Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network.

Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.

Flexible and stretchable polymer optical fibers for chronic brain and vagus nerve optogenetic stimulations in free-behaving animals.

BACKGROUND: Although electrical stimulation of the peripheral and central nervous systems has attracted much attention owing to its potential therapeutic effects on neuropsychiatric diseases, its non-cell-type-specific activation characteristics may hinder its wide clinical application. Unlike electrical methodologies, optogenetics has more recently been applied as a cell-specific approach for precise modulation of neural functions in vivo, for instance on the vagus nerve. The commonly used implantable optical waveguides are silica optical fibers, which for brain optogenetic stimulation (BOS) are usually fixed on the skull bone. However, due to the huge mismatch of mechanical properties between the stiff optical implants and deformable vagal tissues, vagus nerve optogenetic stimulation (VNOS) in free-behaving animals continues to be a great challenge. RESULTS: To resolve this issue, we developed a simplified method for the fabrication of flexible and stretchable polymer optical fibers (POFs), which show significantly improved characteristics for in vivo optogenetic applications, specifically a low Young's modulus, high stretchability, improved biocompatibility, and long-term stability. We implanted the POFs into the primary motor cortex of C57 mice after the expression of CaMKIIα-ChR2-mCherry detected frequency-dependent neuronal activity and the behavioral changes during light delivery. The viability of POFs as implantable waveguides for VNOS was verified by the increased firing rate of the fast-spiking GABAergic interneurons recorded in the left vagus nerve of VGAT-ChR2 transgenic mice. Furthermore, VNOS was carried out in free-moving rodents via chronically implanted POFs, and an inhibitory influence on the cardiac system and an anxiolytic effect on behaviors was shown. CONCLUSION: Our results demonstrate the feasibility and advantages of the use of POFs in chronic optogenetic modulations in both of the central and peripheral nervous systems, providing new information for the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.

Separation of three polar compounds from Rheum tanguticum by high-speed countercurrent chromatography with an ethyl acetate/glacial acetic acid/water system.

The separation of polar compounds by high-speed countercurrent chromatography is still regarded as a challenge. In this study, an efficient strategy for the separation of three polar compounds from Rheum tanguticum has been successfully conducted by using high-speed countercurrent chromatography. X-5 macroporous resin chromatography was used for the fast enrichment of the target compounds. Then, the target fraction was directly introduced into high-speed countercurrent chromatography for separation using ethyl acetate/glacial acetic acid/water (100:1:100, v/v/v) as the solvent system. Consequently, three polar compounds including gallic acid, catechin, and gallic acid 4-O-ß-d-(6'-O-galloyl) glucoside were obtained with purities higher than 98%. The results showed glacial acetic acid could be such an appropriate regulator for the ethyl acetate/water system. This study provides a reference for the separation of polar compounds from natural products by high-speed countercurrent chromatography.

Facile synthesis of V(4+) self-doped, [010] oriented BiVO4 nanorods with highly efficient visible light-induced photocatalytic activity.

Monodispersed monoclinic BiVO4 nanorods grown along the [010] direction were prepared using a one-step low temperature hydrothermal method in the presence of the low-cost, nontoxic sodium oleate serving as a chelating agent. The BiVO4 nanorods with diameters of 15-20 nm possess a huge specific surface area as large as 28.2 m(2) g(-1), which can endow them with high photocatalytic activity and strong adsorption of reactants. Meanwhile, the specific [010] growth direction is capable of facilitating efficient electron-hole separation by accumulating electrons on {010} facets. Thus, the highly efficient photocatalytic activity of the as-prepared BiVO4 nanorods under visible light, which far surpasses that of commercial P25, is demonstrated by the degradation of rhodamine B and phenol. Plentiful V(4+) species, which can create oxygen vacancies, is detected implying that the as-obtained nanorods are self-doped BiVO4. Significantly, 61% of rhodamine B is adsorbed by the BiVO4 nanorods before irradiation owing to the appearance of plentiful O(2-) and OH(-) species on the surface adsorbed by oxygen vacancies. More excitingly, the excellent visible-light-driven photocatalytic activity of the as-obtained BiVO4 nanorods can be further elevated to an unprecedented level, roughly doubled, after applying a low temperature heat treatment process at 230 °C for 2 h and this improvement could primarily be ascribed to their optimized charge-carrier transport characteristics resulting from elevated crystallinity and decreased V(4+) species.

Placebo response in sham-acupuncture-controlled trials for migraine: A systematic review and meta-analysis.

AIM: To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. METHODS: Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model. RESULTS: The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I2 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00). CONCLUSIONS: The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.

A juvenile mouse model of anti-N-methyl-D-aspartate receptor encephalitis by active immunization.

Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models. Methods: We developed a model of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1356 - 385) against NMDARs in 3-week-old female C57BL/6J mice. Results: Immunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar to what is observed in patients affected by anti-NMDAR encephalitis. The mice also exhibited impaired long-term potentiation in hippocampal CA1. Pilocarpine-induced epilepsy was more severe and had a longer duration, while no spontaneous seizures were observed. Conclusion: The juvenile mouse model for anti-NMDAR encephalitis is of great importance to investigate the pathological mechanism and therapeutic strategies for the disease, and could accelerate the study of autoimmune encephalitis.

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect. OBJECTIVE: To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses. METHODS: Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size. RESULTS: A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response. CONCLUSIONS: Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis.

BACKGROUND: The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear. OBJECTIVE: This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects. SEARCH STRATEGY: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included. DATA EXTRACTION AND ANALYSIS: Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response. RESULTS: Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response. CONCLUSION: Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate. OBJECTIVE: To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis. METHODS: Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence. CONCLUSION: Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).

[ASPIRE guidelines and their enlightenment on application of sham acupuncture in clinical researches].

Reasonable and standard application of sham acupuncture control is the key to determine the quality of acupuncture clinical trials, and is also a difficult problem faced by acupuncture clinical research. The UK National Institute for Health Research and the Medical Research Council jointly published the Applying Surgical Placebo in Randomised Evaluation (ASPIRE) guidelines on the application of placebo surgical operation in randomized evaluation, which includes 4 parts: rationale and ethics, design, conduct, and interpretation and translation, providing comprehensive guidance for the application of placebo controls in surgical trials. As an operational intervention, acupuncture is similar to surgery, so, ASPIRE guidelines can also provide certain guidance for the application of sham acupuncture. In the present paper, we introduce the ASPIRE guidelines, and put forward its enlightenment and reference to the application of sham acupuncture control in combination with retrospecting the current situations of sham acupuncture research. We hold that future studies should strengthen the consideration of the rationality and ethics of sham acupuncture, standardize the design of sham acupuncture control, and convey the information related to sham acupuncture to patients with appropriate descriptions.

Low-cost and easy-fabrication lightweight drivable electrode array for multiple-regions electrophysiological recording in free-moving mice.

Objective.Extracellular electrophysiology has been widely applied to neural circuit dissections. However, long-term multiregional recording in free-moving mice remains a challenge. Low-cost and easy-fabrication of elaborate drivable electrodes is required for their prevalence.Approach.A three-layer nested construct (outside diameter, OD ∼ 1.80 mm, length ∼10 mm, <0.1 g) was recruited as a drivable component, which consisted of an ethylene-vinyl acetate copolymer heat-shrinkable tube, non-closed loop ceramic bushing, and stainless ferrule with a bulge twining silver wire. The supporting and working components were equipped with drivable components to be assembled into a drivable microwire electrode array with a nested structure (drivable MEANS). Two drivable microwire electrode arrays were independently implanted for chronic recording in different brain areas at respective angles. An optic fiber was easily loaded into the drivable MEANS to achieve optogenetic modulation and electrophysiological recording simultaneously.Main results.The drivable MEANS had lightweight (∼0.37 g), small (∼15 mm × 15 mm × 4 mm), and low cost (⩽$64.62). Two drivable MEANS were simultaneously implanted in mice, and high-quality electrophysiological recordings could be applied ⩾5 months after implantation in freely behaving animals. Electrophysiological recordings and analysis of the lateral septum (LS) and lateral hypothalamus in food-seeking behavior demonstrated that our drivable MEANS can be used to dissect the function of neural circuits. An optical fiber-integrated drivable MEANS (∼0.47 g) was used to stimulate and record LS neurons, which suggested that changes in working components can achieve more functions than electrophysiological recordings, such as optical stimulation, drug release, and calcium imaging.Significance.Drivable MEANS is an easily fabricated, lightweight drivable microwire electrode array for multiple-region electrophysiological recording in free-moving mice. Our design is likely to be a valuable platform for both current and prospective users, as well as for developers of multifunctional electrodes for free-moving mice.

Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice.

Temporal lobe epilepsy, a chronic disease of the brain characterized by degeneration of the hippocampus, has impaired risk assessment. Risk assessment is vital for survival in complex environments with potential threats. However, the underlying mechanisms remain largely unknown. The intricate balance of gene regulation and expression across different brain regions is related to the structure and function of specific neuron subtypes. In particular, excitation/inhibition imbalance caused by hyperexcitability of glutamatergic neurons and/or dysfunction of GABAergic neurons, have been implicated in epilepsy. First, we estimated the risk assessment (RA) by evaluating the behavior of mice in the center of the elevated plus maze, and found that the kainic acid-induced temporal lobe epilepsy mice were specifically impaired their RA. This experiment evaluated approach-RA, with a forthcoming approach to the open arm, and avoid-RA, with forthcoming avoidance of the open arm. Next, results from free-moving electrophysiological recordings showed that in the hippocampus, ∼7% of putative glutamatergic neurons and ∼15% of putative GABAergic neurons were preferentially responsive to either approach-risk assessment or avoid-risk assessment, respectively. In addition, ∼12% and ∼8% of dorsal lateral septum GABAergic neurons were preferentially responsive to approach-risk assessment and avoid-risk assessment, respectively. Notably, during the impaired approach-risk assessment, the favorably activated dorsal dentate gyrus and CA3 glutamatergic neurons increased (∼9%) and dorsal dentate gyrus and CA3 GABAergic neurons decreased (∼7%) in the temporal lobe epilepsy mice. Then, we used RNA sequencing and immunohistochemical staining to investigate which subtype of GABAergic neuron loss may contribute to excitation/inhibition imbalance. The results show that temporal lobe epilepsy mice exhibit significant neuronal loss and reorganization of neural networks. In particular, the dorsal dentate gyrus and CA3 somatostatin-positive neurons and dorsal lateral septum cholecystokinin-positive neurons are selectively vulnerable to damage after temporal lobe epilepsy. Optogenetic activation of the hippocampal glutamatergic neurons or chemogenetic inhibition of the hippocampal somatostatin neurons directly disrupts RA, suggesting that an excitation/inhibition imbalance in the dHPC dorsal lateral septum circuit results in the impairment of RA behavior. Taken together, this study provides insight into epilepsy and its comorbidity at different levels, including molecular, cell, neural circuit, and behavior, which are expected to decrease injury and premature mortality in patients with epilepsy.

[Enlightenments of DITTO framework and its application for setting up mock acupuncture in clinical research].

How to set up a placebo control scientifically and effectively is a problem in clinical research on acupuncture therapy. In 2020, the UK National Institute of Health Research established a standardized methodological framework DITTO, that is, "Deconstruct""Identify""Take out""Think" and "Optimize" to standardize the setting of invasive console-control intervention. Acupuncture therapy theoretically belongs to the category of invasive therapeutic intervention, and the percutaneous puncture therapy was also considered when the DITTO framework was developed. Therefore, this framework can be applied to clinical research of acupuncture, and may provide a reference for the appropriate setting of simulated acupuncture. In this article, we introduce the formulation process and main contents of the DITTO framework, and analyze the adjustments needed to be made and possible problems encountered in the application of each part of the framework in acupuncture clinical research through medical cases. The DITTO framework can guide and standardize the design of mock acupuncture control in acupuncture clinical research to a certain extent, which is conducive to finding a more suitable implementation method of mock acupuncture, thus promoting the improvement of the quality of acupuncture clinical research. However, because there is no precedent in the field of acupuncture in traditional Chinese medicine, further research is needed in the future practical application so that it can be better combined with the characteristics of acupuncture and the purpose of clinical research.

A neural circuit from the dorsal CA3 to the dorsomedial hypothalamus mediates balance between risk exploration and defense.

An appropriate balance between explorative and defensive behavior is essential for the survival and reproduction of prey animals in risky environments. However, the neural circuit and mechanism that allow for such a balance remains poorly understood. Here, we use a semi-naturalistic predator threat test (PTT) to observe and quantify the defense-exploration balance, especially risk exploration behavior in mice. During the PTT, the activity of the putative dorsal CA3 glutamatergic neurons (dCA3Glu) is suppressed by predatory threat and risk exploration, whereas the neurons are activated during contextual exploration. Moreover, optogenetic excitation of these neurons induces a significant increase in risk exploration. A circuit, comprising the dorsal CA3, dorsal lateral septal, and dorsomedial hypothalamic (dCA3Glu-dLSGABA-DMH) areas, may be involved. Moreover, activation of the dCA3Glu-dLSGABA-DMH circuit promotes the switch from defense to risk exploration and suppresses threat-induced increase in arousal.

Vibrotactile Feedback Rendering of Patterned Textures Using a Waveform Segment Table Method.

Vibrotactile feedback is a common form of rendered haptic feedback used for simulating stylus-texture interaction. Most state-of-the-art stylus-texture interaction vibrotactile feedback synthesizing methods are oriented toward generating signal with resemblance in spectrum in frequency domain. In this paper we set our foot backward and explore more about record-and-playback method for a subset of textures: those that have obvious spatial pattern, which constitutes a significant proportion of man-made textures we interact with in daily life. We propose a method that explicitly renders the periodic vibrotactile feedback for patterned textures. The method uses Dynamic Time Warping to select the most representative signal segment from a long continuous signal captured under a certain interaction condition, and constructs a waveform segment table to store representative signal segments under different conditions. Results of similarity-comparison user study show that subjects gave generally higher similarity scores to our proposed method than to a spectrum-oriented method. The results shed light on the importance of conserving the pattern in the haptic feedback rendering for patterned textures.

The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology.

Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hypertensive rats via network pharmacology and experimental pharmacology. The network pharmacology and bioinformatics analyses were performed to obtain the potential targets of AS-IV and hypertensive heart disease. The rat hypertension model was established by administrated 50 mg/kg/day of L-NAME for 5 weeks. Meanwhile, hypertension rats were intragastrically administrated with vehicle or AS-IV or fosinopril for 5 weeks. Cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rates, and body weight), cardiac function parameters (LVEDd, LVEDs, and fractional shortening), cardiac marker enzymes (creatine kinase, CK-MB, and lactate dehydrogenase), cardiac hypertrophy markers (atrial natriuretic peptide and brain natriuretic peptide), endothelial function biomarkers (nitric oxide and eNOS), inflammation biomarkers (IL-6 and TNF-α) and oxidative stress biomarkers (SOD, MDA, and GSH) were measured and cardiac tissue histology performed. Network pharmacological analysis screened the top 20 key genes in the treatment of hypertensive heart disease treated with AS-IV. Besides, AS-IV exerted a beneficial effect on cardiovascular and cardiac function parameters. Moreover, AS-IV alleviated cardiac hypertrophy via down-regulating the expression of ANP and BNP and improved histopathology changes of cardiac tissue. AS-IV improved endothelial function via the up-regulation of eNOS expression, alleviated oxidative stress via increasing antioxidant enzymes activities, and inhibited cardiac inflammation via down-regulating IL-6 and TNF-α expression. Our findings suggested that AS-IV is a potential therapeutic drug to improve L-NAME-induced hypertensive heart disease partly mediated via modulation of eNOS and oxidative stress.