1.Differentiation and Treatment of Lipid Turbidity Disease Based on Theory of "Spleen Ascending and Stomach Descending"
Yun HUANG ; Wenyu ZHU ; Wei SONG ; Xiaobo ZHANG ; Xin ZHOU ; Lele YANG ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):244-252
Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment, diet, and lifestyle, which is closely related to many diseases in modern medicine, such as hyperlipidemia, obesity, fatty liver, atherosclerosis, metabolic syndrome, and cardiovascular and cerebrovascular diseases, with a wide range of influence and far-reaching harm. According to the Huangdi Neijing, lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids, which has the function of nourishing, and it is the initial state and source of important substances in the human body such as brain, marrow, essence, and blood. Once the grease of the human body is abnormal, it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach, which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments, leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity, which accumulates in the body's meridians, blood vessels, skin pores, and organs, forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays, it was divided into four common pathogenesis types: ''inability to distinguish between the clear and turbid, turbid stagnation in the Ying blood'', ''spleen not rising clear, turbid accumulation in the vessels'', ''spleen dysfunction, lipid retention in the pores'', ''spleen failure to transportation and transformation, and grease accumulation in the liver''. According to the pathogenesis, it could be divided into four common syndromes, namely, turbid stagnation in the Ying blood, turbid accumulation in the vessels, lipid retention in the pores, and grease accumulation in the liver, and the corresponding prescriptions were given for syndrome differentiation and treatment, so as to guide clinical differentiation and treatment of the lipid turbidity disease.
2.Huayu Mingmu Prescription Downregulates PI3K/Akt/mTOR-HIF-1α/VEGFA Signaling Pathway to Intervene in Retinal Angiogenesis of DR Rats
Xiaoqiu MA ; Lei ZHAO ; Huimin ZHOU ; Fanghui ZHENG ; Guoqing YANG ; Tao ZUO ; Xiande MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):78-87
ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)-hypoxia inducible factor-1α/vascular endothelial growth factor A (HIF-1α/VEGFA) signaling pathway in diabetic retinopathy (DR) rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group, while the remaining 53 rats were fed a high-sugar, high-fat diet combined with low-dose streptozotocin (STZ) intraperitoneal injection to establish a type 2 diabetes mellitus (T2DM) rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model, low-dose, medium-dose, and high-dose groups of Huayu Mingmu prescription (9.29, 18.57, 37.14 g·kg-1), and a calcium dobesilate group (0.16 g·kg-1), with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography, and pathological changes in retinal tissue were evaluated using hematoxylin-eosin (HE) staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff (PAS) staining. Immunofluorescence (IF) was used to detect the expression of VEGFA and angiopoietin-2 (Ang-2) in retinal tissue. Western blot was employed to detect the protein expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. ResultsCompared with the normal group, the model group exhibited significant pathological changes in retinal tissue, including the appearance of acellular capillaries, as well as significant endothelial cell (E) proliferation and pericyte (P) loss (P<0.01). The E/P was significantly elevated (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly increased (P<0.01), and the expression of Ang-2 protein was significantly elevated (P<0.01). In contrast, retinal tissue in the treatment groups showed alleviated pathological changes, with reduced endothelial cell proliferation and pericyte loss (P<0.05, P<0.01). Among the treatment groups, the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly reduced (P<0.05, P<0.01), and the expression of Ang-2 protein was significantly decreased (P<0.01). ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats, delay the progression of DR, and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.
3.Epidemiological and etiological characteristics of hand-foot-mouth disease in Hangzhou, Zhejiang Province, 2010‒2023
Shuang FENG ; Xiaobin REN ; Zhe WANG ; Zhaokai HE ; Yanyang TAO ; Qingjun KAO ; Zhou SUN
Shanghai Journal of Preventive Medicine 2025;37(2):129-134
ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.
4.Mechanism of Gegen Qinliantang in Regulating Microglia Polarization to Improve Diabetic Cognitive Impairment
Hui FENG ; Chunxiang ZHOU ; Tianyi REN ; Weiwei TAO ; Yun LING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):1-10
ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment (DCI). MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group, dapagliflozin group (1.0 mg·kg-1·d-1), low-dose Gegen Qinliantang group (6.24 g·kg-1·d-1), and high-dose Gegen Qinliantang group (24.96 g·kg-1·d-1). Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose (FBG) were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 (IBA1) in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 (PSD-95), synapsin (SYN), nuclear factor-κB p65 (NF-κB p65), and phosphorylated NF-κB p65 (p-NF-κB p65) in the hippocampus. ResultsCompared with the normal group, the model group showed significantly increased body weight and FBG levels (P<0.01), significantly prolonged escape latency and reduced platform crossings in the Morris water maze test (P<0.01), disordered arrangement of hippocampal neurons, nuclear pyknosis, increased neuronal necrosis, reduced Nissl bodies, decreased expression of synaptic proteins PSD-95 and SYN (P<0.01), increased CD16/32+ /IBA1+ positive rate, elevated levels of TNF-α and IL-1β, and an increased p-NF-κB p65/NF-κB p65 ratio (P<0.01). Compared with the model group, the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 (P<0.05, P<0.01) and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 (P<0.05). Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group (P<0.05). Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group (P<0.05). Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups, with significantly increased expression of PSD-95 and SYN (P<0.01). Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32+/IBA1+ positive rate of microglia, while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 (P<0.05, P<0.01). ConclusionGegen Qinliantang can improve hyperglycemia, cognitive dysfunction, and synaptic damage in DCI, inhibit M1 polarization of microglia and neuroinflammation, and its mechanism may be related to the inhibition of NF-κB activation.
5.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
6.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
7.Exploration of Zhuyuwan in Treatment of Atherosclerosis from Perspective of Lipid Transport Disorder
Wei SONG ; Zhongyi ZHANG ; Hairong QIU ; Mei ZHAO ; Zubing ZHOU ; Tao SHEN ; Yong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):54-61
This article discusses the key pathogenesis of atherosclerosis (AS) based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS, aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances, lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement, the accumulation of dampness and turbidity, and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors: deficiency of healthy Qi, phlegm-turbidity, and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids, their impaired dispersion may lead to phlegm-turbidity and blood stasis, the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore, AS is rooted in spleen-stomach disorder, manifests as plaques formed by pathological product accumulation in vessels, with lipid transport disorder as its core pathogenesis. Specifically speaking, the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage, and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan, first recorded in Taiping Holy Prescriptions for Universal Relief, contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma, bitter and cold, exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus, pungent-bitter and hot, disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang, assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism, Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance, improving gut microbiota composition and metabolism, and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS, this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder, giving novel insights into the prevention and treatment of AS.
8.Mechanism of Gegen Qinliantang in Regulating Microglia Polarization to Improve Diabetic Cognitive Impairment
Hui FENG ; Chunxiang ZHOU ; Tianyi REN ; Weiwei TAO ; Yun LING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):1-10
ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment (DCI). MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group, dapagliflozin group (1.0 mg·kg-1·d-1), low-dose Gegen Qinliantang group (6.24 g·kg-1·d-1), and high-dose Gegen Qinliantang group (24.96 g·kg-1·d-1). Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose (FBG) were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 (IBA1) in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 (PSD-95), synapsin (SYN), nuclear factor-κB p65 (NF-κB p65), and phosphorylated NF-κB p65 (p-NF-κB p65) in the hippocampus. ResultsCompared with the normal group, the model group showed significantly increased body weight and FBG levels (P<0.01), significantly prolonged escape latency and reduced platform crossings in the Morris water maze test (P<0.01), disordered arrangement of hippocampal neurons, nuclear pyknosis, increased neuronal necrosis, reduced Nissl bodies, decreased expression of synaptic proteins PSD-95 and SYN (P<0.01), increased CD16/32+ /IBA1+ positive rate, elevated levels of TNF-α and IL-1β, and an increased p-NF-κB p65/NF-κB p65 ratio (P<0.01). Compared with the model group, the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 (P<0.05, P<0.01) and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 (P<0.05). Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group (P<0.05). Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group (P<0.05). Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups, with significantly increased expression of PSD-95 and SYN (P<0.01). Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32+/IBA1+ positive rate of microglia, while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 (P<0.05, P<0.01). ConclusionGegen Qinliantang can improve hyperglycemia, cognitive dysfunction, and synaptic damage in DCI, inhibit M1 polarization of microglia and neuroinflammation, and its mechanism may be related to the inhibition of NF-κB activation.
9.Clinical Efficacy of Zhuyuwan in Treatment of Hyperlipidemia with Syndrome of Phlegm Turbidity and Obstruction
Lele YANG ; Danmei LUO ; Jiao CHEN ; Xiaobo ZHANG ; Wei SONG ; Wenyu ZHU ; Xin ZHOU ; Xueping LI ; Tao SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):29-37
ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study, hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally, 162 valid cases were included, encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets, and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery, blood lipid levels, TCM syndrome distribution, efficacy in terms of TCM syndrome, and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery, the total response rate in the observation group was 86.36% (76/88) and that in the control group was 86.49% (64/74), with no statistically significant difference between the two groups. After treatment, both groups showed declines in levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.05) and elevations in the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05). Moreover, the observation group outperformed the control group in recovering the levels of TG, LDL-C, and HDL-C (P<0.05, P<0.01). In terms of TCM syndrome, hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% (55/63), which was higher than that (63.46%, 33/52) in the control group (χ2=9.102, P<0.01). After treatment, the scores of total TCM symptoms, primary symptoms, and secondary symptoms decreased in both groups (P<0.05), and the observation group had lower scores than the control group (P<0.01). The observation group was superior to the control group in alleviating obesity, chest tightness, and low food intake (P<0.05). In terms of safety, the level of aminotransferase was slightly elevated in the control group, and no obvious adverse reaction was observed in the observation group, with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.
10.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

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