Latest Issue

    Volume 31 Issue 11 2025

      Original Article

    • Mehrnaz Shojaei, Fariborz Khorvash, Amirhossein Sahebkar, Thozhukat Sathyapalan, Mohammad Bagherniya
      Vol. 31, Issue 11, Pages: 963-972(2025) DOI: 10.1007/s11655-025-3939-1
      Abstract:Objective:To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine.Methods:In this randomized, double-blind and placebo-controlled trial, 70 patients suffered from migraine without aura were randomized into 2 groups to receive 250 mg/d of phytosomal curcumin (intervention group) or maltodextrin (placebo group) for 8 weeks, 35 cases per group. All patients in both groups received their standard treatment and common medications. The severity, duration, frequency of headaches, quality of life (QoL), mental status, headache impact, and sleep quality of patients were assessed before and after treatment. Adverse effects were also assessed.Results:Sixty-five patients completed the trial (33 in the intervention group and 32 in the placebo group). Phytosomal curcumin supplementation significantly reduced severity, duration and frequency of migraine attacks, stress score, and headache impact, and improved QoL and sleep quality of patients in the intervention group, compared with the placebo group (P<0.05 or P<0.01). However, it had no significant effect on depression and anxiety scores in the intervention group, compared with the placebo group (P>0.05). No adverse effects had been reported in response to the intervention.Conclusion:Phytosomal curcumin as a safe supplement had a beneficial effect on migraine symptoms, stress level, as well as the sleep quality and QoL in patients with migraine. (Trial registration No. IRCT20201129049534N2)  
      Keywords:migraine;curcumin;depression;quality of life;sleep quality;randomized controlled trial   
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      Updated:2025-10-23
    • LIANG Zi-rong, LIN Cui-jun, LIU Yi-han, YUE Qian, HOI Pui Man
      Vol. 31, Issue 11, Pages: 973-981(2025) DOI: 10.1007/s11655-025-3933-7
      Abstract:Objective:To explore the mechanism of crocin, a major active component of Crocus sativus (Zanghonghua), in regulating amyloid beta (Aβ) generation, endoplasmic reticulum (ER) stress, and autophagy in neuronal cells, with potential therapeutic applications in Alzheimer's disease (AD).Methods:Mouse neuroblastoma Neuron2a (N2a) cells stably transfected with the human amyloid precursor protein (APP) Swedish mutant was used as a cellular model for AD (N2a/APP). Control cells were vector transfected (N2a/vector). The effects of 3 different doses of crocin on reactive oxygen species (ROS) generation, cytosolic calcium, and apoptosis were evaluated by flow cytometry. Aβ levels were determined by enzyme-linked immunosorbent assay. APP processing and ER stress proteins expressions were determined by Western blot. Autophagosome formation was evaluated by autophagy detection kit and confocal microscope.Results:Crocin inhibited APP expression in N2a/APP cells and promoted α-cleavage of APP processing, while modestly reduced beta-secretase 1 (BACE1) and presenilin 1 (PS1, P<0.05 or P<0.01). ER stress markers, including the binding immunoglobulin protein/78-kD glucose-regulated protein (Bip/GRP78) and C/EBP homologous protein (CHOP), were elevated in N2a/APP cells compared to N2a/vector cells (P<0.05). Crocin could effectively reduce the levels of ER stress (P<0.05 or P<0.01). In addition, crocin enhanced autophagy by promoting formation of autophagosome (P<0.05 or P<0.01).Conclusion:Crocin significantly inhibited Aβ generation by promoting α-cleavage of APP processing, inhibiting ER stress-associated unfolded protein response, and regulating autophagy.  
      Keywords:crocin;amyloid precursor protein processing;endoplasmic reticulum stress;autophagy;unfolded protein response;Alzheimer's disease   
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      Updated:2025-10-23
    • CHEN Chang-feng, GAO Yin-huan, FANG Qin, ZHOU Yong-feng, LIU Yong, WU Jian, CHEN Hao, WANG Lie-cheng, CHEN Lei
      Vol. 31, Issue 11, Pages: 982-990(2025) DOI: 10.1007/s11655-025-3942-6
      Abstract:Objective:To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits.Methods:The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. Results:SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons.Conclusion:SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.  
      Keywords:Suanzaoren Decoction;anxiety- and depression-like behavior;chronic restraint stress;basolateral amygdala;pyramidal neuron;Chinese medicine   
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      Updated:2025-10-23
    • JIANG Huan-ning, ZHANG Bo, ZHANG Jian, ZHOU Yan-yan
      Vol. 31, Issue 11, Pages: 991-1000(2025) DOI: 10.1007/s11655-025-3936-4
      Abstract:Objective:To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification.Methods:Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg•d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β-protein 1–42 (Aβ1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95).Results:A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and Aβ1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01).Conclusions:DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.  
      Keywords:Dihuang Yinzi;Alzheimer's disease;metabolomics;mitochondria;synapses;cAMP pathway;Chinese medicine   
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      Updated:2025-10-23
    • XU Wen-ting, WANG Qi, WU Xin-yu, HUANG Jing-han, WANG Jing
      Vol. 31, Issue 11, Pages: 1001-1010(2025) DOI: 10.1007/s11655-025-3929-3
      Abstract:Objective:To explore the effects and mechanism of Chinese medicine Liujunzi Decoction (LJZD) on regulating microbial flora in mice with asthma flora disorder.Methods:Thirty BALB/c female mice were divided into control, model, LJZD [3.5 g/(kg•d), by gavage], dexamethasone [DXMS, 0.7 mg/(kg•d), intraperitoneal injection], and Clostridium butyricum [CB, 230 mg/(kg•d), by gavage] groups according to a random number table, 6 mice in each group. The asthma flora disorder mice model was induced with ovalbumin (OVA). Lung and gut lesions were analyzed by hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stainings. The secretory immunoglobulin A (sIgA) protein expression in lung and gut tissues was detected by Western blot. Flow cytometry was used to detect the relative counts of GATA binding protein 3 (GATA3)/type 2 innate lymphoid cells (ILC2) in lung and gut. The levels of inflammatory factors in lung and gut tissues were detected by enzyme-linked immunosorbent assay (ELISA). Chao1 and Shannon index were used to compare microbial abundance and diversity in alveolar lavage fluid and cecal contents. The similarity or difference in the composition of mice microbial communities was analyzed through cluster analysis. The serum short-chain fatty acids (SCFAs) content was detected by ultra performance liquid chromatograph mass spectrometer (LC-MS)/MS.Results:The asthma flora disorder model mice showed obvious asthma-related symptoms, but LJZD treatment effectively alleviated these symptoms. LJZD restored alveolar wall thickening, airway inflammatory cell infiltration, gut tissue structure destruction, and inflammatory cell infiltration in asthma flora disorder mice. LJZD downregulated the sIgA protein expression in mice (P<0.05). Moreover, LJZD decreased the activation of GATA3/ILC2s in lung and gut tissue (P<0.01), and reduced the levels of interleukin (IL)-5, IL-33, IL-25, IL-9 and IL-13 (P<0.01). LJZD treatment returned the abundance of microbial species and the microbial community structure of alveolar lavage fluid and cecal content in asthma flora disorder mice to the normal state. The SCFAs content and body metabolism were also improved.Conclusion:LJZD exerted anti-asthmatic effects by improving the microbial balance of lung–gut axis and affecting systemic metabolism, consequently regulating the GATA3/ILC2s axis to impact the lung inflammatory response.  
      Keywords:Liujunzi Decoction;lung–gut axis;microbial diversity;GATA binding protein 3/type 2 innate lymphoid cells;asthma flora disorder;Chinese medicine   
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      Updated:2025-10-23
    • DING Wei-chao, CHEN Juan, LI Quan, REN Yi, WANG Meng-meng, ZHANG Wei, JI Xiao-hang, WU Xin-yao, NIE Shi-nan, HUANG Chang-bao, SUN Zhao-rui
      Vol. 31, Issue 11, Pages: 1011-1020(2025) DOI: 10.1007/s11655-025-3927-5
      Abstract:Objective:To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).Methods:In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsis-related ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.Results:Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).Conclusion:Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.  
      Keywords:quercetin;sepsis;acute respiratory distress syndrome;reactive oxygen species/p38 mitogen-activated protein kinase pathway;oxidative stress;inflammation;cell apoptosis   
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      Updated:2025-10-23
    • ZHANG Qiao-ju, LUO Xi, ZHENG Yu-wen, ZHENG Jun-qiao, WU Xin-ying, WANG Shu-mei, SHI Jun
      Vol. 31, Issue 11, Pages: 1021-1028(2025) DOI: 10.1007/s11655-025-3931-9
      Abstract:Objective:To explore the anti-photoaging properties of salvianolic acid B (Sal B).Methods:The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking.Results:Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of –7.5 kCal/mol. Conclusion:Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.  
      Keywords:salvianolic acid B;antiphotoaging;oxidative stress;silent information regulator 1   
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      Updated:2025-10-23

      Clinical Experience

    • JIA Ming-yue, ZHANG Mei-yi, XIAO Si-yao, YU Yang, SHAO Xiang, HAN Chun-sheng, HAN Gui-ling
      Vol. 31, Issue 11, Pages: 1029-1036(2025) DOI: 10.1007/s11655-025-3948-0
      Abstract:Objective:To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome.Methods:From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded.Results:Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment.Conclusions:The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589)  
      Keywords:allergic rhinitis;Lu'e Biyan Formula;Fei (Lung)-qi deficiency-coldness syndrome;Chinese medicine;randomized controlled trial   
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      Updated:2025-10-23
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