1.Traditional Chinese Medicine Intervention in Parkinson's Disease Based on Keap1/Nrf2/ARE Signaling Pathway: A Review
Liuping YUE ; Yongkang SUN ; Fangbiao XU ; Yanbo SONG ; Yijun WU ; Huan YU ; Xinzhi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):307-317
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra, abnormal aggregation of alpha-Synuclein (α-Syn), and the formation of Lewy bodies. However, the exact mechanisms remain unclear. In recent years, the PD incidence has gradually increased, while current treatment methods are limited to symptom alleviation, incapable of halting disease progression, and prone to adverse effects, thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is closely related to oxidative stress, neuroinflammation, apoptosis, ferroptosis, and mitochondrial dysfunction, playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine (TCM) can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages, such as multiple targets, multiple pathways, and fewer adverse reactions, TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD, while summarizing the latest research on PD intervention by TCM monomers, active ingredients, and compounds, as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway, aiming to provide a reference for clinical medicine development to prevent and treat PD.
2.Stellate ganglion block versus conventional western medication for the treatment of insomnia:a meta-analysis
Yanbo SONG ; Yongkang SUN ; Fangbiao XU ; Xinzhi WANG
Journal of Interventional Radiology 2025;34(1):48-57
Objective To compare the efficacy and safety of stellate ganglion block(SGB)with those of conventional western medication in the treatment of insomnia.Methods A computerized retrieval of academic papers concerning the clinical randomized controlled trials of SGB versus conventional western medication in the treatment of insomnia from the databases of PubMed,Embase,Cochrane Library,CNKI,Wanfang Data knowledge service platform,VIP database and CBM database was conducted.The retrieval time period was from the establishment of the database to June 13,2023.NoteExpress v3.5 software was used to make literature screening,Stata17.0 software was used to perform meta-analysis of the obtained data,TSA0.9.5.10 beta software was used to make sequential analysis,and GRADEpro was used to perform the grade classification.Results A total of 11 articles including 875 patients with insomnia were included in this analysis.Compared with the conventional western medication,SGB showed certain advantages in the following aspects:improving total clinical effectiveness(RR total=1.24,95%CI:1.16-1.32,P<0.01),increasing the proportion of patients who could sleep for more than 3 hours after treatment(RR total=1.24,95%CI:1.09-1.41,P=0.001),increasing total sleep time(SMD=1.53,95%CI:0.89-2.16,P<0.01),reducing sleep latency(MD=-14.08,95%CI:-18.72--9.43,P<0.01),decreasing PSQI score(MD=-3.54,95%CI:-4.31--2.78,P<0.01),and reducing the recurrence rate within 6 months(RR=0.19,95%CI:0.10-0.37,P<0.01).However,the difference in the proportion of patients who could sleep for more than 6 hours after treatment between the two groups was not statistically significant(RR=1.31,95%CI:0.97-1.76,P=0.078).The traditional SGB therapy had a certain risk of adverse events,ultrasound-guided SGB therapy was much safer.Trial sequential analysis showed that the cumulative sample size of the effective rate crossed the conventional threshold and TSA threshold,the positive results had been obtained in advance although it did not reach RIS.The quality of evidence evaluated by GRADE for the sleep latency,PSQI and recurrence rate within 6 months was medium grade,and the quality for the remaining indexes was low grade.Conclusion Compared with conventional western medication for the treatment of insomnia,the effect of SGB in increasing the total response rate,the proportion of patients who get sleeping for more than 3 hours after treatment and the total sleep duration,in reducing sleep latency,PSQI score and recurrence rate within 6 months has gained some certain evidence supports.The SGB and conventional western medication have similar efficacy in improving the proportion of patients who get sleeping for more than 6 hours after treatment.The results of this study are stable and reliable,but the current level of evidence grade is lower,therefore,large-sample randomized controlled trials need to be conducted before its clinical efficacy can get further evidence-based support.
3.Preliminary study of mesothelin-loaded paclitaxel nanoparticles for ultrasound molecular imaging and treatment of ovarian cancer
Li LUO ; Yujie WAN ; Xinzhi XU ; Na WANG ; Fang LI ; Hang ZHOU
Chinese Journal of Oncology 2025;47(5):395-403
Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.
4.Study on the Improvement Effect of Pinelliae Rhizoma Praeparatum Cum Alumine and Its Active Components on Inflamma-tory Response in Acute Lung Injury
Yanqing XU ; Xinzhi WANG ; Xiaobing CUI ; Yuxin GU ; Qianlin CHEN ; Shengjun CHEN ; Song LI ; Hao WU ; Hongli YU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1055-1065
OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.
5.Exploring the Application of Xuming Decoction in Post-Stroke Limb Movement Disorders Based on the Principle of"Wind Prevailing and Causing Movement"
Yanbo SONG ; Yongkang SUN ; Fangbiao XU ; Xinzhi WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):436-441
Post-stroke limb movement disorder is a common functional disorder after stroke.Xuming Decoction in Ancient and Modern Records of the Proven is an important prescription of Zhang Zhongjing for treating"stroke prickly heat,the body cannot hold it-self".It has been modified and recorded in many later generations,among which Xiaoxuming Decoction in Important Formulas Worth a Thousand Gold Pieces for Emergency is the most commonly used.With the development of the"internal wind theory"of stroke,the pre-scriptions of Xuming Decoction were gradually criticized and even abandoned because they often used"wind drugs"and were difficult to understand the medical theory of"internal wind".Based on the viewpoints of"wind prevailing and causing movement"and"internal wind being the change of yang qi in the body",the paper proposes the theory of"inducing wind to promote movement"of Xuming De-coction and believes that"wind is qi".At the beginning of stroke,wind-yang is violently hyperactive,and wind prevails and causes movement,resulting in stroke;after stroke,yang qi is weak,wind is defeated and static,and limbs are unable to use.However,"wind drugs"such as Ephedra sinica Stapf and Cinnamomum aromaticum Nees have the functions of generating wind and promoting movement,revitalizing the decadent and the useless,exciting yang qi,harmonizing the ying and wei,and raising and lowering qi.The Xuming Decoction is mainly composed of"wind drugs",which warms the yang and replenishes the qi,generates wind to excite yang qi,and revitalizes the weak;replenishes the yang to induce wind and promote movement,replenishes qi and generates blood;relieves muscles to harmonize the ying and wei,and dredges the limbs;restores the pivot to regulate the axis of the internal organs,unblocks the qi,and promotes the recovery of limb motor function after stroke,providing a theoretical basis for the clinical application of Xuming Decoction.
6.Exploring the Application of Xuming Decoction in Post-Stroke Limb Movement Disorders Based on the Principle of"Wind Prevailing and Causing Movement"
Yanbo SONG ; Yongkang SUN ; Fangbiao XU ; Xinzhi WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):436-441
Post-stroke limb movement disorder is a common functional disorder after stroke.Xuming Decoction in Ancient and Modern Records of the Proven is an important prescription of Zhang Zhongjing for treating"stroke prickly heat,the body cannot hold it-self".It has been modified and recorded in many later generations,among which Xiaoxuming Decoction in Important Formulas Worth a Thousand Gold Pieces for Emergency is the most commonly used.With the development of the"internal wind theory"of stroke,the pre-scriptions of Xuming Decoction were gradually criticized and even abandoned because they often used"wind drugs"and were difficult to understand the medical theory of"internal wind".Based on the viewpoints of"wind prevailing and causing movement"and"internal wind being the change of yang qi in the body",the paper proposes the theory of"inducing wind to promote movement"of Xuming De-coction and believes that"wind is qi".At the beginning of stroke,wind-yang is violently hyperactive,and wind prevails and causes movement,resulting in stroke;after stroke,yang qi is weak,wind is defeated and static,and limbs are unable to use.However,"wind drugs"such as Ephedra sinica Stapf and Cinnamomum aromaticum Nees have the functions of generating wind and promoting movement,revitalizing the decadent and the useless,exciting yang qi,harmonizing the ying and wei,and raising and lowering qi.The Xuming Decoction is mainly composed of"wind drugs",which warms the yang and replenishes the qi,generates wind to excite yang qi,and revitalizes the weak;replenishes the yang to induce wind and promote movement,replenishes qi and generates blood;relieves muscles to harmonize the ying and wei,and dredges the limbs;restores the pivot to regulate the axis of the internal organs,unblocks the qi,and promotes the recovery of limb motor function after stroke,providing a theoretical basis for the clinical application of Xuming Decoction.
7.Study on the Improvement Effect of Pinelliae Rhizoma Praeparatum Cum Alumine and Its Active Components on Inflamma-tory Response in Acute Lung Injury
Yanqing XU ; Xinzhi WANG ; Xiaobing CUI ; Yuxin GU ; Qianlin CHEN ; Shengjun CHEN ; Song LI ; Hao WU ; Hongli YU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1055-1065
OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.
8.Preliminary study of mesothelin-loaded paclitaxel nanoparticles for ultrasound molecular imaging and treatment of ovarian cancer
Li LUO ; Yujie WAN ; Xinzhi XU ; Na WANG ; Fang LI ; Hang ZHOU
Chinese Journal of Oncology 2025;47(5):395-403
Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.
9.Study on original identification of Rhei Radix et Rhizoma decoction pieces based on electronic sensory system and GC-IMS technology
Shuo YANG ; Zhongli XU ; Xinzhi ZHAO ; Dianhua SHI ; Yanpeng DAI ; Yu BI ; Yizhou XIN
China Pharmacy 2024;35(9):1076-1081
OBJECTIVE To investigate the variations in taste, aroma and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces derived from different sources, and to identify their origins. METHODS The flavor, odor and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces from different sources were compared and analyzed by using electronic tongue, electronic nose, and gas chromatography-ion mobility spectrometry (GC-IMS). Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA) and Fisher discriminant analysis were employed to identify the origins of Rhei Radix et Rhizoma decoction pieces and establish the basis discrimination criteria. RESULTS The differences in taste of Rhei Radix et Rhizoma decoction pieces from 3 origins were primarily characterized by bitterness, astringency, and bitter-astringent aftertaste. In terms of smell, variations were mainly observed in inorganic sulfides, organic sulfides containing aromatic components, methane and other short-chain alkanes, alcohols, ethers, aldehydes and ketones, as well as nitrogen oxides. Differentially volatile organic compounds mainly consisted of alcohols, aldehydes and ketones. Furthermore, the samples from 8 batches could be effectively classified into 3 categories.Three types of Rhei Radix et Rhizoma decoction pieces can be effectivily identified based on the peak intensity ratio between volatile substances. For example, when the peak intensity of 2-acetylfuran was 3-19 times that of isobutyric acid [dimer], it was considered as Rheum officinale Baill. CONCLUSIONS The discriminant models established in this study, along with the criteria for determining the origins based on the peak intensity ofcharacteristic volatile compounds, can be utilized for the identification of Rhei Radix et Rhizoma decoction pieces.
10.Regulation of Alzheimer's Disease by Chinese Medicine Based on BDNF/TrkB Signaling Pathway: A Review
Liuping YUE ; Yongkang SUN ; Fangbiao XU ; Yanbo SONG ; Xinzhi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):274-282
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by the progressive loss of cognitive and memory functions. Its pathological features mainly include neurofibrillary tangles formed by the aggregation of hyperphosphorylated tau proteins and amyloid plaques formed by the accumulation of β-amyloid. The exact pathogenesis of AD has not been fully elucidated, and there are currently no effective specific drugs or radical treatments available in clinical practice. In recent years, the incidence of AD has been on the rise, severely affecting life and health, making the search for effective drugs and therapeutic components for AD treatment crucial. Modern medical research has found that the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway is closely related to neurogenesis, apoptosis, neuroinflammation, synaptic plasticity, and oxidative stress, playing a vital role in the pathophysiological development of AD. Additionally, Chinese medicine has a long history of treating neurodegenerative diseases with few adverse reactions and features a multi-target, multi-link, and multi-pathway approach to treatment. Therefore, the author reviewed the latest research reports in China and abroad to elaborate on the role of the BDNF/TrkB signaling pathway in the onset and progression of AD, and summarized the research progress on the regulation of the BDNF/TrkB pathway by Chinese medicine compounds and monomers in AD intervention. This study is expected to provide references for the development of clinical drugs for the prevention and treatment of AD and to broaden the perspective on Chinese medicine treatment of AD.

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