Since Ephedra Herba (ephedra) and its major alkaloid ephedrine were prohibited as dietary supplements due to their adverse effects on the cardiovascular and central nervous system (CNS), most studies have focused on their amphetamine-like effects and neurotoxicity. However, ephedra also has a long history of use in the treatment of various CNS diseases (known as "Zhong Feng" syndrome) according to two thousand years of traditional Chinese medicine (TCM) records. Pharmacokinetic reports have also demonstrated that alkaloids of ephedra can quickly penetrate the blood-brain barrier (BBB) once absorbed into the blood and there are multiple alkaloids derived from ephedra which have been identified as natural sympathomimetic drugs. These drugs are capable of interfering with several types of neurotransmitter, and have an especially potent effect on monoamine neurotransmitters. The effects of ephedra on CNS therefore remain both contradictory and confusing. In this review, we summarized the available evidence of pharmacology and toxicology of ephedra and ephedrine on CNS, and aimed to clarify their effects. Given the unmet need for more efficient treatments of neurological disorders, ephedra is potentially valuable herbal medicine which may provide a promising avenue for development of treatments and encourage further drug research and development (R&D).

Coronary microcirculation dysfunction refers to a pathological syndrome characterized by abnormal structural and/or functional changes of the vessels in the microcirculatory systems, including arterioles, venules, and capillaries, which further affect myocardial microperfusion. Although modern medicine has made progress in controlling risk factors and alleviating symptoms, several clinical challenges in treatment remain unresolved, such as low drug response rates, suboptimal therapeutic efficacy, and adverse reactions. TCM can treat the coronary microcirculation dysfunction and achieve the effects of alleviating angina pectoris syndrome, delaying disease progression, improving prognosis, and enhancing patients' quality of life through multiple targets such as regulating neuroendocrine function, improving vascular endothelial function, inhibiting inflammation and oxidative stress, and regulating glucose and lipid metabolism, as well as the holistic regulation. Coronary microcirculation dysfunction falls into the categories of "chest Bi syndrome" and "heart pain" in TCM. Its etiologies include exogenous pathogenic cold, emotional disorders, improper diet, and chronic illness-related debility, while the core pathogenesis involves Qi stagnation, blood stasis, and phlegm turbidity. In terms of treatment strategies, Chaihu Longgu Muli Decoction is recommended for Qi stagnation syndrome, Guizhi Fuling Pills and Xuefu Zhuyu Decoction for blood stasis syndrome, and Gualou Xiebai Banxia Decoction and Wendan Decoction for phlegm turbidity syndrome. In clinical practice, the principles of "combining pathogenesis with pathology, and medicinal properties with pharmacology" should be adhered to, along with the theory of correspondence between formula and syndrome. Flexible selection and combination of formulas are essential to enhance therapeutic efficacy.

Chaihu Guizhi Decoction, originating from ZHANG Zhong-jing's Treatise on Febrile Diseases(Shang Han Lun), is a classic formula used to harmonize the Shaoyang and regulate nutrient-defense. It is primarily used to treat diseases involving both Taiyang and Shaoyang syndromes. The formula's indications are concisely summarized, yet rich in meaning, and reflect a profound connection with modern medical pathophysiological mechanisms. Key indications for Chaihu Guizhi Decoction are listed below. Diseases: it is used for rheumatoid arthritis, Sj9gren's syndrome, systemic lupus erythematosus(SLE), ankylosing spondylitis, overlap syndrome, and other rheumatic autoimmune diseases. It is also applied to diseases that involve immune system changes but do not yet have a clear diagnosis, such as cervical spondylosis, periarthritis of the shoulder, knee arthritis, and other bone-joint diseases. Additionally, it is indicated for skin conditions like eczema and urticaria, digestive system diseases such as gastritis, gastric ulcers, duodenal ulcers, cholecystitis, and ulcerative colitis, allergic diseases like allergic rhinitis and allergic dermatitis, as well as allergic constitution and weak constitutions. Symptoms: these include bitter taste, dry throat, dizziness, fever with aversion to wind, alternating chills and fever, intermittent episodes, sensitivity to cold and heat, tendency to sweat(including spontaneous or night sweats), depression, anxiety, fullness in the chest and sides, bloating in the stomach and abdomen, restlessness, nausea, poor appetite, soreness and pain in large and small joints such as the neck, shoulders, hands, and knees. The tongue may be dark red or dull with a thin white coating, and the pulse is wiry. In terms of formula differentiation, Chaihu Guizhi Decoction should be distinguished from Chaihu plus Longgu Muli Decoction and Chaihu Guizhi Ganjiang Decoction. In terms of treatment duration, it typically takes effect within one week for diseases such as stomach disorders, rhinitis, and dermatitis. However, when used for regulating physical constitution or treating joint pain, rheumatism, and autoimmune diseases, it requires slow and small doses and takes at least three months to show significant effects.

The prevalence of carotid atherosclerotic plaque and hyperlipidemia in China is high and continues to rise. Specifically, the incidence of hyperlipidemia among adults is 40.4%, and nearly one-third of asymptomatic adult patients present with carotid plaque; the co-occurrence rate of hyperlipidemia with carotid atherosclerotic plaque is as high as 48%-62%. Although modern medicine has made progress in lipid lowering, plaque stabilization, and surgical intervention, how to leverage the advantages of multi-target comprehensive intervention and simultaneously inhibit the core inflammatory pathways that drive disease progression to reduce high residual risk while improving lipid metabolism through single-target approaches, has become a pressing clinical challenge. In TCM, hyperlipidemia with carotid atherosclerotic plaque falls under the category of vessel impediment and is related to conditions such as "headache" "dizziness", and "stroke". Its etiology includes dietary irregularities, emotional disturbances, and constitutional insufficiency. The pathogenesis involves the Qi depression pattern in the early stage, the phlegm-turbidity pattern in the progressive stage, and the dampness-heat pattern in the mid-to-late stage. Regarding treatment strategies, Chaihu-based formulas such as Dachaihu Decoction, Xiaochaihu Decoction, Xiaoyao Powder, Chaihu Shugan Powder, and Chaihu Longgu Muli Decoction are recommended for the Qi depression pattern; Wendan Decoction, Chaichen Zexie Decoction, and Banxia Baizhu Tianma Decoction are suggested for the phlegm-turbidity pattern; Gegen Qinlian Decoction is advised for the dampness-heat pattern. Clinical practice should adhere to the principles of "formula-syndrome correspondence" and "pathogenesis combined with pathology, medicinal nature combined with pharmacology", with flexible selection and combination of formulas to enhance therapeutic efficacy. Its mechanism of action may be associated with regulating lipid metabolism, inhibiting inflammatory responses, combating oxidative stress, protecting vascular endothelium, and stabilizing plaque structure.

This study aimed to investigate the neuroprotective effects and potential mechanism of Xiaoxuming Decoction(XXM)against cerebral ischemia-reperfusion injury in mice.The middle cerebral artery occlusion/reperfusion model was established in male KM mice using the suture method.The experimental animals were randomly divided into the following groups:sham,model,nimodipine,XXM,Mahuang-Guizhi(MG),and Xiaoxuming Decoction without Mahuang-Guizhi(DXXM).Neurological function deficit scores were assessed using the Zea Longa scoring system.Cerebral infarction rate was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Pathological changes in brain tissue were observed via hematoxylin and eosin(HE)staining and Nissl staining.Non-targeted metabolomics analysis was performed using the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)to explore the potential mechanism.Serum interleukin-1β(IL-1β)and matrix metalloproteinase-2(MMP-2)levels were detected by the enzyme-linked immunosorbent assay(ELISA).Additionally,the expression of tight junction proteins in the blood-brain barrier was detected by Western blot.According to the results,compared with the model group,both XXM and DXXM interventions significantly improved neurological function scores while reducing cerebral infarction rate,neuronal damage,and pathological changes in brain tissue.XXM exhibited a superior protective effect than DXXM did.MG intervention also improved neurological function scores and alleviated pathological damage.Metabolomics analysis revealed 82,23,and 187 differential metabolites screened from the XXM,MG,and DXXM groups,respectively.The metabolic pathways commonly affected by both XXM and DXXM were purine,alanine,aspartate,and glutamate metabolism,while MG primarily affected the arachidonic acid metabolism pathway.ELISA results showed that XXM and MG significantly reduced IL-1β and MMP-2 levels,while DXXM significantly reduced IL-1β levels.Western blot results indicated that both XXM and DXXM up-regulated the expression of tight junction proteins in the brains of model mice.In conclusion,XXM and DXXM may exert anti-cerebral ischemia-reperfusion injury effects by inhibiting inflammatory factor release,reducing excitatory amino acid toxicity,and enhancing the expression of tight junction proteins in the blood-brain barrier via purine,alanine,aspartate,and glutamate metabolism pathway regulation.XXM exhibited superior effects compared to DXXM.MG may exert neuroprotective effects,to some extent,by regulating arachidonic acid metabolism and reducing pro-inflammatory factor levels.

To determine risk factors associated with the severity of Xuebijing Injection (XBJ)-related adverse events (AEs). Totally 16,031 cases reported XBJ-related AEs were retrospectively analyzed from China national spontaneous reporting system (SRS) from its inception to 2022. Factors including age, gender, weight, ethnicity, family history, and allergic history were examined. Univariate and multivariate logistic regression analyses were performed, followed by propensity score matching (PSM) to control for confounding factors. A total of 11,131 XBJ-related AE cases were identified after excluding duplicates and incomplete reports, including 9,771 general and 1,360 serious AEs. Serious AEs were mainly distributed among respiratory, thoracic and mediastinal disorders (27.00

Hypertension, a common risk factor for cardiovascular diseases, has aroused global concern. As breakthroughs have been achieved in the traditional Chinese medicine(TCM) and western medicine theories related to the heart and brain, top international journals such as Science pay increasing attention to the functional interaction between the heart and brain in modern medicine, known as the "heart-brain" axis, also referred to as the "cardiovascular-brain" circuit. The heart and brain interact and influence each other through the "heart-brain" axis. Increasing evidence suggests that the inflammation-regulated "heart-brain" axis plays a crucial role in the occurrence and development of hypertension, offering new insights for the treatment of cardiovascular diseases. In TCM, there is a connection between the heart and brain by the sharing of blood essence, interconnected blood vessels, and shared governance over the mind. Diseases of the heart and brain share common pathological and physiological foundations, similar risk factors, and TCM pathogeneses, which form the basis for simultaneous treatment of heart and brain diseases in TCM. The principle of simultaneous treatment of the heart and brain diseases aligns with the theory of "heart-brain" axis. Modern research has found that the heart and brain are the main target organs of hypertension. Long-term high blood pressure can easily cause structural changes, mainly characterized by left ventricular hypertrophy and dilation, leading to hypertensive heart disease. Hypertension can change the structure, blood supply, and function of the brain, being closely related to cerebral atherosclerosis, cerebral infarction, cerebral hemorrhage, cognitive dysfunction, dementia and other brain diseases. TCM treatment of hypertension has a long history. According to the pathogenesis(Yang hyperactivity and blood stasis) of hypertension, the team has developed the core treatment principle of subduing Yang and activating blood. Through extensive clinical exploration and experimental research, the team has developed an effective prescription called Tianxiong Granules. This prescription has shown definite efficacy in stabilizing blood pressure, ameliorating clinical symptoms, and reducing target organ damage. The protective effects of Tianxiong Granules on the heart and brain are reflected in aspects such as symptoms related to the heart and brain, pharmacological effects on ventricular hypertrophy, and brain protection. The preliminary research by the team found that Tianxiong Granules might treat hypertension by inhibiting sympathetic nerve excitation and renin-angiotensin-aldosterone system(RAAS) and targeting mitochondrial autophagy to regulate the activation of the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. The activation of the NLRP3 inflammasome mediates pyroptosis, which is a key mechanism of hypertension. Next, the team will construct the adeno-associated viruses with downregulated NLRP3 expression via adenoviral vectors and use viral tracing technology, left stellate ganglionectomy, and a cardiac denervation model to reveal the mechanism of Tianxiong Granules in regulating the heart-brain interaction in hypertensive rats, from both in vivo and in vitro perspectives. In summary, exploring clinical treatment strategies for hypertension from both heart and brain based on the "heart-brain" axis is likely to be a new direction for the development of drugs for hypertension and offers a new target and basis for intervention in hypertension.

Acute myocardial infarction and acute upper gastrointestinal bleeding are both critical internal medicine conditions. The incidence of acute upper gastrointestinal bleeding in patients with acute myocardial infarction ranges from 5.31% to 8.90%, with a mortality rate as high as 20.50% to 35.70%. The pathogenesis may be related to the use of antiplatelet and anticoagulant drugs, as well as stress-induced injury. In treatment, the contradiction between antiplatelet/anticoagulation therapy and bleeding has made this disease a significant challenge in modern medicine. Therefore, re-exploring the etiology, pathogenesis, treatment principles, and methods of traditional Chinese medicine(TCM) for acute myocardial infarction and acute upper gastrointestinal bleeding is of great clinical importance. The research team has been working year-round in the coronary care unit(CCU), managing a large number of such severe patients. By revisiting classic texts and delving into the foundational theories of TCM and historical medical literature, it has been found that this disease falls under the category of "distant blood" in the Synopsis of the Golden Chamber. In terms of etiology, it is primarily associated with weakness of healthy Qi and damage caused by drug toxicity. In terms of pathogenesis, in the acute stage, it mainly manifests as insufficient spleen Yang, deficiency of spleen Qi, and failure of the spleen to control blood. In the remission stage, it is characterized by deficiency of both heart Qi and spleen blood. For treatment, during the acute stage, Huangtu Decoction is used to warm Yang and restrain blood, while in the remission stage, Guipi Decoction is administered to tonify Qi and nourish blood. During the treatment process, for patients with acute myocardial infarction complicated with acute upper gastrointestinal bleeding, it is crucial to flexibly apply the treatment principles of "Nil per os" in western medicine and "where there is stomach Qi, there is life; where there is no stomach Qi, there is death" in TCM. Early intervention with Huangtu Decoction can also prevent bleeding, with large doses being key to achieving hemostasis. It is important to address the pathogenesis of heat syndrome in addition to the core pathogenesis of Yang deficiency bleeding and to emphasize the follow-up treatment with Guipi Decoction for a successful outcome.

Diuretic resistance(DR) is more common in patients with heart failure(especially acute decompensated heart failure), renal dysfunction, and cardiorenal syndrome. DR can accelerate the damage to heart and kidney organ functions, prolong hospitalization time, increase mortality rate, and bring a heavy burden to public health. It has become a major global public health problem. Although there are currently many treatment methods for DR, the complex pathophysiological mechanisms and limited clinical efficacy have led to unsatisfactory relief of heart failure and renal failure. Moreover, some DR patients are prone to adverse reactions such as electrolyte imbalance, hypotension, and worsening infection during the treatment process. Traditional Chinese medicine(TCM) treatment has the characteristics of reducing diuretic resistance while exerting fewer side effects, so some patients have started seeking help from TCM. In TCM, DR falls under the categories of "heart-water disease" and "edema". In terms of etiology, it is mainly associated with aging and chronic illness, innate deficiency, invasion of external pathogens, dietary irregularities, emotional imbalances, and improper work-rest balance. In terms of pathogenesis, it includes water overflow due to Yang deficiency, fluid retention turning into heat, and kidney Yang deficiency. In TCM treatment strategies, for water overflow due to Yang deficiency syndrome, Zhenwu Decoction is recommended; for fluid retention turning into heat syndrome, Mufangji Decoction is recommended; and for kidney Yang deficiency syndrome, Shenqi Pill is recommended. In clinical treatment, based on the principles of "formula-syndrome correspondence" and "integrating disease mechanisms with pathology, and herbal properties with pharmacology", the combined use of TCM and western medicine can help alleviate DR, increase urine output, and improve the quality of life for patients with DR.

Ethnopharmacological relevance Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. Aim of this study To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. Materials and methods In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. Results 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z=-20.26) ; YXB was significantly associated with AS (Z=-4.532) , MI (Z=-29.11) , RhFv (Z=-6.945) , OA (Z=-39.97) , and GA (Z=-13.03) ; and WBFK was significantly associated with MI (Z=-205.5), SLE (Z=-37.65), RhFv (Z=-42.45), and GA (Z=-17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. Conclusions The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

Background Influenza virus-induced pneumonia (IVP) is an infectious pulmonary disease characterized by exacerbated pulmonary inflammation caused by invasion of the influenza virus. IVP continues to threaten public health due to its high morbidity and mortality rates. Geniposide is one of the major bioactive constituents of G. jasminoides, which exerts antiviral and anti-inflammatory effects on influenza A virus (IAV) infection. Purpose To investigate therapeutic effects and comprehensive mechanisms of geniposide on IAV infection and subsequent pneumonia. Methods ICR mice were infected intranasally with H1N1 (A/FM/1/47) to detect the anti-IAV activity of geniposide. Proteomics combined with function-integrated analysis were conducted to gain insight into the comprehensive mechanisms of geniposide. Subsequently, western blot was used to detect the phosphorylation of signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2), Interferon regulatory factor 9 (IRF9) and Janus kinase 1 (JAK1) in Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in lung tissue. Finally, RT-qPCR was used to detect the levels of interleukin 6 (IL-6), interleukin 17 (IL-17), interferon-γ (IFN-γ) and the STAT1 inhibitor (fludarabine) was used to verify the targeting between STAT1 and geniposide in RAW cells. Results Geniposide could significantly reduce the lung index, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by IAV infection. A total of 411 differentially expressed proteins were identified among control, model, and geniposide-treated group in proteomic analysis. According to function-integrated analysis, 15 KEGG pathways were enriched and divided into 9 groups (modules), including influenza A, NOD-like receptor signaling, RIG-I-like receptor signaling, and so on. Among these modules, the most intensely interacting module pair was the NOD-like receptor signaling and influenza A, in which STAT1 and STAT2 acted as hubs with critical bridgeness role in the target network of geniposide. This indicated that geniposide may mitigate inflammation and alleviate IVP by JAK/STAT signaling pathways. Moreover, validation experiments confirmed that geniposide can significantly inhibit STAT1 and STAT2 phosphorylation as well as down-regulated expression of IL-6, IFN-γ and IL-17 in lung. Furthermore, when RAW cells were treated with the STAT1 inhibitor (fludarabine), the inhibitory effect of geniposide on IFN-γ and IL-6 was attenuated significantly. Conclusions Geniposide can attenuate IAV-induced pneumonia by regulating inflammatory cytokines production through the JAK/STAT pathway.

Editorial: Clinical evidence for and advances in translational research on the classic formulas of traditional Chinese medicine

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

Abstract Background Although the pathogenesis of essential hypertension is not clear, a large number of studies have shown that oxidative stress plays an important role in the occurrence and development of hypertension and target organ damage. Purpose This paper systematically summarizes the relationship between oxidative stress and hypertension, and explores the potential mechanisms of Chinese herbal medicine (CHM) in the regulation of oxidative stress in hypertension, aiming to establish a scientific basis for the treatment of hypertension with CHM. Methods To review the efficacy and mechanism by which CHM treat hypertension through targeting oxidative stress, data were searched from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database from their inception up to January 2024. NPs were classified and summarized by their mechanisms of action. Results In hypertension, the oxidative stress pathway of the body is abnormally activated, and the antioxidant system is inhibited, leading to the imbalance between the oxidative and antioxidative capacity. Meanwhile, excessive production of reactive oxygen species can lead to endothelial damage and vascular dysfunction, resulting in inflammation and immune response, thereby promoting the development of hypertension and damaging the heart, brain, kidneys, blood vessels, and other target organs. Numerous studies suggested that inhibiting oxidative stress may be the potential therapeutic target for hypertension. In recent years, the clinical advantages of traditional Chinese medicine (TCM) in the treatment of hypertension have gradually attracted attention. TCM, including active ingredients of CHM, single Chinese herb, TCM classic formula and traditional Chinese patent medicine, can not only reduce blood pressure, improve clinical symptoms, but also improve oxidative stress, thus extensively affect vascular endothelium, renin–angiotensin–aldosterone system, sympathetic nervous system, target organ damage, as well as insulin resistance, hyperlipidemia, hyperhomocysteinemia and other pathological mechanisms and hypertension related risk factors. Conclusions CHM display a beneficial multi-target, multi-component, overall and comprehensive regulation characteristics, and have potential value for clinical application in the treatment of hypertension by regulating the level of oxidative stress.

Based on the systematic deconstruction of multi-dimensional and multi-target biological networks,modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs.It has made progress in the fields of pathogenesis of disease,biological basis of disease and traditional Chinese medicine(TCM)syndrome,pharmacological mechanism of multi-target herbs,compatibility of formulas,and discovery of new drug of TCM compound.However,the complexity of multi-omics data and bio-logical networks brings challenges to the modular deconstruction and analysis of the drug networks.Here,we constructed the"Compu-ting Platform for Modular Pharmacology"online analysis system,which can implement the function of network construction,module identification,module discriminant analysis,hub-module analysis,intra-module and inter-module relationship analysis,and topologi-cal visualization of network based on quantitative expression profiles and protein-protein interaction(PPI)data.This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology.The platform may have broad range of application in disease modular identification and correlation mechanism,interpretation of scientific principles of TCM,analysis of complex mechanisms of TCM and formulas,and discovery of multi-target drugs.

The prevalence of cardiovascular diseases in China has shown a rising trend. With the patient number of about 8.9 million, heart failure has brought a heavy burden to public health and wellness. Despite the modern medical research progress in the pathogenesis and clinical treatment of heart failure, the patients with heart failure still suffer from recurrent episodes of dyspnea(requiring repeated hospital admissions), diuretic resistance, elevated creatinine levels due to prolonged diuretic use, and poor prognosis, among other major clinical and scientific issues. In traditional Chinese medicine(TCM), heart failure belongs to the category of "heart water". The research team has found that because of the changes in the modern disease spectrum, the differences between ancient and modern physical constitutions, and the use of anti-heart failure drugs in modern medicine, the pathological process of heart failure has been altered, and the symptoms of some patients have become unobvious. As a result, the etiology and pathogenesis of heart failure have undergone major changes. The disease causes include external pathogen attack, emotional disorders, excessive labor injury, medication-induced damage, dietary disorders, water-dampness stagnation, and endowment insufficiency. These causes are closely related to the infection aggravation-induced heart failure, cardiac and psychological diseases, and heart volume overload in modern medicine. The pathogeneses of heart failure include edema due to Yang deficiency and water retention turning into heat in the acute stage and liver depression and Qi stagnation, heart Qi deficiency, kidney Yang deficiency, Qi deficiency in lung and spleen, phlegm and water retention, and internal obstruction due to blood stasis in the remission stage. The corresponding treatment strategies were recommended as follows: Zhenwu Decoction for edema due to Yang deficiency, Mufangji Decoction for water retention turning into heat, Chaihu Longgu Muli Decoction for liver depression and Qi stagnation, Guizhi Decoction for heart Qi insufficiency, Shenqi Pills and Yougui Pills for kidney Yang deficiency, Yupingfeng Powder, Lizhong Decoction, Buzhong Yiqi Decoction, and Guipi Decoction for Qi deficiency in lung and spleen, Fangji Huangqi Decoction, Wuling Powder, Linggui Zhugan Decoction, and Tingli Dazao Xiefei Decoction for internal obstruction due to phlegm and water retention, Guizhi Fuling Pills and Danggui Shaoyao Powder for internal obstruction due to blood stasis. The clinical treatment should follow the principle of considering both pathogenesis and pathology as well as both medicine nature and mechanism. The TCM concept of secondary prevention with TCM formulas for replenishing deficiency should be adopted. The treatment based on the principle and concept above will improve the patients' quality of life, reduce the number of hospital admissions, ameliorate diuretic resistance, and improve the clinical outcomes.

Hypertension is the most common chronic disease in clinics and has become the most common risk factor for cardiovascular diseases. Because of its high incidence rate, disability rate, and mortality, it has attracted worldwide attention. Despite continuous progress in modern medicine in the treatment of hypertension with new antihypertensive drugs such as Zilebesiran, a nucleic acid drug that acts on microRNA, direct renin inhibitors, and renal sympathetic blockade, the control rate is still not ideal. How to effectively prevent and control hypertension has become one of the urgent clinical challenges to be solved. Traditional Chinese medicine(TCM) has a long record of treating hypertension and has accumulated rich experience, including theoretical understanding, effective single medicine, compound medicine, traditional Chinese patent medicines, and classic famous prescriptions. In TCM, hypertension belongs to the categories of diseases such as dizziness and headache. Previous literature and clinical studies have found that hypertension has key pathogenesis such as fire syndrome, fluid syndrome, deficiency syndrome, and blood stasis syndrome. Among them, the hyperactivity of liver Yang is closely related to blood pressure fluctuations, blood pressure variability, inflammation, and sympathetic activity stimulation. Internal obstruction by blood stasis is closely related to the damage of target organs such as the heart, brain, and kidneys in hypertension. Therefore, the two key pathogenesis of liver yang hyperactivity and internal obstruction by blood stasis run through the entire process of hypertension. Previous studies have found that the effective empirical formula Tianxiong Granules, based on the principles of suppressing Yang and promoting blood circulation, originated from the classic formula Xiongqiong Tianma Pills in Yu Yao Yuan Fang. It is composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Achyranthis Bidentatae Radix, and Cyathulae Radix and has significant therapeutic effects in the treatment of hypertension. The clinical indications include headache, dizziness, bloating, strong neck, and weak waist and legs. At the same time, it may be accompanied by poor speech, thirst, normal or loose stools, soreness in the waist and legs, lower limb pain, muscle and pulse spasm, menstrual and abdominal pain, dark red tongue, strong pulse strings, or straight and long pulse strings that pass through the mouth of an inch. In the combination rule, it can be used according to the different pathogenesis stages of hypertension patients. In the fire syndrome stage, it is often combined with Tianma Gouteng Decoction and Chaihu Jia Longgu Muli Decoction. In the fluid syndrome stage, it is often combined with Banxia Baizhu Tianma Decoction. In the deficiency syndrome stage, it is often combined with Liuwei Dihuang Pills and Shenqi Pills. In terms of dosage, it is important to focus on the main symptoms and adjust the dosage of key drugs based on blood pressure values. Some drugs can be used in sufficient quantities. By analyzing the compatibility of Tianxiong Granules, clinical application indications, combined formula experience, and dosage application experience, we provide effective treatment methods and more options for TCM to treat hypertension with Yang hyperactivity and blood stasis syndrome.

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.

Angelica sinensis is a rich source of medically important active molecules that need in-depth understanding on its action mechanisms. Therefore, through pharmacodynamics, metabolomics, and network pharmacology, the traditional benefits of A. sinensis in blood circulation was studied using 24 randomly selected Sprague-Dawley (SD) rats. Measurement of the blood rheological parameters for whole blood viscosity (WBV) and plasma viscosity (PV), and inspection of the heart and lung tissues pathological changes were undertaken using molecular and bioinformatic techniques. Multivariate statistical analysis and establishment of the model of the relationship between metabolite expression and sample categories to test the prediction of sample categories were performed. Screening was undertaken to find the potential metabolites for A. sinensis to treat blood stasis syndrome and find related metabolic pathways. Active ingredients of A. sinensis and targets and building of an "effect component-target" network was undertaken, A. sinensis was confirmed to improve blood stasis syndrome in rats and improve heart and lung pathology to varying degrees. Compared with the blood stasis model group, A. sinensis significantly reduced WBV and PV in hemorheology (p<0.05, p<0.01) and regulated blood stasis-induced changes in 22 metabolites including alpha-D-glucose, L-isoleucine, creatine and acetylcarnitine, which are involved in the metabolism of linoleic acid, linolenic acid, phenylalanine, ascorbic acid and uronic acid. Using the network pharmacology to build a "component-target-pathway" network of A. sinensis, 62 active ingredients, 169 active proteins and 18 metabolic pathways were obtained, among which linoleic acid metabolism, ascorbic acid and uronic acid metabolism were consistent with the metabolic pathways obtained by metabolomics.

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.