1.Efficacy of Fufang Lingjiao Jiangya Pills with Different Proportions of Goat Horn Replacing Antelope Horn on Spontaneous Hypertensive Rats
Tengjian WANG ; Wanlu ZHAO ; Yang YU ; Yan LIU ; Kun CAO ; Zheyuan LIN ; Yue WU ; Lilan LUO ; Weizhi LAI ; Zhaohuan LOU ; Qiaoyan ZHANG ; Quanlong ZHANG ; Luping QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):68-78
ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats (SHR). In this experiment, 50 SHR rats were randomly grouped as follows: model (n=8), captopril (0.01 g·kg-1) (n=6), low-dose blank Fufang Lingjiao Jiangya pills (0.342 g·kg-1) (n=6), high-dose blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1) (n=6), low-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), high-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6), low-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), and high-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6). Additionally, 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration, 3 h post administration, and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions, 48 SHR rats were randomly grouped as follows: model, blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1), antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1), 2× goat horn-containing Fufang Lingjiao Jiangya pills (0.824 g·kg-1), 4× goat horn Fufang Lingjiao Jiangya pills (0.969 g·kg-1), and 6× goat horn Fufang Lingjiao Jiangya pills (1.112 g·kg-1). The normal group included 8 WKY rats, and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks, and blood pressure was recorded at various time points (pre-administration, 3 h post administration, and on days 4, 7, 10, and 14 of administration). Serum levels of angiotensin-converting enzyme (ACE), angiotensin Ⅱ(Ang Ⅱ), renin, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart, kidney, and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2, angiotensin Ⅱ type 1 receptor (AT1R), and angiotensinogen (AGT) in the kidney tissue were determined by Western blot, while the expression of nuclear factor (NF)-κB p65 and Toll-like receptor 4 (TLR4) in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group, all treatment groups showed lowered blood pressure (P<0.05, P<0.01), and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group, the model group showed elevated serum levels of ACE, Ang Ⅱ, renin, and IL-6, while the elevations were declined in the Fufang Lingjiao Jiangya pills groups (P<0.05, P<0.01). Pathological changes in the heart, kidney, and thoracic aorta were alleviated in all the treatment groups, with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R, AGT, NF-κB p65, and TLR4 and up-regulated protein levels of ACE2 (P<0.05, P<0.01) compared with model group, with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system (RAAS) and TLR4/NF-κB signaling pathways.
2.Mechanism Study of"Atractylodes Macrocephala Koidz-Atractylodes Rhizoma"Drug Pair on the Prevention and Treatment of Hyperlipidemia Based on Network Pharmacology and Transcriptome Analysis
Yiting DENGZHANG ; Jingyi KANG ; Zhaohuan LOU
Journal of Zhejiang Chinese Medical University 2024;48(1):9-20
[Objective]To clarify the therapeutic effects of the"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair on hyperlipidemia(HLP)and to illuminate the primary mechanism via network pharmacology analysis.[Methods]HLP rat model was established by feeding rats with high-fat diet,and different doses of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair were administrated at the same time.At the end of the experiment,comparing the blood lipid levels of each group of rats and observing the lipid deposition in liver tissue.Using network pharmacology to predict the potential active ingredients and targets of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair for treating HLP,and further experimental verification.[Results]The drug pair of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"had a good effect on anti HLP induced by high-fat diet.Network pharmacology analysis showed that 3[3-acetoatractylodes atractylodes,wogonin,and 3 β-acetoxyatractylodes atractylodes were the potential active ingredients of the drugs in the treatment of HLP,and peroxisome proliferators-activated receptors(PPAR)signaling pathway-related PPARγ and fatty acid binding protein 4(FABP4)were the potential regulatory pathways and targets.The results of the validation experiment further confirmed that the drug pair could significantly up-regulate the expression of PPARy in liver tissue of rats with HLP.[Conclusion]The effect of"Atractylodes macrocephala Koidz-Atractylodes Rhizoma"drug pair on high-fat diet-induced HLP is related to the activation of PPARγ signaling pathway.
3.Comparison of Anti-ulcerative Colitis Effect of Huangqin Decoction Combined with Paeoniae Radix Alba and Paeoniae Radix Rubra
Huajie HU ; Xinyu QIU ; Jiayan JIANG ; Yingying WANG ; Liping HAN ; Zhaohuan LOU
Chinese Journal of Modern Applied Pharmacy 2024;41(4):524-532
OBJECTIVE
To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment.
METHODS
The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively.
RESULTS
There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1.
CONCLUSION
Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.
4.Application of micro-macroscopical identification in quality acceptance of Chinese herbal pieces in medical institutions
Lulu ZHANG ; Zhaohuan LOU ; Xuemei ZHU ; Yongcai CHEN ; Jingjing ZHU ; Leyan HUANG
China Pharmacist 2024;27(8):1309-1319
Objective To identify easily confused Chinese herbal pieces by micro-macroscopical identification method,and study its application value in quality acceptance of Chinese herbal pieces in medical institutions.Methods Using the method of micro-macroscopical identification,with the help of related instruments,the microscopic characteristics of 10 groups of 31 kinds of Chinese herbal pieces,which were easy to be confused and could not be observed by naked eye and ordinary magnifying glass,were analyzed and summarized according to the classification of different medicinal parts,such as flowers,fruits,seeds,whole grass,roots and rhizomes,stems,and others,and pictures were taken to save them.Results The micro-characters of 10 groups of 31 easily confused Chinese herbal medicines,including Eriocauli flos,Eriocaulon sexangulare,Eriocaulon australe,Aurantii fructus,Citrus changshan-huyou,Chaenomelis fructus,Chaenomeles cathayensis,Perillae fructus,Perillae fructus(Physalis alba),Perillae fructus(Wild),Astragali complanati semen,Astragalus chinensis,Selaginellae herba,Selaginella pulvinata,Selaginella moellendorfii,Selaginella doederleinii,Selaginella uncinata,Lysimachiae herba,Lysimachia hemsleyana,Desmodium styracifolium,Dryopteris crassirhizoma,Woodwardia japonica,Brainea insignis,root of Valvate actinidia,Actinidia arguta,Tripterygium wilfordii,root of Romanet grape,Trogopterus dung,Bat dung,Hare dung and Silkworm sand were observed.The various traditional Chinese medicines possessed unique identification characteristics.Flower-based medicines could be studied for their color,tissue structure,and surface features such as texture and trichomes.Fruit-based medicines could be studied for their fruit peel structure,color,degree of development,and outer characteristics such as cuticle layer and wax.Seed-based medicines could be studied for their morphology,size,color,and texture.Whole plant-based medicines could be studied for leaf length-to-width ratio,widest point,surface characteristics,and splitting situation,as well as stem trichomes and stomata.Root-based medicines,rhizome-based medicines,and stem-based medicines could be studied for their bark,wood structure,and the morphology and arrangement of vascular bundles or ducts.Other kinds of medicines could be studied from their sources,and these unique micro-characteristic identification features could be easily discovered with the help of a microscope.Conclusion Compared with the traditional characteristic identification,micro-macroscopical identification is more capable of improving the accuracy of Chinese herbal pieces identification,which is economical,practical,simple and intuitive,and can be popularized as a commonly used identification method of herbal medicines in medical institutions,and it is a feasible solution to realize the rapid inspection of herbal medicines.
5. Mechanisms of Radix Tetrastigma on anti rheumatoid arthritis via regulating the balance of Th17/Treg
Tiefeng WANG ; Wenrui ZHU ; Jie SU ; Rongshuang XIA ; Sifan LI ; Zhaohuan LOU ; Weidong WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(2):138-146
AIM: To explore the possible mechanism of Radix Tetrastigma (RT) on anti-rheumatoid arthritis (RA). METHODS: The rat model of RA was established by intradermal injection of complete Freund]s adjuvant into the right hind foot of SD rats. RT Extract with different dosage was continuous intragastric administration for 3 weeks, then, the degree of foot swelling, arthritis index score, joint heat and grip of each rat was measured respectively. ELISA was used to detect the expression levels of Interleukin (IL) 6, IL-17, IL-10, tumor necrosis factor-α, and rheumatoid factor. Fully automatic hemorheometer was applied to measure hemorheology indexes. The number of CD4
6.Mechanism and intervention of mucosal immune regulation based on "lung and large intestine being interior-exteriorly related" theory of traditional Chinese medicine.
Zhaohuan LOU ; Huajun ZHAO ; Guiyuan LYU
Journal of Zhejiang University. Medical sciences 2020;49(6):665-678
The "lung and large intestine being interior-exteriorly related" is one of the classical theories in traditional Chinese medicine, which indicates a close correlation between the lung and large intestine in physiology and pathology, and plays a pivotal role in guiding the treatment of the lung and bowel diseases. Modern medicine has revealed some connections between the lung and large intestine in tissue origin and mucosal immunity, and preliminarily illuminated the material basis and possible regulatory mechanism of the theory. Recently, this theory has been applied to guide the treatment of refractory lung and intestine diseases such as COVID-19 and ulcerative colitis and has obtained reliable efficacy. Existing research results show that the anatomical homogeneity of lung and large intestine promotes the correlation between lung-bowel mucosal immunity, and mucosal immunity and migration and homing of innate lymphocytes are one of the physiological and pathological mechanisms for lung and large intestine to share. Under the guidance of this theory, Chinese medicines with heat-clearing and detoxifying or tonic effects are commonly used in the treatment of the lung and intestinal diseases by regulating lung-bowel mucosal immunity and they can be candidate drugs to treat lung/intestinal diseases simultaneously. However, the existing studies on immune regulation are mainly focused on the expression levels of sIgA and cytokines, as well as the changes in the number of immune cells such as innate lymphocytes and B lymphocytes. While the following aspects need further investigation: the airway/intestinal mucous hypersecretion, the functional changes of pulmonary and intestinal mucosal barrier immune cells, the dynamic process of lung/intestinal mucosal immune interaction, the intervention effect of local pulmonary/intestinal microecology, the correlation and biological basis between the heat-clearing and detoxifying effect and the tonic effect, and its regulation of pulmonary/intestinal mucosal immunity. In this paper, we try to analyze the internal relationship between lung and intestine related diseases from the point of view of the common mucosal immune system of lung and intestine, and summarize the characteristics and rules of traditional Chinese medicine compound and its active ingredients, which have regulatory effect on lung and intestine mucosal immune system, so as to further explain the theoretical connotation of "lung and large intestine being interior-exteriorly related" and provide reference for the research and development of drugs for related diseases.
COVID-19/immunology*
;
Colitis, Ulcerative/immunology*
;
Humans
;
Intestine, Large/immunology*
;
Lung/immunology*
;
Medicine, Chinese Traditional
7."The Effect of""Gut-liver Axis""on the Development of Alcoholic Liver Disease and the Intervention of Linderae Radix"
Journal of Zhejiang Chinese Medical University 2017;41(6):545-547
[Objective] To analyze relations between alcoholic liver disease(ALD) and gut-liver axis, and the intervention effects of Linderae radix(LR) on both of them. [Methods] Research reports about ALD,gut-liver axisand LR on anti ALD at home and abroad in recent years were reviewed, and effects ofgut-liver axisin the occurrence and development of ALD and LR on ALD treatment were summarized. [Results] Recent studies show that there is an abnormalgut-liver axisin ALD,gut permeability and intestinal endotoxemia(IETM) induced by excessive alcohol consumption is one of the key pathogenic factors for the occurrence and development of ALD. Improving intestinal functions to alleviate IETM would be an efficient way to treat ALD. Linderae radix (LR) is a traditional Chinese medicine commonly used for Qi-regulating in clinic ,it possesses a good effect for gastrointestinal function regulation and as reported in recent researches,it has shown a good protective effect on ALD by improving the abnormal gut-liver axisand alleviating IETM. [Conclusions] The abnormalgut-liver axisinduced by excessive alcohol intake is the key factor for ALD formation and development. LR possesses a protective function on ALD viagut-liver axisimprovement.
8.Preventive and therapeutic effects of compound ginkgo extract in rats with nonalcoholic steatohepatitis induced by high-fat, high-fructose diet
Qing YANG ; Hui ZHAO ; Aizhen ZHOU ; Zhaohuan LOU
Chinese Journal of Hepatology 2016;24(11):852-858
Objective To establish a rat model of nonalcoholic steatohepatitis (NASH),and to investigate the preventative and therapeutic effects of compound ginkgo extract against NASH.Methods A total of 60 male Sprague-Dawley rats were fed with high-fat feed and 10% fructose water for 24 weeks to establish the rat model of NASH.The general behaviors of the rats were observed,and the body weight was recorded.Blood samples from the inferior vena cava and the liver were collected after the last administration to measure serum total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C),as well as liver function parameters.The liver index was calculated,HE staining was performed to observe liver histopathological changes,and the total lipase activity and the levels of TC,TG,and free fatty acid (FFA) in liver tissue were measured.Results After 24 weeks,compared with the normal group,the model group had a significantly faster increase in body weight,significant increases in serum levels of TC (2.20±0.52 mmol/L),TG (0.87±0.22 mmol/L),LDL-C (1.22±0.50 mmol/L),alanine aminotransferase (ALT) (129.4±44.7 U/L),and aspartate aminotransferase (AST) (209.3±42.8 U/L),liver index (3.62%±0.28%),and the levels of TC (4.42±1.39 mmol/mg.prot),TG (0.85±0.11 mmol/mg.prot),and FFA (644.78±36.65 μmol/L) in liver tissue,and significant reductions in serum HDL-C level (0.58±0.11 mmol/L) and the activity of lipoprotein lipase (LPL) (9.95±1.64 U/mg.prot)and hepatic lipase (HL) (9.91±1.03 U/mg.prot) (all P < 0.01).In addition,the pathological results showed severe hepatocyte steatosis,varying degrees of inflammatory cell infiltration,exudation in the portal area,and necrosis of liver cells in the model group.After the intervention with compound ginkgo extract,there were significant reductions in serum levels ofTC (1.78±0.21 mmol/L),TG (0.58±0.07 mmol/L),LDL-C (0.84±0.19mmol/L),and ALT (84.1±17.1 U/L),AST (155.4±20.9 U/L),liver index (2.71 %±0.15%),and the levels of TC (2.24±1.02 mmol/mg.prot),TG (0.46±0.11 mmol/mg.prot),and FFA (580.56±50.63 μmol/L) in liver tissue,as well as significant increases in serum HDL-C level (0.68±0.10 mmol/L) and the activities of LPL (15.54±2.21U/mg.prot) and HL (11.92± 1.87 U/mg.prot) (P < 0.05 or P < 0.01).At the same time,it significantly reduced hepatomegaly in rats and improved fatty degeneration and degree of inflammation in liver cells.Conclusion Compound ginkgo extract can prevent and treat NASH by correcting dyslipidemia,improving liver function and fatty degeneration in hepatocytes,and reducing the degree of inflammation,and its mechanism of action may be associated with increasing total lipase activity,reducing FFA in the liver,increasing the decomposition of TG,and reducing the synthesis of TG.
9.Extraction Process Optimization of Gastrodine in Tianma Gouteng Decoctions
Tiefeng WANG ; Yajing LI ; Mengjiao DENG ; Zhaohuan LOU ; Junyan ZHAO
China Pharmacist 2015;(3):384-386
Objective:To establish an optimal extraction technology for gastrodine in Tianma Gouteng decoctions. Methods: An orthogonal design with extract yield and gastrodine concentration as the indices was carried out to observe the influence of the extraction time, water amount and extract times on the extraction result. Results:The extract times showed significant influence on the extraction percentage of gastrodine. The best extraction parameters were as follows:adding 12-fold water and decocting 3 times with 1. 5h for each time. Conclusion:The established extraction process is feasible, which can be used in the preparation of the effective part for Tianma Gouteng decoctions with gastrodine concentration as the index.
10.Review on the Research of the Components, Pharmacological Actions and Toxicity of Polygonum Multiflorum Thunb(Heshouwu)
Zhaohuan LOU ; Guiyuan LV ; Jingjing YU
Journal of Zhejiang Chinese Medical University 2014;(4):495-500
[Objective] To sum up researches on components, pharmacological actions and toxicity of Polygonum multiflorum Thunb(Heshouwu). [Method] The research reference about Heshouwu in CNKI, VIP and PUBMAD database is col ected and calssified to three aspects on components, pharmacological actions and toxicity.[Result]①On components:Heshouwu contains stilbene, lecithin, anthraquinone, flavonoids, tannin and trace elements. The stilbene and anthraquinone are the mainly active components. Producing area, growth years, harvest time and processing methods are factors affecting the content of the components such as TSG in Heshouwu; Macroporous adsorption resin is the main separation method for preconcentration of TSG and anthraquinone constituents; ② On pharmacological actions and toxicity: Heshouwu has effects of hypolipidemic and liver protection, antioxidative, anti-osteoporosi, hpyerglycemic, antidepressive and antibiosis, the hypolipidemic and liver protection are the main effects which have been studied more. A reversible liver injury which displays as abnormal liver function parameter and bile metabolic disorder would be induced if the Heshouwu is administrated with a large dosage for long term. The possible components which would induce the toxicity in Heshouwu are tannin and anthraquinone, and the anthraquinone is the component with double effects of toxicity and therapy which should be considered in clinical application. [Conclusion]Reducing lipid and protecting liver is the main pharmaceutical function of the herb. As a commonly used Chinese herb for liver protection, the studies on alcoholic hepatic injury protection of Heshouwu may be a point for the researchers to focus on. The comparison studies on hypolipidemic and liver protection between Hesouwu and its processing products, and the correlations between components and pharmacological actions are worth study further.


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