Journal of ethnopharmacology最新文献

Ethnopharmacological relevance: The Danshen (root of Salvia miltiorrhiza Bge.) and Shanzha (fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (SD) herb combination is a commonly used traditional Chinese medicine with potential for treating cardiovascular diseases. This study aimed to evaluate the anti-MASLD efficacy of SD and the potential mechanism of synergistic treatment of MASLD with its active ingredients.

Materials and methods: The chemical composition of SD was elucidated using high-resolution mass spectrometry. A mouse model of MASLD was developed to assess therapeutic efficacy of SD. An integrated method, combining network pharmacology and multi-omics, was utilized to explore the anti-MASLD effects and mechanisms of SD. Additionally, molecular docking, Western blotting (WB), and other methodologies were employed to investigate the synergistic intervention mechanisms of SD's active ingredients in MASLD.

Results: SD can substantially mitigate liver lipid accumulation and inflammation in MASLD mice. We identified 92 components in SD, of which 55 were recognized as potential active ingredients. Notably, four chemical constituents-rutin, quercetin, salvianolic acid B, and hyperoside-have been identified as the active compounds responsible for the anti-MASLD effects of SD. Rutin, hyperoside and salvianolic acid B interacts with the Plin-5, facilitating the recruitment of lipid droplets to the mitochondria. Subsequently, salvianolic acid B, rutin and hyperoside activates PPARα, thereby promoting the oxidation of fatty acids. Concurrently, rutin, hyperoside and quercetin modulates Plin-2 to mitigate excessive fatty acid oxidation, thereby reducing the risk of oxidative stress.

Conclusions: Our research preliminarily confirms the anti-MASLD effects and the mechanism of synergistic intervention by SD's active ingredients, providing valuable evidence to support the use of TCM formulae for treating MASLD.

Ethnopharmacological relevance: Atherosclerosis (AS) severely threatens global health, while current therapies exhibit limitations. Recognized as a 'superior-grade' herb in the Shennong Ben Cao Jing, Salvia miltiorrhiza Bunge (Danshen) has been shown in modern studies to protect against cardiovascular diseases.

Aim of the study: The aim of this study was to investigate the therapeutic potential and protective mechanism of pharmacological components of Salvia miltiorrhiza against AS.

Materials and methods: Relevant animal studies were collected from 8 databases, namely, PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, VIP, and SinoMed. Risk of bias of the included studies was evaluated using the SYRCLE's tool. Statistical analysis was performed using R 4.2.0 and Python 3.14.2 software. Machine learning model was trained to predict optimal intervention parameters and was subsequently validated.

Results: A total of 64 studies were included. The pharmacological components of Salvia miltiorrhiza ameliorated atherosclerotic plaque formation and stability, and modulated various biomarkers, including lipid profiles, inflammatory cytokines, oxidative stress indicators, endothelial function markers, as well as matrix metalloproteinases. Machine learning identified an optimal Tanshinone IIA regimen against AS, which was defined as a single dose of 33.18 mg/kg dose over 84 days and demonstrated predictive robustness in validation.

Conclusions: The pharmacological components of Salvia miltiorrhiza attenuate AS by regulating lipid metabolism, anti-inflammatory and antioxidant actions, improving endothelial function, modulating of vascular smooth muscle cells, remodeling extracellular matrix, and regulating programmed cell death. These findings provide translational insights that pave the way for subsequent preclinical and early-clinical studies, pending systematic validation through more rigorous research.

Ethnopharmacological relevance: Gynostemma pentaphyllum, a traditional Chinese medicine with a history of use dating back over 500 years, was described for treating conditions such as heat-clearing and detoxification. Contemporary pharmacopoeias confirm its therapeutic value, including anti-inflammatory, immunomodulatory, and antioxidant effects. Gynostemma pentaphyllum polysaccharides (GPP) are its primary bioactive macromolecules, however, its underlying pharmacological mechanisms in ulcerative colitis (UC) remain unclear.

Aim of the study: This study aimed to elucidate the protective role and mechanisms of GPP in UC.

Materials and methods: The comprehensive structural characterization of GPP was achieved through integrated chromatography coupled with NMR, FT-IR, and SEM analyses. The efficacy and mechanisms of GPP were investigated in a DSS-induced UC mouse model and an LPS-stimulated Caco-2 cell inflammatory model, employing transcriptomic analysis, GeneCards Human Gene Database, 16S rRNA sequencing, and validation in Nrf2^-/- mice.

Results: GPP alleviated UC symptoms by suppressing inflammation, reducing oxidative stress, and improving gut barrier dysfunction. RNAseq and GeneCards identified Nrf2 as a key target, with GPP exerting anti-inflammatory and antioxidant effects via the Nrf2/HO-1 pathway; this efficacy was attenuated in Nrf2^-/- mice. Furthermore, 16S rRNA sequencing revealed that GPP modulated the gut microbiota, increasing the abundance of Firmicutes while decreasing Proteobacteria, thereby helping to re-establish microbial homeostasis.

Conclusions: Collectively, our findings demonstrate that GPP alleviates UC symptoms by activating the Nrf2/HO-1 pathway, reducing ROS levels, subsequently inhibiting NLRP3 inflammasome activation, mitigating oxidative stress, and improving intestinal barrier dysfunction. These findings identify GPP as a promising macromolecule with translational potential for UC.

Ethnopharmacological relevance: In terms of anti-aging, ginseng has the effect of "lightning the body and prolonging the life" since ancient times. Although Panax ginseng Meyer (ginseng) has demonstrated anti-aging associations in experimental studies, clinical validation of its impact on telomere length and nicotinamide adenine dinucleotide (NAD+)/Nicotinamide adenine dinucleotide (NADH) ratio in healthy middle-aged individuals remains lacking.

Aim of the study: Exploratory hypothesis-generating study on the association of ginseng on the telomere lengths and NAD+/NADH ratio of middle-aged adults.

Methods: This study enrolled overweight middle-aged adults aged 45-50 years (Body mass index, BMI >24 kg/m²), involving two cohorts: high-dose short-term (6 g/day, 7 days; n = 20) and low-dose long-term (3 g/day, 28 days; n = 30), then they were followed up at 21 or 28 days after the completion of medication, respectively. Blood samples were collected before and after supplementation, and follow-up period. The primary outcomes: leukocyte telomere length and the NAD⁺/NADH ratio. The secondary outcomes: protection of telomeres 1 (POT1) expression, nicotinamide phosphoribosyltransferase (NAMPT) activities of peripheral blood mononuclear cells (PBMCs), reactive oxygen species (ROS), malondialdehyde (MDA), advanced glycation end-products (AGEs) and lactic acid (LA) levels. and scores on clinical scales [e.g., Pittsburgh sleep quality index (PSQI), Ascertain dementia 8 (AD8), Fatigue scale-14 (FS-14), International index of erectile function-5 (IIEF-5), and Kupperman index)].

Results: The high-dose and low-dose groups showed a significant association with increased telomere length, POT1 expression, NAD+/NADH ratio, and NAMPT activity. The two cohorts also showed a significant association with reduced levels of ROS, MDA, AGEs, and LA, as well as improved scores on all clinical scales. Furthermore, the beneficial effects of the above indicators persisted during the follow-up period.

Conclusions: Ginseng supplementation is associated with telomere elongation and an increased NAD+/NADH ratio in middle-aged adults, and exerts beneficial effects on human overall health by improving potential biomarkers of aging.

Ethnopharmacological relevance: Huangtu Decoction (HTD), a classic formula in TCM, was first documented in the Synopsis of the Golden Chamber and later included in numerous TCM texts. This formula is commonly used to treat various gastrointestinal disorders, including diarrhea, bloody stools, irritable bowel syndrome, and ulcerative colitis (UC).

Aim of the study: This study aimed to explore the therapeutic efficacy and mechanism of HTD in treating Deficiency-Cold Pattern in Ulcerative Colitis (DCP-UC). The focus was on examining whether HTD alleviates colitis symptoms by regulating macrophage polarization via the HIF-1α signaling pathway.

Materials and methods: We established DSS- and rhubarb-induced DCP-UC models in mice, along with an LPS-stimulated RAW264.7 macrophage inflammation model, to evaluate the effects of HTD on colonic injury, inflammatory responses, and macrophage polarization. To verify the central role of macrophages in HTD efficacy, we conducted macrophage depletion experiments in vivo. Additionally, we induced differentiation of M1 and M2-type bone marrow-derived macrophages (BMDMs) and explored the impact of HIF-1α on HTD efficacy by activating and overexpressing HIF-1α.

Results: HTD therapy significantly alleviated colitis symptoms, reduced colonic histopathological damage, and effectively suppressed intestinal inflammation. Concurrently, it decreases M1 macrophage markers and increases M2 markers, suggesting that HTD modulates macrophage polarization. Macrophage depletion experiments indicate that HTD's therapeutic efficacy may depend on macrophages. In vitro BMDM experiments showed that HTD inhibited HIF-1α expression in M1 macrophages, thereby reducing proinflammatory factors. However, overexpression and activation of HIF-1α could reverse this effect, implying that HIF-1α is a potentially crucial target for HTD in regulating intestinal inflammation.

Conclusion: HTD may exert its therapeutic effects by suppressing the HIF-1α signaling pathway, which in turn may promote a phenotypic switch of macrophages from the proinflammatory M1 state to the anti-inflammatory M2 state. These findings suggest that HTD represents a promising potential therapeutic approach for DCP-UC.

Ethnopharmacological relevance: Elephantopus scaber L. (E. scaber) is a heat-clearing and detoxifying traditional Chinese medicine. Clinically, it is used for treating some immuno-inflammatory diseases associated with excessive T cell activation. However, its action and mechanism on T cells are still ambiguous.

Aim of the study: This study aims to investigate the molecular mechanism of the ethanol extract of E.scaber (ESE) in ConA-induced T cell activation models.

Materials and methods: IL-2 transcription and translation levels were determined by RT-qPCR and ELISA. CD4⁺ naïve T cells were sorted using the flow cytometer. Western blot assay was used for determining intracellular protein levels. Cytoplasmic and mitochondrial Ca²⁺ concentrations were measured by fluorometric assays.

Results: ESE not only dampened the proliferation of splenic lymphocytes, but also decreased IL-2 production in ConA-activated T cells without affecting its mRNA stability. It could inhibit the activation of NFAT and NF-κB pathways, showed as impeding the nuclear translocation of NFAT and p65. Regarding the upstream signaling, ESE significantly decreased cytoplasmic Ca²⁺ (Ca²⁺_[c]) level in a model-independent manner. Although it failed to affect plasma membrane Ca²⁺-ATPase, Na⁺/Ca²⁺ exchanger, and mitochondrial Ca²⁺ uptake, it affected sarco/endoplasmic Ca²⁺-ATPase (SERCA) pathway. It also hindered IκBα phosphorylation and subsequent degradation. In vivo, ESE reduced IL-2 levels in local and systemic T cell activation models.

Conclusion: Through inhibiting the activation of SERCA/Ca²⁺_[c]/NFAT and NF-κB pathways, ESE markedly decreased ConA-induced IL-2 production in vitro and in vivo. This study provides not only a modern explanation for the traditional uses of E. scaber, but also a scientific guidance for clinical practice.

Ethnopharmacological relevance: Lonicera japonica Thunb (honeysuckle), a traditional Chinese medicine, has been historically used to clear heat, detoxify, and dispel wind-heat. Modern research has identified various bioactive constituents from honeysuckle, supporting its potential in managing inflammatory and metabolic disorders. However, the anti-hyperuricemic activity and mechanism of its peptide components remain unexplored.

Aim of the study: This study aimed to investigate the anti-hyperuricemic effect of honeysuckle-derived peptides and the underlying mechanisms, with a focus on uric acid production, excretion, and gut microbiota modulation.

Materials and methods: Nine novel peptides were identified from honeysuckle by HPLC-MS/MS and screened through molecular docking against xanthine oxidase (XOD). In vitro XOD inhibition and antioxidant assays were performed. A hyperuricemic mouse model was induced by potassium oxonate and hypoxanthine. Mice were treated with honeysuckle peptides at low, medium, and high doses. Serum biomarkers, renal and ileal histopathology, protein and mRNA expression of PGC-1α/PPARγ/ABCG2 pathway components, and gut microbiota composition (16S rRNA sequencing) were analyzed.

Results: Molecular docking confirmed strong binding between the peptides and XOD. In vitro, honeysuckle peptides significantly inhibited XOD activity and exhibited potent antioxidant capacity. In vivo, peptide treatment effectively reduced serum uric acid, XOD, creatinine, and blood urea nitrogen levels, alleviated renal and intestinal tissue damage, and suppressed inflammatory cytokines. The treatment also significantly upregulated the renal PGC-1α/PPARγ/ABCG2 pathway at both protein and mRNA levels. Furthermore, the peptides restored gut microbial diversity and corrected the Firmicutes/Bacteroidota ratio.

Conclusion: Honeysuckle peptides ameliorate hyperuricemia through a dual mechanism: inhibiting uric acid production by suppressing XOD activity and promoting its renal excretion by activating the PGC-1α/PPARγ/ABCG2 pathway, coupled with restoring gut microbiota homeostasis. This study provides a pharmacological basis for the traditional use of honeysuckle and highlights its peptides as promising candidates for managing hyperuricemia.