabolites including alkaloids, flavonoids, terpenoids, glycosides, tannins, and saponins that target key pathogenic processes such as oxidative stress, inflammation, fibrosis, apoptosis, and metabolic dysregulation. This review systematically integrates traditional knowledge with modern evidence from in vitro, in vivo, preclinical, and clinical studies to highlight plant-derived phytoconstituents with demonstrated benefits across the spectrum of liver diseases, including clinically investigated agents such as silymarin, glycyrrhizin, curcumin, resveratrol, and ginsenosides. Mechanistic sections summarize disease progression from inflammation to fibrosis, cirrhosis, and hepatocellular carcinoma, and delineate how specific phytoconstituents modulate signaling pathways, redox homeostasis, lipid metabolism, and cell death programs, while pharmacokinetic data address absorption, distribution, metabolism, excretion, and strategies to overcome low oral bioavailability. The article also contrasts the limitations of current synthetic drugs with regulatory advances for botanical products across major agencies (FDA, EMA, WHO, and Asian regulators), and outlines methodological innovations including high-throughput screening, cheminformatics, in silico docking, organoid and liver-on-chip models, and nanotechnology-based delivery systems that can accelerate phytoconstituent-driven drug development. Overall, this review provides a comprehensive framework that links ethnomedicinal use, experimental validation, regulatory context, and technological progress, and identifies priority phytoconstituents and research directions for translating plant-based hepatoprotective agents into standardized, clinically effective therapies for liver disease.
Affecting approximately 85% of expectant mothers during the first trimester, nausea and vomiting of pregnancy (NVP) are frequently reported symptoms. Despite numerous existing systematic reviews and meta-analyses (SRMs), findings remain inconsistent. Consequently, this study assesses the quality of these prior SRMs and investigates the efficacy of ginger as a treatment for NVP. A comprehensive search was conducted across PubMed, Scopus, Cochrane, and Web of Science from their inception through December 30, 2024. This review includes peer-reviewed English-language SRMs investigating ginger as a therapeutic intervention for pregnancy-related nausea and vomiting. Methodological rigor was evaluated using the AMSTAR-2 checklist, while evidence quality was assessed via the GRADE approach. Findings are synthesized narratively through content analysis. The study protocol was prospectively registered in the PROSPERO database. This study analyzed 18 systematic reviews, of which eight (44%) incorporated meta-analyses. The Rhodes Index of Nausea and Vomiting (RINV) emerged as the primary tool for evaluating outcomes. Regarding study reporting and transparency, seven studies registered their protocols in PROSPERO, while eight adhered to the PRISMA checklist. Overall, the included reviews demonstrated low methodological quality, with a mean score of 11.77. Specifically, 28% (n = 5) were rated as high quality, 28% (n = 5) as moderate, 22% (n = 4) as low, and 22% (n = 4) as critically low. Taking ginger supplements (usually between 450 and 1950 mg daily) significantly decreases the severity and occurrence of nausea and vomiting compared to a placebo. This benefit is more noticeable for nausea than for vomiting, where the results are less consistent. Numerous studies have shown that ginger does not raise the risk of adverse effects, such as spontaneous abortion or side effects like heartburn and drowsiness, when compared to a placebo or vitamin B6. Current evidence clearly shows that ginger is a safe and effective treatment for nausea and vomiting during pregnancy, with effectiveness similar to vitamin B6 and some traditional medications, and it has a good safety profile. Ginger can be recommended as a dependable medicinal herb for women dealing with NVP, though more research is needed to determine the best doses and confirm long-term safety.
Osteoarthritis (OA) is a prevalent degenerative joint disease in which ferroptosis and mitochondrial dysfunction contribute critically to disease progression, yet effective therapeutic strategies remain limited. Vitexin, a natural flavonoid with diverse pharmacological activities, has recently attracted attention for its potential protective effects against OA. This study investigated whether Vitexin alleviates OA progression through regulation of Sirtuin 3 (SIRT3)-mediated ferroptosis and mitochondrial dysfunction in chondrocytes. In vitro, erastin-induced rat chondrocytes were treated with Vitexin to evaluate ferroptosis, oxidative stress, and mitochondrial function. In vivo, a rat OA model was established to assess the protective effects of Vitexin on cartilage degeneration and subchondral bone destruction. Vitexin markedly reduced iron accumulation, lipid peroxidation, and reactive oxygen species generation while restoring mitochondrial function and redox homeostasis in chondrocytes. Moreover, Vitexin upregulated SIRT3, GPX4, and xCT expression, whereas SIRT3 knockdown partially abolished these protective effects. In vivo analyses further demonstrated that Vitexin attenuated cartilage degeneration, preserved subchondral bone architecture, and restored SIRT3 and GPX4 expression in OA rats. Collectively, these findings demonstrate that Vitexin alleviates OA progression through SIRT3-mediated inhibition of chondrocyte ferroptosis and mitochondrial dysfunction, highlighting its potential as a novel therapeutic strategy for OA.
Various pharmacological properties and therapeutic effects were shown for Allium cepa L. (Liliaceae), (A. cepa) or onion and its derivatives including their effects on oxidative stress in different conditions. In this article, an update and comprehensive review of antioxidant effects of A. cepa and A. cepa-associated phytochemicals as well as the underlying molecular mechanisms are provided. The literature on antioxidant effects of A. cepa published between 2015 and the end of July 2025 was searched on database like PubMed, WOS, Science direct and Scopus. A. cepa and its constituents showed antioxidant in various conditions such as cardiovascular, endocrine and metabolic, gastrointestinal and liver, immunological, hematological and autoimmune, urogenital, neurologic and respiratory disorders as well as cancer and neoplasia. The antioxidant effects of A. cepa and its derivatives were achieved by decreasing lipid peroxidation (LPO), malondialdehyde (MDA), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS), inhibiting NADPH oxidase (NOX) activity but enhancing antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione peroxidase omega (GSPO), thioredoxin reductase (TrxR), glutathione-S-transferase (GST) and glutathione reductase (GR) activities and thiol levels. Therefore A. cepa and A. cepa-associated phytochemicals showed potent antioxidant effects indicating their possible therapeutic value for treatment of disorders associated with oxidative stress.
Bioactive compounds derived from natural products (NPs) continue to attract considerable scientific interest due to their wide range of beneficial biological activities. This review examines the role of these compounds in the prevention and management of cardiovascular disease (CVD), with particular emphasis on their involvement in thrombotic processes. Specifically, this review addresses whether bioactive NPs can serve as complementary therapeutic agents in preventing and modulating thrombotic events associated with CVD. Special attention is given to natural food sources with well-documented antithrombotic properties, as well as to current methodologies used for the processing, extraction, and isolation of their biologically active constituents. Furthermore, emerging evidence regarding the impact of chronic dietary intake of bioactive compounds on the pharmacokinetics and therapeutic efficacy of antithrombotic agents is discussed, including potential interactions with commonly prescribed anticoagulant drugs. The contribution of nutritional epigenetics to personalized strategies for CVD prevention and treatment-especially through gene-diet interactions-is also explored. In addition, the growing role of artificial intelligence in accelerating the discovery and optimization of novel natural antithrombotic agents is highlighted within the context of recent technological advances. Overall, this review underscores the potential of NPs as integral components of innovative and complementary strategies for CVD management, primarily through their pronounced antiplatelet and antithrombotic activities.
To elucidate the mechanism by which Resveratrol (Res) ameliorates hypertrophic scar (HS) formation by targeting acid-sensing ion channel 3 (ASIC3) to modulate macrophage-fibroblast (FB) crosstalk. A rabbit-ear HS model was established in vivo. Hematoxylin-eosin (H&E) staining, Masson staining, immunofluorescence (IF), Western blot (WB), and quantitative real-time PCR (RT-qPCR) were used to assess the effects of Res on scar hyperplasia, collagen deposition, FB activation, and macrophage polarization. In vitro, FB activation was stimulated by combined treatment with TGF-β1 and lactic acid, and a Transwell co-culture system comprising FB and human monocyte-derived M0 macrophages was established. Scratch assay, FCM, IF, and WB were performed to assess the impacts of Res on FB activation, migration, and macrophage polarization. Additionally, ASIC3 gene knockout experiments were conducted both in vivo and in vitro to confirm the mechanism underlying Res-mediated HS improvement. In vitro, Res significantly inhibited FB migration in a dose-dependent manner and downregulated the protein expression of α-SMA, COL1A1, COL3A1, reduced M-CSF secretion, suppressed macrophage polarization toward the M2 phenotype, and decreased TGF-β1 mRNA expression. It also blocked activation of the PI3K/Akt signaling pathway downstream of ASIC3. These effects were completely abolished after ASIC3 gene knockdown. In vivo, Res significantly reduced the scar elevation index (SEI) in rabbit-ear HS. It improved collagen fiber arrangement and decreased collagen deposition. It markedly inhibited M2 macrophage polarization and TGF-β1 mRNA expression. After ASIC3 knockout, the anti-HS effects of Res, as well as its regulatory effects on macrophage polarization and fibrotic factors, were abrogated. Res ameliorates HS by inhibiting ASIC3 expression. This disrupts the ASIC3-M-CSF-TGF-β1 positive feedback loop. It restores the balance of macrophage polarization, inhibits FB activation, reduces abnormal collagen deposition, and ultimately attenuates HS formation.
Psoralea corylifolia Linn. exhibits osteogenic effects; however, the mechanism by which its active component Bakuchiol (BAK) alleviates glucocorticoid-induced osteoporosis (GIOP) remains unclear. We aim to investigate BAK's therapeutic effects and potential mechanisms in GIOP. We treated GIOP mice with BAK. We evaluated BAK's therapeutic efficacy using micro-CT and histopathological staining. We performed transcriptomic analysis and identified significantly enriched GO pathways. We then used biochemical assays and Western blotting to examine the effects of BAK on osteogenic differentiation-related signaling factors in GIOP mice. We conducted in vitro experiments using osteoblasts. We employed RT-qPCR, Western blot, ALP & ARS staining, immunofluorescence and dual-luciferase reporter assays to assess BAK's influence on signaling pathways related to osteoblast differentiation. We used molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) to confirm the direct binding interaction between BAK and FAT4. Finally, we silenced Fat4 to validate that BAK exerts its anti-GIOP effects by activating YAP1 through FAT4. BAK treatment significantly enhanced bone quality and strength in GIOP mice, and mitigated femoral pathological damage. BAK upregulated key osteoblast differentiation-related transcription factors and enhanced serum alkaline phosphatase activity. Western blot confirmed that BAK increased protein levels of YAP1 while reducing levels of FAT4 and DCHS1. In vitro, BAK similarly promoted osteoblast differentiation and activated YAP1 expression and Runx2 transcription. Molecular docking, CETSA and DARTS analyses demonstrated that BAK directly binds to FAT4. Silencing Fat4 abolished the pro-osteogenic effects of BAK. BAK likely exerts its therapeutic effects in GIOP by targeting FAT4, activating YAP1 and promoting osteoblast differentiation.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein (α-syn) aggregation, often linked to lysosomal dysfunction. Cathepsin D (CTSD), a lysosomal hydrolase essential for α-syn clearance, becomes functionally impaired when its maturation is disrupted, exacerbating proteostatic stress. This study investigated whether ginsenoside Rg1(Rg1) restores CTSD maturation and lysosomal function to mitigate PD pathology. MPTP-induced zebrafish and mouse PD models, as well as MPP+-treated SH-SY5Y cells, animals and cells were treated with Rg1 at different concentrations. Motor behavior, dopaminergic neuron survival, α-syn clearance, CTSD maturation, lysosomal activity, endoplasmic reticulum (ER) stress, oxidative stress, autophagic flux, and apoptosis were systematically evaluated. Rg1 improved locomotor performance and preserved dopaminergic neurons, promoted α-syn clearance, and enhanced CTSD maturation in lysosomes. These effects coincided with reduced ER and oxidative stress, normalized autophagic flux, and decreased apoptosis. Rg1 functions as a natural lysosomal enhancer, restoring lysosome-ER homeostasis and counteracting multiple pathogenic pathways in PD. The findings reveal a CTSD-dependent regulatory axis in α-syn homeostasis and highlight Rg1 as a promising multi-target therapeutic candidate for PD.
Quercetin has anti-inflammatory properties. This study aims to explore the association between dietary quercetin intake, stroke risk, and long-term survival in chronic kidney disease (CKD) patients. The analysis included 2001 CKD participants from National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018, with a weighted total population of 25,005,023. A weighted logistic regression model, restricted cubic splines (RCS) curve, weighted COX proportional hazards model, subgroup analysis, and Kaplan-Meier curve were constructed to comprehensively analyze the relationship between dietary quercetin intake and stroke prevalence as well as long-term survival. At the same time, propensity score matching (PSM) was used to reduce the influence of confounding factors. After adjusting for all covariates, for every 1 mg/day increase in dietary quercetin intake, the prevalence of stroke decreases by 4% (OR = 0.96, 95% CI: 0.92-1.00). The RCS curve indicates that the protective effect of dietary quercetin intake on the prevalence of stroke is a linear relationship. Moreover, subgroup analysis indicated that the protective effect of dietary quercetin intake on the prevalence of stroke might be achieved by reducing inflammation. Meanwhile, for every 1 mg/day increase in dietary quercetin intake, the mortality decreases by 2% (HR = 0.98, 95% CI: 0.96-1.00). This observational cohort study showed that increased dietary quercetin intake is associated with reduced stroke risk and increased long-term survival in CKD patients. It is necessary to recommend increasing dietary quercetin intake as a supplementary treatment for CKD patients.
Acne vulgaris is a common chronic inflammatory skin disorder that begins in adolescents and often persists into adulthood, with substantial psychosocial impact. Tea tree oil (TTO) has been explored as a topical treatment for acne, but clinical evidence for its efficacy and safety remain limited and inconsistent. This systematic review and meta-analysis synthesizes available clinical data to evaluate TTO's therapeutic effects and safety profile in acne management. PubMed, Embase, and Web of Science were systematically searched for clinical studies published up to August 2025 that evaluated TTO for acne treatment. Study selection, data extraction, and risk-of-bias assessment were independently conducted by trained reviewers. Pooled estimates were calculated using fixed- or random-effects models according to heterogeneity, quantified using the I 2 statistic. Seven studies comprising 445 patients were included. The use of TTO was associated with a reduction in acne severity compared with control groups (pooled odds ratio [pOR] = 0.74, 95% confidence intervals [CI]: 0.63-0.88). Adverse events were predominantly local and mild. An exploratory pooled analysis indicated a lower incidence of mild itching with TTO compared to the corresponding control treatments in the included studies (pOR = 0.09, 95% CI: 0.03-0.23), with similar trends observed for dryness, burning sensation, erythema, and scaling. Publication bias was not evident based on Egger's test and the trim-and-fill analysis, and overall risk of bias was assessed as low. Current evidence suggests that TTO is associated with a modest reduction in acne severity and generally acceptable short-term tolerability. Larger, high-quality trials with standardized formulations and long-term follow-up are needed to define its clinical role.
Myocardial hypertrophy represents a maladaptive response in numerous cardiovascular disorders, and potentiating mitophagy has emerged as a potential therapy. Trilobatin (TLB) possesses multiple pharmacological properties, including the alleviation of cardiotoxicity. However, it remains uncertain whether TLB exerts anti-hypertrophic effects or, if so, by what mechanisms. This study was designed to determine whether TLB can attenuate hypertrophy and to elucidate the underlying pathways, focusing on mitophagy. We employed in vivo spontaneously hypertensive rats (SHR) and in vitro angiotensin II-stimulated cardiomyocytes to evaluate anti-hypertrophic effects. A comprehensive approach was employed, incorporating echocardiography, histological staining, transmission electron microscopy observations, and immunofluorescence to assess phenotypic changes. RNA sequencing, western blotting, immunofluorescence, and ELISA were utilized to elucidate the underlying mechanisms. Additionally, molecular docking, molecular dynamics simulations, and siRNA transfection techniques were applied to identify the target of TLB. The results showed that TLB markedly alleviated hypertrophy in SHR and inhibited angiotensin II-induced cardiomyocyte hypertrophy. Mechanistically, TLB enhanced mitophagy and reduced oxidative stress via activation of the sentrin-specific protease 1/sirtuin 3 (SENP1/SIRT3) axis, with direct binding to SENP1. Crucially, SENP1 knockdown abolished TLB's cardioprotective effects, confirming SENP1 as a pivotal mediator. Our findings indicate that TLB exerts anti-hypertrophic effects by promoting mitophagy and suppressing oxidative injury through the SENP1/SIRT3 axis, highlighting SENP1 as a promising therapeutic target for myocardial hypertrophy.
Ginseng (Panax ginseng Meyer), one of the most widely known Chinese herbs, has been used in traditional medicine for centuries. Ginsenoside Rg5 (Rg5) can exert protective effects on the liver and activate the Nrf2 pathway. This study aims to investigate the mechanism of Rg5 alleviating acute liver injury (ALI), and the related mechanisms will be discussed. In vitro experiments, an ALI model was established using HepG2 cells. The DCFHDA, the JC-1, and the ferrous ion fluorescent probe detected the reactive oxygen species (ROS) level, the mitochondrial membrane potential change, and the iron ions level. The oxidative stress indexes were detected by biochemical analysis. Western blot was used to detect the m6A demethylation, Nrf2, and ferroptosis signaling pathways. For in vivo experiments, C57BL/6J mice were administered ethanol by gavage to establish the ALI model. In vitro, we observed that m6A methylation and FTO downregulation were involved in the ferroptosis process. Rg5 treatment alleviated ferroptosis after ethanol exposure, which was reflected by the decrease of intracellular iron content and ferroptosis-related proteins. The FTO knockdown exhibited ferroptosis-related proteins and YTHDF2 increase. The regulatory effect of FTO on ferroptosis was inhibited when Nrf2 was inhibited or knocked down. In vivo, HE staining revealed liver injury in the model group, with elevated liver-to-body weight ratios and serum ALT and AST levels. The Rg5 treatment has improved these phenomena. FTO, Nrf2, and anti-ferroptosis proteins were downregulated in the ethanol group, while the ferroptosis marker ACSL4 was upregulated. This study demonstrates that Rg5 alleviates ethanol-induced ALI by inhibiting ferroptosis via the FTO/YTHDF2/Nrf2 axis. Our work not only establishes a link between FTO-mediated m6A demethylation and ferroptosis but also provides new mechanistic insights into the hepatoprotective action of ginsenosides.
Lipid metabolic imbalance is a major contributor to metabolic disorders in humans and livestock, creating an urgent need for safe and effective regulatory approaches. Plant-derived compounds, characterized by favorable bioavailability and low toxicity, serve as promising candidates that regulate host lipid metabolism through dynamic crosstalk with the gut microbiota. This review systematically investigates the bidirectional crosstalk between plant bioactive compounds (e.g., polysaccharides, flavonoids, saponins and polyphenols) and the gut microbiota. We detail how gut microbes metabolize these compounds to enhance their bioactivity and bioavailability, while plant extracts reshape microbial community structure to enrich beneficial taxa. Furthermore, we elucidate the mechanisms underlying lipid metabolism regulation, focusing on three critical signaling pathways: (1) SCFAs-GPR43/41 signaling, (2) TLR4/NF-κB inflammation suppression, and (3) bile acid-FXR axis modulation. Collectively, this review synthesizes emerging evidence on plant-microbiota interactions as a novel therapeutic strategy to restore lipid homeostasis in animal models, offering foundational insights for agricultural and biomedical applications.
Cancer remains a leading cause of global mortality, with the therapeutic efficacy of anticancer drugs often hampered by late diagnosis and the development of chemotherapy resistance. Ferroptosis is an iron-dependent form of regulated non-apoptotic cell death driven by lipid peroxidation. It has emerged as a potential therapeutic target to overcome drug resistance in cancer. Isothiocyanates (ITCs) from cruciferous vegetables have garnered attention for their multi-target anticancer properties. In this review, we present the key mechanisms of ferroptosis and critically evaluate current evidence indicating that ITCs can induce ferroptosis through multiple, compound-specific redox- and iron-dependent mechanisms. We further discuss whether targeting ferroptosis with ITCs may represent a novel strategy to improve anticancer treatment. Overall, ITCs emerge as versatile but tightly regulated modulators of ferroptosis in cancer, whose effective therapeutic exploitation requires further in vivo and clinical studies, biomarker-guided dose optimization, and rational combination strategies with standard anticancer chemotherapy to translate their preclinical findings into therapeutic benefit.