18β-glycyrrhetinic acid improves pulmonary hypertension by regulating the vascular non-inflammatory molecule-1/L-arginine/nitric oxide signaling pathway

Article

Author: Abudukeremu, Asimuguli ; Shanahati, Daliya ; Aihemaitituoheti, Adilai ; Fang, Lei ; Aikemu, Ainiwaer ; Nijiati, Yiliyaer ; Yang, Tao

PURPOSEPulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by elevated pulmonary arterial pressure and resistance. 18β-Glycyrrhetinic acid (18β-GA), a major bioactive component in Glycyrrhiza glabra L., exhibits various pharmacological activities. Although 18β-GA has been found to alleviate PH, the underlying mechanisms are still unclear. This study was aimed to elucidate the molecular processes by which 18β-GA attenuates PH.PATIENTS AND METHODSA monocrotaline-induced PH rat model was created, and cardiac function and pulmonary arterial pressure were assessed. Rat blood markers were analyzed via enzyme-linked immunosorbent assay, and protein levels of Vanin-1, NF-κB, IL-6, TNF-α, PPAR-γ, and iNOS in lung tissue were determined by western blotting. A hypoxia-induced pulmonary artery smooth muscle cell (PASMCs) proliferation model was created, and cell proliferation and migration were evaluated using CCK-8 and scratch wound assays. Cell cycle, apoptosis, and mitochondrial membrane potential were assessed via flow cytometry, and protein levels were measured using western blotting.RESULTSPH rats treated with, 18β-GA exhibited reduced mean pulmonary arterial pressure (mPAP) and delayed pulmonary vascular remodeling. In lung tissue, Vanin-1, NF-κB, IL-6, and TNF-α were downregulated, while PPAR-γ and iNOS were upregulated. PASMCs treated with 18β-GA exhibited reduced hypoxia-induced proliferation and increased apoptosis. In addition, NO levels in the supernatant of PASMCs were elevated, and Vanin-1 and NF-κB were downregulated, whereas PPAR-γ and iNOS were upregulated.CONCLUSIONOur findings reveal a novel mechanism by which 18β-GA attenuates PH by improving pulmonary vascular remodeling and inhibiting PASMCs proliferation via the Vanin-1/L-Arg/NO pathway.

01 May 2025·Journal of Ethnopharmacology

Study on the compatibility of japonica rice in Xie-Bai-San decoction based on characterization, multi components quantification, and pharmacokinetics

Article

Author: Li, Kai ; Wang, Wenqian ; Liu, Dailin ; Li, Guotong ; Dong, Wenxuan ; Wang, Xinrui ; Luo, Lifei ; Zhang, Jingze

ETHNOPHARMACOLOGICAL RELEVANCEXie-Bai-San decoction (XBS), which is effective in treating coughs associated with lung heat, is composed of four Chinese medicines: Morus alba L. (known as Sangbaipi), Lycii Cortex (known as Digupi), licorice (Glycyrrhiza uralensis Fisch.), and japonica rice. The original prescription of XBS and its modified prescriptions have been greatly expanded in clinical application. However, japonica rice as a guiding drug is often ignored, which effects on composition and metabolism in vivo have not been fully studied.AIM OF THE STUDYThe purpose of this study was to explain the compatibility of japonica rice in the XBS. By comparing the physical state of the XBS without japonica rice decoction (XBS-JM) and measuring the content of 26 indicative components in both XBS and XBS-JM decoctions, this study illustrated how japonica rice affected the overall physical state and the dissolution of components during the decoction process. Combined with the analysis of the pharmacokinetic characteristics of 18 active components absorbed into the blood, the effect of japonica rice and the scientific basis of prescription compatibility were comprehensively discussed.METHODSA sensitive and reliable UPLC-Q-TOF-MS qualitative analysis method was developed to analyze the chemical constituents of XBS. Taking the change of the remaining volume of the decoction as the index, the decoction time of 30, 50 and 90 min was selected. A Malvern particle size apparatus and transmission electron microscopy (TEM) were utilized to investigate the influence of japonica rice on phase states. Additionally, a highly selective and sensitive UPLC-MS/MS quantitative analysis method was established to detect changes in the content of 26 chemical components in the decoctions at three different decoction time. The pharmacokinetic parameters of 18 components were also studied following the oral administration of XBS and XBS-JM in both control and model animals.RESULTSThe results showed that the particle size of the XBS and XBS-JM decoction, following dialysis-ultracentrifugation, was predominantly in the nano-scale range. The addition of japonica rice (JM) enhanced the stability of the nanoparticles, and the concentrations of guanosine, chlorogenic acid, kukoaMine B, astragalin, and naringenin in the XBS decoction were significantly higher than those in the XBS without japonica rice (XBS-JM) decoction. The results of pharmacokinetics showed that compared with the administration of XBS-JM, XBS significantly enhanced the absorption of eight components in the control group, such as kukoaMine B, kuwanon G, wogonoside, and liquiritin. In the model group, following the administration of XBS, the absorption rates of six components, such as kukoaMine B, kuwanon G, and 18β-glycyrrhetinic acid were significantly increased (p<0.05), with the peak concentration of 60% of the components also showing a notable rise.CONCLUSIONThis study provides experimental evidence regarding physical characterization, multi components quantification, and pharmacokinetics, which might help to explain the rationality of the compatibility of japonica rice in the prescription, and the influence on the effective substance basis of traditional Chinese medicine (TCM).

01 May 2025·International Immunopharmacology

IL-17 enhanced the susceptibility to fluoxetine resistance in depression via the JAK1-STAT6 signaling pathway

Article

Author: Yang, Qingqing ; Huang, Xueru ; Pang, Zixin ; Zhang, Xin ; Cai, Ziling ; Jia, Ruiting ; Shen, Yineng ; Ao, Haiqing ; Liu, YueYing ; Huang, Yike ; Zhang, Mingjia ; Qu, Yuanguo ; Hong, Yaonan ; Zhang, Yi ; Gao, Xing ; Zhu, Aisong ; Yu, Wumin

AIMSThis study aims to investigate the role of IL-17 in fluoxetine resistance in depression.METHODSThe Weighted Gene Coexpression Network Analysis (WGCNA) was utilized to analyze differentially expressed genes between response to antidepressant (GRA) group and the resistance to antidepressant (AR) group. Furthermore, a treatment resistance model of depression was established in Chronic unpredictable mild stress (CUMS) mice administrated with fluoxetine (widely used clinical medication for the treatment of depression) according to sucrose preference rate. Depression-like behaviors in mice were detected in Control group, CUMS group, GRA group, AR group, and SR1001 (Th17 differentiation inhibitor) group. Subsequently, HT22 cells were exposed to IL-17 secreted by Th17 differentiation. Transcriptome sequencing from the Control and IL-17 group was used to screen differential genes. HT22 cells were then transfected with si-JAK1 or si-STAT6. Th17 differentiation, the integrity of the blood-brain barrier (BBB), JAK1-STAT6 signaling pathway related proteins were detected by western blot, immunocytochemistry, flow cytometric analysis, ELISA experiments, immunofluorescence, and PCR.RESULTThe WGCNA showed that Th17 differentiation played an important role in the treatment resistance of depression. The results of the following animal experiments showed that fluoxetine resistance resulted in a reduction in total distance and average speed in the Open Field Test (OFT), an increase in immobility time during the Forced Swim Test (FST) and Tail Suspension Test (TST). It also regulated the expression of the SERT protein, Th17 differentiation, IL-17 secretion, and compromised the integrity of BBB, yielding similar outcomes in CUMS mice. However, these results could be reversed by SR1001. Moreover, IL-17 effectively elevated the SERT protein level and activated the JAK1-STAT6 signaling pathway in vivo and in vitro.CONCLUSIONThe inhibition of Th17 differentiation and the reduction of peripheral IL-17 release could decrease sensitivity to fluoxetine resistance and relieve the depression-like behavior. This process might be associated with the JAK1-STAT6 pathway.

100 Deals associated with 18β-Glycyrrhetinic acid

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Indication	Highest Phase	Country/Location	Organization	Date
Idiopathic Pulmonary Fibrosis	Preclinical	China	Anhui University of Science & Technology	01 Oct 2024
Psoriasis	Preclinical	China	Guangzhou University of Chinese Medicine	01 Jun 2024
Intestinal Diseases	Preclinical	China	Chinese Academy of Agricultural Sciences	16 Apr 2024
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	United States	Montana State University	19 Oct 2012

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