Search Results (395)

Petroglyph motifs from 23 sites and 37 panels in northern Georgia and western North Carolina foothills and mountains are analyzed within their archaeological, ethnographic, and landscape contexts. The Track Rock Tradition comprises 10 chronologically sequenced marking categories: (1) Cupules/Meanders/Open Circles; (2) Soapstone Extraction cars; (3) Vulva Shapes; (4) Figures; (5) Feet/Hands/Tracks; (6) Nested Circles; (7) Cross-in-Circles; (8) Spirals; (9) Straight Lines; and (10) Thin Incised Lines. Dating spans approximately 3800 years. Early cupules and meanders predate 3000 years ago, truncated by Late Archaic soapstone extraction. Woodland period (3000–1050 years ago) motifs include vulva shapes, figures, feet, tracks, and hands. Early Mississippian concentric circles date to 1050–600 years ago, while Middle Mississippian cross-in-circles span 600–350 years ago. Late Mississippian spirals (350–200 years ago) and post-contact metal tool incisions represent the most recent phases. The Track Rock Tradition differs from western Trapp and eastern Hagood Mill traditions. Given the spatial overlap with Iroquoian-speaking Cherokee territory, motifs are interpreted through Cherokee beliefs, supplemented by related Muskogean Creek ethnography. In Cherokee cosmology, the matrilocal Thunderers hierarchy includes the Female Sun/Male Moon, Selu (Corn Mother)/Kanati (Lucky Hunter), Medicine Woman/Judaculla (Master of Game), and Little People families. Ritual practitioners served as intermediaries between physical and spirit realms through purification, fasting, body scratching, and rock pecking. Meanders represent trails, rivers, and lightning. Cupules and lines emphasize the turtle appearance of certain rocks. Vulva shapes relate to fertility, while tracks connect to life-giving abilities. Concentric circles denote townhouses; cross-in-circles and spirals represent central fires. The tradition shows continuity in core beliefs despite shifting emphases from hunting (Woodland) to corn cultivation (Mississippian), with petroglyphs serving as necessary waypoints for spiritual supplicants. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Background: Fructus Meliae Toosendan (FMT) is a traditional Chinese medicine used to treat ascariasis; however, its reported hepatotoxicity limits its application. Toosendanin (TSN), as a principal active component, is recognized as the primary toxic ingredient responsible for FMT-induced hepatotoxicity, but the underlying mechanisms remain elusive. Methods: HepG2 cells were treated with TSN and analyzed using Western blotting and qPCR assays for related gene transcription and protein expression. Lipid peroxidation and ferroptosis markers were measured. Balb/c and C57BL/6 mice received various doses of TSN administration, and their liver function was assessed with serum biochemistry and histopathology. Network pharmacology and oxidative lipidomics were performed to identify key targets and metabolites. Results: TSN triggered ferroptosis both in vitro and in vivo, accompanied by the elevated expression of 5-lipoxygenase (ALOX5) and its downstream metabolites. The ALOX5 level modulated hepatocyte sensitivity to TSN-induced ferroptotic damage. An ALOX5 knockdown alleviated TSN-induced liver injury and ferroptosis in vivo. Conclusions: Our study demonstrated that TSN induces hepatotoxicity by facilitating ALOX5-mediated lipid peroxidation, thereby sensitizing cells to ferroptosis. Full article

Early medical traditions include those of ancient Babylonia, China, Egypt, and India. The roots of modern Western medicine, however, go back to ancient Greece. During the Renaissance, physicians increasingly relied on observation and experimentation to understand the human body and develop new techniques for diagnosis and treatment. The discovery of antibiotics, antiseptics, and other drugs in the 19th century accelerated the development of modern medicine, the latter being fueled further by advances in technology, research, a better understanding of the human body, and, most recently, the introduction of evidence-based medicine (EBM). The EBM model de-emphasized intuition, unsystematic clinical experience, and pathophysiologic rationale as sufficient grounds for clinical decision-making and stressed the examination of evidence from clinical research. A later EBM model additionally incorporated clinical expertise and the latest model of EBM patients’ preferences and actions. In this review article, we argue that in the era of precision medicine, major EBM principles must be based on (a) the systematic identification, analysis, and utility of big data using artificial intelligence; (b) the magnifying effect of medical interventions by means of the physician–patient interaction, the latter being guided by the physician’s expertise, intuition, and philosophical beliefs; and (c) the patient preferences, since, in healthcare under precision medicine, the patient will be a central stakeholder contributing data and actively participating in shared decision-making. Full article

Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of M^pro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting M^pro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the major subtype, accounting for more than 85% of all lung cancer cases. Recent advances in precision oncology have allowed NSCLC patients bearing specific oncogenic epidermal growth factor receptor (EGFR) mutations to respond well to EGFR tyrosine kinase inhibitors (TKIs). Due to the high EGFR mutation frequency (up to more than 50%) observed particularly in Asian NSCLC patients, EGFR-TKIs have produced unprecedented clinical responses. Depending on their binding interactions with EGFRs, EGFR-TKIs are classified as reversible (first-generation: gefitinib and erlotinib) or irreversible inhibitors (second-generation: afatinib and dacomitinib; third-generation: osimertinib). While the discovery of osimertinib represents a breakthrough in the treatment of NSCLC, most patients eventually relapse and develop drug resistance. Novel strategies to overcome osimertinib resistance are urgently needed. In Asian countries, the concomitant use of Western medicine and traditional Chinese medicine (TCM) is very common. Ganoderma lucidum (Lingzhi) and Coriolus versicolor (Yunzhi) are popular TCMs that are widely consumed by cancer patients to enhance anticancer efficacy and alleviate the side effects associated with cancer therapy. The bioactive polysaccharides and triterpenes in these medicinal mushrooms are believed to contribute to their anticancer and immunomodulating effects. This review presents the latest update on the beneficial combination of Lingzhi/Yunzhi and EGFR-TKIs to overcome drug resistance. The effects of Lingzhi/Yunzhi on various oncogenic signaling pathways and anticancer immunity, as well as their potential to overcome EGFR-TKI resistance, are highlighted. The potential risk of herb–drug interactions could become critical when cancer patients take Lingzhi/Yunzhi as adjuvants during cancer therapy. The involvement of drug transporters and cytochrome P450 enzymes in these herb–drug interactions is summarized. Finally, we also discuss the opportunities and future prospects regarding the combined use of Lingzhi/Yunzhi and EGFR-TKIs in cancer patients. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism and/or reduced uric acid (UA) excretion. Chicory (Cichorium intybus L.), recognized in Traditional Chinese Medicine, is noted for its anti-HUA effects, particularly in enhancing intestinal UA excretion, though the underlying mechanisms remain unclear. Studies indicate that disruptions in gut microbiota and its metabolites are associated with HUA, and chicory has been demonstrated to ameliorate gut microbiota dysbiosis. Among gut microbiota-derived metabolites, butyrate, a short-chain fatty acid, plays a crucial role in gut functions and is linked to HUA. Therefore, butyrate may be pivotal in elucidating the mechanism by which chicory promotes intestinal UA excretion. This study aims to investigate whether chicory facilitates intestinal UA excretion through gut microbiota-derived butyrate and to elucidate the underlying mechanism. We employed an integrated methodology combining network biology with the NHANES database analysis to explore the pathological relationship between butyrate and HUA. Our findings were subsequently validated through animal experiments. We administered chicory to rats with HUA to ascertain whether butyrate serves as the key gut microbiota metabolite through which chicory promotes intestinal UA excretion. Furthermore, we utilized western blotting to assess the expression of core targets within the PPARγ-ABCG2 pathway associated with butyrate under conditions where animals received butyrate supplements and PPARγ agonists separately. The network biology indicates that butyrate is a crucial short-chain fatty acid influencing HUA. Analyses of NHANES data and animal experiments further confirm a significant negative correlation between butyrate and serum uric acid (SUA) levels. HUA rats exhibited intestinal barrier damage, impaired intestinal UA excretion, reduced butyrate levels, and decreased expression of PPARγ and ABCG2 proteins. Intervention with chicory in HUA rats repaired intestinal barrier damage, enhanced intestinal UA excretion, and increased both butyrate levels and the expression of PPARγ and ABCG2 proteins. Similarly, interventions with butyrate supplements or PPARγ agonists in HUA rats effectively promoted intestinal UA excretion and increased the expression of PPARγ and ABCG2 proteins. This study demonstrates that butyrate is a key metabolite produced by gut microbiota, through which chicory regulates gut microbiota to enhance intestinal UA excretion. The underlying mechanism involves the activation of the PPARγ-ABCG2 pathway, which is facilitated by elevated butyrate levels in the intestine. Full article

Background: With an aging population, dementia prevalence is increasing in Korea. Vascular dementia (VaD), often caused by cerebrovascular disease (CVD), is more common in Korea compared to Western countries. Hwanhon decoction, a traditional medicine containing Ephedrae Herba, Armeniacae Semen, and Glycyrrhizae Radix et Rhizoma, is traditionally used for CVD-related loss of consciousness. This study aimed to assess the cognitive improvement and anti-inflammatory effects of Hwanhon decoction extract (HHex) in a mouse model of VaD caused by chronic cerebral hypoperfusion (CCH). Methods: Key pharmacologically active ingredients of Hwanhon decoction were identified using network pharmacology analysis. VaD was induced in C57Bl/6 male mice through bilateral common carotid artery stenosis (BCAS). Mice were divided into sham surgery, BCAS control, low-dose HHex (L-HHex), and high-dose HHex (H-HHex) groups (n = 5/group). After CCH induction, L-HHex or H-HHex was administered thrice weekly for six weeks. Cognitive function, inflammatory markers, and RNA sequencing data were analyzed. Results: HHex administration reduced cognitive impairment and mitigated CCH-induced astrocyte activation. Inflammatory responses mediated by reactive astrocytes were suppressed, and network pharmacology predicted central proteins influencing HHex’s activity. Conclusions: HHex alleviated cognitive dysfunction and reduced inflammation in a VaD mouse model, suggesting its potential as a therapeutic agent for vascular dementia associated with impaired cerebral blood flow. Full article

Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases. Full article

Aletris spicata (Thunb.) Franch. (AS), a traditional edible and medicinal plant for treating asthma, was investigated for its therapeutic mechanisms. Liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis identified 33 compounds in AS. In ovalbumin (OVA)-induced asthmatic mice, AS significantly reduced inflammatory cells (neutrophils, lymphocytes, eosinophils) in bronchoalveolar lavage fluid (BALF) and decreased IL-4, IL-5, IL-13, TNF-α, and serum IgE while increasing IFN-γ. AS alleviated lung and intestinal inflammation, reduced ROS and MDA levels, and enhanced SOD activity. Immunohistochemistry and Western blot revealed AS upregulated Nrf2/HO-1 expression and inhibited NF-κB p65 nuclear translocation. Gut microbiota studies demonstrated AS restored intestinal flora homeostasis by modulating the richness, diversity, and composition. Spearman correlation analysis identified significant relationships between oxidative stress markers, inflammatory cytokines, and specific gut bacteria. These findings indicate that AS mitigates asthma through antioxidant effects (Nrf2/HO-1 pathway), anti-inflammatory actions (NF-κB pathway), and gut microbiota modulation. The study provides a scientific basis for developing AS as a natural anti-asthma treatment or functional food. The multi-target mechanism involving oxidative stress, inflammation, and gut flora highlights AS’s comprehensive therapeutic potential for asthma management. Full article

Cellular therapeutics, encompassing stem cell-based regeneration and engineered immune cell platforms, have demonstrated efficacy in treating degenerative diseases, immune-related diseases, and oncology. However, low engraftment rates and limited long-term efficacy remain critical translational barriers. This review compiled clinical projects on cell therapy in China over the past five years (over 1200 patients across 172 clinical trials) to highlight its rapid development in recent years and illustrate the directions of indications for application. This review also analyzes published clinical achievements all over the world, revealing significant therapeutic improvements in degenerative disorders (40–60% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and oncology (78% ctDNA clearance, p < 0.001)). We propose integrating traditional Chinese medicine (TCM) bioactive compounds to enhance cell viability via C-X-C motif chemokine receptor (CXCR4) upregulation and mitochondrial biogenesis. Despite mechanistic insights, translational barriers include limited TCM validation (72% lacking single-cell omics) and regulatory misalignment. Future efforts should prioritize randomized trials and standardized TCM-cell therapy protocols to bridge discovery and clinical translation. Full article

The flower buds of Magnolia biondii Pamp. (MBP), one of the botanical sources of Xinyi (Flos Magnoliae), are widely used in traditional medicine; however, their potential role in melanoma treatment remains unexplored. In this study, the phytochemical composition, antioxidant activity, and anti-melanoma mechanisms of MBP extracts were systematically investigated. Phytochemical profiling using UHPLC-Q-Exactive Orbitrap MS identified 26 bioactive compounds. The ethanol extract exhibited high total flavonoid and polyphenol contents, correlating with enhanced antioxidant capacity as demonstrated by DPPH and ABTS assays. Network pharmacology analysis highlighted the JAK/STAT signaling pathway, identifying STAT3 and STAT1 as core targets. Western blot analysis confirmed MBP significantly inhibited the phosphorylation of JAK1 and STAT1 in melanoma cells. Connectivity Map (CMap) and network analyses further pinpointed naringenin as a primary active constituent. In vitro assays demonstrated that MBP and naringenin inhibited the proliferation and migration of A375 and B16F10 melanoma cells, while exhibiting relatively low cytotoxicity toward normal keratinocytes. Molecular docking and dynamics simulations revealed strong and stable binding interactions between naringenin and JAK1/STAT1 proteins. These findings collectively support MBP and naringenin as promising candidates for melanoma treatment, providing mechanistic evidence for their targeted activity and laying a foundation for future research and clinical applications. Full article

The distribution of suitable habitats for medicinal plants is affected by climate, soil, land use, and other factors. Arnebiae Radix, an important traditional Chinese medicinal resource in Xinjiang, includes Arnebia euchroma (Royle) I. M. Johnst. and Arnebia guttata Bunge and is at risk of over-exploitation. This study predicted suitable planting areas by integrating habitat and phytochemical suitability using the MaxEnt model and ArcGIS. The AUC values for A. euchroma and A. guttata were 0.977 and 0.952, with TSS values of 0.829 and 0.725, respectively, validating the high accuracy of the prediction model. Under the current scenario, the areas of suitable habitats for A. euchroma and A. guttata were 108,914 and 176,445 km², mainly distributed along the main mountains in Xinjiang. Under future climate scenarios, the suitable habitat area of A. euchroma increased by 11–18%, except in the ssp126-2090s scenario, while the suitable habitat area of A. guttata area decreased by 3–18%. Both species were influenced by land use/land cover and soil available nitrogen content; additionally, A. euchroma was affected by the precipitation in the driest month, and A. guttata by the mean diurnal range. The content of secondary metabolites was positively correlated with habitat suitability, with soil factors contributing 35.25% to the total secondary metabolite content. Their suitable habitats predominantly occur in grasslands (42–82%). As habitat and phytochemical suitability distributions aligned, the eastern and western sides of the northern Kunlun Mountain Pass emerged as key areas for cultivation. This research can provide a scientific foundation for selecting optimal planting regions for the two Arnebia species. Full article

Sinhyotaklisan (SHTLS) is a traditional herbal prescription composed of Lonicerae Flos, Angelicae Gigantis Radix, Astragali Radix, and Glycyrrhizae Radix et Rhizoma, commonly used to treat skin disorders. This study aimed to investigate the therapeutic effects and underlying mechanisms of SHTLS in psoriasis through the network pharmacology analysis and experimental validation in vitro and in vivo. Bioactive compounds and molecular targets were identified using the Traditional Chinese Medicine Systems Pharmacology database, and key protein–protein interaction networks were analyzed via STRING and Cytoscape. In vitro, HaCaT cells were pretreated with SHTLS and stimulated with TNF-α, followed by assessments using proliferation assays, scratch assays, quantitative real-time PCR, and Western blotting. In vivo, the anti-psoriatic effects of SHTLS were evaluated in an imiquimod-induced psoriatic mouse model. A total of 36 key targets were significantly enriched in TNF-α, MAPK, HIF-1α, and IL-17 signaling pathways. SHTLS suppressed TNF-α-induced expression of VEGF and HIF-1α, while upregulating p53, thereby inhibiting keratinocyte hyperproliferation and angiogenesis. It also reduced IL-6 and IL-8 levels and blocked activation of the NF-κB and MAPK pathways. Histological analysis confirmed that SHTLS alleviated psoriatic lesions in vivo. These findings suggest that SHTLS may be a promising therapeutic candidate for psoriasis by targeting hyperproliferation, angiogenesis, and inflammation. Full article