Search Results (239)

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article

The genus Scutellaria (Lamiaceae) is a phytochemically rich and medicinally important group of plants. Scutellaria species have been characterized by biologically active flavonoids such as baicalin, baicalein, and wogonin. In the present study, the essential oils of S. angustifolia, S. baicalensis, S. barbata, and S. lateriflora, cultivated in eastern Oregon, were obtained by means of hydrodistillation and analyzed using gas chromatographic methods. We hypothesize that the essential oils have compositions that may play a role in the traditional uses and biological activities of the genus. The major components in S. angustifolia essential oils were germacrene D (32.5–58.3%), (E)-β-caryophyllene (4.9–29.2%), and β-bourbonene (2.8–9.4%). Scutellaria barbata essential oil was dominated by 1-octen-3-ol (59.9%), with lower concentrations of linalool (9.5%) and (2E)-hexenal (5.1%). The major components in the essential oil of S. lateriflora were 1-octen-3-ol (28.3%), acetophenone (24.8%), benzaldehyde (7.5%), limonene (6.0%), (E)-benzalacetone (5.9%), and β-phellandrene (5.1%). The major components of the essential oil of S. baicalensis were 1-octen-3-ol (22.3%), (E)-β-caryophyllene (22.3%), and germacrene D (28.3%). This study demonstrates that Scutellaria can be cultivated in eastern Oregon. Additionally, S. angustifolia essential oil has been characterized for the first time. Full article

Allergic rhinitis (AR) and allergic asthma are chronic airway inflammatory diseases characterized by three phases: sensitization, acute exacerbation, and chronic remodeling. While conventional antiallergic drugs provide symptomatic relief, they often face limitations including drug resistance, side effects, and inability to reverse chronic airway remodeling. Natural products have emerged as promising therapeutic alternatives due to their multi-target effects and safety profiles. This review systematically summarizes natural small molecules targeting distinct pathological mechanisms across the three phases of AR and asthma, introducing a chronopharmacological perspective for stage-specific therapeutic strategies. During sensitization, flavonoids (quercetin, luteolin, apigenin, baicalin) and polyphenols (curcumin, resveratrol) target the epithelial–dendritic cell axis by suppressing alarmin release and blocking dendritic cell maturation. In acute exacerbation, flavonoids (hispidulin, quercetin) and isoquinoline alkaloids (coptisine) exhibit rapid intervention through mast cell stabilization and neurogenic inflammation suppression. In chronic remodeling, stilbenes (resveratrol) and flavones (baicalin, baicalein) reverse established structural changes through TGF-β1/Smad, PTEN/PI3K/AKT, and PDGF-BB/PDGFR-β pathways. Mapping natural compounds to specific disease stages provides a molecular basis for precision medicine approaches. Full article

Bovine viral diarrhea virus (BVDV), a globally persistent pathogen, causes bovine viral diarrhea-mucosal disease (BVD-MD), a contagious bovine disease posing significant pressures on both public health and economic development. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits broad antiviral activities but suffers from poor aqueous solubility and low bioavailability, limiting its therapeutic potential against BVDV. To address this limitation, we developed BA-loaded poly (ethylene gly-col)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (BA-PEG-PLGA NPs). While autophagy and NLRP3 inflammasome activation have been individually implicated in viral pathogenesis, their functional crosstalk during BVDV infection remains uncharacterized. Herein, we evaluated the antiviral efficacy of BA-PEG-PLGA NPs through integrated in vitro and in vivo experiments. We employed quantitative polymerase chain reaction (qPCR), transcriptome sequencing, Western blot analysis, immunofluorescence microscopy, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms by which BA and BA-PEG-PLGA NPs combat bovine viral diarrhea virus (BVDV) infection. We found that both free BA and BA-PEG-PLGA NPs effectively attenuated BVDV replication in vitro and in vivo; notably, the nano-formulation exhibited superior efficacy. Mechanistically, BA and its nano-formulation restored autophagy homeostasis, suppressed ROS overproduction, and blocked NLRP3 inflammasome activation and pyroptotic cell death effects comparable to the specific NLRP3 inhibitor MCC950. These findings establish the autophagy–NLRP3/pyroptosis axis as a critical pathogenic mechanism in BVDV infection and reveal that nano-formulated baicalin represents an antiviral strategy by coordinately targeting this axis. This work not only provides a translatable nanomedicine approach for BVDV control but also expands the mechanistic understanding of flavonoid-based interventions in viral inflammatory diseases. Full article

5-Fluorouracil (5-Fu) remains essential in colorectal cancer (CRC) treatment, but monotherapy causes severe toxicity and faces chemoresistance. Combination regimens are encouraged to improve efficacy and safety. Natural compounds like Baicalin show anti-tumor potential in other gastrointestinal cancers, yet their role in CRC, particularly in overcoming 5-Fu resistance, is underexplored. The combined effect of Baicalin and 5-Fu was evaluated through in vitro functional assays and an in vivo xenograft model. Mechanisms were investigated using Western blot, qPCR, and RNA-seq. Baicalin enhanced 5-Fu to inhibit CRC progression both in vitro and in vivo. Mechanistically, Baicalin enhanced 5-Fu cytotoxicity by activating the MLKL-dependent necroptosis pathway. This study proposes the Baicalin and 5-Fu combination as a novel and potent chemosensitizing strategy for CRC, especially in 5-Fu-resistant cases, and provides a mechanistic rationale for Baicalin as a chemotherapy-enhancing agent. Full article

This study aims to establish an origin identification method for Scutellariae radix that integrates multidimensional quality indicators and machine learning algorithms, enabling accurate and rapid traceability of Scutellariae radix medicinal materials from four production areas: Hebei (HB), Shanxi (SX), Shaanxi (SAX), and Chengde (CD). The study collected a total of 43 batches of Scutellariae radix samples from the aforementioned origins. It systematically measured 12 key quality indicators covering flavonoids, physicochemical parameters, chromaticity values, and biological activity. These specifically include four flavonoid components: baicalin, wogonoside, baicalein, and wogonin; three physicochemical parameters: moisture content, ash content, and alcohol-soluble extract; four chromaticity values: L*, a*, b*, and ΔE; and in vitro anti-inflammatory activity (IC₅₀ value for NO clearance). On the basis of these parameters, in this study there were five machine learning models constructed based on the following algorithms and methods: Random Forest (RF), Extreme Learning Machine (ELM), Backpropagation Neural Network (BP), and Radial Basis Function Neural Network (RBF). A comparative analysis was conducted to evaluate the origin identification performance of each model. The results indicate significant differences (p < 0.05) in the contents of baicalin, wogonoside, L*, a*, b*, ΔE, and alcohol-soluble extract among Scutellariae radix from different origins. The comparative analysis of four machine learning models reveals that RF outperforms ELM, BP, and RBF in multiclass classification, achieving a test accuracy of 75% and consistent precision, recall, and F1-score of 79.17%. In contrast, the three neural networks attain only 66.67% test accuracy, with RBF showing high precision but low recall, ELM delivering moderate performance, and BP performing poorly. These results underscore the strength of ensemble methods like RF in small-sample settings, where they mitigate overfitting and enhance generalization, whereas neural networks struggle with limited data. We therefore recommend RF for deployment under current data constraints and suggest future work should focus on data expansion, especially for under-performing classes, along with hyperparameter tuning to further improve classification. Full article

Background: Glaucoma requires therapies that extend beyond intraocular pressure (IOP)-lowering strategies, and baicalein (BA) offers dual IOP-lowering and neuroprotective potential. This study evaluated the pharmacokinetics of BA and its major metabolite baicalin (BG) in mouse eyes and serum after intravitreal (IVT) and oral administration to determine whether non-invasive oral dosing can achieve IVT-comparable ocular exposure. Methods: BA was administered via IVT injection (100 μM) or oral gavage (20 and 200 mg/kg) in mice, and concentrations of BA and BG in serum and ocular tissues were quantified using a validated ultra-performance liquid chromatography–mass spectrometry (UHPLC/MS) method. Results: After IVT, ocular BA peaked at 331.56 ± 17.75 ng/g at 5 min and declined to 7.13 ± 0.79 ng/g at 4 h, with minimal systemic exposure. Oral administration achieved comparable or higher peak ocular BA levels (380.43 ± 52.85 ng/g at 15 min for 20 mg/kg; 309.70 ± 24.75 ng/g at 5 min for 200 mg/kg), with markedly higher ocular area under the concentration–time curve (AUC: 2455.48 ± 667.83 h·ng/g for 200 mg/kg and 1224.88 ± 751.13 h·ng/g for 20 mg/kg) versus IVT (247.07 h·ng/g). Serum BA and BG peaked at 5 min after oral dosing, with systemic BG exposure substantially exceeding BA. Conclusions: Non-invasive oral BA dosing achieves ocular concentrations comparable to IVT injection, with significantly greater overall exposure and favorable pharmacokinetic profiles. This study provides the first demonstration in mice that non-invasive oral BA administration can replace invasive IVT delivery, establishing a strong rationale for its clinical development in glaucoma and retinal disease management. Full article

Natural compounds have experienced increasing clinical application, but their association with rapid-onset anaphylactoid reactions (ARs) present a significant challenge to their safe use. These ARs, clinically resembling Type I hypersensitivity, are non-IgE-mediated and involve direct mast cell activation, primarily through the human Mas-related G protein-coupled receptor X2 (MRGPRX2). We computationally screened a natural compound library for MRGPRX2 activation. A human MRGPRX2-expressing cell model was established. Cell viability assays (0–80 μM) were performed to determine appropriate drug concentrations. Compared to the controls, Baohuoside I (10 μM), along with Kaempferol-3-O-rutinoside, Epigallocatechin gallate (EGCG), Isochlorogenic Acid B, Baicalin, Andrographolide, Isorhamnetin, and Dehydroandrographolide (all at 20 μM), significantly increased intracellular calcium flux (p < 0.05) and boosted tryptase and β-hexosaminidase secretion (ELISA) (p < 0.05) in mast cells. Furthermore, the degranulation induced by these compounds was inhibited by the MRGPRX2 inhibitor Z3578 at 20 μM. Neutral red staining was employed to observe cellular morphological changes. Specific compounds capable of mediating ARs through MRGPRX2 activation on mast cells were identified. This contributes to safer and more effective drug use by elucidating the potential triggers of ARs. Full article

Major depressive disorder (MDD) is a leading cause of global morbidity and mortality. Although pharmacological treatments are widely used, their effects are often limited, and nearly half of patients show resistance to current antidepressants, including those unresponsive to all available therapies. These challenges highlight the need to better understand the neurobiological mechanisms driving MDD and to develop novel therapeutic strategies, especially those involving natural compounds with multitarget actions. Baicalin, a bioactive flavonoid from Scutellaria baicalensis, exhibits antioxidant, anti-inflammatory, and neuroprotective properties and has recently gained attention for its potential to improve cognitive deficits and mood disorders. In this study, we investigated baicalin’s antidepressant potential and its underlying mechanisms across multiple experimental levels. We found that oral administration of baicalin produced antidepressant-like effects in both naïve mice and those subjected to chronic restraint stress (CRS). CRS impaired hippocampal long-term potentiation (LTP), whereas baicalin restored these synaptic deficits. Importantly, intra-dorsal hippocampal microinjection of the TrkB receptor antagonist ANA-12 abolished baicalin’s antidepressant effects, indicating the involvement of BDNF–TrkB signaling. Baicalin also reduced reactive oxygen species (ROS)/H₂O₂ production in a BDNF-associated manner, demonstrating clear antioxidant activity. Molecular docking further suggested that baicalin binds more effectively to the TrkB receptor than ANA-12, supporting its capacity to activate TrkB-mediated signaling. By integrating in vivo, ex vivo, in vitro, and in silico approaches, our study shows that baicalin exerts robust antioxidant in vitro and antidepressant effects in vivo. These benefits are primarily mediated through activation of BDNF–TrkB signaling, leading to reduced ROS/H₂O₂ accumulation and alleviation of CRS-induced depression-like behaviors. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, in which fibroblast-like synoviocytes (FLSs) serve as the primary effector cells that drive the destruction of joints. Baicalin has previously demonstrated efficacy in significantly ameliorating joint symptoms in rats with CIA. As such, this study aims to investigate its underlying molecular mechanisms and impact on the FLSs of rats with CIA through an integrated proteomics and transcriptomics analysis. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted based on two datasets; it revealed that the retrograde endocannabinoid signaling pathway—associated with susceptibility to RA—is the only one involved in both the signaling and metabolic processes modulated by baicalin. Nineteen differentially expressed proteins (DEPs) downregulated by baicalin comprise seventeen subunits of NADH dehydrogenase and two receptors, glutamate receptor 2 (GRIA2) and γ-aminobutyric acid receptor subunit alpha-5 (GABRA5). Three differential metabolites (DMs) were also affected by baicalin: γ-aminobutyric acid (GABA) and phosphatidylcholine (PC) were upregulated and phosphatidylethanolamine (PE) was downregulated. Our findings suggest that the baicalin-mediated alleviation of joint synovitis is closely related to the upregulation of GABA and PC; downregulation of GRIA2, GABRA5, and PE; and preservation of mitochondrial homeostasis within the retrograde endocannabinoid signaling pathway in FLSs. Full article

The human lifespan has increased dramatically over the last few decades; however, reaching older age increases the risk of age-related diseases and ailments. To extend the healthspan, many have turned to supplements, including plant-based remedies used in traditional medicine, to promote healthy aging. One of these is Scutellaria lateriflora L. (S. lateriflora), native to North America, which has traditionally been used to treat anxiety, stress, and insomnia. However, clinical trials addressing its effects are very limited. Furthermore, plant material is intrinsically complex, and the preparation method affects the composition of extracts. We therefore used Drosophila to test whether S. lateriflora can confer resilience against age-related sleep and mobility deficits, using aqueous (SLAq) and ethanol extracts (SLE). Whereas both SLE and SLAq improved mobility, only SLE reduced sleep fragmentation in older males. By testing several flavonoids present in S. lateriflora, we found that the beneficial effects on mobility were mainly due to baicalin, whereas sleep was improved by a wogonin mix. Since neither the extracts nor the compounds extend the lifespan, this suggests that they improve neuronal health and function and do not generally slow down the aging process. This was supported by our finding that neuronal degeneration was reduced by S. lateriflora (SL) supplementation. Full article

The incidence of kidney diseases has been increasing due to changes in modern lifestyles and the ecological environment. The progression of kidney disease is characterized by ongoing renal damage and a gradual decline in renal function, ultimately leading to end-stage renal disease. The limitations of present medications have brought many disadvantages to patients. Consequently, identifying bioactive molecules has emerged as a critical strategy in the development of novel therapies for kidney diseases, particularly those derived from natural medicinal resources. This review presents a comprehensive analysis of renoprotective effects and underlying mechanisms of the medicinal plant Scutellaria baicalensis Georgi based on evidence retrieved from multiple databases, including Web of Science, PubMed, and CNKI. Flavonoids from S. baicalensis have been demonstrated to have good renoprotective properties by mitigating inflammation and oxidative stress, inhibiting cell apoptosis, reducing renal fibrosis, etc. Baicalein, wogonin, baicalin, and wogonoside are considered as the main bioactive components of the renoprotective effect of S. baicalensis. Further research on candidate molecules derived from S. baicalensis represents a promising strategy for the development of novel therapeutic agents targeting kidney diseases. Full article

α-Zearalenol (α-ZOL), the primary metabolite of zearalenone (ZEN), is a prevalent mycotoxin in agricultural products (e.g., corn, wheat) and poses health risks due to its toxicity. However, strategies to mitigate its toxicity are needed. Therefore, this study aims to determine whether selected polyphenols (quercetin, baicalin, rosmarinic acid, naringenin) can competitively displace α-ZOL from human serum albumin (HSA) and to clarify the interaction mechanisms. The results showed that competitive interactions between α-ZOL, HSA, and the polyphenols were observed. The polyphenols bound HSA more tightly than α-ZOL (higher K_a) and significantly reduced α-ZOL’s K_a, indicating direct competition. Moreover, as evidenced by synchronous fluorescence, the polyphenols altered the microenvironments of tyrosine and tryptophan residues, directly impacting α-ZOL binding. The HPLC-ultrafiltration results revealed that the polyphenols tested competitively displaced α-ZOL from HSA, with the relative potency of quercetin ≈ baicalin > rosmarinic acid > naringenin. Collectively, our competitive binding assays demonstrate that quercetin, baicalin, rosmarinic acid, and naringenin competitively displace α-ZOL from its binding site(s) on HSA. Thus, our study not only suggests a novel mechanism to alleviate the toxicity of ZEN and α-ZOL but also provides a scientific basis for developing dietary interventions against these mycotoxins. Full article

The utilization of agro-byproducts for textile dyeing and finishing is strongly suggested to meet sustainability and cost-efficiency objectives. Despite recently proliferating studies, three major issues hinder the industrialization of such a technique: identifying reasonable bio-resources, ensuring compatibility between agro-byproducts and textile substrates, and achieving satisfactory color depth, functionality, and durability. This research introduces an approach that forms and fixes silver nanoparticles (AgNPs) on silk using three representative flavonoids (FLs)—Quercetin (QUE), Baicalin (BAI), and Rutin (RUT)—through a single-step in situ bio-reduction. Results demonstrate that FLs-synthesized AgNPs@silk generates attractive spectra of hues, varying from pale cream-brown to deep golden-brown. Using an equivalent quantity of FLs, the color intensity of silk descends in QUE-Ag@silk > BAI-Ag@silk > RUR-Ag@silk, due to the decreasing reactivity and binding affinity of FLs to silk. SEM reveals uniformly distributed spherical AgNPs in dimensions between 20 and 40 nm on silk and the dimension inversely correlates with FLs concentration while being directly proportional to silver nitrate. The modified silk exhibits remarkable antimicrobial performance (>98% pathogen elimination) and exceptional wash resistance (>90% reduction both of E. coli and S. aureus after ten cycles of washing). Additionally, the FLs-synthesized AgNPs provide silk with superior UV shielding capability. This study stems from environmental awareness and sustainable production of AgNPs by FLs, ready for developing hygienic and therapeutic textile materials. Full article

Background: Using Huanglian Jiedu decoction (HJD) as a model, this study systematically compares the traditionally prepared combined decoction with mixtures of separately decocted components, focusing on differences in chemical composition, material properties, and transcriptomic responses. Methods: To maintain consistency, both the combined HJD decoction and the single-herb mixture were prepared using a standardized method, and their chemical profiles were analyzed by HPLC and UPLC-MS/MS to identify constituent differences. Physical properties were examined through key parameter measurements and phase behavior analysis, and the integration of chemical and physical data identified the components driving the observed material changes. Transcriptome sequencing compared the two decoction types, highlighting differentially expressed genes and the major regulatory pathways involved. Results: HPLC analysis showed a clear redistribution of components between the two decoction methods, with the combined decoction containing higher levels of alkaloids such as coptisine chloride, epiberberine, palmatine chloride, jatrorrhizine hydrochloride, and phellodendrine chloride, while the single decoction mixture had higher levels of berberine hydrochloride and baicalin. In the combined decoction, the berberine hydrochloride content was 37.04 mg/g, and the baicalin content was 15.57 mg/g; in the single decoction, the berberine hydrochloride content was 41.15 mg/g; in the combined decoction, the baicalin content was 40.07 mg/g. UPLC-MS/MS analysis confirmed clear differences between the two decoctions, mainly in flavonoid and alkaloid compositions. The combined decoction contains 110 flavonoid compounds and 67 alkaloid compounds, while the single decoction contains 100 flavonoid compounds and 80 alkaloid compounds. Physical measurements showed that the combined decoction had higher total dissolved solids, conductivity, and salinity, while the single decoction had higher resistivity. The combined decoction had a TDS of 2480 mg/L, σ of 4.95 ms/cm, S of 0.26%, and ρ of 202 Ω·cm; the single decoction had a TDS of 1190 mg/L, σ of 2.37 ms/cm, S of 0.12%, and ρ of 419 Ω·cm. Phase separation analysis indicated that the combined decoction formed a stable nanoscale phase structure, whereas the single decoction remained unstable. Transcriptome sequencing at various concentrations revealed marked differences in gene expression between the two preparations, reflecting their distinct biological activities. Conclusions: Analysis showed clear differences in chemical composition, physical properties, and gene expression in the combined decoction. Taking Huanglian Jiedu decoction as a representative example, we systematically compared the specific differences between combined and single decoction methods, providing a reference basis for subsequent pharmacodynamic evaluation and clinical application. Full article