1.TCMHTI: a Transformer-based herb-target interaction prediction model for Qingfu Juanbi Decoction in rheumatoid arthritis
Zhenzhong LIANG ; Changsong DING
Digital Chinese Medicine 2025;8(2):206-218
[Objective] :
To predict the potential targets of Qingfu Juanbi Decoction (青附蠲痹汤, QFJBD) in treating rheumatoid arthritis (RA) using an improved Transformer model and investigate the network pharmacological mechanisms underlying QFJBD’s therapeutic effects on RA.
Methods:
First, a traditional Chinese medicine herb-target interaction (TCMHTI) model was constructed to predict herb-target interactions based on Transformer improvement. The performance of the TCMHTI model was evaluated against baseline models using three metrics: area under the receiver operating characteristic curve (AUC), precision-recall curve (PRC), and accuracy. Subsequently, a protein-protein interaction (PPI) network was built based on the predicted targets, with core targets identified as the top nine nodes ranked by degree values. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the targets predicted by TCMHTI and the targets identified through network pharmacology method for comparison. Then, the results were compared. Finally, the core targets predicted by TCMHTI were validated through molecular docking and literature review.
Results:
The TCMHTI model achieved an AUC of 0.883, PRC of 0.849, and accuracy of 0.818, predicting 49 potential targets for QFJBD in RA treatment. Nine core targets were identified: tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-17A, cluster of differentiation 40 (CD40), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), IL-4, and signal transducer and activator of transcription 3 (STAT3). The enrichment analysis demonstrated that the TCMHTI model predicted 49 targets and enriched more pathways directly associated with RA, whereas classical network pharmacology identified 64 targets but enriched pathways showing weaker relevance to RA. Molecular docking demonstrated that the active molecules in QFJBD exhibit favorable binding energy with RA targets, while literature research further revealed that QFJBD can treat RA through 9 core targets.
Conclusion
The TCMHTI model demonstrated greater accuracy than traditional network pharmacology methods, suggesting QFJBD exerts therapeutic effects on RA by regulating targets like TNF-α, IL-1β, and IL-6, as well as multiple signaling pathways. This study provides a novel framework for bridging traditional herbal knowledge with precision medicine, offering actionable insights for developing targeted TCM therapies against diseases.
2.A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.
Jianbing WU ; Duorui JI ; Weijie JIAO ; Jian JIA ; Jiayi ZHU ; Taijun HANG ; Xijing CHEN ; Yang DING ; Yuwen XU ; Xinglong CHANG ; Liang LI ; Qiu LIU ; Yumei CAO ; Yan ZHONG ; Xia SUN ; Qingming GUO ; Tuanjie WANG ; Zhenzhong WANG ; Ya LING ; Wei XIAO ; Zhangjian HUANG ; Yihua ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
3.Progress in the Study of the Chemical Composition and Biological Activity of Hypericum Attenuatum Choisy
Xiling FAN ; Wenjun LIU ; Xueni NIU ; Liang CAO ; Jinzhou TIAN ; Xin WANG ; Zhenzhong WANG ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1578-1591
Hypericum attenuatum Choisy.is dry whole grass of the genus Hypericum L.,is a kind of commonly used folk medicinal herbs more than 2400 years.And it is often used to treat heart disease,hemostasis,scald.Based on a review of domestic and international literature,the main chemical components of Hypericum attenuatum Choisy.include PPAPs,flavonoids,and volatile oil,of which PPAPs and xanthone have received the attention of a large number of scholars because of their complex and novel structures and unique pharmacological effects.Modern pharmacological studies have shown that Hypericum attenuatum Choisy.exerts various pharmacological activities,including anti-arrhythmia,reducing blood sugar,anti-tumor,anti-virus,anti-inflammation,as well as the treatment of depression.As a valuable folk medicine,there is relatively little related traditional Chinese medicine products,this review focus on its phytochemistry,and pharmacology,providing a comprehensive perspective and novel ideas for exploring its current and potential applications.
4.Progress in the Study of the Chemical Composition and Biological Activity of Hypericum Attenuatum Choisy
Xiling FAN ; Wenjun LIU ; Xueni NIU ; Liang CAO ; Jinzhou TIAN ; Xin WANG ; Zhenzhong WANG ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1578-1591
Hypericum attenuatum Choisy.is dry whole grass of the genus Hypericum L.,is a kind of commonly used folk medicinal herbs more than 2400 years.And it is often used to treat heart disease,hemostasis,scald.Based on a review of domestic and international literature,the main chemical components of Hypericum attenuatum Choisy.include PPAPs,flavonoids,and volatile oil,of which PPAPs and xanthone have received the attention of a large number of scholars because of their complex and novel structures and unique pharmacological effects.Modern pharmacological studies have shown that Hypericum attenuatum Choisy.exerts various pharmacological activities,including anti-arrhythmia,reducing blood sugar,anti-tumor,anti-virus,anti-inflammation,as well as the treatment of depression.As a valuable folk medicine,there is relatively little related traditional Chinese medicine products,this review focus on its phytochemistry,and pharmacology,providing a comprehensive perspective and novel ideas for exploring its current and potential applications.
5.Identification of Chemical Constituents in Shangketianshao Gel by LC-Q-TOF/MS
Li YANG ; Mengxuan LI ; Mengyu QIAN ; Wenjun LIU ; Ming YAN ; Liang CAO ; Chenfeng ZHANG ; Juan FU ; Zhenzhong WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1515-1527
Objective The study analyzed and identified the components in Shangketianshao Gel by LC-Q-TOF/MS.Methods The analysis was performed on Agilent Eclipse Plus C18(250 mm×4.6 mm,5 μm)column was applied with methanol and 0.1%formic acid as mobile phase for gradient elution,flow rate was 1 mL·min-1 and column temperature was 30℃.The analytes were determined by positive and negative ion modes with electro-spray ionization source,combined message of standard reference and the literature.Results 103 constituents were identified,all compounds were classified to their medicinal materials derivation.22 compounds from Paeoniae Radix Rubra,33 compounds from Rhei Radix et Rhizoma,20 compounds from Angelicae Dahuricae,23 compounds from Cortex Phellodendr and 14 compounds from Trichosanthes kirilowii Maxim.9 components were jointly owned.Conclusion The study provided a suitable way for Chemical fundamentals and quality control of Shangketianshao Gel and laid a foundation for in depth studies of its pharmacodynamics and the quality control.
6.Research Progress on Chemical Constituents of Alpinia oxyphylla and its Pharmacological Activities
Haibo LI ; Mi ZHOU ; Jie DONG ; Zhenzhong WANG ; Liang CAO ; Xinsheng YAO ; Yang YU ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(7):1870-1887
As a commonly used traditional Chinese medicine,Alpinia oxyphylla is widely used as both medicine and edible resources.A.oxyphylla has the effects of warming the kidney,consolidating essence,contracting urine,warming the spleen,stopping diarrhea and absorbing saliva,which mainly treated diseases caused by kidney deficiency and spleen cold.A.oxyphylla is rich in chemical components,mainly including 194 volatile oil,121 terpenoids(including 111 sesquiterpenoids),19 diphenylheptanes,ten flavonoids,ten bases and nucleosides,four steroids,eight glycosides and 13 organic acids.It has a wide range of pharmacological effects such as anti-AD/PD,anti-tumor,anti-inflammatory,antioxidant,etc.This article reviews the chemical components and pharmacological effects of A.oxyphylla,in order to provide reference for its further development and rational application.
7.The value of right atrial myocardial fibrosis in evaluating the prognosis of isolated tricuspid valve surgery after left heart valve surgery
Yanchen YANG ; Lishan ZHONG ; Zhenzhong WANG ; Liang YANG ; Yingjie KE ; Haijiang GUO ; Biaochuan HE ; Kan ZHOU ; Junfei ZHAO ; Huanlei HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):1008-1013
Objective To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.
8.Effect of Alcohol Extract of Oroxylum indicum on Reducing Uric Acid and Protecting Kidney in Hyperuricemia Mice
Mingke YIN ; Liang LI ; Yaozhong LYU ; Chenfeng ZHANG ; Zhenzhong WANG ; Wei XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):57-63
ObjectiveTo investigate the effect of alcohol extract of Oroxylum indicum (MHD-80) on reducing uric acid (UA) and protecting the kidney in the hyperuricemia (HUA) model in vivo. MethodPotassium oxazine (350 mg·kg-1) and adenine (80 mg·kg-1) were used to construct an HUA model of mice in vivo to evaluate the mechanism related to UA reduction and the protective effect of renal function of MHD-80. Seventy male ICR mice were randomly divided into seven groups, including the normal group, model group, allopurinol group (5 mg·kg-1), febusotan group (5 mg·kg-1), and MHD-80 low-, medium-, and high-dose groups (3, 6, 12 mg·kg-1), with 10 in each group. Except for the normal group, the other groups were given intragastric administration of potassium oxazine and adenine for 14 consecutive days to establish the HUA model. On the 8th to 14th day after modeling, each group was given corresponding drugs by intragastric administration, once a day. 1 h after the last administration, blood was collected from the eyeballs, and kidney and liver tissues of mice were collected. Serum levels of UA, urea nitrogen (BUN), and creatinine (Cr) and liver activity of xanthine oxidase (XOD) were determined by enzyme colorimetry. Serum contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxilin-eosin (HE) staining was used to observe the pathological changes in kidney tissues. The protein expression levels of ATP-binding box transporter G2 (ABCG2) and glucose-facilitating transporter 9 (GLUT9) in kidney tissues were detected by Western blot. ResultIn vivo experiment shows that compared with the normal group, the serum levels of UA, Cr, BUN, inflammatory factors TNF-α, IL-1β, and liver XOD activity in the serum of mice in the model group were significantly increased (P<0.05, P<0.01), and the expression of GLUT9 in kidney tissues was significantly up-regulated (P<0.05). ABCG2 protein expression was significantly down-regulated (P<0.05), and renal injury was obvious. Compared with the model group, the levels of UA, BUN, Cr, TNF-α, IL-1β, and liver XOD activity in the serum of mice in the high-dose group of MHD-80 were decreased to different degrees (P<0.05, P<0.01), GLUT9 protein expression was significantly down-regulated (P<0.01), ABCG2 protein expression was significantly up-regulated (P<0.05) in the high-dose group of MHD-80, and the degree of renal injury was reduced. ConclusionMHD-80 has certain uric acid reduction, anti-inflammatory, and anti-renal injury effects, which are related to inhibiting XOD activity and regulating the expression of ABCG2 and GLUT9 uric acid transporter.
9. Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis
Xia GAO ; Jiajia WANG ; Xialin CHEN ; Shanli WANG ; Chaojie HUANG ; Quanchang ZHANG ; Liang CAO ; Zhenzhong WANG ; Wei XIAO ; Xia GAO ; Jiajia WANG ; Xialin CHEN ; Shanli WANG ; Chaojie HUANG ; Quanchang ZHANG ; Liang CAO ; Zhenzhong WANG ; Wei XIAO ; Xia GAO ; Jiajia WANG ; Xialin CHEN ; Shanli WANG ; Chaojie HUANG ; Quanchang ZHANG ; Liang CAO ; Zhenzhong WANG ; Wei XIAO ; Shanli WANG ; Chaojie HUANG
Chinese Herbal Medicines 2022;14(4):583-591
Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE
10.Effects of Guizhi Fuling Capsules and Its Main Components on Intestinal Flora of Primary Dysmenorrhea Model Rats
Kun DUAN ; Xia GAO ; Ting GENG ; Liang CAO ; Wei XIAO ; Zhenzhong WANG
China Pharmacy 2020;31(11):1320-1326
OBJECTIVE:To investigate the effects of Guizhi ful ing capsules and its principal components (paeoniflorin, paeonol and amygdalin )on the intestinal flora of primary dysmenorrhea model rats. METHODS :Female SD rats were randomly divided into normal group ,model group ,capsule group(Guizhi fuling capsule ,1 000 mg/kg),paeoniflorin group (15.0 mg/kg), paeonol group (10.3 mg/kg)and amygdalin group (12.1 mg/kg),with 6 rats in each group. Except for normal group ,other groups were given estradiol benzoate subcutaneously on the back of rats and oxytocin intraperitoneally to induce primary dysmenorrhea model. From the 4th day after subcutaneous injection of estradiol benzoate ,normal group was given constant volume of normal saline intragastrically ;model group was given constant volume of 0.5%CMC-Na solution intragastrically ;administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 7 days. The writhing times and the contents of and MDA in uterus tissue of rats were determined ,and then com the contents of short-chain fatty acids (SCFAs)such as acetic acid,propionic acid ,butyric acid in colonic contents were detected by GC method. Using diver sity index as index , Rep-PCR and Eric-PCR were used to evaluate the d iversity of intestinal flora in feces of rats. RESULTS :Compared with normal group,the writhing times of rats were increased significantly in model group ;the contents of NO and MDA in uterus were increased significantly ,while the contents of acetic acid ,propionic acid and butyric acid in colonic contents and total content of SCFAs were decreased significantly (P<0.05 or P<0.01);the number of DNA electrophoresis bands of intestinal flora was significantly reduced ,the brightness of most bands was significantly reduced ,and the diversity indexes (by Rep-PCR and Eric-PCR method ,hereinafter)1 h after administration were significantly reduced (P<0.05 or P<0.01). Compared with model group,writhing times of rats were decreased significantly in capsule group ,paeoniflorin group and paeonol group ;the contents of NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group ,paeoniflorin group and paeonol group were decreased significantly (P<0.05 or P<0.01);the propionic acid content and total content of SCFAs in colon of rats in capsule group ,the contents of acetic acid ,propionic acid and butyric acid ,total content of SCFAs in paeoniflorin group as well as the contents of propionic acid and butyric acid ,total content of SCFAs in paeonol group were increased significantly;the content of isovaleric acid was decreased significantly in paeoniflorin group (P<0.05 or P<0.01);DNA electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups ,and the diversity indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group ,while those indexes were decreased significantly in paeonol group and amygdalin group (P<0.05 or P<0.01). CONCLUSIONS :Guizhi fuling capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At the same time ,the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above effects may be related to paeoniflorin and paeonol in the capsules.

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