Abstract Alzheimer’s disease (AD) is a neurological disorder that causes memory loss and progressive cognitive deterioration. Current therapy options for AD concentrate on symptom management rather than treating the illness’s underlying cause. The capacity of plant-based acetylcholinesterase inhibitors (AChEIs) to raise acetylcholine levels in the brain has made them a promising treatment option for AD. Acetylcholine is a neurotransmitter that is essential for memory, learning, and cognitive functions. The acetylcholinesterase (AChE) breaks down acetylcholine in AD, resulting in a shortage of this crucial neurotransmitter and causing cognitive deficits. These chemicals produced from plants can help maintain higher amounts of acetylcholine in the brain by blocking AChE, which may improve cognitive function and slow the progression of the disease. These substances have been shown to improve learning and memory, lessen amyloid-beta plaques and disease-related neuroinflammation in the brain. In addition, as compared to the synthetic medications now used to treat AD, plant-derived AChEIs have demonstrated better safety profiles and fewer adverse effects. In general, plant-based AChEIs are a new and potentially effective treatment strategy for AD. Additional research is required to further understand these substances’ mechanisms of action and efficacy. As interest in natural remedies for neurodegenerative diseases increases, AChEIs derived from plants hold significant promise to improve the quality of life in AD patients.
Abstract Eucommia ulmoides Oliv., a traditional Chinese medicinal herb, has long been used to strengthen bones, tonify the liver and kidneys, and alleviate inflammation-induced bone damage, particularly in rheumatoid arthritis (RA). Modern pharmacological studies have confirmed its anti-inflammatory, antioxidant, and antiosteoclastic properties, as well as its ability to inhibit synovial hyperplasia and angiogenesis, key pathological processes in RA progression. This review synthesizes existing knowledge on the bioactive components of E. ulmoides Oliv. and their underlying mechanisms of action, aiming to establish a scientific basis for its clinical application in RA therapy. E. ulmoides Oliv. is a safe, edible plant with high nutritional value, containing a variety of bioactive compounds, including lignans, iridoids, flavonoids, and phenolic acids. These constituents collectively contribute to its anti-RA effects by targeting multiple pathological pathways. Specifically, E. ulmoides Oliv. extracts inhibit vascular endothelial growth factor expression, thereby reducing synovial angiogenesis and hyperplasia. They also modulate critical inflammatory pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), downregulating the expression of proinflammatory cytokines. In addition, E. ulmoides Oliv.-derived components suppress osteoclast activity, preventing bone erosion and protecting joint integrity. Emerging research suggests that E. ulmoides Oliv. may also influence RA pathogenesis through the modulation of gut microbiome composition. Pharmacokinetic studies have identified 24 E. ulmoides Oliv.-derived compounds with potential for anti-RA drug development. In summary, E. ulmoides Oliv. offers a multifaceted approach to RA treatment, simultaneously addressing inflammation, synovial proliferation, and bone destruction. These findings bridge the gap between the traditional medicinal use of E. ulmoides Oliv. and modern scientific evidence, positioning E. ulmoides Oliv. as a promising candidate for integrative RA management. Future research should focus on well-designed clinical trials to assess its efficacy and safety, optimize dosing regimens, and explore potential synergies with conventional RA therapies.
Abstract Objective: The primary aim of this study was to develop and optimize a novel infrared-ultrasound hydrodistillation method coupled with in-line gas chromatography–mass spectrometry (IR–US–HD–GC/MS) for the eco-efficient extraction of Salvia sclarea essential oil (EO). The secondary aim was to evaluate the antioxidant, anti-inflammatory, and gastroprotective effects of the optimized EO in validated in vivo models. Materials and Methods: A novel IR–US–HD–GC/MS apparatus was assembled and compared with microwave-assisted hydrodistillation (MW-HD) and conventional hydrodistillation (HD). The EOs were chemically characterized, and the most promising extract was tested in two gastric ulcer models (HCl/ethanol and hypothermia). Anti-inflammatory mechanisms were investigated through cytokine assays, NF-κB, cyclooxygenase-2 (COX-2), and antioxidant markers. Results: The novel IR–US–HD–GC/MS method significantly improved EO yield (5.8 mL/kg vs. 3.0 mL/kg with HD), reduced extraction time (15 min vs. 5 h), and lowered energy consumption by 90%. The optimized EO (200 mg/kg) produced strong gastroprotection, reducing ulcer area by 74.9% in the HCl/ethanol model and 49.6% in the hypothermia model, comparable to ranitidine. Biochemically, treatment reduced tumor necrosis factor-alpha (72.8%), interleukin-6 (IL-6) (71.2%), NF-κB (IC 50 = 88.7 mg/kg), and COX-2 (IC 50 = 112.2 mg/kg), while increasing IL-10 (1.3-fold) and restoring antioxidant balance (MDA decreased by 46%; GSH increased by ca. 2-fold; CAT increased by 1.25-fold). Conclusions: The IR–US–HD–GC/MS method is a green, time- and energy-efficient technology that enhances both yield and bioactivity of S. sclarea EO. The optimized oil demonstrates significant multi-targeted antioxidant, anti-inflammatory, and gastroprotective effects, supporting its potential as a safe phytotherapeutic candidate for inflammatory gastric disorders.
Abstract Objective: Previously, we demonstrated that polydatin (PD) protected against acute lung injury (ALI) by upregulation of mitophagy; however, the mechanism remains unclear. In the present study, we aimed to determine whether PD facilitates mitophagy by downregulating p53 and then alleviates ferroptosis in ALI. Materials and Methods: Lipopolysaccharide (LPS) was administered intratracheally to the mice to induce ALI. ALI was induced by stimulating mouse lung epithelial cell line-12 (MLE-12) cells with 5 μg/mL LPS for 12 h in vitro . Results: We found that the downregulation of mitophagy by silencing Prkn (Parkin) exacerbated LPS-induced ferroptosis, suggesting the protective effect of Parkin-dependent mitophagy prevents LPS-induced ferroptosis. Furthermore, PD treatment alleviated LPS-induced ferroptosis; however, the protective effect of PD was attenuated by mitophagy inhibition. We previously reported that p53 promotes ferroptosis in ALI via an as-yet-unknown mechanism. Herein, p53 was observed to interact with Parkin to prevent its translocation into mitochondria, thereby decreasing mitophagy in ALI. Moreover, upregulating p53 exacerbated LPS-induced ferroptosis, which was rescued by upregulation of mitophagy, indicating that p53 facilitates ferroptosis by depressing mitophagy. In the present study, we found that PD treatment prevented LPS-induced upregulation of p53. Moreover, overexpression of p53 inhibited PD-mediated upregulation of mitophagy and its protective effect against ferroptosis. Interestingly, upregulation of mitophagy rescued the reduced protective effect of PD against ferroptosis due to overexpression of p53. Conclusions: This study reveals that PD treatment prevents LPS-induced ferroptosis by upregulation of Parkin-dependent mitophagy in ALI. Additionally, p53 interacts with Parkin to facilitate ferroptosis by depressing mitophagy. We further found that PD enhances Parkin-dependent mitophagy by downregulating p53.
Abstract Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death, and the treatments are often constrained by side effects and resistance. Hovenia dulcis Thunb. ( H. dulcis ), a traditional herb rich in triterpenoids, possesses antitumor potential, but its mechanisms of action in NSCLC have not been elucidated. Objective: This research aimed to assess the antitumor effects of H. dulcis bark total triterpenoid fraction (H-TP) in NSCLC and to determine the underlying molecular mechanisms via in vivo and in vitro studies. Materials and Methods: H-TP components were analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. Antitumor activity was tested in a nude mouse xenograft model. Serum metabolites were profiled using ultra-performance liquid chromatography–quadrupole/time-of-flight mass spectrometry. Effects on A549 cells were evaluated using counting kit-8, colony formation, wound healing, and Transwell assays, as well as flow cytometry, Western blot, immunofluorescence, and transmission electron microscopic analysis. Results: A total of 27 compounds were identified in H-TP, which significantly inhibited NSCLC tumor growth, invasion, and metastasis and induced G1-phase arrest. Mechanistically, H-TP suppressed the phosphatidylinositol 3 kinase–protein kinase B–mammalian target of rapamycin (PI3K–AKT–mTOR) pathway while upregulating Bax, cleaved caspase-3/8, LC3-II, and ATG proteins and downregulating Bcl-2 and p62, thereby promoting apoptosis and autophagy. Conclusions: H-TP exerts potent anti-NSCLC effects by inducing both apoptosis and autophagy via PI3K–AKT–mTOR inhibition, confirming its promising potential as a natural therapeutic candidate.
Abstract The Pharmacopoeia of the People’s Republic of China (ChP) is the official compendium of drug standards issued by the Chinese government. Volume I, dedicated to traditional Chinese medicines (TCMs), serves as an authoritative standard for their production, testing, clinical application, and regulatory oversight. The ChP is updated every 5 years, and the current 2025 edition was officially implemented on October 1, 2025. Compared with the 2020 edition, the 2025 revision introduces substantial updates. This review summarizes the major additions and revisions to Volume I of the 2025 ChP across three sections: General Notices ; General Technical Requirements and Guidelines related to TCMs; and Monographs . Relative to the previous edition, the General Notices have undergone seven revisions. In the General Technical Requirements and Guidelines , three new items have been added, and five have been revised, with particular emphasis on strengthening safety controls for exogenous harmful substances, including pesticide residues, heavy metals and harmful elements, and mycotoxins. Regarding the Monographs , Volume I now includes 28 new entries, removes 19 previously listed entries, and revises 420 entries. The major updates involve refinements to fingerprint or characteristic chromatograms, assay methods, and test items. Collectively, the 2025 revision emphasizes enhanced safety requirements and improved standards for crude drugs and prepared slices, thereby strengthening the overall quality assurance framework for TCMs. This review aims to facilitate accurate interpretation and effective implementation of the 2025 edition of Volume I of the ChP.
Abstract Objective: This study aimed to investigate the effects of Wuling San (WLS) on nonalcoholic fatty liver disease (NAFLD) progression and to elucidate its underlying mechanisms, with particular emphasis on mitochondrial dynamics and protein kinase B (AKT)-mediated signaling. Materials and Methods: Ultra-performance liquid chromatography tandem mass spectrometry and network pharmacology were employed to identify the major bioactive components of WLS and predict their potential molecular targets. Both in vivo (db/db mice) and in vitro (free fatty acid-induced alpha mouse liver 12 hepatocyte) models were used to evaluate the effects of WLS. A series of biochemical assays, histological evaluations, metabolomic analyses, mitochondrial function assessments, and molecular docking studies were performed to elucidate the mechanisms of action. Results: WLS significantly reduced hepatic lipid accumulation, improved liver function, and attenuated inflammatory responses. Metabolomic profiling revealed substantial modulation of lipid metabolites, whereas mitochondrial assays confirmed restored dynamics and structural integrity. AKT was identified as a key regulatory target, and inhibition by MK2206 abolished the beneficial effects of WLS and ursolic acid. Conclusions: WLS alleviates NAFLD by enhancing mitochondrial dynamic function through AKT activation, suggesting that it may represent a promising therapeutic strategy for metabolic liver disease.
Abstract Objective: To investigate the effects of Xi Huang Wan on the expression of myeloid-derived suppressor cells (MDSCs) and the activity of the tumor necrosis factor-alpha (TNF-α)/nuclear factor kappa B (NF-κB) signaling pathway in mice with breast cancer. Materials and Methods: This study comprised six experimental groups: a blank control group, a model control group, three treatment groups receiving low, medium, and high doses, respectively, and a group treated with capecitabine tablets. Flow cytometry was employed to quantify the levels of MDSCs and their subsets. Serum concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Tissue expression of inflammatory mediators was evaluated using immunohistochemistry. The mRNA and protein expression levels of the TNF-α/NF-κB signaling pathways were assessed using real-time polymerase chain reaction and Western blotting, respectively. Results: The model group exhibited the highest levels of MDSCs overall. In contrast, the Xi Huang Wan treatment groups showed a reduction in total MDSCs. The granulocytic MDSCs were most elevated in the model group, whereas monocytic MDSCs were least expressed. No statistically significant differences in granulocytic or monocytic MDSC levels were observed between any Xi Huang Wan dosage groups and the model group. Compared with the model group, Xi Huang Wan treatment significantly reduced the expression levels of TNF-α, interleukin-6 (IL-6), and interferon-gamma in peripheral blood. Immunohistochemical analysis indicated minimal TNF-α protein expression and elevated IL-6 expression in the model group, showing opposing trends. The mRNA and protein expression levels of TNF-α and NF-κB p65 were highest in the model group but markedly reduced across all Xi Huang Wan dosage groups. Conclusions: Xi Huang Wan has the potential to inhibit the growth of transplanted tumors. In addition, it could modulate MDSC levels, regulate the expression of associated inflammatory factors, and alter the mRNA and protein expression linked to the TNF-α/NF-κB signaling pathway.
Abstract Objective: Ischemic stroke is a leading cause of disability and mortality worldwide, and thrombosis plays a crucial role in its pathogenesis. Cooked Rhubarb (CR) has been traditionally used in stroke treatment, but its mechanisms of action remain unclear. This study aims to investigate the therapeutic effects of CR on IS from a thrombosis-related perspective, and using a rat model, we employ multiomics approaches to investigate its potential mechanisms. Materials and Methods: This study employed an integrative approach combining differential compound analysis, weighted gene co-expression network analysis (WGCNA), network pharmacology, metabolomics, gut microbiota analysis, and in vivo experiments using a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry identified key bioactive compounds in CR. Bioinformatics analysis, including WGCNA and network pharmacology, was conducted to predict CR-related targets and pathways in IS. The therapeutic efficacy of CR was evaluated through behavioral assessments, histopathological examination, coagulation function tests, and metabolomic profiling of brain and colon tissues. In addition, 16S rRNA sequencing was performed to explore CR’s influence on gut microbiota composition. Results: Wine cooking significantly increased the content of five anthraquinone compounds (emodin, aloe emodin, rhein, rhein methylester, and hydroxyl-emodin) and two others (p-coumaric-6-glucoside and ethyl gallate 4-glucuronide) in Rhubarb. WGCNA identified key stroke-associated modules, which were further analyzed through network pharmacology to predict that CR exerts its anti-IS effects primarily through the MAPK signaling pathway, sphingolipid signaling pathway, PI3K-Akt signaling pathway, and FoxO signaling pathway. In vivo experiments demonstrated that CR improved neurological function, reduced infarct volume, and alleviated histopathological damage in MCAO/R rats. Furthermore, CR significantly modulated coagulation function, reducing hypercoagulability and thrombosis-related biomarkers. Metabolomic analysis revealed that CR regulated sphingolipid and glycerophospholipid metabolism in brain tissue and arachidonic acid metabolism in colon tissue, suggesting a role in lipid homeostasis. Gut microbiota analysis indicated that CR intervention significantly enriched Akkermansia and Romboutsia while reducing Escherichia-Shigella abundance, highlighting its potential impact on the gut–brain axis. Integrative multiomics analysis revealed significant correlations between gut microbiota, lipid metabolism, and thrombus. Notably, Escherichia–Shigella abundance was closely correlated with lipid metabolism, particularly arachidonic acid, sphingolipid, and glycerophospholipid metabolism, suggesting a key role of the gut microbiota–metabolite axis in CR’s antithrombotic effects. Conclusions: This study systematically evaluated the pharmacological effects of CR in IS treatment, revealing that its protective effects are primarily mediated through the regulation of lipid metabolism, coagulation function, and gut microbiota composition. These findings expand the understanding of CR’s potential mechanisms in IS therapy and provide important theoretical support for future intervention strategies.
Abstract Background: Tripterygium wilfordii Hook. F. (TW) has significant anti-inflammatory, anti-tumor, and immunosuppressive effects, and is often used in the treatment of rheumatic immune diseases, inflammation, and tumors; however, its liver toxicity is also prominent. Combination treatment with Rehmannia glutinosa (Gaertn.) DC (RG) and TW for detoxification originates from the Qingluotongbi formula and are also representative of a combination of strengthening the body’s resistance to attenuation (Fuzheng Zhidu). Objective: This study aimed to explore the protective effect of RG against TW-induced liver injury and its regulatory mechanism of mitophagy to explain the connotation of combination of strengthening body resistance to attenuation. Materials and Methods: After the administration of RG and TW and their main and active ingredients (triptolide [TP] and catalpol [CAT]), C57BL/6J mice and HL7702 cells were tested for liver pathological changes, liver function indicators, and mitophagy index. The protein and gene expression of the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway were analyzed. In HL7702 cells, PINK1 mRNA was knocked down using siRNA to verify the role of the PINK1/Parkin pathway in mitophagy regulation. Results: RG/CAT reduced the pathological injury and alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels, while reversing the protein and gene levels of microtubule-associated proteins 1A/1B-light chain 3, sequestosome-1, and dynamin-related protein 1 and inhibiting the PINK1/Parkin pathway caused by TW/TP. Knockdown of the PINK1/Parkin pathway in vitro alleviates TP-induced hepatotoxicity in HL7702 cells. Conclusions: RG inhibited excessive mitophagy to reduce TW-induced hepatotoxicity by downregulating the PINK1/Parkin pathway, providing research support for explaining the connotation of RG’s combination of strengthening the body resistance and attenuating the hepatotoxicity of TW.
Abstract Objective: Ding-Zhi Xiao-Wan decoction (DZXW), a traditional remedy for neurological disorders, shows potential in alleviating poststroke cognitive impairment (PSCI), yet its mechanisms remain unclear. Materials and Methods: This study aimed to elucidate DZXW’s therapeutic effects and molecular pathways in PSCI. Using network pharmacology, key bioactive compounds (kaempferol, 3,6’-disinapoyl sucrose, quercetin, pachymic acid, and 8-isopentenyl-kaempferol) were identified, targeting IL17-associated synaptic pathways and binding matrix metalloproteinase 2/amyloid precursor protein (MMP2/APP). Results: In a transient middle cerebral artery occlusion (tMCAO) mouse model, DZXW administration for 4 weeks improved cognitive function, as evidenced by Morris water maze, novel object recognition, and open-field tests. Histological analyses (H and E, Nissl staining, and transmission electron microscopy) revealed reduced neuronal damage and enhanced synaptic ultrastructure. Mechanistically, DZXW downregulated PSCI-related genes (APP, glycogen synthase kinase 3 beta (GSK3β), caspase-3, beta-secretase 1, MMP2/9) and serum inflammatory markers (MMP2, MMP9, and interleukin 17) via real-time quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Critically, DZXW-activated p-protein kinase B (Akt), p-mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) while inhibiting p-GSK3β, indicating modulation of the Akt/GSK3β/mTOR/HIF-1α axis. Conclusions: These results demonstrate that DZXW mitigates cognitive deficits by synergistically suppressing neuroinflammation, oxidative stress, and synaptic dysfunction through multi-target regulation. Our findings provide novel insights into DZXW’s neuroprotective mechanisms, positioning it as a promising therapeutic candidate for PSCI via pathway-specific intervention.
Abstract Objective: To investigate the mechanisms underlying the amelioration of metabolic dysfunction-associated steatotic liver disease (MASLD) by hydroxysafflor yellow A (HYA). Materials and Methods: A mouse model of MASLD induced by administration of high-fat high-sugar water (HFSW)-, an oleic acid-palmitic acid (OAPA)-stimulated hepatocyte model, and a hepatocyte-macrophage coculture system were used. Transcriptomic analysis was used to elucidate the function and mechanisms of these models. Results: HYA significantly decreased lipid accumulation, restored fatty acid oxidation, and improved inflammatory responses, thereby alleviating hepatic steatosis in HFSW-fed mice. Furthermore, HYA promoted hepatocyte proliferation and suppressed apoptosis through activation of the viral oncogenic cellular-myelocytomatosis (c-Myc) signaling pathway. It concurrently polarized macrophages toward the M2 anti-inflammatory phenotype and enhanced their lysosomal phagocytic function to clear apoptotic hepatocytes. Conclusions: HYA exerts multifaceted anti-MASLD effects through the coordinated regulation of lipid metabolism and maintaining the balance between apoptosis and proliferation and immune microenvironment homeostasis; thus, HYA is a promising therapeutic candidate for clinical intervention.
Abstract Objective: Combing, a common daily practice, may promote brain health by improving both extracranial and intracranial blood circulation, as demonstrated in stroke models. However, the optimal combing direction for maximizing circulatory benefits remains unclear. This study was to investigate how the combing direction affects extracranial circulation in healthy adults. Materials and Methods: In this open-label randomized controlled trial, a total of 62 healthy participants were assigned to two groups: Group F–B (front-to-back combing) and Group B–F (back-to-front combing). Participants combed their hair for 5 min using their dominant hand at a consistent frequency, ensuring uniform coverage of the scalp. Blood flow and skin temperature in the ear concha and auricle were measured before and after combing using laser speckle flow imaging and thermometry. Results: Both groups showed significant increases in scalp, ear, and hand skin temperatures. Group B–F exhibited a significant increase in ear blood flow ( P = 0.0027), whereas Group F–B showed no significant change ( P > 0.05). Conclusions: Back-to-front combing significantly enhanced extracranial blood flow, particularly in the ear, indicating that combing direction influenced circulatory outcomes. These findings support back-to-front combing as a simple approach to promoting head circulation within traditional Chinese medicine practices. Clinical trial registration: The study was approved by the Ethics Committee of Beijing University of Chinese Medicine (2020BZHYLL0108), and all participants provided written informed consent.
Abstract Objective: To address the critical gap in traditional gout animal models that fail to recapitulate the traditional Chinese medicine (TCM) syndrome of Damp-Heat Pouring Downward Syndrome (DHPDS), this study aims to establish a disease-syndrome integrated model that aligns with TCM theory. Materials and Methods: Six DHPDS gout rat models were developed by integrating endogenous dampness-heat induction (high-fat diet, ethanol, and ginger extract) and exogenous pathogenic stimulation (artificial climate chamber), followed by phenotypic, biochemical, and histopathological evaluations. Serum metabolomic profiling was performed using ultra-high-performance liquid chromatography-Q/Orbitrap/LTQ MS. Non-negative matrix factorization (NMF) distilled clinical topic features from data of 92 patients with DHPDS gout. Model fitting analysis employed a dual-module framework: NMF-derived feature coefficients were converted to weighted phenotypic scores, and metabolomic congruence analysis was used to evaluate biomarker overlap between animal models and clinical cohorts. Results: Comprehensive evaluations (phenotypic, biochemical, and histopathological) confirmed the successful establishment of DHPDS gout rat models. Metabolomic profiling detected 31, 37, 38, 38, 46, and 42 differentially expressed metabolites in models 1–6, primarily linked to gout-related pathways: purine/pyrimidine metabolism, amino acid homeostasis, lipid metabolism, and arachidonic acid metabolism. Clinical topic features of DHPDS gout included high uric acid, high low-density lipoprotein, high triglyceride, diet reduction, and high creatinine. Model 5 demonstrated superior congruence with clinical DHPDS gout features, achieving the highest composite fitting score (172/200). Conclusions: This study established six DHPDS gout animal models guided by TCM theory. Through multimodal fitting analysis combining clinical features with metabolomic profiling, Model 5 was identified as the most clinically representative. The multimodal fitting framework establishes a novel paradigm for precision modeling of TCM syndromes.
Abstract Curcumae Rhizoma (CR), known as Ezhu in China, is the dried rhizome of Curcuma phaeocaulis VaL, Curcuma kwangsiensis S. G. Lee et C. F. Liang, or Curcuma wenyujin Y. H. Chen et C. Ling, as defined by the 2020 edition of the Chinese Pharmacopoeia. According to Traditional Chinese Medicine theory, CR primarily promotes qi to break blood stasis, thereby eliminating accumulation and relieving pain, which accounts for its extensive use in chronic cardiovascular disease, fibrosis, and gynecological conditions. Current evidence suggests that CR mainly consists of essential oils and curcumin, which exhibit significant biological activities, including antithrombotic, antitumor, anti-inflammatory, antiviral, hepatoprotective, bacteriostatic, and other pharmacological activities. However, the specific pharmacological mechanisms of its bioactive ingredients remain unclear. Therefore, this review sought to summarize the pharmacokinetics and recent advances in pharmacological research of the main bioactive ingredients in CR, aiming to provide a research basis for its clinical application and new drug development.
Abstract Objective: This study investigates the effects of Celastrus orbiculatus Thunb extract (COE) on the metastasis of gastric cancer (GC) through MED12, aiming to elucidate the underlying mechanisms. Materials and Methods: Cell viability was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Adhesion and transwell assays were conducted to assess the adhesion, invasion, and migration capabilities of mediator complex subunit 12 (MED12)-deficient GC cells. Cell movement was tracked using the high-content imaging system. Western blotting was employed to examine the impact of COE on the expression of MED12 and the alterations in proteins related to invasion and migration in GC cells. Results: COE reduces MED12 expression in GC cells through a distinct mechanism. Experimental data demonstrate that COE and direct modulation of MED12 expression significantly impair the infiltration and movement of GC cells, with a notable reduction in movement distance. Furthermore, both treatments substantially downregulate matrix metalloproteinases expression, thereby inhibiting the invasive potential of tumor cells. In addition, COE treatment and MED12 deficiency reverse epithelial-mesenchymal transition-related protein alterations, providing new insights into the mechanisms driving tumor metastasis. Conclusions: MED12 deficiency serves as a critical barrier to GC invasion and metastasis, while COE modulation of MED12 expression offers a promising strategy for inhibiting GC progression. These results not only suggest new therapeutic strategies for GC but also propose possible routes for the creation of anti-tumor drugs.
Abstract Background: During prediabetes, increased free fatty acid levels induce negative actions on cardiomyocytes, but effective approaches to prevent these negative actions and the development of diabetic cardiomyopathy are limited. Saturated fatty acids such as palmitate have been shown to contribute to the development of diabetic cardiomyopathy (DbCM), with ferroptosis being recognized as a potential mechanism of palmitate-induced cardiac injury. ALOX15 is a driving factor of ferroptosis and also contributes to inflammation and oxidative stress in DbCM. Baicalein is a natural inhibitor of ALOX15, but the effects of baicalein on ferroptosis in DbCM remain unknown. Aims and Objectives: The overall objective of the present study was to elucidate the potential effects of baicalein on ferroptosis in cardiomyocytes when exposed to elevated free fatty acid levels. Materials and Methods: H9c2 cardiomyocytes were treated with palmitic acid at different concentrations to induce lipid peroxidation and ferroptosis-related responses. The cells were subsequently incubated with baicalein to evaluate its protective effects. Lipid peroxidation and intracellular reactive oxygen species (ROS) levels were measured. Production of 12- and 15-hydroxyeicosatetraenoic acid (15-HETE), as well as mitochondrial function indicators including mitochondrial membrane potential, cytochrome c release, and mitochondrial ROS, were assessed. Protein expression levels of GPX4, ACSL4, and ALOX15 were analyzed by Western blot. Statistical analysis was performed to determine concentration-dependent effects and treatment efficacy. Results: Our results revealed that 12-, 15-HETE production, lipid peroxidation and intracellular reactive oxygen species (ROS) levels increased in a concentration-dependent manner when treated with palmitic acid. Baicalein effectively inhibited the ALOX15 associated 12-, 15- HETEs production and decreased lipid peroxidation in H9c2 cells. Furthermore, baicalein also ameliorated mitochondrial dysfunction through restoring mitochondrial membrane potential and decreasing the release of cytochrome c, as well as mitochondrial ROS. Treatment with baicalein also increased GPX4 and reduced ACSL4 and ALOX15 protein expression in H9c2 cells. Conclusions: These results suggest that baicalein may protect cardiomyocytes against ferroptosis through an ACSL4-ALOX15-GPX4 axis.
Abstract Objective: Huangqi Guizhi Wuwu Decoction (HGWD), a Traditional Chinese Medicine prescription known for warming the meridians and promoting blood circulation, has shown therapeutic potential for diabetic hepatopathy (DH). However, the precise molecular mechanisms by which HGWD regulates hepatic lipid remodeling in DH remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of HGWD, with an emphasis on its dual modulation of lipid metabolism and inflammation. Methods and Results: DH mice were treated with low, medium, or high doses of HGWD for 8 weeks. Serum biochemical analyses and histopathological assessments confirmed the efficacy of HGWD, with the high-dose group demonstrating the most significant reductions in hyperglycemia, hepatic lipid accumulation, and liver injury. Lipidomics identified 118 dysregulated hepatic metabolites, predominantly fatty acyls associated with lipogenesis and pro-inflammatory eicosanoids. Network pharmacology and Western blot analyses revealed AMPK-FASN and PI3K-AKT as the core pathways targeted by HGWD. HGWD restored AMPK phosphorylation, suppressed FASN-mediated lipogenesis, and inhibited PI3K-AKT-driven inflammatory responses, thereby normalizing fatty acid synthesis, degradation, and arachidonic acid metabolism. It also reduced inflammatory markers and alleviated mitochondrial-ER lipid-signaling dysfunction. Molecular docking showed strong binding of key HGWD constituents, paeoniflorin and cinnamic acid, to proteins within the AMPK-FASN and PI3K-AKT pathways. Conclusions: Collectively, these findings demonstrate that HGWD exerts dual-pathway regulatory effects by reprogramming lipid metabolism via AMPK-FASN and attenuating inflammation through PI3K-AKT, providing a pharmacological basis for its use in DH and supporting the development of precision therapies for diabetic complications.
Abstract Liver diseases are characterized by a prolonged course and numerous late-stage complications. Lycium barbarum polysaccharides (LBPs) are the main active ingredients of L. barbarum , a traditional Chinese herbal medicine that has been used for thousands of years. LBPs exhibit a wide range of pharmacological effects, such as antitumor, anti-inflammatory, and antioxidant effects, showing broad application prospects in the clinical treatment of liver diseases. This article focuses on research conducted during the past two decades (2003–2025), summarizes the regulatory role of LBPs in different liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), liver fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC), and provides new therapeutic strategies for the treatment of liver diseases. We searched for digitized journal articles on the use of LBPs for the treatment of various liver diseases in the PubMed, Embase, and Cochrane Library databases, followed by searches using Google Scholar and Web of Science. In total, 172 papers were retrieved, and 33 papers were ultimately selected and included through screening and filtering. We summarized the regulatory role of LBPs in different liver diseases, such as Nonalcoholic fatty liver disease (NAFLD), ALD, fibrosis, DILI, and HCC. LBPs play regulatory roles in various liver diseases, such as fatty liver, cirrhosis, and liver cancer, and exert favorable therapeutic effects on liver disease models in vitro and in vivo . However, further in-depth research on the mechanism of action of LBPs in the treatment of liver diseases is needed.
Abstract Objective: Astragalus Radix (AR) and Angelicae Sinensis Radix (ASR) are a common herb pair for preventing and treating cardiovascular and cerebrovascular diseases in traditional Chinese medicine. However, the major pharmacodynamic components have not yet been revealed. Materials and Methods: An in vivo experiment was performed to investigate the protective effects of AR and ASR on vascular endothelial injury (VEI). Network pharmacology, bioinformatics, and molecular docking were conducted to explore the active ingredients, potential targets, biological processes, and pathways involved in AR-ASR compatibility against VEI. Liquid chromatography–mass spectrometry was used to evaluate changes in the dissolution, intestinal absorption, and blood entry rate of major pharmacodynamic components. In addition, an in vitro vascular endothelial cell (VEC) injury model was used to verify the protective effects and mechanisms of the major pharmacodynamic components used alone and in combination. Results: AR-ASR compatibility significantly mitigated vascular intimal hyperplasia and reduced collagen deposition caused by VEI. Network pharmacology and bioinformatics evaluations revealed a vital role for the major pharmacodynamic components of AR-ASR (calycosin-7-O-glucoside, calycosin, formononetin, astragaloside IV, astragaloside I, and ferulic acid) in the regulation of VEC functional homeostasis (apoptosis, proliferation, vascular systolic and diastolic function, extracellular matrix, coagulation, and fibrinolysis), which was validated through molecular docking and in vitro experiments. Conclusions: This study demonstrated the protective effect of AR and ASR on VECs and their related mechanisms, including promoting endothelial cell proliferation, reducing apoptosis, protecting vascular systolic and diastolic function, and regulating coagulation and fibrinolysis.
