1.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
2.Pathological changes and macrophage polarization in the liver and spleen of mice infected with Angiostrongylus cantonensis
Xiaoyu QIN ; Yuchun CAI ; Yang HONG ; Fanna WEI ; Yahong HU ; Yumeng CAI ; Yuan HU ; Ting ZHANG ; Xiaojin MO ; Bin XU ; Yan LU ; Jiahui SUN ; Yan ZHOU ; Zelin ZHU ; Muxin CHEN
Chinese Journal of Schistosomiasis Control 2026;38(2):169-183
Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86+ and CD206+ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206+ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.
3.Trend in disease burden of interstitial lung disease in China from 1990 to 2021
SUN Yuefeng ; GUO Sijia ; WEI Yuan ; HE Tiantian ; GUO An ; ZENG Zhaolu ; SUN Luyan ; DOU Wenjing ; SUN Zengtao
Journal of Preventive Medicine 2025;37(11):1124-1128
Objective:
To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases.
Methods:
Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden.
Results:
In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively.
Conclusions
From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.
4.Intermittent fasting ameliorates rheumatoid arthritis by harassing deregulated synovial fibroblasts.
Lei LI ; Jin DONG ; Yumu ZHANG ; Chen ZHAO ; Wen WEI ; Xueqin GAO ; Yao YU ; Meilin LU ; Qiyuan SUN ; Yuwei CHEN ; Xuehua JIAO ; Jie LU ; Na YUAN ; Yixuan FANG ; Jianrong WANG
Chinese Medical Journal 2025;138(23):3201-3203
5.Chemical constituents from Ecballium elaterium and their cytotoxicity.
Yu-Wei SUN ; AYIZUOKELAMU YASEN ; Xue-Rui AN ; Wei LIU ; Tao YUAN
China Journal of Chinese Materia Medica 2025;50(8):2159-2166
To explore the chemical constituents of Ecballium elaterium and their cytotoxicity, this study employed multiple chromatographic techniques including normal-phase silica gel, MCI, octadecylsilyl(ODS), Sephadex LH-20 gel, and semi-preparative liquid chromatography for compound isolation from its active fraction. A total of 12 compounds were obtained, and they were identified according to the analysis of a variety of spectral data and literature comparison as 24Z-20,27-dihydroxy-16α,23α-epoxy-cucurbita-2-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(1), cucurbitacin R(2), cucurbitacin B(3), cucurbitacin D(4), cucurbitacin I(5), cucurbitacin L(6), dehydrodiconiferyl alcohol(7), 3-hydroxy-4-methoxycinnamic acid(8), ferulaic acid(9), p-coumaric acid(10), rutin(11), and lariciresinol-4'-O-β-D-glucoside(12), among which compound 1 was a new compound. Compounds 2-6 had strong cytotoxicity against human lung carcinoma A549 cells with the IC_(50) values of(0.48±0.09),(0.03±0.002),(0.13±0.03),(0.87±0.14),(0.15±0.03) μmol·L~(-1), respectively, which were stronger than the positive control doxorubicin \[IC_(50)=(3.92±1.60) μmol·L~(-1)\].
Humans
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Drugs, Chinese Herbal/toxicity*
;
Cell Line, Tumor
;
Cucurbitaceae/chemistry*
;
Cell Survival/drug effects*
6.Tanreqing Capsules protect lung and gut of mice infected with influenza virus via "lung-gut axis".
Nai-Fan DUAN ; Yuan-Yuan YU ; Yu-Rong HE ; Feng CHEN ; Lin-Qiong ZHOU ; Ya-Lan LI ; Shi-Qi SUN ; Yan XUE ; Xing ZHANG ; Gui-Hua XU ; Yue-Juan ZHENG ; Wei ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2270-2281
This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified_f_Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals
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Drugs, Chinese Herbal/administration & dosage*
;
Mice
;
Lung/metabolism*
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Mice, Inbred C57BL
;
Capsules
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Orthomyxoviridae Infections/virology*
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Gastrointestinal Microbiome/drug effects*
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Male
;
Humans
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Female
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Influenza A virus/physiology*
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Influenza, Human/virology*
7.Network Meta-analysis of efficacy of different Chinese medicine injections in treating transient ischemic attack.
Jin HAN ; Yong-Kang SUN ; Yue YUAN ; Fang-Biao XU ; Yan-Bo SONG ; Wei-Jie WANG ; Xin-Zhi WANG
China Journal of Chinese Materia Medica 2025;50(8):2282-2297
This study aims to evaluate the efficacy of Chinese medicine injections in treating transient ischemic attack(TIA) based on network Meta-analysis. Randomized controlled trial(RCT) about Chinese medicine injections in treating TIA were retrieved from PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed with the time interval from inception to March 1, 2024. The methodological quality of the included articles was assessed by ROB 2.0, and the GRADE system was employed to evaluate the quality of evidence. The gemtc package of R 4.1.2 was used to perform the network Meta-analysis. Finally, 63 RCTs with a total sample size of 5 750 cases were included, involving 11 Chinese medicine injections(Shuxuetong Injection, Danhong Injection, Shuxuening Injection, Ginkgo Damo Injection, Shenxiong Glucose Injection, Ligustrazine Injection, Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection, Salvianolic Acids for Injection, Dengzhan Xixin Injection, Guhong Injection, and Xueshuantong Injection). All patients received conventional western medicine treatment, and the experimental group was additionally treated with Chinese medicine injection. Network Meta-analysis yielded the following results.(1) In terms of improving the clinical total response rate, 11 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Dengzhan Xixin Injection + conventional western medicine had the best effect.(2) In terms of reducing plasma viscosity, 7 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shenxiong Glucose Injection + conventional western medicine had the best effect.(3) In terms of reducing whole blood high shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Guhong Injection + conventional western medicine had the best effect.(4) In terms of reducing whole blood low shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect.(5) In terms of reducing fibrinogen, 9 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Ginkgo Damo Injection + conventional western medicine had the best effect.(6) In terms of increasing the average blood flow velocity, 3 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect. In summary, compared with conventional western medicine alone, Chinese medicine injections combined with conventional western medicine were effective in improving the clinical total response rate and the average blood flow velocity, as well as reducing plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, and fibrinogen. However, due to the limited quality and quantity of the included articles, the above conclusions need to be verified by more high-quality, multi-center, and large-sample RCT.
Humans
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Drugs, Chinese Herbal/administration & dosage*
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Injections
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Ischemic Attack, Transient/drug therapy*
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Randomized Controlled Trials as Topic
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Treatment Outcome
8.Optimal harvesting period of cultivated Notopterygium incisum based on HPLC specific chromatogram combined with chemometrics and entropy weight-gray correlation analysis.
Jing-Cheng WANG ; Hong-Bing SUN ; Teng LIU ; Wen-Tao ZHU ; Hong-Lan WANG ; Yi ZHOU ; Wei-Yan WANG ; Ping YANG ; Shun-Yuan JIANG
China Journal of Chinese Materia Medica 2025;50(14):3878-3886
To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods*
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Apiaceae/chemistry*
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Entropy
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Chemometrics/methods*
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Drugs, Chinese Herbal/chemistry*
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Principal Component Analysis
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Quality Control
9.Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway.
An-Na XIE ; Sun-Zheng-Yuan ZHANG ; Yu ZHANG ; Jin-Long CAO ; Cheng-Long WANG ; Li-Bo WANG ; Hong-Jin WU ; Jie ZHANG ; Wei-Wei DAI
Journal of Integrative Medicine 2025;23(6):670-682
OBJECTIVE:
Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms.
METHODS:
The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.
RESULTS:
Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.
CONCLUSION
CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals
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Chlorogenic Acid/therapeutic use*
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Osteoporosis/metabolism*
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Signal Transduction/drug effects*
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Proto-Oncogene Proteins c-akt/metabolism*
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TOR Serine-Threonine Kinases/metabolism*
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Mice
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Glucocorticoids/adverse effects*
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Receptor, ErbB-2/metabolism*
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Proto-Oncogene Mas
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Dexamethasone/adverse effects*
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Osteocytes/drug effects*
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Osteogenesis/drug effects*
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Male
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Cell Line
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Mice, Inbred C57BL
;
Humans
10.Bisdemethoxycurcumin suppresses liver fibrosis-associated hepatocellular carcinoma via inhibiting CXCL12-induced macrophage polarization.
Wei YUAN ; Xinxin ZENG ; Bin CHEN ; Sihan YIN ; Jing PENG ; Xiong WANG ; Xingxing YUAN ; Kewei SUN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1232-1247
Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals
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Liver Neoplasms/etiology*
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Humans
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Carcinoma, Hepatocellular/immunology*
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Liver Cirrhosis/complications*
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Macrophages/drug effects*
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Male
;
Rats
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Chemokine CXCL12/genetics*
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Diarylheptanoids/pharmacology*
;
Rats, Sprague-Dawley
;
beta Catenin/genetics*


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