1.Sanren Runchang Formula Regulates Brain-gut Axis to Treat IBS-C: A Randomized Controlled Trial
Teng LI ; Xinrong FAN ; He YAN ; Zhuozhi GONG ; Mengxi YAO ; Na YANG ; Yuhan WANG ; Huikai HU ; Wei WEI ; Tao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):154-161
ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome (IBS-C) by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and substance P (SP). MethodsA randomized controlled design was adopted, and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups (36 cases).The observation group received Sanren Runchang formula granules twice daily, and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale (IBS-SSS), IBS Quality of Life Scale (IBS-QOL), and Bristol Stool Form Scale (BSFS) were used to assess clinical symptoms, and bowel movement frequency was recorded. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT, VIP, and SP. ResultsThe total response rate in the observation group was 91.67% (33/36), which was higher than that (77.78%, 28/36) in the control group (χ2=4.50, P<0.05). After treatment, both groups showed increased defecation frequency and BSFS scores, decreased IBS-SSS total score, abdominal pain and bloating scores, IBS-QOL health anxiety, anxiety, food avoidance, and behavioral disorders scores, SAS and SDS scores, serum 5-HT and VIP levels, and increased SP levels (P<0.05, P<0.01). Moreover, the observation group showed more significant changes in the indicators above than the control group (P<0.05, P<0.01). The SP level showed no significant difference between the two groups. During the 4-week follow-up, the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group, and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients, with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP, suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However, its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.
2.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
3.Effect of community comprehensive management model intervention among patients with dyslipidemia
GAO Hui ; XIE Liang ; YAO Chunyang ; WANG Linhong ; JIN Liu ; HU Jie
Journal of Preventive Medicine 2026;38(1):15-19
Objective:
To evaluate the effect of community comprehensive management model intervention among patients with dyslipidemia, so as to provide the reference for optimizing community management strategies and improving the target achievement rate for blood lipids among this population.
Methods:
From May to June 2023, a multi-stage stratified random sampling method was employed to select patients with dyslipidemia from primary healthcare institutions in Jiaxing City, Zhejiang Province. Eligible participants were randomly assigned to either a control group or an intervention group. The control group received routine management, while the intervention group was subjected to a community comprehensive management model in addition to the routine care. Both groups were followed up for 24 months. Data on demographic characteristics, lifestyle behaviors, physical examination indices, and blood biochemical indicators were collected at baseline and after the intervention through questionnaires, physical examinations, and laboratory tests. Changes in obesity rate, central obesity rate, target achievement rates for blood lipids, blood pressure, and blood glucose, as well as lifestyle modifications, were analyzed. Differences between the two groups before and after the intervention were assessed using generalized estimating equations (GEE).
Results:
The control group consisted of 560 patients, including 303 females (54.11%) and 430 individuals aged ≥65 years (76.79%). The intervention group also included 560 patients, with 300 females (53.57%) and 431 individuals aged ≥65 years (76.96%). Before the intervention, no statistically significant differences were observed between the two groups in terms of gender, age, educational level, history of chronic diseases, and atherosclerotic cardiovascular disease risk stratification (all P>0.05). After 24 months of intervention, interaction effects between group and time were observed for obesity rate, central obesity rate, target achievement rate for blood lipids, target achievement rate for blood glucose, composite target achievement rate, physical activity rate, and medication adherence (all P<0.05). Specifically, the intervention group demonstrated lower rates of obesity and central obesity, and higher target achievement rate of blood lipids, target achievement rate of blood glucose, composite target achievement rate, physical activity rate, and medication adherence compared to the control group.
Conclusion
The community comprehensive management model contributed to improvements in multiple metabolic parameters (including body weight, waist circumference, blood lipids, and blood glucose) among patients with dyslipidemia, and was associated with increased physical activity rate and medication adherence.
4.Staged Characteristics of Mitochondrial Energy Metabolism in Chronic Heart Failure with Heart-Yang Deficiency Syndrome and Prescription Intervention from Theory of Reinforcing Yang
Zizheng WU ; Xing CHEN ; Lichong MENG ; Yao ZHANG ; Peng LUO ; Jiahao YE ; Kun LIAN ; Siyuan HU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):129-138
Chronic heart failure (CHF) is a complex clinical syndrome caused by ventricular dysfunction, with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome, as the core pathogenesis of CHF, persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions, resulting in the accumulation of phlegm-fluid, blood stasis, and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention, forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang, the clinical experience of the traditional Chinese medicine (TCM) master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome, and achievements from molecular biological studies, this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild (Stage Ⅰ-Ⅱ), severe (Stage Ⅲ), and critical (Stage Ⅳ) stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical, pathophysiological, and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance, corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α(PGC-1α)/silent information regulator 2 homolog 1 (SIRT1) and ATPase activity. The severe stage centers on oxidative stress and structural damage, reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage, Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage, increase adenosine triphosphate (ATP) content, and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration, leading to the collapse of Yin-Yang equilibrium. At this stage, Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore (MPTP), reduce cardiomyocyte apoptosis rate, and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF, this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.
5.Danhong Injection Regulates Ventricular Remodeling in Rat Model of Chronic Heart Failure with Heart-Blood Stasis Syndrome via p38 MAPK/NF-κB Signaling Pathway
Zizheng WU ; Xing CHEN ; Jiahao YE ; Lichong MENG ; Yao ZHANG ; Junyu ZHANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):149-159
ObjectiveTo explore the mechanism of ventricular remodeling mediated by the p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signaling pathway in the rat model of chronic heart failure (CHF) with heart-blood stasis syndrome, as well as the intervention effect of Danhong injection. MethodsIn vivo experiment: SPF-grade male SD rats were assigned via the random number table method into 4 groups: Sham operation, model, captopril (8.8 mg·kg-1), and Danhong injection (6.0 mL·kg-1). The model of CHF with heart-blood stasis syndrome was established by abdominal aortic constriction, and the sham operation group only underwent laparotomy without constriction. All the groups were treated continuously for 15 days. The tongue color of rats was observed. Echocardiography, hemorheology, heart mass index (HMI), and left ventricular mass index (LVMI) were measured. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the pathological and fibrotic changes of the myocardial tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), angiotensin Ⅱ (AngⅡ), tumor necrosis factor-α (TNF-α), and Creactive protein (CRP) in the serum, as well as the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the myocardial tissue. Western blot was used to quantify the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue. In vitro experiment: H9C2 cardiomyocytes were treated with 1×10-6 mol·L-1 AngⅡ to establish a model of myocardial hypertrophy. H9C2 cardiomyocytes were allocated into normal, model, inhibitor + Danhong injection, Danhong injection (20 mL·L-1), and inhibitor (SB203580, 5 μmol·L-1) groups. CCK-8 assay was used to detect the viability of H9C2 cardiomyocytes. Rhodamine-labeled phalloidin staining was used to reveal the area of cardiomyocytes. Real-time PCR was performed to determine the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Western blot was used to assess the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65. ResultsIn vivo experiment: Compared with the sham operation group, the model group showed purplish-dark tongue with decreased R, G, B values of the tongue surface (P<0.01), increased whole blood viscosity (at low, medium, and high shear rates) (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01), increased left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), and left ventricular posterior wall thickness at end-diastole (LVPWd) (P<0.01), raised LVMI and HMI (P<0.01), and elevated levels of NT-proBNP, TNF-α, IL-6, and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue (P<0.01). The HE and Masson staining of the myocardial tissue showed compensatory myocardial hypertrophy, fibrosis, and massive inflammatory cell infiltration in the model group. Additionally, the model group presented up-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue (P<0.01). Compared with the model group, each administration group showed increased R, G, B values of the tongue surface (P<0.05, P<0.01), decreased whole blood viscosity (at low, medium, and high shear rates) (P<0.05, P<0.01), increased LVEF and LVFS (P<0.01), decreased LVIDd, LVIDs, and LVPWd (P<0.05, P<0.01), declined LVMI and HMI (P<0.05, P<0.01), and lowered levels of NT-proBNP, TNF-α, IL-6, and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue (P<0.01). HE and Masson staining showed alleviated compensatory myocardial hypertrophy, reduced fibrosis, and decreased expression of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue (P<0.01). In vitro experiment: When the concentration of Danhong injection reached 20 mL·L-1, the survival rate of H9C2 cardiomyocytes was the highest (P<0.01). Compared with the normal group, the model group showed up-regulated mRNA levels of ANP and BNP (P<0.01), increased relative cell surface area (P<0.01), and raised protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 (P<0.01). Compared with the model group, each administration group showed down-regulated mRNA levels of ANP and BNP (P<0.01), reduced relative cell surface area (P<0.05, P<0.01), and down-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 (P<0.05, P<0.01). ConclusionDanhong injection can regulate ventricular remodeling through the p38 MAPK/NF-κB pathway, thereby exerting a protective effect on the rat model of CHF with heart-blood stasis syndrome.
6.Skin pharmacokinetics of inositol nicotinate in heparin sodium inositol nicotinate cream
Yaling CUI ; Qiong WU ; Liangyu MA ; Bei HU ; Dong YAO ; Zihua XU
Journal of Pharmaceutical Practice and Service 2025;43(1):6-9
Objective To establish an HPLC method to determine the concentration of inositol nicotinate(IN) in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t1/2 was (4.555±2.054) h, Tmax was (6±0)h, Cmax was (16.929±2.153)mg/L, AUC0−t was (150.665±16.568) mg·h /L ,AUC0−∞ was (161.074±23.917) mg·h /L, MRT(0−t) was (9.044±0.618)h, MRT(0−∞) was (10.444±1.91) h, CLz/F was (0.19±0.03) L/(h·kg), and Vz/F was (1.19±0.437) L/(h·kg). Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.
7.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
8.Clinicopathological Characteristics of HER2-Positive Breast Cancer Patients with BRCA1/2 Pathogenic Variants and Their Response to Neoadjuvant Targeted Therapy
Xingyu LIAO ; Huimin LIU ; Jie SUN ; Li HU ; Juan ZHANG ; Lu YAO ; Ye XU ; Yuntao XIE
Cancer Research on Prevention and Treatment 2025;52(6):491-495
Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.
9.Association analyses of early medication clocking-in trajectory with smart tools and treatment outcome in pulmonary tuberculosis patients
Chunhua XU ; Zheyuan WU ; Yong WU ; Qing WANG ; Zichun WANG ; Nan QIN ; Xinru LI ; Yucong YAO ; Kehua YI ; Yi HU
Shanghai Journal of Preventive Medicine 2025;37(3):210-214
ObjectiveTo construct a group-based trajectory model (GBTM) for early medication adherence check-in, and to analyze the relationship between different trajectories and treatment outcomes in tuberculosis patients using data that were generated from smart tools for monitoring their medication adherence and check-in. MethodsFrom October 1, 2022 to September 30, 2023, a total of 163 pulmonary tuberculosis patients diagnosed in Fengxian District were selected as the study subjects. The GBTM was utilized to analyze the weekly active check-in trajectories of the subjects during the first 4 weeks and establish different trajectory groups. The χ² tests were employed to compare the differences between groups and logistic regression analysis was conducted to explore the relationship between different trajectory groups and treatment outcomes. ResultsA total of four groups were generated by GBTM analyses, of which a low level of punch card was maintained in group A, 6% of the drug users increased rapidly from a low level in group B, 17% of drug users increased gradually from a low level in group C, and 18% of drug users maintained a high level of punch card in group D. The trajectory group was divided into two groups according to homogeneity, namely the low level medication punch card group (group A) and the high level medication punch card group (group B, group C, and group D). The results of multivariate logistic regression analyses revealed that low-level medication check-in (OR=3.250, 95%CI: 1.089‒9.696), increasing age (OR=1.030, 95%CI: 1.004‒1.056), and not undergoing sputum examination at the end of the fifth month (OR=2.746, 95%CI: 1.090‒7.009) were significantly associated with poor treatment outcomes. ConclusionThe medication check-in trajectory of pulmonary tuberculosis patients within the first 4 weeks is correlated with adverse outcomes, or namely consistent low-level medication adherence check-ins are associated with poor treatment outcomes, while high-level medication adherence check-ins are associated with a lower incidence of adverse outcomes.
10.Chaihu Shugansan Combined with Ferulic Acid Regulates BDNF/TrkB Signaling Pathway and Monoamine Neurotransmitters in Frontal Cortex of Rat Model of CUMS
Yuexin LI ; Zhijing ZHANG ; Ziyi GUO ; Di YAN ; Xueyan HU ; Jianping YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):28-37
ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress (CUMS) and explore the mechanism from the histomorphology of frontal cortex, expression of key molecules in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway, and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups (n=10): blank control, depression model, Chaihu Shugansan (3.3 g·kg-1·d-1), ferulic acid (50 mg·kg-1·d-1), Chaihu Shugansan (3.3 g·kg-1·d-1) + ferulic acid (50 mg·kg-1·d-1), and fluoxetine (2.1 mg·kg-1·d-1). Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used, including fasting with free access to water for 24 h, water deprivation with free access to food for 24 h, wetting the bedding with water in the cage, restraint for 3 h, tail clamping for 1 min, swimming in ice water at 4 ℃, and day and night reversal. Each stimulus was used 1 to 3 times, and the modeling lasted for a total of 21 days. At the same time of stimulation, rats in each medication group were treated with corresponding agents by gavage, while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test, sucrose preference test, and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium, and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF, TrkB, and cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group, the depression model group showed reduced body mass (P<0.05, P<0.01), decreased number of crossings and rearings in the open field test and sucrose preference (P<0.01), prolonged time of immobility in the forced swimming test (P<0.01), reduced neuronal cells, increased necrotic cells, and darkening cell staining in the frontal cortex, down-regulated mRNA and protein levels of BDNF, TrkB, CREB, and lowered levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Compared with the depression model group, each intervention group showed improved general state, increased body mass (P<0.05), increased number of crossings (P<0.05), shortened immobility time in the forced swimming test (P<0.01), increased neuronal cells, reduced necrotic cells, and lightened cellular staining in the frontal cortex, up-regulated mRNA and protein levels of BDNF, TrkB and CREB, and elevated levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Moreover, the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex (P<0.05). The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex (P<0.05), and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test, up-regulating the mRNA levels of BDNF, TrkB, and CREB and the protein levels of BDNF and CREB in the frontal cortex, and increasing the DA content in the frontal cortex (P<0.05). ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover, the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.


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