1.Study on Medication Law of National Patented Chinese Herbal Prescriptions for the Treatment of Benign Prostatic Hyperplasia Based on Data Mining
Lichong MENG ; Kun LIAN ; Jin GUO ; Ziyi WANG ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):60-66
Objective To explore the prescribing law of TCM in national patents for the treatment of benign prostatic hyperplasia(BPH);To provide a reference for clinical medication.Methods Data on TCM compound prescriptions for the treatment of BPH were retrieved from the China National Intellectual Property Administration(CNIPA)patent retrieval and analysis system,covering the period from January 1,2000,to October 31,2023.The frequency,efficacy category,properties and tastes,meridian tropism,core complex co-occurrence network,and potential TCM clusters mentioned in the patents were analyzed using Excel 2016,SPSS Modeler 18.0,SPSS Statistics 27,and Cytoscape 3.10.0 software.Results A total of 182 patents were included,involving 404 kinds of Chinese materia medica,with a total frequency of 2054 times.Among them,22 kinds of Chinese materia medica had a frequency of≥20,with the most frequently used Chinese materia medica being Astragali Radix,Glycyrrhizae Radix et Rhizoma,Phellodendri Chinensis Cortex,Epimedii Folium,Salviea Miltiorrhizae Radix et Rhizoma,Plantaginis Semen,Poria,Vaccariae Semen,Alismatis Rhizoma and Paeoniae Radix Rubra.The high-frequency herbs primarily consisted of tonifying herbs(267 times,13.00%),blood circulation-activating and stasis-resolving herbs(216 times,10.52%),and diuretic and dampness-percolating herbs(147 times,7.16%).The properties of the herbs were mainly sweet and cold,and they were mainly attributed to the liver and kidney meridians.Association rule analysis yielded 10 common drug pairs,including Cornus Officinalis-Rehmannize Radix et Praeparata,Curcumae Rhizoma-Sparganii Rhizoma,and Astragali Radix-Codonopsis Radix.The drug combination with the highest confidence was Angelicae Sinensis Radix-Phellodendri Chinensis Cortex-Glycyrrhizae Radix et Rhizoma.Clustering analysis revealed five drug combinations,while potential TCM clustering analysis identified five groups,among which the"Zingiberis Rhizoma-Os Draconis-Angelicae Pubescentis Radix-Scallion-Rice Bran-Speranskiae Herba"network demonstrated the highest degree of interconnection(Score=6).Conclusion The high-frequency herbs in national patents for the treatment of BPH with TCM compound prescriptions mainly focus on tonifying the spleen and kidney,activating blood circulation to remove stasis,and clearing heat and draining dampness,providing a reference for clinical practice.
2.Evaluation of Animal Models of Dilated Cardiomyopathy Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Lichong MENG ; Jin GUO ; Ziyi WANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):194-202
The prevalence of dilated cardiomyopathy (DCM) has been increasing year by year,which seriously endangers the physical and mental health of patients. Establishing an animal model that conforms to the clinical characteristics of the disease is a prerequisite for conducting experimental research on DCM. This study sorted out and summarized the commonly used DCM animal models and evaluated the degree of consistency between the models and clinical practice based on the etiology and pathogenesis of traditional Chinese and western medicine and clinical diagnostic criteria. The models with high consistency with western medicine include immune models,drug toxicity models,and tachycardia models,while the models with high consistency with traditional Chinese medicine include drug toxicity models,gene correlation models,and tachycardia models. With consideration of the characteristics of the symptoms,consistency,and their respective advantages and disadvantages,the more ideal models are drug toxicity models,tachycardia models,and gene correlation models. In addition to evaluating the clinical consistency of traditional Chinese and western medicine in DCM animal models,this study also analyzed the advantages and disadvantages of existing DCM animal models,existing problems,and observation indicators of the models and pointed out the lack of standardized and unified syndrome model differentiation standards. Due to the complexity of the disease and the unclear pathogenesis,there are few studies on DCM models,and there is room for improvement. On this basis,four improvement directions are proposed to make the animal models as close to the clinical pathological and physiological processes as possible,so that the combination of disease and syndrome in animal models is more practical. These animal models can provide an experimental basis for the pathogenesis,drug intervention,efficacy evaluation,and scientific research of DCM and better serve scientific research and clinical practice.
3.Syndrome Treatment of Chronic Heart Failure and Diabetes Mellitus omorbidity Based on "Syndrome-based Treatment of Disease"
Lichong MENG ; Kun LIAN ; Xinchun LI ; Cong LU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):233-242
Chronic heart failure (CHF) and diabetes mellitus (DM) comorbidity presents a myriad of symptoms and a complex pathogenesis, making the traditional diagnostic and treatment model of "using disease to treat syndrome" often inadequate in clinical practice. The concept of "syndrome-based treatment of disease" is rooted in the core thinking of traditional Chinese medicine (TCM) syndrome differentiation and treatment, emphasizing the importance of syndrome as the guiding principle. This approach categorizes various diseases according to their corresponding syndrome categories for exploration, adhering to the principle of starting from the syndrome and addressing the disease thereafter, which highlights the advantages of TCM holistic view and syndrome differentiation and treatment. The pathogenesis of CHF is characterized by deficiency of both Qi and Yin, along with blood stasis, affecting organs such as the lung, spleen, and kidney, which in turn impacts the distribution and metabolism of body fluids. Dysfunction in body fluid regulation leads to stagnation, resulting in pathological products like phlegm and turbidity, which exacerbates syndromes of Yin deficiency and excessive heat. As the conditions of Yin deficiency and dryness-heat intensify, and as body fluid depletion continues, the patient's DM symptoms worsen, contributing to or aggravating the comorbidity. Following the diagnostic approach of "syndrome-based treatment of disease", TCM diagnosis and treatment of CHF and DM comorbidity should focus on the core pathogenesis of "deficient Qi retention". This study categorized CHF and DM comorbidity into four stages: A (comorbid risk period), B (precomorbid period), C (intermediate stage of comorbidity), and D (advanced comorbidity), proposing corresponding TCM syndrome types for each stage. In terms of treatment, adhering to the principle of "tonifying deficiency and relieving stagnation", the specific methods included invigorating Qi and strengthening the body, nourishing Yin and generating body fluids, activating blood circulation and Qi, and promoting diuresis and removing toxins. This study reviewed recent research progress on Chinese medicine compound prescriptions for CHF combined with DM, aiming to achieve precise treatment for both diseases and provide a scientific basis for the application of TCM in the prevention and treatment of CHF and DM comorbidity.
4.Danhong Injection Regulates Mitochondrial Dynamics in Rat Model of Chronic Heart Failure via AMPK/Drp1 Pathway
Jiahao YE ; Zizheng WU ; Yao ZHANG ; Lichong MENG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):126-135
ObjectiveTo investigate the effects of Danhong injection on mitochondrial dynamics, morphology, and function in the rat model of chronic heart failure by mediating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/dynamin-related protein 1 (Drp1) pathway. MethodsFrom 75 SD rats, 15 rats were randomly selected as the sham group, and the remaining 60 rats were used to prepare a rat model of chronic heart failure by abdominal aortic constriction (AAC). The modeled rats were randomly allocated into model, Danhong Injection (6 mL·kg-1), and captopril (8.8 mg·kg-1) groups and administrated with corresponding agents for 15 consecutive days. The levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by enzyme-linked immunosorbent assay. The changes in cardiac function were detected by echocardiography. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to assess the protein levels of AMPK, p-AMPK, Drp1, p-Drp1, optic atrophy 1 (Opa1), mitofusin (Mfn2), and fission l (Fis1) in the myocardial tissue. Real-time PCR was performed to determine the mRNA levels of Opa1, Mfn2, and Fis1, and immunohistochemistry to detect the expression of p-AMPK. ResultsCompared with the sham group, the model group showed elevated levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), declined ATP level (P<0.01), weakened activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01), and increased left ventricular internal diameter at end-diastole (LVDd) and leaf ventricular internal diameter at end-systole (LVIDs) (P<0.01). Electron microscopy results showed that the model group presented heavily abnormal myocardial structure, with large areas of myofilament structure destroyed and dissolved, significantly enlarged residual structural gaps, and fragmented mitochondria. Western blot results showed that the model group demonstrated down-regulated protein levels of p-AMPK, Mfn2, and Opa1 (P<0.01) and up-regulated protein levels of p-Drp1 and Fis1 (P<0.01) in the myocardial tissue. Real-time PCR results showed that the model group presented up-regulated mRNA level of Fis1 (P<0.01) and down-regulated mRNA levels of Mfn2 and Opa1 (P<0.01). Immunohistochemistry results showed reduced expression of p-AMPK in the model group compared with sham group (P<0.01). Compared with the model group, Danhong injection lowered the levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), raised the level of ATP (P<0.01), increased the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.05, P<0.01), increased the LVEF and LVFS (P<0.01), decreased the LVDd and LVIDs (P<0.05, P<0.01), alleviated mitochondrial damage, up-regulated the protein levels of p-AMPK, Mfn2, and Opa1 (P<0.05, P<0.01), down-regulated the protein levels of p-Drp1 and Fis1 (P<0.01), reduced the mRNA level of Fis1 (P<0.01), elevated the mRNA levels of Mfn2 and Opa1 (P<0.05, P<0.01), and promoted the expression of p-AMPK (P<0.05). ConclusionDanhong injection repairs the imbalance of mitochondrial dynamics, restores the mitochondrial function, improves the myocardial energy metabolism, and reduces the inflammatory response by regulating the AMPK/Drp1 pathway, thus improving the cardiac function.
5.Pathogenesis of Chronic Heart Failure with Anxiety and Depression and Therapeutic Mechanisms of Bupleuri Radix-based Formulas from Theory of Shaoyang Pivot
Duoting TAN ; Kun LIAN ; Hao LIANG ; Lichong MENG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):156-164
Chronic heart failure (CHF), as the terminal stage of various cardiovascular diseases, is characterized by a prolonged clinical course and recurrent exacerbations. The coexistence of CHF with anxiety and depression falls under the category of psycho-cardiological diseases. Studies have demonstrated that anxiety and depression are closely associated with adverse outcomes including elevated risks of cardiovascular events and increased mortality in CHF patients. The complex pathogenesis poses challenges to modern medical treatments, which often face limited efficacy and concurrent side effects. According to the theory of Shaoyang Pivot in traditional Chinese medicine (TCM), this paper elucidates that obstructed Shaoyang Pivot—manifested as Qi transformation disorder, dysregulated fluid metabolism, and abnormal distribution of ministerial fire-serves as a critical pathological basis for CHF with anxiety and depression. Bupleuri Radix-based Formulas, such as Xiao Chaihu Tang, Chaihu Guizhi Tang, and Chaihu Jia Longgu Muli Tang, aim to harmonize lesser Yang to restore the Qi transformation, activate Yang to promote water excretion, and redistribute ministerial fire, thus effectively alleviating pathological states such as Qi stagnation, blood stasis, water retention, and phlegm-fire disturbing the heart in CHF patients with anxiety and depression. Consequently, they mitigate symptoms of this psycho-cardiological disease. Mechanism studies have revealed that Bupleuri Radix-based formulas exhibit multi-target effects, including modulation of neurotransmitters, suppression of inflammatory responses, regulation of lipid metabolism, protection of cardiomyocytes, and improvement of the endothelial function. By interpreting the TCM pathogenesis of CHF with anxiety and depression from the theory of Shaoyang Pivot, this paper delves into the therapeutic principles and mechanisms of Bupleuri Radix-based formulas, providing a theoretical foundation for optimizing TCM diagnosis and treatment strategies for psycho-cardiological diseases.
6.Shenfu Injection Improve Chronic Heart Failure by Regulates Glycolytic Pathway Mediated by HIF-1α/PFKFB3 Pathway
Ji OUYANG ; Kun LIAN ; Xiaoqian LIAO ; Lichong MENG ; Lin LI ; Zhenyu ZHAO ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):136-145
ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α (HIF-1α)/ 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol (ISO). After successful modeling, the rats were randomly divided into the Sham group, Model group, Shenfu injection (SFI, 6 mL·kg-1) group, and inhibitor (3PO, 35 mg·kg-1) group, according to a random number table, and they were treated for 15 days. Cardiac function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were detected by enzyme-linked immunosorbent assay (ELISA). Fasting body weight and heart weight were measured, and the heart index (HI) was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin (HE) and Masson staining, and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose (GLU), lactic acid (LA), and pyruvic acid (PA). Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway (HIF-1α and PFKFB3), glycolysis-related proteins (HK1, HK2, PKM2, and LDHA), and fibrosis-related proteins [transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and Collagen type Ⅰ α1 (ColⅠA1)]. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group, the Model group showed significantly decreased left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), interventricular septal thickness (IVSd), and interventricular septal strain (IVSs) (P<0.05), while left ventricular internal dimension at end-diastole (LVDd) and end-systole (LVIDs) were increased (P<0.05). Serum NT-proBNP levels were significantly increased (P<0.01), and body weight was decreased. Heart weight was increased, and the HIT index was increased (P<0.05). Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition, and the fibrosis rate was significantly increased (P<0.05). Serum GLU was decreased (P<0.05), while LA and PA levels were increased (P<0.05). Protein expressions of HIF-1α, PFKFB3, HK1, HK2, PKM2, LDHA, TGF-β1, α-SMA, and ColⅠA1, as well as the mRNA expression of HIF-1α and PFKFB3 were increased (P<0.05). Compared with the Model group, both the SFI group and 3PO groups showed significant improvements in LVEF, LVFS, IVSd, and IVSs (P<0.05) and decreases in LVDd, LVIDs, and NT-proBNP levels (P<0.05). Body weight was significantly increased. Heart weight was significantly decreased, and the HIT index was significantly decreased (P<0.05). Inflammatory cell infiltration, collagen fiber deposition, and the fibrosis rate were significantly decreased (P<0.05). Serum GLU levels were significantly increased (P<0.05), while LA and PA levels were decreased (P<0.05). Expressions of glycolysis-related proteins, fibrosis-related proteins, and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed (P<0.05). ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins, regulating glycolysis, and inhibiting myocardial fibrosis.