Introduction: Obesity, a global health challenge, is characterized by excessive fat accumulation and associated metabolic disorders. The ZhiZhu decoction, a traditional Chinese herbal formula consisting of Citrus aurantium L. (ZS, ZhiShi in Chinese) and Atractylodes macrocephala Koidz (BZ, Baizhu in Chinese), is widely recognized in clinics for its gastrointestinal regulatory effects. Methods: The chemical composition of ZS-BZ essential oil (ZBEO) was characterized using gas chromatography-mass spectrometry (GC-MS). Concurrently, we conducted in vitro investigations using HepG2 hepatoma cells to evaluate its anti-lipid deposition potential. To further elucidate the anti-obesity mechanisms, an in vivo model was established through high-fat diet (HFD)-induced obese rats, followed by transdermal ZBEO administration. Systemic analyses were performed integrating serum metabolomic profiling via UPLC-QTOF-MS and gut microbiota dynamics assessment through 16S rRNA gene sequencing. Results: ZBEO, rich in atractylon, D-limonene, and γ-elemene and shown to reduce lipid accumulation. Transdermal ZBEO administration in obese rats led to significant weight loss and improved serum metabolic indexes related to the POMC/CART signaling pathway. Additionally, ZBEO altered gut microbiota, enhancing beneficial bacteria and affecting metabolic pathways linked to obesity. Discussion: We discovered that ZBEO exerts a significant influence on obesity by modulating key biological processes, including glucose metabolism, lipid metabolism, and the composition of gut microbiota.

G protein-coupled receptor 35 (GPR35), a member of the largest druggable gene family, has emerged as a critical regulator of tumor metabolism and immune modulation. Aberrant expression of GPR35 is frequently observed in digestive system malignancies and is associated with poor prognosis. This review comprehensively explores GPR35’s role in metabolic reprogramming, highlighting its regulatory functions in glucose, lipid, amino acid, and microbial metabolite metabolism. GPR35 shapes the tumor microenvironment through modulation of metabolite signaling, influencing angiogenesis, immune cell infiltration, and inflammation. It also acts as a key interface between host cells and the gut microbiota, contributing to cancer progression via microbial-derived metabolites. Pharmacological targeting of GPR35 shows promise, with several agonists and antagonists advancing through preclinical and early clinical development. However, challenges such as species-specific pharmacodynamics, ligand selectivity, and receptor isoform variability complicate drug development. Recent advances, including the creation of humanized GPR35 models, have facilitated translational research. Targeting GPR35-mediated metabolic reprogramming represents a novel therapeutic strategy, particularly for metabolically active digestive cancers. Future studies should focus on clarifying the metabolic pathways governed by GPR35 and optimizing receptor-specific therapeutics for clinical application.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder characterized by intrahepatic lipid accumulation, oxidative stress, and inflammatory responses, underscoring the urgent need for effective therapeutic strategies. D-limonene, a cyclic monoterpenoid primarily derived from citrus fruits, possesses well-documented antioxidant, anti-fibrotic, and wound-healing properties. However, its therapeutic potential in MASLD remains largely unexplored. Methods: To evaluate the therapeutic efficacy of D-limonene, a rat model of MASLD was established using a high-fat diet (HFD). An integrated approach combining metabolomics, transcriptomics, and network analysis was employed to identify key signaling pathways and molecular targets. The expression levels of candidate targets were validated by RT-qPCR and Western blotting. Molecular docking simulations were performed to predict the binding affinity between D-limonene and the target proteins. Furthermore, a cellular thermal shift assay (CETSA) was conducted to confirm direct binding and protein stabilization. In parallel, cellular experiments using BRL-3A and HepG2 cells were carried out to assess the effect of D-limonene on lipid accumulation. Results: D-limonene treatment significantly ameliorated liver injury, reduced excessive lipid deposition, attenuated inflammation, and suppressed oxidative stress in HFD-induced rats. Integrated multi-omics and network analyses identified the PPAR signaling pathway as the core pathway mediating the regulatory effects of D-limonene on lipid metabolism, with PPARγ and SCD-1 pinpointed as key downstream targets. RT-qPCR and Western blot analyses confirmed that D-limonene significantly downregulated the expression of both PPARγ and SCD-1. Molecular docking simulations revealed stable binding of D-limonene to PPARγ and SCD-1. Importantly, CETSA further demonstrated that D-limonene directly binds to and stabilizes these two proteins. Consistently, cellular assays showed that D-limonene significantly reduced lipid accumulation in BRL-3A and HepG2 cells by inhibiting the PPARγ/SCD-1 axis. Conclusion: Collectively, these findings suggest that D-limonene alleviates HFD-induced MASLD, and its protective effects may be mediated, at least in part, through inhibition of the PPARγ/SCD-1 axis. This study provides preliminary evidence supporting the potential development of D-limonene as a targeted therapeutic agent for MASLD. Further studies are warranted to validate these findings and elucidate additional underlying mechanisms.

Characterizing how localized physical stimulation at acupoints elicits systemic therapeutic effects is essential to understanding acupuncture biology. Spatial omics technologies offer a transformative approach to this challenge by enabling high-resolution, multiplexed analysis of biomolecules directly within their native tissue contexts, thereby decoding the spatial molecular architecture of acupoints and mapping the systemic regulatory networks underlying acupuncture effects. This review synthesizes the spatial and anatomical properties of acupoints and the established molecular mechanisms of acupuncture, focusing on key receptors and signaling pathways. We further provide a comprehensive overview of spatial omics technologies and their groundbreaking applications in both Western and Chinese medicine. Critically, we explore the potential of spatial omics to revolutionize acupuncture research by delineating the spatial biological architecture of acupoints, visualizing the local tissue response to stimulation, and ultimately deciphering the spatiotemporal dynamics of the remote network responses that underpin acupuncture’s systemic effects. Overcoming current technical and analytical challenges will be pivotal in harnessing spatial omics to investigate the proposed spatial principles of acupuncture, thereby bridging a critical gap between its empirical practice and mechanistic understanding.

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomodulation. Crucially, we evaluate recent advances in drug delivery systems, such as liposomes, polymeric nanoparticles, inorganic frameworks, and stimuli-responsive (e.g., pH, redox, enzyme) release systems that successfully overcome traditional pharmacological barriers. These bioengineering strategies not only improve solubility and tumor targeting but also significantly widen the therapeutic window, as evidenced by enhanced tumor suppression and reduced systemic toxicity in preclinical models. Despite this progress, challenges regarding in vivo chemical transformations and tumor heterogeneity remain. Ultimately, we propose a closed-loop “Composition–Mechanism–Delivery” design paradigm to guide future research, facilitating the translation of ethnopharmacological heritage into precision mineral-based therapeutics.