1.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P0.01), whereas it was significantly increased in the Sini San group compared with the model group (P0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P0.05), and compared with the model group, both were significantly increased in the Sini San group (P0.05, P0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P0.05, P0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
2.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P<0.01), whereas it was significantly increased in the Sini San group compared with the model group (P<0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P<0.05), and compared with the model group, both were significantly increased in the Sini San group (P<0.05, P<0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P<0.05, P<0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P<0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
3.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
4.Clinical Observation of Modified Huanglian Wendantang in Treatment of Cardiovascular Risk Factors in Patients with Metabolic Syndrome Under Guidance of Treating Disease before Its Onset
Yi HAN ; Yubo HAN ; Guoliang ZOU ; Ruinan WANG ; Chunli YAO ; Xinyu DONG ; Li LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):142-149
ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group (41 cases) and a control group (41 cases) by the random number table method. The control group received routine treatment, and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators, blood pressure indicators, glucose and lipid metabolism indicators, inflammatory factors, and vascular endothelial function indicators before and after treatment in the two groups were measured, and the treatment safety was evaluated. ResultsAfter treatment, the total response rate of TCM symptoms in the observation group was 97.56% (40/41), which was higher than that (87.80%, 36/41) in the control group (χ2=5.205, P<0.05). After treatment, both groups showed declines (P<0.05) in systolic blood pressure (SBD), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), leptin (LEP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and inducible nitric oxide synthase (iNOS). Moreover, the declines in the observation group were more obvious than those in the control group (P<0.05, P<0.01). After treatment, both groups showed elevated levels of high density lipoprotein cholesterol (HDL-C), adiponectin (ADP), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.01). ConclusionUnder the guidance of the thought of treating disease before its onset, modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity, reducing inflammation, and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions, being worthy of clinical application and promotion.
5.Effect of Video-based Educational Intervention Combined with Maternal Presence on Perioperative Adverse Outcomes in Preschool Children under General Anesthesia
Jiayu TAN ; Fengqiu GONG ; Wenqi HUANG ; Xia FENG ; Qiongfang ZHU ; Yubo KANG ; Wenyan WU ; Xiuhong LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):519-527
ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia, including cooperation in anesthesia induction, perioperative anxiety, pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group (n=150) and intervention group (n=150). The control group received routine recovery care. For the intervention group, in addition to routine recovery care, a preoperative visit was scheduled one day before surgery. During this visit, mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening, the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system, and the children’s anesthetic induction compliance, perioperative anxiety, pain, and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale (m-YPAS), the Induction Compliance Scale (ICC), the Children’s Pain Behavior Scale (FLACC), and the Pediatric Agitation and Emergence Delirium Scale (PAED). ResultsOn the preoperative visit day, there were no statistically significant differences in baseline data between the two groups (P > 0.05). For perioperative anxiety, the m-YPAS scores of the intervention group were significantly lower than those of the control group, both when entering the operating room waiting area (35.27±6.48 vs. 41.79±6.68, P < 0.05) and 30 minutes after postoperative recovery (20.13±7.05 vs. 35.75±9.51, P < 0.05). In terms of anesthesia induction cooperation, the ICC scores of the intervention group were significantly lower than those of the control group (1.84±0.95 vs. 3.17±0.62, P < 0.05), and the proportion of good induction cooperation was significantly higher than that of the control group (24.00% vs. 12.67%, P < 0.05). There was no significant difference in awakening duration between the two groups, but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group (0.90±0.29 hours vs. 1.29±0.42 hours, P < 0.001). For perioperative agitation, the PAED scores of the intervention group were significantly lower than those of the control group (entering in the operating room waiting area: 8.5 vs. 9.2, P < 0.05; 30 minutes after postoperative recovery: 4.2 vs. 7.8, P < 0.05). In terms of pain scores, the FLACC scores of the intervention group were also significantly lower than those of the control group, both when entering the operating room waiting area ( 5.3 vs. 6.7, P < 0.05; 30 minutes after postoperative recovery: 2.1 vs. 4.9, P < 0.05). ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety, pain and agitation of preschool children undergoing general anesthesia, and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.
6.DiPTAC: A degradation platform via directly targeting proteasome.
Yutong TU ; Qian YU ; Mengna LI ; Lixin GAO ; Jialuo MAO ; Jingkun MA ; Xiaowu DONG ; Jinxin CHE ; Chong ZHANG ; Linghui ZENG ; Huajian ZHU ; Jiaan SHAO ; Jingli HOU ; Liming HU ; Bingbing WAN ; Jia LI ; Yubo ZHOU ; Jiankang ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):661-664
7.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
8.New acylphloroglucinol-sesquiterpenoid adducts with antiviral activities from Dryopteris atrata.
Jihui ZHANG ; Jinghao WANG ; Wei TANG ; Xi SHEN ; Jinlin CHEN ; Huilin OU ; Qianyi SITU ; Yaolan LI ; Guocai WANG ; Yubo ZHANG ; Nenghua CHEN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(3):377-384
Seven novel acylphloroglucinol-sesquiterpenoid adducts, designated as dryatraols J-P (1-7), were isolated from the rhizomes of Dryopteris atrata (Wall. ex Kunze) Ching. The structures, including absolute configurations, were elucidated using comprehensive spectroscopic data, calculated 13C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus (13C NMR-DP4+) probability analysis, and ECD calculations. These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties. Notably, compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane- or rulepidanol-type sesquiterpene, while compound 7 features a hydroxylated monomeric acylphloroglucinol motif. A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus (RSV) with IC50 values ranging from 0.75 to 3.12 μmol·L-1 compared to the positive control (ribavirin).
Antiviral Agents/isolation & purification*
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Phloroglucinol/isolation & purification*
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Sesquiterpenes/isolation & purification*
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Molecular Structure
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Dryopteris/chemistry*
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Respiratory Syncytial Viruses/drug effects*
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Humans
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Rhizome/chemistry*
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Drugs, Chinese Herbal/pharmacology*
9.Structurally novel tryptamine-derived alkaloids from the seeds of Peganum harmala and their antiviral activities against respiratory syncytial virus.
Zhongnan WU ; Yubo ZHANG ; Guocai WANG ; Qing TANG ; Yaolan LI ; Xiaoqing XIE ; Yushen LIANG ; Wen CHENG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(8):972-979
Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC50 5.01 ± 0.14 μmol·L-1) surpassed that of the positive control (ribavirin, IC50 6.23 ± 0.95 μmol·L-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification*
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Tryptamines/isolation & purification*
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Peganum/chemistry*
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Seeds/chemistry*
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Alkaloids/isolation & purification*
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Molecular Structure
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Humans
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Respiratory Syncytial Viruses/drug effects*
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Plant Extracts/pharmacology*
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Drugs, Chinese Herbal/pharmacology*
10.Erastin induces ferroptosis in lung fibroblasts through MAPK mediated oxidative stress signaling pathway
Yiran WANG ; Shijie ZHANG ; Yubo GUAN ; Miaomiao LI ; Ruyi CAI ; Qi WU
Acta Universitatis Medicinalis Anhui 2024;59(5):820-825
Objective To investigate the mechanism by which Erastin affects ferroptosis in lung fibroblasts.Meth-ods Mouse lung fibroblasts (C57/B6-L) were treated with varying concentrations of the iron death inducer Eras-tin.Cell viability was assessed using the cell counting Kit-8 (CCK-8) assay.Oxidative stress levels were visualized using a fluorescence microscope, and the expression of proteins related to the mitogen-activated protein kinase (MAPK) signaling pathway was analyzed using Western blot.Additionally, the p38 and extracellular regulated protein kinase (ERK) inhibitors SB203580 and U0126 were employed to further elucidate the mechanism by which Erastin induces iron death in lung fibroblasts.Results At a concentration of 100 μmol/L, Erastin effectively in-duced ferroptosis in lung fibroblasts, leading to an upregulation of oxidative stress.Furthermore, the phosphoryla-tion levels of p38 and ERK proteins in the MAPK pathway were elevated (P<0.05) .The addition of SB203580 and U0126 inhibitors resulted in a significant reduction in oxidative stress levels and a notable increased in cell ac-tivity in lung fibroblasts (P<0.05).Conclusion It can be concluded that Erastin induces ferroptosis in lung fi-broblasts, potentially through the mediation of oxidative stress via the MAPK signaling pathway.


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