1.Effects of borneol on pharmacodynamics and pharmacokinetics of Corydalis saxicola total alkaloids in depression model rats
Yu YE ; Guoliang DAI ; Huaxi HANG ; Meishuang YU ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
China Pharmacy 2025;36(1):30-36
OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group, negative control group, positive control group (fluoxetine 10 mg/kg, i.g.), single drug group (C. saxicola total alkaloids 210 mg/kg, i.g.) and combined drug group (C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg, i.g.) according to the random number table method, with 6 rats in each group. By lipopolysaccharide (LPS) induction modeling, except blank control group (no model and no administration) received intraperitoneal injection of the same amount of normal saline, the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling, each administration group was given relevant drug intragastrically according to the corresponding dose, and blank control group and negative control group (without drug treatment) were administered intragastrically with an equal volume of solvent to dissolve the drug; continued modeling while administering the drug. After two weeks of continuous administration, the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments; the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in rats were determined; the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day, and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted, the area under the curve (AUC) was calculated, and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group, the negative control group had a decrease in body mass and sugar water preference rate, a decrease in the total distance of open field, a prolonged swimming immobility time, and a increased in the expression of inflammatory factors in serum (P<0.05); compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water, increased the total distance of open field, shortened the time of swimming immobility, and decreased the expression of inflammatory factors in serum (P<0.05). There was no significant difference in the above indicators between the single drug group and the combined drug group in rats (P>0.05). Pharmacokinetic results showed that compared with single drug group, AUC0-t of coptisine, AUC0-t, AUC0-∞, tmax and cmax of jatrorrhizine, AUC0-t, AUC0-∞, t1/2 and cmax of berberrubine, and AUC0-t of epiberberine, cmax of dehydrocarvedine, cmax of palmatine were significantly increased in combined drug group, but there was no significant difference, indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats, reduce serum inflammatory cytokine levels, and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone, the combination with borneol do not show significant pharmacodynamic differences, bu can improve the absorption of coptisine, jatrorrhizine in model rats.
2.Tension hydrocele: report of 2 cases and literature review
Xun ZHAO ; Shumin WANG ; Min QIU ; Chuxiao XU ; Guoliang WANG ; Shudong ZHANG
Journal of Modern Urology 2025;30(1):69-72
[Objective] To explore the diagnosis and treatment experience of tension hydrocele. [Methods] The clinical data of 2 patients with tension hydrocele treated in our hospital were retrospectively analyzed.Relevant literature was retrieved to analyze the clinical characteristics of this disease. [Results] Case 1 was diagnosed due to swelling and pain of the left scrotum after trauma for more than one month, which worsened for one day.Physical examination showed high tension in the left scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the left testis disappeared.Emergency left scrotal exploration and hydrocelectomy were performed.There was no sign of testis torsion during the operation.Case 2 was diagnosed mainly due to hydrocele of the right testis for 1 year, which worsened for 1 week and complicated with testis distension and pain.Physical examination showed high tension in the right scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the right testis decreased.After 40ml of fluid was extracted under ultrasound monitoring, the blood flow signal in the right testis recovered.Hydrocelectomy was performed the next day.During the follow-up of 8 months, there was no recurrence of hydrocele.A search of domestic and foreign literature showed that there were no reports in domestic literature, while a total of 11 cases were reported in foreign literature. [Conclusion] Tension hydrocele of the testis is a rare emergency of the scrotum.Surgery or decompression should be performed as soon as possible to restore testicular blood supply, and hydrocelectomy should be performed simultaneously or in stages to prevent recurrence.
3.Internal tension relieving technique assisted anterior cruciate ligament reconstruction to promote ligamentization of Achilles tendon grafts in small ear pigs in southern Yunnan province
Bohan XIONG ; Guoliang WANG ; Yang YU ; Wenqiang XUE ; Hong YU ; Jinrui LIU ; Zhaohui RUAN ; Yajuan LI ; Haolong LIU ; Kaiyan DONG ; Dan LONG ; Zhao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(4):713-720
BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).
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.Relationship between metabolic score for insulin resistance and overactive bladder in the US population based on NHANES data from 2005 to 2018
Guoliang XU ; Feiyang GAO ; Xihao WANG ; Jiangtao ZHU ; Wei LIN ; Pengyue LIU ; Yongjun YAN
Journal of Modern Urology 2025;30(5):416-423
Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population,so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018,a cross-sectional design was employed,and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations,subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001),and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females,participants younger than 55 years,and non-diabetic individuals (P<0.05). Furthermore,smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB,with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study,based on the NHANES 2005-2018 database,found a linear positive correlation between METS-IR and OAB.
6.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
7.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
8.Quality Evaluation of Atractylodis Macrocephalae Rhizoma in Different Production Methods Based on Traditional Traits
Jinxiu QIAN ; Yihan WANG ; Yapeng WANG ; Guoliang YU ; Qiuxiang PAN ; Jiawei SHI ; Meiping CHEN ; Yangqing LIU ; Lun LU ; Yanmeng LIU ; Tiegui NAN ; Liping KANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):43-52
ObjectiveBased on the experience of traditional quality evaluation, the quality of Atractylodis Macrocephalae Rhizoma(AMR) with different production methods such as direct seeding, transplanting after seedling raising, topping and non-topping, and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining, and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides, oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography(UPLC), and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA). ResultIn terms of traits, the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck, strong sweetness and clear aroma" recorded in ancient materia medica, followed by the 3-year-old AMR with topping after transplanting, while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect, the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang, the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition, the contents of 70% ethanol extract, fructose, glucose, sucrose, 1-kestose, atractylenolide Ⅰ, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples(P<0.05). The contents of cellulose, 70% ethanol extract, sucrose, atractylenolide Ⅰ, atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate(P<0.05), while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting, direct seeding and without topping(P<0.05). ConclusionUnder the current mainstream production mode, too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield, but the accumulation of sweet substances, fragrant substances and fiber substances is insufficient, which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it, it is suggested to revise the quality standard of AMR, supplement the quantitative analysis of secondary metabolites, and strengthen the production of imitation wild AMR.
9.The First Application of Domestically Produced Self-expanding Transcatheter Aortic Valve Controllable Bending Delivery System in China
Yang CHEN ; Guoliang CHEN ; Di SONG ; Hongliang ZHANG ; Moyang WANG ; Guannan NIU ; Zheng ZHOU ; Qian ZHANG ; Qingrong LIU ; Zhenyan ZHAO ; Jie ZHAO ; Bin ZHANG ; Dejing FENG ; Wence SHI ; Jicheng XI ; Yongjian WU
Chinese Circulation Journal 2024;39(3):285-289
A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.
10.Effect of Borneol on Pharmacodynamics,Pharmacokinetics and Brain Tissue Distribution of Main Active Ingredients of Jiaotaiwan in Depression Model Rats
Meishuang YU ; Guoliang DAI ; Huaxi HANG ; Yu YE ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):18-27
ObjectiveTo investigate the pharmacodynamics, pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide(LPS)-induced depression rats. MethodRats were randomly divided into the control group, model group, fluoxetine group(10 mg·kg-1), Jiaotaiwan group(1.5 g·kg-1) and combination group(1.5 g·kg-1 of Jiaotaiwan+0.05 g·kg-1 of borneol), with 8 rats in each group. Except for the control group, the depression model was established by intraperitoneal injection of LPS for 7 consecutive days, and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors[interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α(TNF-α)] of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin(HE) and Nissl staining. After the behavioral tests of sucrose preference, open field and forced swimming were completed, blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage, the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed, and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group, rats in the model group showed decreased sucrose preference rate and total distance of open field, prolonged swimming immobility time, and increased expression of inflammatory factors in serum(P<0.01). Compared with the model group, the sucrose preference rate and total distance of open field were increased, and the swimming immobility time was shortened in the rats of each administration group, and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group(P<0.05, P<0.01). The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group, the area under the curve(AUC0-t, AUC0-∞), peak concentration(Cmax) and the average steady-state plasma concentration(Cav) of berberine and epiberberine in the combination group were increased(P<0.05, P<0.01), AUC0-t, AUC0-∞, mean residence time(MRT0-∞) and Cav of coptisine were significantly increased(P<0.05, P<0.01), Cmax of jatrorrhizine increased significantly(P<0.05), but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group, the contents of jatrorrhizine, epiberberine, coptisine, palmatine and berberine in the brain tissue of combination group were increased(P<0.05, P<0.01), the content of magnoflorine increased and that of berberrubine decreased, but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats, reduce the levels of serum inflammatory factors, improve the pathological damage of hippocampus, and have antidepressant effect. Compared with Jiaotaiwan alone, the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats, improve its bioavailability, promote its absorption, and improve the brain targeting of the drug, which is more conducive to the antidepressant effect of Jiaotaiwan.

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