Cerebral infarction is a predominant cause of global disability and mortality, characterized by pathogenesis that includes vascular stenosis, thrombosis, ischemic necrosis, and neuroinflammation. Despite progress in medical science, effective treatments for cerebral infarction are still constrained, prompting the investigation of alternative therapeutic strategies.

The objective of this review is to assess the efficacy of Traditional Chinese Medicine (TCM) as a treatment for cerebral infarction, emphasizing its mechanisms of action, effectiveness, and clinical relevance.

An extensive review of the existing literature regarding the role of TCM in the management of cerebral infarction, encompassing investigations on specific remedies, Chinese medicinal formulations, and contemporary advancements in preparation methodologies.

This review analyzes diverse TCM remedies recognized for their antioxidant, anti-inflammatory, and neuroprotective properties. Furthermore, it examines the synergistic effects of Chinese medicine formulations in modulating inflammation, enhancing blood circulation, and facilitating neural repair. Contemporary technological advancements that improve the accuracy and efficacy of Chinese medicine are also taken into account.

TCM has shown considerable promise in tackling the complex aspects of cerebral infarction. Specific remedies and formulations have demonstrated potential in modulating inflammatory responses, enhancing cerebral blood flow, and promoting neural repair mechanisms. Contemporary formulations have enhanced these effects, facilitating more precise and effective treatment.

While TCM presents a promising multi-faceted and multi-tiered strategy for addressing cerebral infarction, obstacles such as elucidating mechanisms and achieving standardization must be addressed. Continued research and clinical trials are crucial to fully exploit the therapeutic potential of TCM in the management of cerebral infarction.

The lack of effective drugs for treating ischemia-reperfusion injury (IRI) in lung transplants (LTx) remains an issue. Traditional Chinese medicine (TCM) ingredients are promising but poorly studied in LTx. This study aimed to identify potential ingredients and elucidate their mechanisms.

Ten TCM ingredients, including (-)-epigallocatechin-3-gallate, quercetin, wogonin, triptolide, berberine, fisetin, coumestrol, luteolin, nobiletin, and baicalein, were identified as promising candidates using a network pharmacology approach. All the candidates were tested for their ability to improve clamp-induced IRI. Multiple-dose validation was conducted in LTx models, with a focus on baicalein. The pharmacological efficacy of baicalin was verified in an ex-vivo rat lung perfusion model.

All ten TCM ingredients improved clamp-induced IRI. Multiple-dose validation confirmed that baicalein mitigated IRI-induced graft damage and dysfunction. Baicalein reduced the elevated levels of advanced glycation endproducts (AGEs) and their downstream pathogenic effects induced by IRI. Exogenous AGEs counteracted the therapeutic effect of baicalein. Baicalein inhibited AGE formation by modulating glucose oxidation rather than polyol metabolism.

This study provides a laboratory foundation for the use of TCM ingredients in the treatment of IRI in LTx.

Shear-induced platelet activation and aggregation (SIPA) play crucial roles in arterial thrombosis. Piezo1 is a mechanosensitive calcium channel that promotes platelet hyperactivation under pathological high-shear conditions. This study explores the function of platelet Piezo1 in SIPA and arterial thrombosis, and the inhibitory effects and mechanisms of ginsenoside Rb1 on these processes.

Transgenic mice with platelet-specific Piezo1 deficiency (Piezo1ΔPlt) were used to elucidate the role of platelet Piezo1 in SIPA and arterial thrombosis. A microfluidic channel system was employed to assess platelet aggregation, calcium influx, calpain activity, talin cleavage, integrin αIIbβ3 activation and P-selectin expression under shear flow. Cellular thermal shift assay was used to determine binding between Rb1 and Piezo1. Folts-like model in mice was used to evaluate antithrombotic effects of Rb1.

Piezo1 deficiency in platelets reduced platelet activation and aggregation induced by a high shear rate of 4000 s-1 and attenuated arterial thrombosis induced by Folts-like mouse model. Rb1 inhibited SIPA with an IC50 of 10.8 μM. Rb1 inhibited shear-induced Ca2+-dependent platelet activation and aggregation, as well as thrombus formation in Folts-like model in Piezo1fl/fl mice. Rb1 significantly improved thermal stability of Piezo1 in platelets by binding to Piezo1. Treatment of Piezo1ΔPlt mice with Rb1 did not exhibit further inhibitory effects on SIPA and thrombosis.

Platelet Piezo1 is essential for SIPA and arterial thrombosis induced by high shear. Rb1 exerted anti-platelet and anti-thrombotic effects at high shear rates via Piezo1 channels, providing a potential candidate as antiplatelet therapeutic agent.

Insomnia, a prevalent sleep disorder, significantly impacts global health. While Western medications provide temporary relief, their risks of dependency and cognitive impairment have spurred the search for safer alternatives. Traditional Chinese Medicine (TCM) offers a promising approach to treating insomnia by focusing on harmonizing the balance of Yin and Yang and the functions of internal organs. This review explores recent research advances in TCM for insomnia treatment, integrating classical theories with modern scientific understanding of key pathological mechanisms, including neurotransmitter regulation (GABA, monoamines), immune-inflammatory responses, the HPA axis, and interactions with the gut microbiota. Growing clinical evidence supports the effectiveness of classical TCM prescriptions and treatments like acupuncture in improving sleep quality, particularly when combined with Western medications to enhance efficacy and reduce dependency. However, TCM also has its limitations. Future research directions should focus on modernizing TCM applications, addressing comorbidities associated with insomnia, exploring the role of gut microbiota, and optimizing medicinal and edible homologous products. By integrating traditional knowledge with cutting-edge technologies, TCM holds great potential for advancing personalized and effective insomnia treatments globally.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory and learning deficits. Circadian rhythm disruption-induced sleep disruption is frequently observed in AD patients. The Shuangxia Decoction (SXD) comprising Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao), has been effectively used to treate sleep disruption for thousands of years. However, the mechanisms by which SXD treated AD through circadian rhythm-related pathways remain unexplored.

This research sought to determine the efficacy, mechanisms, and active compounds of SXD in AD treatment via an integrative approach.

We conducted a chronic jet lag (CJL) protocol in wild-type (WT) mice and monitored their rest/activity to compare their rest/activity period among WT, CJL, and CJD + SXD groups. In addition, we evaluated the impact of SXD on the cognitive and Aβ burden of 5 × FAD mice by behavioral tests and Thioflavin staining. The underlying pathway analysis of SXD was revealed through transcriptomic and biology experimental validation. The active compounds of SXD were further analyzed using the UPLC-MS, molecular docking, and cellular thermal shift assay (CESTA).

Our study demonstrated a rapid recovery of rest/activity period in CJL mice following SXD treatment. Additionally, SXD treatment alleviated Aβ plaque accumulation, subsequently preserving cognitive behavior and motor ability in 5 × FAD mice. Moreover, SXD significantly enhanced neuronal synaptic plasticity dendritic plasticity in CA1 neurons of 5 × FAD mice. Transcriptomic analysis showed upregulation of the neuroinflammation-related pathway in 5 × FAD mice. Subsequent heatmap analysis indicated a suppression of inflammatory factor secretion (Cd68, Trem2, IL-6, IL-1β, Cxc3r1, Tnf et al.) and an increase of anti-inflammatory factor secretion (IL4, Ccl19, Ccl21a et al.) following SXD treatment in the 5 × FAD mice. Meanwhile, SXD upregulated positive regulators involved in the circadian rhythm like Bmal1 and Clock, and downregulated negative regulators like Nr1d1. Moreover, microglia exhibited an amoeboid morphology characterized by few processes and rounded cell bodies in 5 × FAD mice, whereas the age-matched SXD group maintained microglia with a ramified appearance. Additionally, our study identified 20 major components of SXD and identified 3-(3,4-Dihydroxyphenyl) lactic acid, Salviaflaside, and Ilexhainanoside D for further molecular docking with REV-ERBα (NR1D1), a commonly used circadian target. Salviaflaside further showed a strong bind with REV-ERBα via CESTA.

Our findings indicate that SXD may rescue circadian rhythm in 5 × FAD mice through specifically binding to REV-ERBα in microglia to activate the BMAL1/CLOCK pathway, thus inhibiting transcription of inflammatory factors, contributing to alleviating neuroinflammation and impeding AD progression. Our results offer a scientific foundation for developing SXD-based therapies in the early stage of AD, where sleep disruption precedes cognitive decline, offering potential leads for clinical trials to improve sleep quality thus delaying neurodegeneration in AD patients.

Hyperlactatemia is intimately correlated with severity and poor prognosis of patients with sepsis. However, little experimental evidence on this process is known. We report here that lactate dehydrogenase B (LDHB), the glycolytic enzyme that catalyzes conversion of lactate to pyruvate, is transcriptionally downregulated in blood samples of hyperlactatemic patients, while mice receiving lactate injection have reduced LDHB activity in liver and kidney. LDHB knockout (Ldhb-/-) mice with hyperlactatemia are vulnerable to lethality, hypotension and vascular leakage. The hyperlactatemic Ldhb-/- mice develop severe liver and kidney injuries accompanied by increased hepatic and renal SLC16A1 abundance but unaltered morphology. Pharmacological targeting of SLC16A1 with AZD3965 in Ldhb-/- mice rescues the hyperlactatemia-induced lethality, liver and kidney injuries. Loss of LDHB renders hyperlactatemia, lethality, vascular leakage, liver and kidney injuries in response to abdominal sepsis. AZD3965 treatment partially abrogates liver and kidney injuries of septic Ldhb-/- mice without affecting necrosis. Blockade of necroptosis significantly protects Ldhb-/- mice against septic liver and kidney injuries, enabling a compensation towards the therapeutic efficacy of AZD3965. Our study together unearth the coordination of hyperlactatemia and necroptosis in septic liver and kidney injuries in the context of LDHB deficiency, and support further investigation of combined targeting SLC16A1 and necroptosis for clinical treatment of sepsis with low LDHB activity.

Transforming growth factor-β-activated kinase 1 binding protein 2 (TAB2) plays a vital role in inflammatory pathways. It has also been considered a potential target for the enhancement of the the antiestrogen effects. Previous evidence has indicated that TAB2 gene variants are associated with several diseases, whereas their potential correlation with endometrial cancer (EC) is unclear. This study aims to initially explore the association between TAB2 gene polymorphisms (rs237028 /AG, rs521845 T/G, and rs652921 T/C) and EC.

Polymerase chain reaction-restriction fragment length polymorphism was applied to determine the genotype composition and the allele frequencies of TAB2 gene variant polymorphisms in 270 EC patients and 294 healthy controls.

The G allele of rs521845 was related to the increase of EC risk [p=0.08, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.56-0.91]. Moreover, EC risk was associated with rs521845 in different genetic models (p=0.017, OR: 0.63, 95% CI: 0.44-0.91 in the codominant model; p=0.0051, OR: 0.61, 95% CI: 0.43-0.87 in the dominant model). For rs237028, the percentage of AG genotype in patients with highly differentiated tumours (G1) was significantly higher than that in moderately, poorly differentiated patients (G2/G3) (p=0.031, OR: 0.77, 95% CI: 0.45-1.30).

Our results showed that the rs521845 polymorphism of TAB2, was associated with EC risk, suggesting that TAB2 may play a crucial role in EC prognosis.

We tried to define the association of adverse cardiovascular (CV) events, such as CV death and all-cause death among patients with heart failure (HF) and/or atrial fibrillation (AF) receiving traditional Chinese medicine (TCM) or not. We used data from the Taiwan National Health Insurance Research Database in a retrospective cohort study using propensity scoring (PS) matching. We matched 54,859 and 18,307 patients each to the treatment vs. non-treatment group and found a significantly decreased risk of adverse CV events after PS score matching, suggesting that TCM reduces the risk of these adverse outcomes. Compared to HF patients without AF in non-TCM user, HF patients without AF in TCM user and HF patients with AF in TCM user had decreased risk of CV death by 0.50 times (95% CI 0.49, 0.52) and 0.84 times (95% CI 0.49,0.52), respectively. HF patients without AF in TCM user and HF patients with AF in TCM user had decreased risk of all-cause death relative to HF patients without AF in non-TCM user by 0.53 times (95% CI 0.52, 0.54) and 0.74 times (95% CI 0.72,0.76), respectively. The results said that there is significant reduction of decrease in risk of CV death and all death among the patients receiving TCM, especially those without AF.

Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia-reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I-V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission-fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes.

Intestinal ischemia-reperfusion (II/R) injury is a common clinical emergency with high morbidity and mortality. Given the absence of efficacious prophylactic and therapeutic interventions and specific drugs, sustained efforts are essential to develop new targeted drugs. Corilagin, a naturally polyphenolic tannic acid widespread in longan, rambutan and many other edible economic crops with medicinal properties in China, is of interest due to its multiple bioactivities, including the potential to mitigate II/R injuries. Nevertheless, a clear understanding of its molecular targets and the intricate mechanisms against II/R injury remains obscure and requires further elucidation.

This study aimed to investigate corilagin's pharmacological impact and molecular mechanism for II/R injury.

An animal II/R model was established by clamping superior mesenteric artery (SMA), and the therapeutic efficacy of corilagin against II/R was evaluated by biochemical and pathological analysis. Next, integrated transcriptomic and proteomic analyses was performed to identify key targets. Moreover, endoplasmic reticulum stress (ERS) damage was respectively observed by transmission electron microscope (TEM), immunohistochemistry, TUNEL, flow cytometry and western blotting (WB). Finally, molecular docking, molecular dynamics (MD) simulation, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays were utilized to assess the interaction between corilagin and binding immunoglobulin protein (Bip, Grp78 or Hspa5), and co-IP assay was conducted to investigate the interaction between Bip and its substrate proteins.

Corilagin exhibited robust protection against II/R injuries, effectively alleviating intestinal tissue damage and oxidative stress induced by II/R. The modulation of ERS as a potential regulatory mechanism was investigated through an integrated transcriptomic and proteomic analysis, identifying Bip as a key target contributing to corilagin's protective effects. Further experimental evidence using molecular docking, MD simulation, CETSA, and DARTS assays confirmed the potentially direct interaction of corilagin with Bip. This interaction promoted the ubiquitin-dependent degradation of the Bip-substrate complex, thereby suppressing ERS-related signalling pathways, including the IRE1 branch, PERK branch, and ATF6 branch, to alleviate tissue damage.

This study confirmed that corilagin could selectively bind to Bip, facilitating its ubiquitin-dependent recognition and degradation, thereby inhibiting severe endoplasmic reticulum stress signalling and alleviating II/R injury. A detailed mechanistic insight into the action mode of corilagin had been proposed, supporting its potential usage as an ERS inhibitor.

Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of β cells.

We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used.

The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 μg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin-eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining.

28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic β-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKβ/AMPK pathway.

The present study findings show that JTTF may protects β-cells by inhibiting the CaMKKβ/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM.

The liver, a complex parenchymal organ, possesses a distinctive microcirculatory system crucial for its physiological functions. An intricate interplay exists between hepatic microcirculatory disturbance and the manifestation of pathological features in diverse liver diseases. This review updates the main characteristics of hepatic microcirculatory disturbance, including hepatic sinusoidal capillarization, narrowing of sinusoidal space, portal hypertension, and pathological angiogenesis, as well as their formation mechanisms. It also summarized the detection methods for hepatic microcirculation. Simultaneously, we have also reviewed the characteristics of microcirculatory disturbance in diverse liver diseases such as acute liver failure, hepatic ischemia-reperfusion injury, viral hepatitis, non-alcoholic fatty liver disease, hepatic fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Finally, this review also summarizes the advancement in hepatic microcirculation attributed to traditional Chinese medicine (TCM) and its active metabolites, providing novel insights into the application of TCM in treating liver diseases.

Liver ischemia-reperfusion injury (LIRI) commonly occurs in liver resection, liver transplantation, shock, and other hemorrhagic conditions, resulting in profound local and systemic effects via associated inflammatory responses and hepatic cell death. Hepatocyte death is a significant component of LIRI and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of programmed cell death (PCD), necroptosis, ferroptosis, pyroptosis, autophagy, NETosis, and parthanatos have been shown to be involved in LIRI. Understanding the mechanisms underlying cell death following LIRI is indispensable to mitigating the widespread effects of LIRI. Here, we review the roles of different PCD and discuss potential therapy in LIRI.

Chronic coronary syndrome (CCS) has always been controversial in its therapeutic strategy. Although invasive treatment and optimal medication therapy (OMT) are the most commonly used treatments, doctors continue to debate the best strategy. However, traditional Chinese medicine (TCM) for CCS is effective clinically.

To identify potentially eligible observational and experimental studies, we searched Pubmed, the Web of Science, and the China National Knowledge Internet. To be eligible, studies had to report with end-of treatment outcomes, such as major adverse cardiac events (MACE), deaths from myocardial infarctions (MI), all-cause mortality, angina, cardiac mortality, the effectiveness rate of electrocardiographs, and the reduction rate of the Nitroglycerin tablets. Risk differences (RDs) and 95 % confidence intervals (95 % CIs) were calculated based on random-effects models or fixed-effects models. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers.

In Section 1 (13 studies, involving 17,287 patients), showed no significant difference between invasive treatment and medication treatment in MACE (RD = -0.04, 95% CI = -0.08 to 0.00, I2 = 76.4 %), all-cause mortality (RD = -0.01, 95%CI = -0.022 to 0.01, I2 = 73.44 %), MI (RD = 0.00, 95%CI = -0.00 to 0.01, I2 = 0.00 %) and cardiac mortality (RD = 0.00, 95 %CI = -0.01 to 0.01, I2 = 34.9 %). In Section 2 (21 studies, including 1820 patients), compared with WM treatment, TCM + WM treatment increased ECG effectiveness by 18 %, angina effectiveness by 20 %, and stopping or reducing Nitroglycerin tablets by 20 %. In Section 3 (25 studies, including 2859 patients) showed that TCM revealed a better electrocardiogram effective rate (RD = 0.10, 95 %CI = 0.05 to 0.14, I2 = 44.7 %) and angina effective rate (RD = 0.12, 95 %CI = 0.09 to 0.15, I2 = 44.9 %). We identified that TCM treatment properties of "Circulating blood and transforming stasis" and application of warm/heat-properties medicines were frequently used in CCS treatment.

TCM treatment has shown superior beneficial cardioprotective in CCS therapy strategy, among which "Circulating blood and transforming stasis" and the application of warm/heat-properties medicine are its characteristics.

Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed. The infiltration of inflammatory cells and production of inflammatory mediators in the liver tissue were determined by immunofluorescence and immunohistochemical staining. The protein levels of toll-like receptor 4 (TLR4) and related proteins such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), p65, and p38 were detected by western blotting. The results showed that plasma aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte apoptosis, oxidative stress, and inflammatory cell infiltration significantly increased in HIRI mice. Piperine pretreatment notably repaired liver function, improved the histopathology and apoptosis of liver cells, alleviated oxidative stress injury, and reduced inflammatory cell infiltration. Further analysis showed that piperine attenuated tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-κB in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-κB signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.

The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved.

Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels.

AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP.

AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.

Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots.

First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content.

The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-β-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.

Chrysin is a natural flavonoid with powerful neuroprotective capacity. Cerebral ischemia/reperfusion injury (CIRI) is associated with oxidative stress and ferroptosis. Hypoxia-inducible factor 1α (HIF-1α) and ceruloplasmin (CP) are the critical targets for oxidation reactions and iron transport. But the regulatory mechanism between them is still unclear. Transient middle cerebral artery occlusion (tMCAO) model in rats and oxygen and glucose deprivation/re-oxygenation (OGD/R) model in PC12 cells were applied. Pathological tissue staining and biochemical kit were used to evaluate the effect of chrysin. The relationship between HIF-1α and CP was verified by transcriptomics, qRT-PCR and Western blot. In CIRI, HIF-1α/CP loop was discovered to be the regulatory pathway of ferroptosis. CIRI led to activation and nuclear translocation of HIF-1α, which promoted CP transcription and translation, and downstream ferroptosis. Inhibition of HIF-1α had opposite effect on CP and ferroptosis regulation. Overexpression of CP increased the expression of HIF-1α, nevertheless, inhibited the nuclear translocation of HIF-1α and alleviated CIRI. Silencing CP promoted HIF-1α elevation in nucleus and aggravated CIRI. Mechanistically, chrysin restrained HIF-1α nuclear translocation, thereby inhibiting CP transcription and translation, which in turn reduced downstream HIF-1α expression and mitigated ferroptosis in CIRI. Our results highlight chrysin restrains ferroptosis in CIRI through HIF-1α/CP loop.

Hepatic Ischemia-Reperfusion Injury (HIRI) is a major complication in liver transplants and surgeries, significantly affecting postoperative outcomes. The role of mitophagy, essential for removing dysfunctional mitochondria and maintaining cellular balance, remains unclear in HIRI.

To unravel the role of mitophagy-related genes (MRGs) in HIRI, we assembled a comprehensive dataset comprising 44 HIRI samples alongside 44 normal control samples from the Gene Expression Omnibus (GEO) database for this analysis. Using Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE), we pinpointed eight pivotal genes and developed a logistic regression model based on these findings. Further, we employed consensus cluster analysis for classifying HIRI patients according to their MRG expression profiles and conducted weighted gene co-expression network analysis (WGCNA) to identify clusters of genes that exhibit high correlation within different modules. Additionally, we conducted single-cell RNA sequencing data analysis to explore insights into the behavior of MRGs within the HIRI.

We identified eight key genes (FUNDC1, VDAC1, MFN2, PINK1, CSNK2A2, ULK1, UBC, MAP1LC3B) with distinct expressions between HIRI and controls, confirmed by PCR validation. Our diagnostic model, based on these genes, accurately predicted HIRI outcomes. Analysis revealed a strong positive correlation of these genes with monocytic lineage and a negative correlation with B and T cells. HIRI patients were divided into three subclusters based on MRG profiles, with WGCNA uncovering highly correlated gene modules. Single-cell analysis identified two types of endothelial cells with different MRG scores, indicating their varied roles in HIRI.

Our study highlights the critical role of MRGs in HIRI and the heterogeneity of endothelial cells. We identified the macrophage migration inhibitory factor (MIF) and cGAS-STING (GAS) pathways as regulators of mitophagy's impact on HIRI. These findings advance our understanding of mitophagy in HIRI and set the stage for future research and therapeutic developments.

Diabetes mellitus (DM) is one of the fastest-growing diseases worldwide; however, its pathogenesis remains unclear. Complications seriously affect the quality of life of patients in the later stages of diabetes, ultimately leading to suffering. Natural small molecules are an important source of antidiabetic agents.

Astragaloside IV (AS-IV) is an active ingredient of Astragalus mongholicus (Fisch.) Bunge. We reviewed the efficacy and mechanism of action of AS-IV in animal and cellular models of diabetes and the mechanism of action of AS-IV on diabetic complications in animal and cellular models. We also summarized the safety of AS-IV and provided ideas and rationales for its future clinical application.

Articles on the intervention in DM and its complications using AS-IV, such as those published in SCIENCE, PubMed, Springer, ACS, SCOPUS, and CNKI from the establishment of the database to February 2022, were reviewed. The following points were systematically summarized: dose/concentration, route of administration, potential mechanisms, and efficacy of AS-IV in animal models of DM and its complications.

AS-IV has shown therapeutic effects in animal models of DM, such as alleviating gestational diabetes, delaying diabetic nephropathy, preventing myocardial cell apoptosis, and inhibiting vascular endothelial dysfunction; however, the potential effects of AS-IV on DM should be investigated.

AS-IV is a potential drug for the treatment of diabetes and its complications, including diabetic vascular disease, cardiomyopathy, retinopathy, peripheral neuropathy, and nephropathy. In addition, preclinical toxicity studies indicate that it appears to be safe, but the safe human dose limit is yet to be determined, and formal assessments of adverse drug reactions among humans need to be further investigated. However, additional formulations or structural modifications are required to improve the pharmacokinetic parameters and facilitate the clinical use of AS-IV.

Intestinal ischemia-reperfusion (I/R) is a multifaceted pathological process, and there is a lack of clear treatment for intestinal I/R injury. During intestinal I/R, oxidative stress and inflammation triggered by cells can trigger a variety of cell death mechanisms, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. These cell death processes can send a danger signal for the body to be damaged and prevent intestinal I/R injury. Therefore, identifying key regulatory molecules or markers of these cell death mechanisms when intestinal I/R injury occurs may provide valuable information for the treatment of intestinal I/R injury. This paper reviews the regulatory molecules and potential markers that may be involved in regulating cell death during intestinal I/R and elaborates on the cell death mechanism of intestinal I/R injury at the molecular level to provide a theoretical basis for discovering new molecules or markers regulating cell death during intestinal I/R injury and provides ideas for drug development for the treatment of intestinal I/R injury.

Salvia miltiorrhiza (Salvia miltiorrhiza) root, as a traditional herb, is widely applied to pharmacotherapy for vascular system disease. In this study, we elucidate the therapy mechanism of Salvia miltiorrhiza by using a model of hindlimb ischemia. Blood perfusion measurement showed that intravenous administration of the Water Extract of Salvia miltiorrhiza (WES) could facilitate damaged hindlimb blood flow recovery and blood vessel regeneration. In vitro mRNA screen assay in cultured human umbilical vein endothelial cells (HUVECs) show that WES induced increased NOS3, VEGFA, and PLAU mRNA levels. Endothelial NOS (eNOS) promotor reporter analysis revealed that WES and the major ingredients danshensu (DSS) could enhance eNOS promoter activity. Additionally, we found that WES and its ingredients, including DSS, protocatechuic aldehyde (PAI), and salvianolic acid A (SaA), promoted HUVECs growth by the endothelial cell viability assays. A mechanistic approach confirmed that WES augments HUVECs proliferation through the activation of extracellular signal-regulated kinase (ERK) signal pathway. This study reveals that WES promotes ischemic remodeling and angiogenesis through its multiple principal ingredients, which target and regulate multiple sites of the network of the blood vessel endothelial cell regenerating process.

Liver ischemia/reperfusion (I/R) injury commonly occurs after various liver surgeries. Adelmidrol, an N- palmitoylethanolamide analog, has anti-inflammatory, anti-oxidant, and anti-injury properties. To investigate whether adelmidrol could reduce liver I/R injury, we established a mouse of liver I/R injury and an AML12 cell hypoxia-reoxygenation model to perform experiments using multiple indicators. Serum ALT and AST levels, and H&E staining were used to measure liver damage; MDA content, superoxide dismutase and glutathione activities, and dihydroethidium staining were used to measure oxidative stress; mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, MCP-1, and Ly6G staining were used to measure inflammatory response; and protein expression of Bax, Bcl-2, C-caspase3, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were used to measure apoptosis. The experimental results showed that adelmidrol reduced liver I/R injury. In addition, adelmidrol pretreatment elevated AML12 cell activity and reduced I/R-and H/R-induced apoptosis, inflammatory injury, and oxidative stress. ML385, an inhibitor of nuclear factor erythroid2-related factor 2 (Nrf2), reverses liver I/R injury attenuated by adelmidrol. These results suggest that adelmidrol ameliorates liver I/R injury by activating the Nrf2 signaling pathway.

Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.

The therapeutic effects of traditional Chinese medicine (TCM) involve intricate interactions among multiple components and targets. Currently, computational approaches play a pivotal role in simulating various pharmacological processes of TCM. The application of network analysis in TCM research has provided an effective means to explain the pharmacological mechanisms underlying the actions of herbs or formulas through the lens of biological network analysis. Along with the advances of network analysis, computational science has coalesced around the core chain of TCM research: formula-herb-component-target-phenotype-ZHENG, facilitating the accumulation and organization of the extensive TCM-related data and the establishment of relevant databases. Nonetheless, recent years have witnessed a tendency toward homogeneity in the development and application of these databases. Advancements in computational technologies, including deep learning and foundation model, have propelled the exploration and modeling of intricate systems into a new phase, potentially heralding a new era. This review aims to delves into the progress made in databases related to six key entities: formula, herb, component, target, phenotype, and ZHENG. Systematically discussions on the commonalities and disparities among various database types were presented. In addition, the review raised the issue of research bottleneck in TCM computational pharmacology and envisions the forthcoming directions of computational research within the realm of TCM.

Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.

Cerebral ischaemia‒reperfusion (I/R) frequently causes late-onset neuronal damage. Breviscapine promotes autophagy in microvascular endothelial cells in I/R and can inhibit oxidative damage and apoptosis. However, the mediation mechanism of breviscapine on neuronal cell death is unclear.

First, transcriptome sequencing was performed on three groups of mice: the neuronal normal group (Control group), the oxygen-glucose deprivation/ reoxygenation group (OGD/R group) and the breviscapine administration group (Therapy group). Differentially expressed genes (DEGs) between the OGD/R and control groups and between the Therapy and OGD/R groups were obtained by the limma package. N6-methyladenosine (m6A) methylation-related DEGs were selected by Pearson correlation analysis. Then, prediction and confirmation of drug targets were performed by Swiss Target Prediction and UniProt Knowledgebase (UniProtKB) database, and key genes were obtained by Pearson correlation analysis between m6A-related DEGs and drug target genes. Next, gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA) were used to obtain the pathways of key genes. Finally, a circRNA-miRNA‒mRNA network was constructed based on the mRNAs, circRNAs and miRNAs.

A total of 2250 DEGs between the OGD/R and control groups and 757 DEGs between the Therapy and OGD/R groups were selected by differential analysis. A total of 7 m6A-related DEGs, including Arl4d, Gm10653, Gm1113, Kcns3, Olfml2a, Stk26 and Tfcp2l1, were obtained by Pearson correlation analysis. Four key genes (Tfcp2l1, Kcns3, Olfml2a and Arl4d) were acquired, and GSEA showed that these key genes significantly participated in DNA repair, e2f targets and the g2m checkpoint. IPA revealed that Tfcp2l1 played a significant role in human embryonic stem cell pluripotency. The circRNA-miRNA‒mRNA network showed that mmu_circ_0001258 regulated Tfcp2l1 by mmu-miR-301b-3p.

In conclusion, four key genes, Tfcp2l1, Kcns3, Olfml2a and Arl4d, significantly associated with the treatment of OGD/R by breviscapine were identified, which provides a theoretical basis for clinical trials.

Acute Lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury that can lead to acute respiratory distress syndrome (ARDS) a fatal illness for there is no specific therapy. The semisynthetic artemisinin Artesunate (Art) extracted from Artemisia annua has been found lots of pharmaceutical effects such as anti-malaria, anti-inflammatory, and anti-apoptosis. This study aimed to investigate the effect of Artesunate on intestinal ischemia/reperfusion and the mechanism of how Artesunate works in mice. To establish the II/R model, the C57BL/c mice were subjected to occlude superior mesenteric artery (SMA) for 45 min and 120 min reperfusion, and the lung tissue was collected for examination. Severe lung injury occurred during the II/R, meanwhile Art pretreatment decreased the lung injury score, wet/dry ratio, the level of MDA, MPO, IL-1β, TNFα, CXCL1, MCP-1, the TUNEL-positive cells, Bax and Cleaved-Caspase3 protein expression obviously, and increased the activity of SOD and the expression of Bcl-2. In addition, the protein of P-AKT and HO-1 were upregulated during the Art pretreatment. Then the AKT inhibitor Triciribin and HO-1 inhibitor Tin-protoporphyrin IX were administered which reversed the protein expression of apoptosis, AKT and HO-1. Our study suggests that Art mitigated the II/R induced acute lung injury by targeting the oxidative stress, inflammatory response and apoptosis which is associated with the activating of AKT and HO-1, providing novel insights into the therapeutic candidate for the treatment of II/R induced acute lung injury.

Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated.

The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation.

In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting.

A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed.

SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.

The progression of neurological diseases is mainly attributed to oxidative stress, apoptosis, inflammation, and trauma, making them a primary public concern. Since no drugs can stop these neurological disorders from happening, active phytochemical intervention has been suggested as a possible treatment. Among the several phytochemicals being studied for their potential health advantages, tanshinone-IIA (Tan-IIA ) stands out due to its wide range of therapeutic effects. Tan-IIA, derived from the Salvia miltiorrhiza plant, is a phenanthrenequinone. The pharmacological characteristics of Tan-IIAagainst various neurodegenerative and neuropsychiatric illnesses have led researchers to believe that the compound possesses neuroprotective potential. Tan-IIA has therapeutic potential in treating neurological diseases due to its capacity to cross the blood-brain barrier and its broad range of activities. In treating neurological disorders, Tan-IIA has been shown to have neuroprotective effects such as anti-apoptotic, anti-inflammatory, BBB protectant, and antioxidant properties. This article concisely summarises the latest scientific findings about the cellular and molecular aspects of Tan-IIA neuroprotection in relation to various neurological diseases. The results of preclinical studies on Tan-IIA provide insight into its potential application in future therapeutic development. This molecule rapidly establishes as a prominent bioactive compound for clinical research.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 μM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor β-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

Ischemic stroke is caused by local lesions of the central nervous system and is a severe cerebrovascular disease. A traditional Chinese medicine, Yiqi Tongluo Granule (YQTL), shows valuable therapeutic effects. However, the substances and mechanisms remain unclear.

We combined network pharmacology, multi-omics, and molecular biology to elucidate the mechanisms by which YQTL protects against CIRI.

We innovatively created a combined strategy of network pharmacology, transcriptomics, proteomics and molecular biology to study the active ingredients and mechanisms of YQTL. We performed a network pharmacology study of active ingredients absorbed by the brain to explore the targets, biological processes and pathways of YQTL against CIRI. We also conducted further mechanistic analyses at the gene and protein levels using transcriptomics, proteomics, and molecular biology techniques.

YQTL significantly decreased the infarction volume percentage and improved the neurological function of mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Fifteen active ingredients of YQTL were detected in the brains of rats. Network pharmacology combined with multi-omics revealed that the 15 ingredients regulated 19 pathways via 82 targets. Further analysis suggested that YQTL protected against CIRI via the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway.

We confirmed that YQTL protected against CIRI by inhibiting nerve cell apoptosis enhanced by the PI3K-Akt signaling pathway.

Phospholipid peroxidation signaling was recently revealed as a novel pathological mechanism of coronary heart disease (CHD), and small molecules involved in this redox-metabolic pathway are suggested as the potential anti-CHD drugs. Danlou Tablet (DLT), a famous traditional Chinese medicine (TCM) formula characterized by multi-component and multi-target regulation, is widely used in the clinical treatment of CHD by regulating lipid metabolism. However, little information is available addressing the corresponding pharmacological mechanisms and associated active components of DLT.

To study whether phospholipid peroxidation involves a novel mechanism of DLT for the therapeutic effect of CHD and to explain the essential active components.

Firstly, the HPLC fingerprint was constructed to ensure the controllability of the quality of DLT. Then, a CHD animal model with the characteristics of lipid disorder and myocardial ischemia was established by a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation. The therapeutic effect of DLT was further evaluated based on the results of the rat survival rate, cardiac function, cardiac histopathology, and myocardial ischemia indicators. Correspondingly, whether DLT can regulate the key indicators (ALOX15, GPX4, MDA, GSH, and NADPH) of the phospholipid peroxidation pathway was investigated, and Alox15^-/- mice have been applied to confirm the mechanism of DLT. Finally, the target-mediated characterization strategy based on ALOX15, including the integration of in vivo component characterization, network pharmacology, molecular docking analysis, and activity verification, has been further implemented to reveal the key bio-active components in DLT.

In this study, a high-fat diet (HFD) combined with left anterior descending coronary artery (LAD) ligation was utilized to generate a CHD model, and DLT significantly improved the cardiac dysfunction and reduced the myocardial cell death susceptibility. Further results revealed that DLT reversed the protein expression of ALOX15 and GPX4, the key proteins of phospholipid peroxidation pathways, which subsequently influenced the parameters of phospholipid peroxidation (MDA, GSH, and NADPH). The ALOX15 knockout transgenic animal model confirmed that Alox15^-/- mice lost their cardioprotective effects with DLT, suggesting that DLT exerted therapeutic effects on CHD by regulating ALOX15-mediated phospholipid peroxidation. Finally, the target-mediated characterization strategy identified that daidzein is an active component in DLT against CHD by modulating ALOX15.

Innovatively, ALOX15-mediated phospholipid peroxidation was identified as one of the critical mechanisms of DLT exerting cardioprotective effects. Our findings elucidate a novel mechanism of DLT and provide some new drug evaluation targets and therapeutic strategies for CHD.

Traditional Chinese medicine theory believes that qi deficiency and blood stasis are the key pathogenesis of heart failure with preserved ejection fraction (HFpEF). As a representative prescription for replenishing qi and activating blood, QiShenYiQi dripping pills (QSYQ) has been used for treating heart diseases. However, the pharmacological mechanism of QSYQ in improving HFpEF is not well understood.

The objective of the study is to investigate the cardioprotective effect and mechanism of QSYQ in HFpEF using the phenotypic dataset of HFpEF.

HFpEF mouse models established by feeding mice combined high-fat diet and N^ω-nitro-L-arginine methyl ester drinking water were treated with QSYQ. To reveal causal genes, we performed a multi-omics study, including integrative analysis of transcriptomics, proteomics, and metabolomics data. Moreover, adeno-associated virus (AAV)-based PKG inhibition confirmed that QSYQ mediated myocardial remodeling through PKG.

Computational systems pharmacological analysis based on human transcriptome data for HFpEF showed that QSYQ could potentially treat HFpEF through multiple signaling pathways. Subsequently, integrative analysis of transcriptome and proteome showed alterations in gene expression in HFpEF. QSYQ regulated genes involved in inflammation, energy metabolism, myocardial hypertrophy, myocardial fibrosis, and cGMP-PKG signaling pathway, confirming its function in the pathogenesis of HFpEF. Metabolomics analysis revealed fatty acid metabolism as the main mechanism by which QSYQ regulates HFpEF myocardial energy metabolism. Importantly, we found that the myocardial protective effect of QSYQ on HFpEF mice was attenuated after RNA interference-mediated knock-down of myocardial PKG.

This study provides mechanistic insights into the pathogenesis of HFpEF and molecular mechanisms of QSYQ in HFpEF. We also identified the regulatory role of PKG in myocardial stiffness, making it an ideal therapeutic target for myocardial remodeling.

QiShen YiQi (QSYQ) dropping pill, a component-based Chinese medicine consisting of benefiting Qi (YQ) and activating blood (HX) components, has been reported to exert a beneficial effect on cerebral ischemia-induced stroke. However, its efficacy and pharmacological mechanism on acute thromboembolic stroke is not clear.

This study is to explore the preventative effect and pharmacological mechanism of QSYQ and its YQ/HX components on the formation of platelet-leukocyte aggregation (PLA) in acute thromboembolic stroke.

In vivo thromboembolic stroke model and FeCl₃-induced carotid arterial occlusion models were used. Immunohistochemistry, Western blot, RT-qPCR, and flow cytometry experiments were performed to reveal the pharmacological mechanisms of QSYQ and its YQ/HX components.

In thromboembolic stroke rats, QSYQ significantly attenuated infarct area, improved neurological recovery, reduced PLA formation, and inhibited P-selection (CD62P)/ P-selectin glycoprotein ligand-1 (PSGL-1) expressions. The YQ component preferentially down-regulated PSGL-1 expression in leukocyte, while the HX component preferentially down-regulated CD62P expression in platelet. In carotid arterial thrombosis mice, QSYQ and its YQ/HX components inhibited thrombus formation, prolonged vessel occlusion time, reduced circulating leukocytes and P-selectin expression. PLA formation and platelet/leukocyte adhesion to endothelial cell were also inhibited by QSYQ and its YQ/HX components in vitro.

QSYQ and YQ/HX components attenuated thromboembolic stroke and carotid thrombosis by decreasing PLA formation via inhibiting CD62P/PSGL-1 expressions. This study shed a new light on the prevention of thromboembolic stroke.

Both ligustrazine and tangeretin are usually prescribed in the treatment of cardiovascular diseases, which makes their co-administration possible. The investigation of the interaction between ligustrazine and tangeretin is necessary for the clinical compatibility of their source herbs. This study aimed to investigate the interaction of ligustrazine and tangeretin during their co-administration. The pharmacokinetics of ligustrazine (15 mg/kg) was investigated in the presence of 50, 100, and 150 mg/kg tangeretin in rats with six of each. A single dose of ligustrazine was set as the control. The effect of tangeretin on the in vitro metabolic stability of ligustrazine was also investigated in rat liver microsomes. Tangeretin significantly reduced the system exposure of ligustrazine under all experimental concentrations. Specifically, tangeretin reduced the AUC (from 48.86 ± 12.57 to 41.02 ± 4.85 (50 mg/kg tangeretin), 31.47 ± 5.26 (100 mg/kg tangeretin), and 27.55 ± 9.60 (150 mg/kg) μg/mL × h), MRT (from 7.05 ± 0.26 to 6.33 ± 0.48, 5.53 ± 0.68, and 5.21 ± 1.31 h), C_max (from 7.45 ± 0.44 to 6.03 ± 0.44, 5.24 ± 0.47, and 5.02 ± 0.56 μg/mL), and t_1/2 (from 5.90 ± 1.27 to 4.84 ± 1.19, 3.48 ± 1.33, 3.09 ± 0.62 h) in rats. In vitro, tangeretin also reduced the metabolic stability of ligustrazine behaved as the decreased half-life and increased intrinsic clearance rate. Co-consumption of ligustrazine with tangeretin induced interactions, which shortens the system exposure of ligustrazine. This study provides theoretical guidance for the clinical prescription of ligustrazine- and tangeretin-containing herbs.

Chrysin is a natural flavonoid compound that has antioxidant and neuroprotective effects. Cerebral ischemia reperfusion (CIR) is closely connected with increased oxidative stress in the hippocampal CA1 region and homeostasis disorder of transition elements such as iron (Fe), copper (Cu) and zinc (Zn). This exploration was conducted to elucidate the antioxidant and neuroprotective effects of chrysin based on transient middle cerebral artery occlusion (tMCAO) in rats. Experimentally, sham group, model group, chrysin (50.0 mg/kg) group, Ginaton (21.6 mg/kg) group, Dimethyloxallyl Glycine (DMOG, 20.0 mg/kg) + chrysin group and DMOG group were devised. The rats in each group were performed to behavioral evaluation, histological staining, biochemical kit detection, and molecular biological detection. The results indicated that chrysin restrained oxidative stress and the rise of transition element levels, and regulated transition element transporter levels in tMCAO rats. DMOG activated hypoxia-inducible factor-1 subunit alpha (HIF-1α), reversed the antioxidant and neuroprotective effects of chrysin, and increased transition element levels. In a word, our findings emphasize that chrysin plays a critical role in protecting CIR injury via inhibiting HIF-1α against enhancive oxidative stress and raised transition metal levels.