ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Traditional Chinese medicine (TCM) demonstrates distinctive advantages in disease prevention and treatment. However, analyzing its biological mechanisms through the modern medical research paradigm of "single drug, single target" presents significant challenges due to its holistic approach. Network pharmacology and its core theory of network targets connect drugs and diseases from a holistic and systematic perspective based on biological networks, overcoming the limitations of reductionist research models and showing considerable value in TCM research. Recent integration of network target computational and experimental methods with artificial intelligence (AI) and multi-modal multi-omics technologies has substantially enhanced network pharmacology methodology. The advancement in computational and experimental techniques provides complementary support for network target theory in decoding TCM principles. This review, centered on network targets, examines the progress of network target methods combined with AI in predicting disease molecular mechanisms and drug-target relationships, alongside the application of multi-modal multi-omics technologies in analyzing TCM formulae, syndromes, and toxicity. Looking forward, network target theory is expected to incorporate emerging technologies while developing novel approaches aligned with its unique characteristics, potentially leading to significant breakthroughs in TCM research and advancing scientific understanding and innovation in TCM.
Artificial Intelligence ; Medicine, Chinese Traditional ; Humans ; Network Pharmacology/methods* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Multiomics

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

Drug development remains a critical issue in the field of biomedicine. With the rapid advancement of information technologies such as artificial intelligence (AI) and the advent of the big data era, AI-assisted drug development has become a new trend, particularly in predicting drug-target associations. To address the challenge of drug-target prediction, AI-driven models have emerged as powerful tools, offering innovative solutions by effectively extracting features from complex biological data, accurately modeling molecular interactions, and precisely predicting potential drug-target outcomes. Traditional machine learning (ML), network-based, and advanced deep learning architectures such as convolutional neural networks (CNNs), graph convolutional networks (GCNs), and transformers play a pivotal role. This review systematically compiles and evaluates AI algorithms for drug- and drug combination-target predictions, highlighting their theoretical frameworks, strengths, and limitations. CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions. GCNs provide deep insights into molecular interactions via relational data, whereas transformers increase prediction accuracy by capturing complex dependencies within biological sequences. Network-based models offer a systematic perspective by integrating diverse data sources, and traditional ML efficiently handles large datasets to improve overall predictive accuracy. Collectively, these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy. This review summarizes the application of AI in drug development, particularly in drug-target prediction, and offers recommendations on models and algorithms for researchers engaged in biomedical research. It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Background Organic phosphate flame retardants are emerging environmental pollutants. While there have been multiple toxicities reported following organic phosphate flame retardants exposure, few studies focus on their potential developmental toxicities. It is necessary to elucidate these developmental toxicological effects and underlying mechanisms to improve risk assessments and better protect sensitive populations. Objective To evaluate potential developmental toxicities in early chicken embryos following exposure to triphenyl phosphate (TPhP) or cresyl diphenyl phosphate (CDP), to reveal TPhP and CDP’s capabilities to activate peroxisome proliferator-activated receptor γ (PPARγ) in vivo in an established chicken embryo gene reporter system, and to investigate the roles of PPARγ in TPhP/CDP-induced developmental toxicities with lentivirus-mediated in vivo gene silencing. Methods Firstly, diverse doses of TPhP and CDP were injected into the air sacs of fertilized eggs to assess the development of chicken embryos after 6 d of incubation, and an optimal dose was chosen for subsequent experiments. Subsequently, the report gene system was employed to evaluate the intraembryonic activation of PPARγ by TPhP and CDP. Eventually, PPARγ was silenced using lentivirus, and the embryos were co-treated with TPhP and CDP to further disclose the roles of PPARγ in the observed developmental toxicity. Results Following developmental exposure to TPhP or CDP, significantly lower chicken embryo weights (normalized with egg weights) were observed in the 6 d embryos (10, 30 mg·kg⁻¹ TPhP and 3, 10, 30 mg·kg⁻¹ CDP), indicating that both chemicals have general developmental toxicities and CDP is more potent. Additionally, exposure to CDP also resulted in remarkably increased sagittal brain area (normalized to embryo weights) and decreased sagittal eye area (normalized to embryo weights) (P<0.05), suggesting that CDP has specific developmental neurotoxicity and ocular toxicity. The PPARγ reporter gene experiment results revealed that rosiglitazone (positive control), TPhP, and CDP all significantly activated PPARγ relative to control (P<0.05). The potency order was rosiglitazone > CDP > TPhP. The lentivirus microinjection successfully achieved in vivo silencing of PPARγ in developing chicken embryos, and the estimated silencing efficacy was approximately 55% according to the real-time quantitative polymerase chain reaction (qRT-PCR) results. The in vivo silencing of PPARγ effectively alleviated TPhP or CDP-induced decrease of embryo weights (P<0.05), as well as CDP-induced increase of brain areas and decrease of eye areas (P<0.05). Conclusions Both TPhP and CDP can induce general developmental toxicities in early chicken embryos, and CDP is more potent than TPhP. Meanwhile, CDP can induce specific enlarged brain area and decreased eye area. The observed toxicities are associated with in vivo activation of PPARγ.

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.