1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.Chufeng Yisuntang Ameliorates PM2.5-induced Dry Eye via ROS/p38 MAPK Signaling Pathway
Yuan ZHONG ; Pan ZHAO ; Shi TAN ; Yu TANG ; Dongdong LI ; Lihao CHEN ; Jun PENG ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):191-200
ObjectiveTo establish a mouse model of particulate matter 2.5 (PM2.5)-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM2.5-induced ocular surface damage by regulating the reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop (0.1 mL) of 5 g·L-1 PM2.5 suspension in both eyes, four times daily. Successfully modeled mice were randomized into four groups (n=10): Model, p38 MAPK inhibitor, Chufeng Yisuntang, and combination (Chufeng Yisuntang at 7.3 g·kg-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg-1). Chufeng Yisuntang was administered via gavage, and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion, tear film break-up time, and corneal fluorescein staining were assessed. After intervention for 4 weeks, hematoxylin and eosin (HE) staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure serum levels of ROS, malondialdehyde (MDA), superoxide dismutase (SOD) 1, and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels, respectively, of p38 MAPK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteinyl aspartate-specific proteinase-3 (Caspase-3) in the corneal tissue. ResultsCompared with the control group, the model group exhibited reduced tear secretion volume and tear film breakup time, along with increased corneal fluorescein staining scores (P<0.01). Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group demonstrated increased tear secretion volume and tear film breakup time, along with decreased corneal fluorescein staining scores (P<0.01). HE staining revealed that compared with the control group, the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness, along with reduced meibomian gland acini and intensely stained, densely packed nuclei around the acini. Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group showed intact corneal structure, improved cell morphology, and reduced damage severity. ELISA revealed elevated ROS and MDA levels (P<0.01) and decreased SOD1 and SOD2 levels (P<0.01) in the model group compared with the control group. Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination lowered ROS and MDA levels (P<0.01), while raising SOD1 and SOD2 levels (P<0.05, P<0.01). Western blot revealed that compared with the control group, the model group exhibited increased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and reduced protein level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the protein level of Bcl-2 (P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and increased protein level of Bcl-2 (P<0.01). Real-time PCR revealed that compared with the control group, the model group exhibited upregulated mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), and downregulated mRNA level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the mRNA level of Bcl-2 (P<0.05, P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased mRNA levels of p38 MAPK, Bax, and Caspase-3 expression (P<0.05, P<0.01) and increased mRNA level of Bcl-2 (P<0.01). ConclusionChufeng Yisuntang may partially protect against PM2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway, enhancing antioxidant defense, and reducing epithelial apoptosis.
3.Interpretation of the key points of the 2025 AHA/ACC guideline for the prevention, detection, evaluation and management of high blood pressure in adults
Qin SUN ; Aiai LI ; Jing YU ; Dongze LI ; Haihong ZHANG ; Yan ZHONG ; Zhi WAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):204-210
The American Heart Association (AHA) and the American College of Cardiology (ACC), in collaboration with multiple professional organizations, jointly released the "Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults" in August 2025. Based on the latest evidence-based medical findings from February 2015 to January 2025, the guideline proposes an individualized treatment strategy grounded in total cardiovascular disease risk stratification, incorporates the novel PREVENT risk assessment model, lowers the medication initiation threshold and control targets for high-risk populations, and provides specific management recommendations for special populations. This article provides an interpretation of these updates and conducts a comparative analysis with the current status of hypertension prevention and treatment in China as well as Chinese guidelines, aiming to offer reference for hypertension control practices in China.
4.Interpretation of the heart disease section in 2025 AHA Heart Disease and Stroke Statistics
Aiai LI ; Qin SUN ; Jing YU ; Dongze LI ; Haihong ZHANG ; Yan ZHONG ; Zhi WAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):339-346
The American Heart Association (AHA) officially released the "2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association" on January 27, 2025. This report systematically compiles the latest statistics on major cardiovascular diseases worldwide, while simultaneously integrating relevant outcome indicators, including quality of care, procedures, and economic costs, and updating the global prevalence patterns and evolving trends of diverse risk factors impacting cardiovascular health, providing essential guidance for the prevention, diagnosis, and treatment of cardiovascular diseases. Synthesizing insights from this pivotal report and other relevant studies, this article highlights key findings concerning the global prevalence and mortality of heart diseases, associated risk factors, and emerging diagnostic and therapeutic technologies.
5.Effect of Dingzhi Xiaowan on PI3K/Akt/mTOR/HIF-1α Pathway in Post-stroke Cognitive Impairment Model Mice
Han ZHANG ; Yu WANG ; Xiaoqin ZHONG ; Zhenqiu NING ; Dafeng HU ; Minzhen DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):1-11
ObjectiveTo investigate the effect of Dingzhi Xiaowan (DZXW) in post-stroke cognitive impairment (PSCI) model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group, model group, low-dose DZXW group (1.43 g·kg-1), and high-dose DZXW group (2.56 g·kg-1), with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage, and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein (APP), amyloid 42 (Aβ42), acetylcholinesterase (AChE), and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay (ELISA). Deoxyribonucleotide end transferase-mediated nick end labelling (TUNEL) assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), hypoxia-inducible factor 1-alpha (HIF-1α), B-cell lymphoma 2 (Bcl-2) homologous structural domain protein (Beclin1), sequestosome 1 (p62), microtubule-associated protein light chain 3 (LC3), Bcl-2, and Bcl-2-associated X protein (Bax) in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group, the latency, APP, Aβ42, AChE, TUNEL positivity, ferric ion deposition, HIF-1α, Beclin1, Bax, and LC3Ⅱ/Ⅰ were significantly increased in the model group (P<0.01), while the number of crossing platforms, SOD, p-PI3K, p-Akt, p-mTOR, p62, and Bcl-2 were significantly decreased (P<0.01). Compared with the model group, the latency, APP, Aβ42, AChE, TUNEL positivity rate, ferric ion deposition, HIF-1α, Beclin1, Bax, and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups (P<0.05), while the number of crossing platforms, SOD, p-PI3K, p-Akt, p-mTOR, p62, and Bcl-2 were significantly higher (P<0.05). ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.
6.Effectiveness of the integrated schistosomiasis control programme in Sichuan Province from 2015 to 2023
Chen PU ; Yu ZHANG ; Jiajia WAN ; Nannan WANG ; Jingye SHANG ; Liang XU ; Ling CHEN ; Lin CHEN ; Zisong WU ; Bo ZHONG ; Yang LIU
Chinese Journal of Schistosomiasis Control 2025;37(3):284-288
Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ2 = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm2 in Sichuan Province from 2015 to 2023, with 204 602.81 hm2 treated by chemical control and 4 637.74 hm2 by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm2 in 2016 to 3 709.72 hm2 in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm2 in 2016 to 473.09 hm2 in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m2). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm2, hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm2, renovation of snail control forests covering 8 720 hm2 and newly building of shelterbelts covering 764 686.67 hm2. All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.
7.Clinical research and characteristic analysis of patients with advanced colorectal cancer treated with Yinyang Gongji Pills and capecitabine.
Lei WANG ; Chao-Yue YAO ; Jie-Ru ZHAN ; Xiao-Xia SUN ; Zhong-Xin YU ; Xiao-Ya LIANG ; Jian WANG ; Xue GONG ; Da-Rong WEI
China Journal of Chinese Materia Medica 2025;50(5):1404-1411
Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans
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Capecitabine/adverse effects*
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Colorectal Neoplasms/mortality*
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Drugs, Chinese Herbal/adverse effects*
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Male
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Middle Aged
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Female
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Aged
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Adult
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Treatment Outcome
8.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
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Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Surveys and Questionnaires
9.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
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Rats
10.Mechanistic of Yueju Wan volatile oil in inhibiting inflammation for antidepressant effects by regulating AGE/PI3K/Akt pathway.
Tan-Lu CHU ; Ze-Jun GUO ; Wei ZHANG ; Ling-Feng WANG ; Shu-Rui LYU ; Wan-Yu GUO ; Xiao-Ming ZHONG ; Feng-Mei QIU ; Zhen HUANG
China Journal of Chinese Materia Medica 2025;50(11):3147-3158
The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals
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Antidepressive Agents/chemistry*
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Mice
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Proto-Oncogene Proteins c-akt/immunology*
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Phosphatidylinositol 3-Kinases/immunology*
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Oils, Volatile/chemistry*
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Male
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Drugs, Chinese Herbal/chemistry*
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Signal Transduction/drug effects*
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Depression/metabolism*
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Glycation End Products, Advanced/immunology*
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Humans

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