This article aims to investigate the inhibitory effect and molecular mechanism of sculponeatin A (STA) on triple negative breast cancer (TNBC). MDA-MB-436 and MDA-MB-468 were selected as cell models. The MTT assay, real-time cell analysis (RTCA), and colony formation assay were used to evaluate the effects of different concentrations of STA on the proliferation of TNBC cells. JC-1 staining and Annexin V-FITC/PI double staining combined with flow cytometry were used to measure the effect of STA on the apoptosis of TNBC cells. Western blot was employed to determine the expression changes of apoptosis-related proteins [cysteinyl aspartate-specific proteinase (caspase)-9, caspase-3, and poly-ADP-ribose polymerase (PARP)] and cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein kinase B (AKT) signaling pathway proteins [CIP2A, AKT, phosphorylated (p)-AKT] in TNBC cells after STA treatment. To clarify the function of CIP2A in the action of STA, a CIP2A overexpression or CIP2A knockdown plasmid was transfected into cells, which were then treated with STA. Cell proliferation, apoptosis, and protein expression changes were evaluated by CCK-8, flow cytometry, and Western blot. Further, RT-qPCR and Western blot both showed that STA significantly downregulated the mRNA and protein levels of CIP2A and the protein level of c-Myc. The overexpression of c-Myc antagonized the downregulating effects of STA on the protein and mRNA levels of CIP2A, while the knockdown of c-Myc enhanced this effect. The drug affinity-responsive target stability (DARTS) assay and microscale thermophoresis (MST) assay confirmed the existence of direct binding between STA and c-Myc protein. The results indicated that STA significantly inhibited the proliferation and colony formation and induced the apoptosis of TNBC cells, manifested by an increased apoptosis rate, downregulated precursor protein expression of caspase-9 and caspase-3, and increased PARP cleavage. STA treatment reduced the p-AKT level but did not affect total AKT. Functionally, the knockdown of CIP2A enhanced the STA effects of inhibiting proliferation and inducing apoptosis, while the overexpression of CIP2A produced antagonistic effects. From a mechanism perspective, STA directly targets and binds to c-Myc to downregulate its expression, thereby inhibiting the transcription and translation of CIP2A and ultimately blocking the c-Myc/CIP2A signaling pathway. In conclusion, STA inhibits the malignant progression of TNBC by targeting the c-Myc/CIP2A signaling axis.

The stem bark of Aquilaria yunnanensis (Thymelaeaceae) is traditionally used to treat cough and asthma in folk medicine. However, its active components have not been reported. In the present study, the chemical constituents of A. yunnanensis stem bark were isolated and identified, and their inhibitory activities against nitric oxide (NO) production in RAW264.7 cells induced by lipopolysaccharide (LPS) were evaluated to clarify the anti-inflammatory components in the stem bark of A. yunnanensis. A total of 22 compounds, including a new norlignan [(±)-1], were isolated from the ethanolic extract of A. yunnanensis stem bark by column chromatography, high-performance liquid chromatography (HPLC), recrystallization, etc. Through chiral separation of (±)-1, (-)-1 and (+)-1 were obtained. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of (-)-1 and (+)-1 were determined to be (-)-(7R, 8S, 8′S)-4-O- (1, 3-dihydroxypropan-2-yl) zhebeiresinol and (+)-(7S, 8R, 8′R)-4-O- (1, 3-dihydroxypropan-2-yl) zhebeiresinol. The known compounds included (±)-zhebeiresinol (2), (+)-syringaresinol (3), (+)-episyringaresinol (4), orcinol (5), orsellinic acid (6), methyl orsellinate (7), 3, 4-dihydroxybenzoic acid (8), lecanoric acid (9), barbatic acid (10), 7β-hydroxy-β-sitosterol (11), β-sitosterol (12), stigmasterol (13), ergosterol peroxide (14), genkwanin (15), pilloin (16), 5-hydroxy-3′, 4′, 7-trimethoxyflavone (17), (-)-epicatechin (18), (-)-epicatechin gallate (19), tectorigenin 2-O-α-L-rhamnopyranoside (20), 2, 3-dihydroxypropyl docosanoate (21), and 1-O-linolenoylglycerol (22). According to the bioassay testing results, compounds 4 and 22 which inhibited NO production with IC₅₀ values of (32.82±1.04) and (18.50±0.95) μmol·L^-1, respectively, exhibited anti-inflammatory activities.

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose specific markers and acquire a mesenchymal phenotype under pathological stimulation, contributing to the occurrence and progression of atherosclerosis (AS). Recent studies have shown that TCM, with its unique advantages of holism and treatment based on syndrome differentiation, can inhibit AS by regulating EndMT-related signaling pathways at multiple levels, through multiple pathways and targets. This article systematically reviews the mechanisms of EndMT in AS, as well as the research progress of TCM monomers and compounds in counteracting AS via EndMT intervention, providing new ideas and a scientific basis for the prevention and treatment of AS with TCM.

Bacopa monnieri, a plant of Scrophulariaceae, has a long history of medicinal use and is recognized as a traditional medicinal herb in multiple countries. Neurological disorders, due to their extensive damage to neural functions, have become a major public health challenge and garnered worldwide attention. In ancient times, B. monnieri was documented for treating cognitive and memory impairments. Recent studies have elucidated its pharmacological mechanisms and therapeutic targets underpinning the neuroprotective effect. However, the molecular mechanisms of its active ingredients have not been systematically summarized. This study is the first to integrate the target sites of its core ingredients across multiple categories of neurological disorders. It summarizes the pharmacological mechanisms of B. monnieri as well as its active ingredients and derivatives in various neurological diseases, which exert neuroprotective effects through multi-target interactions. This paper provides novel strategies for developing botanical drugs targeting diseases like Alzheimer's and epilepsy and aims to offer evidence-based guidance for the development and application of B. monnieri in functional foods, health supplements, and pharmaceuticals.

This study investigates the inducing effects of jatrorrhizine (JAT), a bioactive compound extracted from Coptidis Rhizoma, on the p53-mediated ferroptosis in human colorectal cancer (CRC) cell lines HT29 and HCT116, specifically through the modulation of spermidine/spermine N1-acetyltransferase 1 (SAT1). Cell viability was assessed via the cell counting kit-8 (CCK-8) assay, while the colony formation assay was employed to determine the proliferative capacity. Cell cycle distribution was analyzed by flow cytometry, and mitochondrial membrane potential was evaluated via JC-1 dye. High-throughput RNA sequencing (RNA-seq) was performed to analyze transcriptomic changes in JAT-treated HT29 and HCT116 cells. Lentiviral transduction was utilized to generate SAT1-overexpressing HCT116 and HT29 cell lines, with transfection efficiency confirmed by qPCR. The levels of intracellular Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were quantified via specific commercial assay kits. The protein and mRNA levels of key ferroptosis-related markers: solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), tumor protein p53, and SAT1 were determined by Western blot and qPCR, respectively. The results demonstrated that JAT treatment significantly inhibited both cell viability and proliferation, induced cell cycle arrest, and reduced mitochondrial membrane potential in HCT116 and HT29 cells. RNA-seq results revealed that the KEGG pathways most significantly enriched in JAT-treated cells were protein digestion and absorption, arginine and proline metabolism, glycine, serine and threonine metabolism, and ferroptosis. Notably, the mRNA level of SAT1 in the arginine metabolism pathway was significantly upregulated following JAT treatment. Furthermore, JAT treatment increased the levels of Fe²⁺, ROS, and MDA, while markedly decreasing GSH content in a dose-dependent manner. In addition, the treatment downregulated the protein levels of the ferroptosis inhibitors SLC7A11 and GPX4, and upregulated the expression of the pro-ferroptotic proteins ACSL4, SAT1, and p53. SAT1 overexpression inhibited cell proliferation and activated the p53-mediated ferroptosis signaling pathway. The combination of SAT1 overexpression and JAT treatment (oveSAT1+JAT group) exhibited a synergistic effect, showing superior efficacy over SAT1 overexpression alone (oveSAT1 group). In conclusion, JAT activates the p53-dependent ferroptosis signaling pathway by upregulating the key metabolic enzyme SAT1, which is involved in proline metabolism, thereby inhibiting colorectal cancer cell proliferation.

This study aims to investigate the mechanism by which modified Xiangsha Liujunzi Decoction (M-XS) ameliorates hepatic inflammation in hyperlipidemic mice by regulating the intestinal high-density lipoprotein 3 (HDL3) level. Intestine-specific ATP-binding cassette transporter A1 (ABCA1) knockout mice (Abcal-Villin-cre-Tg) were randomized into 3 groups (n = 8): intestine-specific knockout group (Abcal^△Vill), intestine-specific knockout mice fed a high-fat diet group (Abcal^△Vill + HFD), and intestine-specific knockout with Chinese herbal medicine intervention group (Abcal^△Vill + HFD + M-XS). Littermate control mice were randomly allocated into 3 groups (n = 8): blank group (Abcal^fl/fl), high-fat diet group (Abcal^fl/fl+HFD), and Chinese herbal medicine intervention group (Abcal^fl/fl +HFD+M-XS). Except the Abcal^fl/fl and Abcal^△Vill groups, the other groups were fed a HFD for 10 weeks. Drug administration lasted for 6 weeks at a dose of 23.66 g·kg^-1·d^-1. Serum lipid profiles (four items), hepatic histopathology (HE and oil red O staining), and ileal histopathology (HE staining) were assessed. Ileal HDL3 levels were measured by ELISA, hepatic triacylglycerol (TG) levels by the GPO-PAP method, and co-localization of CD86 and Toll-like receptor 4 (TLR4) in the liver tissue by immunofluorescence. The mRNA levels of hepatic lipopolysaccharide-binding protein (LBP), nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), inhibitor of nuclear factor kappa-B alpha (IκBα), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were determined by real-time PCR. The protein levels of ABCA1 and apolipoprotein A-I (apoA-I) in the ileum, as well as LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β in the liver, were assessed by Western blot. Compared with the Abcal^fl/fl group, the Abcal^fl/fl +HFD group showed increased blood lipid levels, numerous vacuoles and lipid droplets in the liver, shortened intestinal villi, elevated hepatic TG level, reduced levels of HDL3, ABCA1, and apoA-I in the ileum, co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β as well as protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β in the liver (P<0.05). Compared with the Abcal^fl/fl +HFD group, the Abcal^fl/fl +HFD+M-XS group showed decreased blood lipid levels, reduced vacuoles and lipid droplets in the liver, increased intestinal villus length, decreased hepatic TG level, elevated levels of HDL3, ABCA1, and apoA-I in the ileum, weakened co-localization of CD86 and TLR4 in the liver, and down-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β (P<0.05). Compared with the Abcal^fl/fl+HFD group, the Abcal^△Vill+HFD group showed raised blood lipid levels, increased vacuoles and lipid droplets in the liver, elevated hepatic TG level, enhanced co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, TNF-α, and IL-1β (P<0.05). Compared with the Abcal^fl/fl+HFD+M-XS group, the Abcal^△Vill+HFD+M-XS group showed raised blood lipid levels, increased vacuoles and lipid droplets in the liver, elevated hepatic TG level, enhanced co-localization of CD86 and TLR4 in the liver, and up-regulated mRNA levels of LBP, NF-κB, IκBα, IL-6, TNF-α, and IL-1β and protein levels of LBP, p-NF-κB, p-IκBα, IL-6, TNF-α, and IL-1β (P<0.05). In conclusion, modified Xiangsha Liujunzi Decoction ameliorates hepatic inflammation and corrects dyslipidemia by modulating intestinal HDL3 levels.

This study investigated the asthma-alleviating effects of Poria cocos from the perspectives of immuno-inflammation and gut microbiota (GM), providing a theoretical basis for its rational clinical use. Male Balb/c mice were randomly divided into normal, model, positive control (montelukast sodium, 1.5 mg·kg^-1), low-dose P. cocos (0.057 g·kg^-1), medium-dose P. cocos (0.114 g·kg^-1), and high-dose P. cocos (0.227 g·kg^-1) group. Except for the normal group, the other groups were sensitized with ovalbumin (OVA) by intraperitoneal injection combined with nebulization to establish an asthma model, and treated with the corresponding drugs. After modeling, cough and wheezing indices, lung function, and asthma characteristic indicators including immunoglobulin E (IgE), interferon-γ (IFN-γ), interleukin 4 (IL4), and interleukin 10 (IL10) levels were measured. Lung tissue pathology was observed by hematoxylin-eosin (HE) and Masson staining. Quantitative real-time PCR (qRT-PCR) was used to detect airway inflammation-and remodeling-related mRNA levels in lung tissue. Levels of 12 inflammatory factors in serum and bronchoalveolar lavage fluid were detected by multiplex assay. Furthermore, the asthma-alleviating mechanism of P. cocos was analyzed by network pharmacology and GM 16S rRNA sequencing. Results showed that P. cocos reduced cough frequency in asthmatic mice, improved lung function, alleviated pathological damage in lung tissue, decreased serum IgE and IL 4 levels, increased IL 10 and IFN-γ levels, and multi-target regulated related inflammatory factors in serum and alveolar lavage fluid, maintaining immune homeostasis. Network pharmacology predicted that P. cocos exerts its asthma-alleviating effects via inflammation regulation pathways. GM sequencing showed that P. cocos effectively alleviated dysbiosis induced by OVA sensitization, significantly downregulated Muribaculum intestinale and Alistipes inops, and correlation analysis revealed both were positively correlated with pro-inflammatory factors. Therefore, it is speculated that P. cocos restores intestinal microecological homeostasis by reducing levels of M. intestinale and A. inops, decreases pro-inflammatory factor production, blocks the inflammatory cascade, and thereby exerts its asthma-alleviating effects.

This study observed the effect of Chaihu Jia Longgu Muli Decoction on myocardial fibrosis in the rat model of myocardial infarction (MI) and explored the effect of this decoction on ventricular remodeling induced by myocardial fibrosis after MI based on transforming growth factor-β1 (TGF-β1)/Smad proteins (Smads) pathway, aiming to reveal the therapeutic mechanism of this decoction. MI model rats were established by coronary artery ligation and assigned into sham, model, and low-dose, medium-dose, and high-dose (2.09, 4.19, and 8.37 g·kg^-1, respectively) Chaihu Jia Longgu Muli Decoction groups, with 10 rats in each group. Chaihu Jia Longgu Muli Decoction groups were administrated with the decoction at different doses by gavage, and the sham and model groups received an equal volume of distilled water once daily for 4 weeks. The cardiac function of rats after MI was assessed via echocardiography. Myocardial fiber deposition and collagen volume fraction (CVF) were observed by Sirius red staining and Masson staining. Ultrastructure changes of myocardial cells were observed by transmission electron microscopy. Creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), and soluble growth stimulation expressed gene 2 (sST2) levels were measured by ELISA. Western blot was employed to assess the protein levels of collagen Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA) associated with myocardial fibrosis, and TGF-β1, Smad3, and Smad7 associated with the TGF-β1/Smads pathway. Compared with the sham group, the model group had significantly decreased body weight, compromised cardiac function, abnormal ventricular structure, collagen fiber deposition, increased fibrosis area and CVF, seriously damaged ultrastructure of myocardium, a part of mitochondria being swollen or even ruptured, disarrangement and lysis of myofibril, and broken myotome and myofilament with emergence of space. Furthermore, the model group showed risen levels of cTnT, sST2 and CK-MB, obvious myocardial fibrosis, up-regulated protein levels of pro-fibrotic cytokines TGF-β1 and Smad3, down-regulated protein level of the inhibitory cytokine Smad7, and increased expression of myocardial fibrosis-related proteins Col Ⅰ and α-SMA. Compared with the model group, Chaihu Jia Longgu Muli Decoction groups showed increased body weight, improved cardiac function and ventricular structure, reduced collagen fiber deposition, fibrosis area, and CVF, intact ultrastructure of myocardium, normal mitochondrial structure, and well-arranged myofibril and myofilament. In addition, Chaihu Jia Longgu Muli Decoction groups presented declined cTnT, sST2, and CK-MB levels, down-regulated protein levels of TGF-β1 and Smad3, up-regulated protein level of Smad7, and reduced expression of Col Ⅰ and α-SMA. Chaihu Jia Longgu Muli Decoction may reduce excessive deposition of extracellular matrix by regulating the expression of proteins in the TGF-β1/Smads pathway, thereby alleviating myocardial fibrosis and ameliorating ventricular remodeling.

The chemical constituents from Sanguisorba officinalis were isolated and purified through macroporous resin, silica gel, polyamide, ODS, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined by extensive analysis of data from MS, NMR, OR, and calculated NMR and ECD. Twenty-six compounds (1-26) were isolated from the 95% ethanol extract of S. officinalis and identified as (1S, 4S, 5R, 7S, 10R, 11R)-1α, 11, 12-trihydroxy-eudesmane (1), vomifolilol (2), (3S, 5R, 6R, 7E)-3, 5, 6-trihydroxy-7-megastigmen-9-one (3), threo-1, 2-bis- (4-hydroxy-3-methoxyphenyl)-propane-1, 3-diol (4), erythro-1, 2-bis- (4-hydroxy-3-methoxyphenyl)-propane-1, 3-diol (5), phenylformic acid (6), vanillic acid (7), veratric acid (8), 3, 4-dimethoxy-5-hydroxybenzoic acid (9), 4- (1-hydroxy-1-methylethyl)-benzoic acid (10), p-hydrocoumaric acid (11), 4-hydroxyphenethyl alcohol (12), ω-hydroxypropioguaiacone (13), cytosporone V (14), indazole (15), 1H-indole-3-carboxylic acid (16), 7, 8-dimethyl-iso-alloxazine (17), (-)-jasmonic acid (18), 12-hydroxyjasmonic acid (19), (-)-methyl 12-hydroxyjasmonate (20), 5-hydroxyhexan-4-olide (21), (8R^*, 9R^*, 10S^*, 6Z)-trihydroxyoctadec-6-enoic acid (22), (9S, 10R, 11E, 13R)-9, 10, 13-trihydroxyoctadec-11-enoic acid (23), methyl (9S, 10R, 11E, 13R)-9, 10, 13-trihydroxyoctadec-11-enoate (24), pinellic acid (25), and (9E)-8, 11, 12-trihydroxyoctadecenoic acid methyl ester (26). Compound 1 was a new eudesmane-type sesquiterpenoid and named sanguisorbaol M. Compounds 3-5, 8, 10, 14-17, 19-23, 25, and 26 were isolated from Rosaceae for the first time. Compounds 2, 11, 12, 18, and 24 were firstly isolated from the genus Sanguisorba and compound 6 was isolated from S. officinalis for the first time. The inhibitory effects of the isolated compounds on melanin synthesis were evaluated via the 3-isobutyl-1-methylxanthine (IBMX)-induced B16F10 melanoma cell model. The results showed that compounds 1-3 at a concentration of 50 μmol·L^-1 had a significant anti-melanogenic activity.

Epilepsy is a common neurological disorder characterized by refractoriness and recurrence. In China, the prevalence rate is 0.4%-0.7%, with currently over nine million patients, among whom approximately 30% suffer from refractory epilepsy. Although antiepileptic drugs (AEDs) are the mainstay of treatment, they are associated with multi-system adverse reactions and drug resistance issues. In contrast, traditional Chinese medicine (TCM) treatment exhibits significant efficacy with lower toxicity and side effects, and integrated TCM and western medicine treatment can achieve complementary advantages. Studies have shown that integrated therapy demonstrates benefits in various types of epilepsy, including status epilepticus, post-stroke epilepsy, post-traumatic epilepsy, pediatric epilepsy, refractory epilepsy, and epilepsy comorbid with depression and anxiety. It exerts synergistic effects by enhancing AED bioavailability (borneol improves blood-brain barrier permeability), reducing seizure frequency, preventing recurrence, and minimizing western medicine toxicity (Dingxian Decoction decreases digestive/neurological adverse reactions). The underlying mechanisms involve regulating neurotransmitters (modulating glutamate and γ-aminobutyric acid levels) and ion channels (inhibiting sodium/calcium ion channels). In terms of preventive care, TCM plays an important role in preventing epileptic seizures by correcting biased constitutional states. In the future, integrated TCM and western medicine in epilepsy prevention and treatment will move toward individualized treatment, etiological treatment, preventive rehabilitation, and integration of scientific research with clinical practice, forming a three-dimensional development pattern of "technology empowerment, standard guidance, and whole-process management".