1.Research progress on the relationship between early life obesogen exposure and childhood obesity
GAO Lei ; YE Zhen ; WANG Wei ; ZHAO Dong ; XU Peiwei ; ZHANG Ronghua
Journal of Preventive Medicine 2026;38(1):48-54
Childhood obesity has become a global public health issue. Current research indicates that early life obesogen exposure has emerged as a significant risk factor for childhood obesity. While obesogens have been confirmed to influence the development and progression of childhood obesity through mechanisms such as endocrine disruption and epigenetic programming, controversies remain regarding the establishment of causal relationships, assessment of combined exposures, and validation of transgenerational effects in humans. In recent years, novel approaches including multi-omics technologies, exposome-based analysis, and multigenerational cohort studies have integrated dynamic biomarker monitoring with analyses of social-environmental interactions, offering new perspectives and methodologies for constructing a systematic "exposure-mechanism-outcome" research framework. This article reviews literature from PubMed and Web of Science up to August 2025 on the association between early life obesogen exposure and childhood obesity, summarizing evidence on the health effects of early life obesogen exposure, major exposure pathways and internal exposure assessment, interactions and amplifying effects of social and environmental factors, as well as the biological mechanisms underlying obesogen action. It further examines current research frontiers and challenges, aiming to provide a theoretical foundation for early prevention and precision intervention of childhood obesity.
2.Molecular Mechanisms of Qingfei Paidu Decoction in the Prevention and Treatment of Acute Lung Injury in Mice Based on miRNA Sequencing
Longxue LI ; Chongfan WAN ; Qi ZHANG ; Ruting LEI ; Xiaoyue WANG ; Leyan CHENG ; Qi LAI ; Ronghua LIU ; Xuan LIU ; Tielong XU
Laboratory Animal and Comparative Medicine 2026;46(3):311-320
ObjectiveTo investigate the preventive and therapeutic effects of Qingfei Paidu decoction (QFPDD) on acute lung injury (ALI) in mice and its underlying molecular mechanisms based on miRNA sequencing technology. MethodsTwenty-four 4-week-old male KM mice were randomly divided into a control group, a model group, and a QFPDD group (n = 8 per group). After one week of acclimatization, mice in the control and model groups were intragastrically administered ultrapure water (0.2 mL per dose), whereas mice in the QFPDD group were intragastrically administered QFPDD (1.6 g crude drug/mL, 0.2 mL per dose), twice daily for 8 consecutive days. On days 2–8, mice in the model and QFPDD groups were exposed to aerosolized lipopolysaccharide (LPS) solution (2.5 g/L, 4 mL per exposure) for 7 consecutive days. On day 9, blood was collected via the retro-orbital venous plexus under deep anesthesia, and lung tissues were harvested. Body weight and lung weight were measured, and the lung coefficient was calculated. Serum levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by ELISA. Lung histopathological changes were observed by HE staining of paraffin-embedded sections. miRNA expression profiles in lung tissues were analyzed using the Illumina HiSeq 2500 sequencing platform. Target genes of differentially expressed miRNAs were predicted using bioinformatics databases, and functional enrichment analysis of these target genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Differentially expressed miRNAs were validated by reverse transcription quantitative real-time PCR (RT-qPCR). ResultsCompared with the control group, the model group showed a consistent body weight growth trend but a significantly increased lung coefficient (P < 0.01). ELISA results showed that serum levels of TNF-α and IL-6 were significantly elevated in the model group compared with the control group (P < 0.01), whereas QFPDD treatment significantly reduced serum TNF-α and IL-6 levels compared with the model group (P < 0.05). HE staining showed that, compared with the control group, the model group exhibited widened alveolar septa, massive inflammatory cell infiltration, partial alveolar expansion, and mild capillary dilation with congestion. In contrast, the QFPDD group showed only slightly widened alveolar septa and mild inflammatory cell infiltration compared with the model group. Intersection analysis of miRNA sequencing data identified 13 differentially expressed miRNAs common to both the model vs. control and QFPDD vs. model comparisons. Among them, 6 miRNAs (mmu-miR-203-3p, mmu-miR-181b-5p_R-1, hsa-miR-4286_R+1, mmu-miR-1843b-5p_L+1R-1_2, mmu-miR-22-3p, and mmu-miR-1964-3p) were significantly up-regulated in the model group (P < 0.05) and significantly down-regulated after QFPDD treatment (P < 0.05), showing a therapeutic reversal trend. GO analysis revealed that the target genes of the differentially expressed miRNAs were mainly enriched in biological processes such as RNA polymerase Ⅱ transcriptional regulation. KEGG analysis indicated that target genes were mainly enriched in signaling pathways including the mitogen-activated protein kinase (MAPK) pathway. RT-qPCR validation result for mmu-miR-203-3p was consistent with the sequencing analysis results. ConclusionQFPDD may exert preventive and therapeutic effects against ALI by regulating the expression of mmu-miR-203-3p and other miRNAs, thereby modulating inflammatory responses and the MAPK signaling pathway and participating in the pathological process of lung injury.
3.Repreparation and clinical application of apheresis platelets from a donor with positive anti-M antibody
Ronghua DIAO ; Qianying RUAN ; Chenxi LIU ; Shichun WANG
Chinese Journal of Blood Transfusion 2026;39(7):942-946
Objective: To evaluate the safety and efficacy of transfusing apheresis platelets from an anti-M-positive donor. Methods: A retrospective analysis was conducted on two units of apheresis platelets collected from a single anti-M-positive donor at Chongqing Blood Center of the Chinese People’s Liberation Army. These platelets were transfused into two unexpected antibodies-negative patients with hematological diseases at the First Affiliated Hospital of the Army Medical University. In vitro, the quality of the anti-M-positive low-plasma apheresis platelets was analysed. In vivo, transfusion efficacy and safety was observed. Results: Following transfusion of anti-M-positive plasma-depleted platelets, the platelet counts of the two patients increased from 13 and 5×10
/L to 24 and 18×10
/L, respectively. The CCI
values were 7.02 and 9.10, both exceeding 4.5. The transfusions were effective, and no transfusion-related adverse reactions occurred in either patient. Conclusion: Anti-M-positive apheresis platelets can be used clinically after plasma removal.
4.Analysis of Pharmacodynamic Material Basis, Mechanisms, and Efficacy-related Quality Markers of Puerariae Lobatae Radix and Puerariae Thomsonii Radix with Different Therapeutic Effect
Xiaowei MENG ; Zhenzhen YANG ; Wenting WU ; Ronghua LIU ; Yongmei GUAN ; Hui OUYANG ; Liping HUANG ; Yaqi WANG ; Qiong LI ; Huanhuan DONG ; Jianping GONG ; Weifeng ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):269-281
Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family, respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China, the two herbs have been individually recorded. Although they share the same functions and indications, the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator, puerarin, which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production, thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents, while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis, cardiovascular and cerebrovascular protection, and central analgesia, while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation, hypoglycemia, and peripheral analgesia. Based on this, the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects, namely "relieving exterior syndrome and clearing heat", "promoting fluid production to quench thirst", and "dredging channels and activating collaterals", were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway, and their common core target is prostaglandin-endoperoxide synthase 2 (PTGS2). This review provided clinical application recommendations based on the therapeutic differences between the two herbs, elucidated the scientific connotation of their "same origin but different effects", and, grounded in the quality marker (Q-Marker), proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association, as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix, the improvement of quality standards, and the high-quality development of the industry.
5.Evaluation of the safety and efficacy of ABO non-identical apheresis platelets with reduced plasma transfusion
Ronghua DIAO ; Qianying RUAN ; Lu BAI ; Hong ZHANG ; Zerong WANG ; Lei FU ; Shichun WANG
Chinese Journal of Blood Transfusion 2025;38(7):909-914
Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10
per therapeutic dose vs (2.46±0.28)×10
per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.
6.Evaluation of the safety and efficacy of ABO non-identical apheresis platelets with reduced plasma transfusion
Ronghua DIAO ; Qianying RUAN ; Lu BAI ; Hong ZHANG ; Zerong WANG ; Lei FU ; Shichun WANG
Chinese Journal of Blood Transfusion 2025;38(7):909-914
Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10
per therapeutic dose vs (2.46±0.28)×10
per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.
7.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.
8.Therapeutic Effect of Jidesheng Sheyao Tablets on VZV-induced Skin Vesicles in Guinea Pigs and Postherpetic Neuralgia in Rats
Rui XIE ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Shuran LI ; Qiyue SUN ; Xinwei WANG ; Jingsheng ZHANG ; Xihe CUI ; Xiaolan CUI ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):38-47
ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus (VZV) and its associated postherpetic neuralgia (PHN) to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight, namely the normal group, the model group, the positive control group, the high-dose group, medium-dose group, and low-dose group of Jidesheng Sheyao tablets (1.92, 0.96, 0.48 g·d-1), and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets (0.96 g·d-1 + 1.2 g·kg-1·d-1). The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group, 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups, and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7th day, the guinea pigs were sacrificed by CO2 anesthesia. The locally infected skin was taken, and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction (Real-time PCR). The pathological histology examination was carried out after hematoxylin-eosin (HE) staining. Seventy rats were randomly divided into seven groups according to their body weight, namely the normal group, the model group, the positive control group, the high-dose group, medium-dose group, and low-dose group of Jidesheng Sheyao tablets (1.08, 0.54, 0.27 g·d-1), and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets (0.54 g·d-1 + 1.2 g·kg-1·d-1). The rats in each group (except the normal group) were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated, and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1st, 3rd, 6th, 8th, and 10th days after inoculation, and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10th day after the virus inoculation, the rats were anesthetized after the behavioral examination, and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P (SP), neurokinin (NK), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with those in the normal group, the guinea pigs in the model group had obvious skin herpes lesions (P<0.01). The viral nucleic acid load was high (P<0.01), and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis (P<0.01). The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased (P<0.05), and the contents of NK, SP, TNF-α, and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection (P<0.01), reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs (P<0.01), alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue (P<0.05), significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats (P<0.05), and decrease the contents of NK, SP, TNF-α, and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats (P<0.01). ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia (PHN), providing a promising candidate for the prevention and treatment of VZV infections.
9.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
10.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.


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