Search Results (1,067)

Ethnopharmacological relevance: Dioscorea nipponica Makino is a traditional medicinal plant widely used in East Asia for the treatment of rheumatic disorders, inflammatory diseases, and cardiovascular conditions. Its rhizome has long been applied in clinical practice for relieving pain, promoting blood circulation, and reducing swelling. Aim of the study: This narrative review aims to provide a comprehensive and critical overview of the phytochemical constituents, pharmacological activities, and underlying mechanisms of D. nipponica and to identify current research gaps and future perspectives. Materials and methods: The literature was searched in PubMed, Web of Science, ScienceDirect, CNKI and Wanfang Data from database inception to December 2025. The combined retrieval keywords were set as: (Dioscorea nipponica Makino OR Chuanshanlong) AND (chemical constituents OR steroidal saponins OR flavonoids OR phenols) AND (biological activity OR anti-inflammatory OR cardioprotective OR hepatotoxicity OR clinical application). Both English and Chinese publications were retrieved, and studies written in other languages were excluded. Results: Phytochemical studies have identified diverse secondary metabolites, particularly steroidal saponins, along with diarylheptanoids and phenanthrenes. These compounds exhibit multiple pharmacological activities, including anti-inflammatory, anti-tumor, immunomodulatory, and cardioprotective effects. Mechanistic studies indicate that these activities are mediated through the modulation of key signaling pathways such as NF-κB, PI3K/Akt, AMPK, and the NLRP3 inflammasome. However, current research remains fragmented, with limited integration of chemical composition, molecular targets, and therapeutic outcomes. Conclusions: D. nipponica represents a promising source of bioactive natural products, with steroidal saponins as the major contributors to its pharmacological effects. Future studies should focus on multi-component interactions, pharmacokinetics, quality control, and clinical validation to support its rational development and sustainable utilization. Full article

Metabolic diseases are characterized by a complex interplay between metabolic dysregulation and chronic low-grade inflammation. Fetuin-A (FetA), a liver-derived hepatokine, has emerged as a key mediator linking these processes through its pro-inflammatory and insulin resistance-promoting effects. Accumulating evidence indicates that FetA not only serves as a biomarker but also actively contributes to disease pathogenesis by modulating multiple signaling pathways. In this review, we present an overview of the molecular mechanisms underlying FetA-induced suppression of peroxisome proliferator-activated receptor (PPAR) signaling, a central regulator of metabolic homeostasis. Emerging evidence suggests that FetA may promote Toll-like receptor 4 (TLR4)-mediated inflammation, activate nuclear factor kappa B (NF-κB) signaling, suppress key energy regulators such as Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), and inhibit PPAR activity through Wnt and extracellular signal-regulated kinase (ERK) pathways. These interconnected mechanisms may contribute to impaired lipid metabolism, increased insulin resistance, and metabolic inflammation. Furthermore, we highlight the role of FetA glycosylation, particularly fucosylation, as a regulatory layer influencing its biological activity. Fucosylated FetA may more effectively activate TLR4 signaling and suppress PPAR activity, suggesting functional heterogeneity among glycoforms. Overall, the FetA–PPAR interaction may represent a key mechanistic link between metabolic inflammation and disease progression. Full article

Tumor-associated macrophages (TAMs) represent a predominant immune cell population within the tumor microenvironment (TME). To adapt to the metabolically hostile conditions of the TME, characterized by nutrient deprivation and accumulation of metabolic waste products, TAMs undergo metabolic reprogramming to evade cell death. These adaptations enable TAMs to utilize alternative metabolites as energy sources and mitigate metabolic stress through enhanced cystine uptake and activation of hypoxia-inducible factor pathways, thereby supporting their survival and function. However, the key molecular regulators that prevent TAMs death in response to dynamic metabolic changes during tumor progression remain poorly understood. Through integrated multi-omics analyses and experimental validation, we observed that increased AMPK activation during tumor progression is associated with transcriptomic and proteomic features indicative of reduced susceptibility of TAMs to multiple forms of cell death. Conditional deletion of AMPK in TAMs reprogrammed the expression of cell death-related genes and was associated with increased apoptosis, ferroptosis, and notably, disulfidptosis. Clinical correlation analyses revealed that AMPK activity in TAMs was inversely associated with the expression of disulfidptosis-, ferroptosis-, and apoptosis-related gene signatures. Furthermore, tumors characterized by concurrent enrichment of AMPK signaling and TAMs infiltration exhibited lower disulfidptosis, ferroptosis, and apoptosis signature scores, which were associated with a more malignant phenotype. Collectively, our findings suggest that AMPK activity is associated with TAM survival and tumor progression and with reduced susceptibility to multiple forms of cell death, including disulfidptosis. These findings provide evidence linking AMPK activity to metabolic adaptation and cell death resistance in TAMs and suggest its potential as a therapeutic target for cancer intervention. Full article

Skeletal muscle is increasingly recognized as a dynamic secretory organ capable of translating contractile, metabolic, mechanical and inflammatory stimuli into systemic biological signals. Among these signals, myokines and myokine-associated exerkines mediate communication between skeletal muscle and distant organs, influencing glucose and lipid metabolism, immune regulation, bone remodeling, neuroplasticity, vascular function and tissue regeneration. Representative mediators considered include IL-6, IL-15, myostatin, follistatin, decorin, FNDC5/irisin, FGF21, myonectin/CTRP15, BDNF, cathepsin B, SPARC, apelin and extracellular-vesicle cargo. However, current evidence remains fragmented across individual molecules, exercise modalities, sampling windows, assay platforms and disease contexts. This narrative mechanistic review proposes the concept of the “myokine adaptome” as an integrated, context-dependent signaling network through which skeletal muscle contributes to systemic homeostasis in health and disease. We synthesize evidence on cellular triggers of myokine release, including AMPK-PGC-1α signaling, mTORC1-dependent mechanical sensing, calcium flux, redox signaling, inflammatory pathways and extracellular-vesicle-mediated communication. We further examine how exercise modality, aging, obesity, type 2 diabetes, sarcopenia, osteoporosis, cardiovascular disease, COPD, cancer/cachexia and chronic inflammation reshape myokine production and target-organ responsiveness. The central argument is that myokine biology should be interpreted not as a catalog of isolated mediators, but as a dynamic adaptive code defined by signal amplitude, temporal pattern, molecular composition, delivery route and recipient-tissue sensitivity. Its novelty is operational rather than nominal: it requires source confidence, temporal kinetics, co-signal context, delivery route and functional decoding to be evaluated together. This framework may improve biomarker design, disease-specific exercise prescription and therapeutic strategies aimed at restoring adaptive muscle–organ communication. The framework is further strengthened by testable predictions concerning adaptive pulsatility, modality-specific signatures, source attribution, recovery quality, disease-specific decoding and the superiority of multi-marker panels over single-molecule readouts. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing global health burden driven by complex interactions among hepatic lipid accumulation, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Exercise remains the cornerstone of lifestyle therapy for MASLD/MASH; however, its therapeutic benefits extend well beyond weight reduction and involve coordinated molecular adaptations across multiple organ systems. In this review, we introduce hepatic mitochondrial reprogramming as a conceptual framework describing the coordinated remodeling of mitochondrial energetics, quality-control pathways, and redox homeostasis that collectively restore metabolic flexibility and hepatocellular resilience. Exercise activates key metabolic regulators, including AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuin signaling, promoting mitochondrial biogenesis, fatty acid oxidation, oxidative phosphorylation, and mitophagy while suppressing hepatic lipogenesis and oxidative injury. Skeletal muscle-derived myokines, alterations in gut microbial metabolism, and thyroid hormone signaling converge upon hepatic mitochondrial function through complementary endocrine and metabolic pathways. Together, these adaptations reduce hepatic steatosis, lipotoxicity, inflammation, and fibrogenesis while improving insulin sensitivity and metabolic flexibility. Emerging evidence further suggests that exercise-induced mitochondrial remodeling may complement pharmacologic therapies targeting hepatic metabolism, including thyroid hormone receptor-β agonists. Although multi-omics technologies continue to expand our understanding of these adaptive responses, the present review emphasizes the underlying molecular and physiological mechanisms through which exercise remodels hepatic mitochondrial function. We propose that exercise acts as a systems-level mitochondrial remodeling stimulus integrating skeletal muscle-, gut-, and thyroid-derived signals to improve hepatic metabolism and attenuate MASLD/MASH progression. This conceptual framework provides a mechanistic basis for precision exercise prescriptions and future combination therapeutic strategies targeting mitochondrial health. Full article

Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has emerged as a potential candidate for mitigating alcohol-induced toxicity. This systematic review aimed to comprehensively evaluate the therapeutic effects of DHM across alcohol-related conditions. Methods: A systematic literature search was conducted in PubMed from inception through December 2025 for studies investigating the effects of DHM or DHM-containing extracts on alcohol-related outcomes. Both preclinical (in vitro and in vivo) and clinical studies were considered. Study quality was assessed qualitatively due to heterogeneity precluding use of a standardized risk-of-bias tool. Results were synthesized narratively by outcome category; meta-analysis was not performed. This review was unregistered with no prior protocol. Results: A total of 22 studies were included, comprising 8 in vitro, 17 in vivo, and 2 clinical studies, with some studies contributing data to more than one category. Across models, DHM consistently attenuated ethanol-induced cytotoxicity, oxidative stress, inflammation, and hepatic steatosis. DHM improved liver injury biomarkers (e.g., AST and ALT), enhanced antioxidant defenses, and modulated key signaling pathways including Nrf2 and AMPK. Additionally, DHM supported mitochondrial function and intestinal barrier integrity. However, findings related to ethanol metabolism and neurobehavioral outcomes were inconsistent. Clinical evidence was limited to two small trials using Hovenia dulcis extracts, which demonstrated reductions in hangover severity and selected inflammatory markers but did not directly evaluate isolated DHM. Conclusions: DHM demonstrates robust preclinical efficacy in mitigating alcohol-induced injury, particularly in hepatic outcomes. Despite promising mechanistic and experimental evidence, clinical data remain limited. The certainty of evidence is constrained by preclinical study heterogeneity, the absence of formal risk-of-bias assessment, and the lack of clinical trials using isolated DHM. Well-designed clinical trials using standardized DHM formulations are needed to establish its complete therapeutic potential in alcohol-related disorders. Full article

Considered by some to be the largest metabolic organ of the body, the functional integrity of skeletal muscle is highly dependent on its exceptional plasticity, which is primarily governed by mitochondrial quality control. The signaling axis composed of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) serves as a critical hub that senses cellular energy status, coordinates mitochondrial biogenesis, regulates muscle fiber type switching, and maintains protein homeostasis. This review systematically delineates the structural functions and synergistic regulatory network of the AMPK/SIRT1/PGC-1α signaling axis. It further elucidates the regulatory roles of this pathway under physiological conditions—such as exercise adaptation and muscle fiber-type transformation—and its dysregulated mechanisms in the pathogenesis of various skeletal muscle disorders, including sarcopenia, disuse atrophy, cachexia, neurogenic atrophy, muscular dystrophy, and type 2 diabetes mellitus-related myopathy. Building on this foundation, this review critically analyzes current multifaceted therapeutic strategies targeting this pathway, encompassing exercise and physical therapy, nutritional and natural products, and small molecule drugs, as well as gene and cell-based therapies. Finally, this review delves into the challenges facing clinical translation in this field, such as the complexity of the signaling network, individual variability, and bioavailability issues. It also proposes future research directions focused on developing precision intervention tools, establishing effective biomarker systems, and exploring combination intervention strategies. Collectively, the AMPK/SIRT1/PGC-1α signaling axis is central to maintaining skeletal muscle metabolic homeostasis, and targeting this pathway provides a robust theoretical foundation and broad application prospects for the prevention and treatment of skeletal muscle-related diseases. Full article

Pregnancy is a physiological state of transient, reversible insulin resistance accompanied by major adaptations in glucose and lipid metabolism. Although placental hormones are key drivers of gestational insulin resistance, the mechanisms underlying the rapid restoration of insulin sensitivity after delivery remain incompletely understood. This review proposes a conceptual framework in which fibroblast growth factor 21 (FGF21) and sex hormone-binding globulin (SHBG) are considered as complementary hepatic signals potentially involved in maternal metabolic adaptation. During late pregnancy, FGF21 may function as a metabolic stress-response factor associated with fatty acid oxidation, lipid handling, and mitochondrial adaptation through AMPK–PPARα-related pathways. Reduced SHBG, in contrast, may reflect hepatic insulin resistance and altered hepatic metabolic regulation. After delivery, changes in FGF21 and SHBG levels may be associated with recovery of hepatic metabolic homeostasis and insulin sensitivity, while persistent adaptive FGF21 signaling facilitate metabolic reprogramming may contribute to ongoing metabolic adaptation. Postpartum metabolic recovery may therefore represent an active and dynamic process rather than a purely passive consequence of placental hormone withdrawal. Disruption of FGF21- and SHBG-mediated pathways may contribute to persistent insulin resistance and increased cardiometabolic risk after gestational diabetes. Understanding hepatokine-mediated regulation of maternal metabolic flexibility may provide further insight into postpartum metabolic recovery and may support future development of risk stratification strategies, biomarker-based approaches, and preventive interventions aimed at reducing the risk of type 2 diabetes after pregnancy. Full article

Background/Objective: An obesogenic diet triggers intestinal inflammation and oxidative stress, leading to epithelial barrier dysfunction and increased risk of metabolic disorders. This study investigated the mechanisms by which quercetin protects intestinal integrity in high-fat diet (HFD)–fed mice. Methods: Mice were fed an HFD or a low-fat diet (LFD) with or without 1% quercetin, intestinal gene and protein expression, microRNA levels, permeability, and circulating intestinal biomarkers were assessed. Results: Mice fed an HFD with quercetin (HFDQ) showed a 17% improvement in intestinal barrier integrity with increased expression of tight junction and mucin genes and proteins. The nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit in the ileum decreased by 34%, whereas its acetylation was reduced by 50–57% throughout the intestine, with downregulation of NF-κB-regulated pro-inflammatory genes and proteins. Quercetin increased the nuclear factor erythroid 2-related factor 2 (NRF2) by ~ 25% across intestinal segments and upregulated antioxidant enzyme genes. It suppressed toll-like receptor 4 (TLR4) by 50% and restored AMP-activated protein kinase (AMPK) and sirtuin 1 to levels comparable to those in LFD mice. Altered microRNAs (miRNA-16, 200b, 122, 34a, and 21) supported these molecular changes. Quercetin also restored short-chain fatty acid receptors and serotonin transporters that were affected by HFD. Plasma lipopolysaccharide (LPS), cluster of differentiation 14, LPS-binding protein, and myeloperoxidase activity decreased by 36, 31, 42, and 37%, while glucagon-like peptide-1 increased by 23%. Conclusions: Quercetin protects epithelial barrier integrity against HFD-induced intestinal inflammation and oxidative stress via the AMPK-mediated NF-κB and NRF2 signaling pathways. Full article

Background: Mitochondrial bioenergetic dysregulation disrupts immune−metabolic homeostasis and promotes pro−inflammatory microenvironments in osteoarthritis (OA) synovitis. However, the mechanistic contributions of mitochondrial energy metabolism to synovitis pathogenesis in OA remain poorly defined. Methods: We analyzed mitochondrial energy metabolism−related genes (MEMRGs) in OA synovitis by integrating transcriptomic data from OA synovial tissues (GSE55235, GSE55457). LASSO regression and maximal clique centrality (MCC) algorithms were applied to identify hub genes, and single−cell RNA sequencing (GSE152805) was used to examine cell−type−specific expression patterns. Functional validation was performed in IRS2−knockdown THP−1 macrophages. Results: We identified 22 mitochondrial energy metabolism−related differentially expressed genes (MEMR−DEGs), which were enriched in the AMPK signaling, glucagon signaling, and insulin signaling pathways. Four hub genes (FOXO3, FASN, PTGS2, IRS2) were identified, and their expression was negatively correlated with synovial macrophage infiltration. Single−cell RNA sequencing revealed that IRS2 was specifically upregulated in a synovial macrophage cluster. Functional studies in IRS2−knockdown THP−1 macrophages demonstrated that IRS2 deficiency impaired IL−4−induced M2 macrophage polarization and reduced mitochondrial membrane potential and ATP synthesis, which was mediated by the suppression of the AKT/FOXO1 signaling. Conclusions: IRS2 potentially influences mitochondrial energy metabolism, as evidenced by the maintenance of mitochondrial membrane potential and ATP synthesis, via the AKT/FOXO1 signaling pathways to maintain synovial macrophage M2 polarization homeostasis. These findings provide novel molecular targets for addressing immune−metabolic pathways in OA therapy. Full article

As a traditional element of Chinese medicine, Hippocampus erectus is well known for promoting adolescent growth, yet its active fractions and underlying molecular mechanisms remain unclear. In this study, the aqueous extract of H. erectus was subjected to in vitro simulated gastrointestinal digestion and ultrafiltration to separate three molecular weight fractions (<10 kDa, 10–30 kDa, >30 kDa). Their chemical profiles were characterized, and osteogenic activities were systematically evaluated using cell assays, a juvenile rat model, and integrated transcriptomics and data-independent acquisition (DIA) proteomics. Results revealed that chemical profiling showed the >30 kDa fraction was mainly composed of hemocyanin subunits, and the 10–30 kDa fraction was enriched in growth-related amino acids and steroid derivatives; functionally, the 10–30 kDa fraction promoted preosteoblast proliferation and early differentiation via enhanced alkaline phosphatase (ALP) activity, while the >30 kDa fraction dominated late osteoblast maturation and mineralization. Both fractions significantly increased rat body and bone length by expanding growth plate proliferative zones and elevating serum insulin-like growth factor-1 (IGF-1)/bone morphogenetic protein-2 (BMP-2) levels. Transcriptomic and proteomic analyses identified vascular endothelial growth factor (VEGF), Wingless-related integration site (Wnt), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and extracellular matrix (ECM)–receptor interaction as potential core regulatory pathways. Integrated multi-omics analysis further confirmed Frizzled-related protein B (Frzb) and AKT1 substrate 1 (Akt1s1) as candidate key regulatory targets enriched in the Wnt and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. These findings elucidate the multi-fraction, multi-pathway mechanism of H. erectus in promoting skeletal development, providing scientific evidence for its traditional use and a theoretical basis for growth-promoting functional food development. Full article

Background/Objectives: Glucocorticoid therapy remains clinically indispensable, yet its long-term use is profoundly constrained by insulin resistance (IR), hepatic steatosis, and progressive metabolic dysfunction. Methylsulfonylmethane (MSM), a naturally occurring sulfur-containing nutraceutical with established antioxidant and anti-inflammatory activities, has emerged as a promising metabolic modulator; however, its therapeutic relevance in glucocorticoid-induced hepatic IR has not previously been explored. Methods: Male Wistar rats received MSM (200 or 400 mg/kg/day, p.o.) for 14 days, while dexamethasone (DEX) (8 mg/kg/day, i.p.) was administered during the final 7 days to induce severe metabolic dysfunction. Results: DEX provoked profound IR, dyslipidemia, oxidative stress, hepatocellular injury, and steatotic degeneration accompanied by marked ultrastructural abnormalities. Remarkably, MSM conferred dose-dependent metabolic and hepatoprotective effects, significantly restoring glucose homeostasis, insulin responsiveness, lipid metabolism, and hepatic structural integrity. Mechanistically, MSM exerted a pleiotropic regulatory effect through suppression of the glucocorticoid-responsive kinase SGK1, restoration of AMPK/mTOR signaling balance, and normalization of insulin signaling pathways and metabolic transcriptional regulators. Furthermore, MSM effectively attenuated oxidative stress and inflammatory amplification consistent with modulation of the NLRP3/NF-κB/IL-6 axis. Importantly, the current work identifies angiogenic remodeling demonstrated by DEX-induced upregulation of VEGF and CD34, both of which were substantially suppressed by MSM treatment. Conclusions: This study provides novel evidence that MSM mitigates glucocorticoid-induced hepatic IR through coordinated modulation of glucocorticoid-responsive kinases, metabolic signaling networks, redox–inflammatory cascades, and pathological angiogenesis. Consequently, MSM may represent a promising candidate for further preclinical and clinical evaluation regarding its capacity to limit glucocorticoid-associated metabolic burdens. Full article

Metformin is a cornerstone medication for type 2 diabetes and exhibits anti-tumor activities. Previous studies have demonstrated that metformin suppresses tumor progression by regulating multiple signaling pathways, including the AMPK, PI3K/AKT/mTOR, and JNK pathways. However, most previous studies have focused on its direct effects on tumor cells, with limited attention to its effects in the TME. The TME constitutes a multifaceted ecosystem that drives tumor development and therapeutic resistance via physical barrier formation, immune evasion, and abnormal angiogenesis. In this review, we systematically summarize the impact and underlying regulatory mechanisms of metformin on distinct components of the TME. In addition, we discuss the individual and combined roles of metformin in immunity and inflammation, as well as vascular, matrix, and metabolic regulation. By elucidating the mechanisms of metformin-mediated TME reprogramming, we aim to provide new perspectives for understanding its anti-tumor effects and facilitating its clinical translation in cancer therapy. Full article

Cancer stem cells (CSCs) drive therapeutic resistance and tumor relapse by exploiting redundant regulatory networks that integrate Wnt/β-catenin, Notch, and Hedgehog signaling with metabolic reprogramming, epigenetic plasticity, and tumor microenvironment crosstalk, a network architecture that renders single-pathway inhibition strategies insufficient. This review systematically examines evidence that natural compounds (curcumin, sulforaphane, resveratrol, EGCG, berberine, and quercetin) act as multitarget modulators of CSC plasticity, analyzing their molecular mechanisms of action in specific cancer models. Each compound engages distinct regulatory nodes: curcumin suppresses β-catenin nuclear translocation and STAT3 phosphorylation in lung cancer CSC models; sulforaphane represses ΔNp63α-driven stemness transcription in colorectal cancer and reduces CSC self-renewal in prostate and head and neck models; resveratrol dissociates the β-catenin–GLI-1 interaction in oral and lung CSC populations and induces Wnt/β-catenin-dependent autophagy in breast CSCs; EGCG inhibits DNMT and HDAC activity in glioblastoma and colorectal models; berberine activates AMPK-mediated suppression of mTORC1 in colorectal cancer; and quercetin suppresses PI3K/AKT/mTOR signaling while downregulating EMT transcription factors in breast and colorectal systems. We critically assess persistent methodological limitations, including bulk cell-line models, supraphysiological concentrations, and the absence of functional tumor-initiating validation, that currently prevent stronger translational conclusions. Natural compounds from Latin American biodiversity are identified as an underexplored source of CSC-active molecules. We conclude by defining the experimental standards required to reposition natural compounds as clinically relevant network-level modulators of CSC plasticity. Full article

Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10–20 µg/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management. Full article