1.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
2.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
3.Effect of NEP1-40/PLGA on facial nerve repair in rats
XUE Bing ; XI Hualei ; YAO Lihong ; XU Wanqiu ; XU Xiaohang ; LIN Song ; PIAO Guiyan ; WANG Xiumei
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(2):110-119
Objective:
To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats.
Methods:
According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks.
Results :
At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05)
Conclusion
NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.
4.Current status of eating behaviors and its predictive role in overweight and obese of adolescents
Chinese Journal of School Health 2025;46(1):53-57
Objective:
To explore the current status and influencing factors of eating behaviors in adolescents, so as to provide a theoretical foundation for health promotion education among adolescents.
Methods:
Based on the database from Survey of Chinese Family Health Index (2021), by a random number table method, 1 065 teenagers were selected from the provincial capitals of 22 provinces and 5 autonomous regions in China, as well as 4 municipalities directly under the central government. A general characteristic questionnaire, Patient Health Questionnaire-9 (PHQ-9), Short Form of the Family Health Scale (FHS-SF), 10-item Short Version of the Big Five Personality(BFP-10), Content-based Media Exposure Scale (CM-E) and Sakata Eating Behavior Scale Short Form(EBS-SF) were used to collect information. Multivariate stepwise linear regression analysis was employed to identify and analyze related factors of eating behaviors among adolescents. Receiver operating characteristic was used to validate the predictive ability of the EBS-SF score for overweight and obesity among adolescents.
Results:
The average scores of BFI-10,C-ME, FHS-SF, PHQ-9 and EBS-SF were (33.08±4.64)(19.20±4.55)(38.48±6.65)(6.09±5.63)(16.75±4.36), respectively. Multivariate linear regression showed that family type (other types), agreeableness, conscientiousness, family health and depression were the main related factors of EBS-SF scores among adolescents( B =2.61,-0.42,0.20,-0.11,0.23, P <0.05).The analysis of receiver operating characteristic curve showed that the EBS-SF scores had a good ability in predicting obesity among male adolescents ( AUC= 0.73, P <0.01).
Conclusions
Family type, big five personality, family health,depression are the related factors of eating behaviors among adolescents. EBS-SF scores are predictive of obesity in adolescents, which would provide a new perspective for promoting healthy eating habits among adolescents.
5.Verruciform xanthoma in mandibular gingiva and vestibular sulcus: two cases report and literature review
YANG Mengxin ; ZHAN Yao ; SONG Zhifeng
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(4):305-312
Objective:
To explore the clinical and pathological characteristics, diagnosis, and differential diagnosis of oral verruciform xanthoma, and to provide a reference for accurate clinical identification and treatment.
Methods:
Two cases of verruciform xanthoma occurring on the gingiva and vestibular mucosa are reported. The clinical features and pathological characteristics of both cases are described in detail, and information from a literature review on verruciform xanthoma is provided.
Results:
Case 1: a 37-year-old female patient presented with a pink, rough lesion on the gingiva of the right mandibular posterior teeth for one month. The lesion measured approximately 14 mm × 7 mm, and it was firm and painless. After periodontal therapy, the lesion was excised under local anesthesia. Postoperative pathological examination showed that the epithelial nail protruded and was elongated, and a large number of foam cells filled the connective tissue papilla, leading to the diagnosis of verrucous xanthoma. Case 2: a 36-year-old male patient presented with a pale pink lesion on the right lower vestibular mucosa for three months. The lesion measured approximately 18 mm × 10 mm with irregular margins, and it was firm and painless. The lesion was excised under local anesthesia, and postoperative pathological examination showed parateratosis of epithelium, hypertrophy and elongation of the nail process, and more foam cells in the lamina propria papilla area. The diagnosis was xanthoma verrucosa. The results of a literature review show that the incidence of verruciform xanthoma is 0.025%-0.094%, it primarily occurs in patients aged 50-70 years, the incidence in males is slightly higher than that in females, and it primarily occurs in areas of the oral cavity that include the hard palate and gums. It is generally non-invasive. The etiology and pathogenesis remain unclear. Clinically, verruciform xanthoma lacks specific characteristics, so these lesions are frequently misdiagnosed as other conditions, such as papilloma, common warts, condyloma acuminatum, squamous cell carcinoma, or verrucous carcinoma. The key to diagnosis lies in histopathology, with the hallmark feature being the accumulation of foam cells in the connective tissue papilla beneath the epithelium.
Conclusion
Verruciform xanthoma is a rare oral mucosal lesion with non-specific clinical manifestations and a high rate of misdiagnosis. It must be differentiated from conditions that include squamous papilloma, common warts, condyloma acuminatum, squamous cell carcinoma, and verrucous carcinoma. Definitive diagnosis depends on histopathological examination, and the primary treatment is surgical excision, with a low recurrence rate and minimal risk of malignant transformation.
6.Study on the role of butyric acid-producing bacteria in periodontitis-induced interference with long bone homeostasis in mice fed a high-fat/high-sugar diet
XU Zhonghan ; YAO Yujie ; WANG Xinyue ; SONG Shiyuan ; BAO Jun ; YAN Fuhua ; TONG Xin ; LI Lili
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(6):445-456
Objective:
To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases.
Methods:
This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same.
Results:
①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05).
Conclusion
Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.
7.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
8.Analysis of Clinical Diagnosis and Traditional Chinese Medicine Medication Rule of Children with Nephrotic Syndrome in Single Center
Tingting XU ; Xia ZHANG ; Ying DING ; Long WANG ; Shanshan XU ; Yijin WANG ; Yue WANG ; Feiyu YAO ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):176-184
ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine (TCM) medication rule of children with primary nephrotic syndrome (PNS) in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected, and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria, an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting, association rule analysis, and cluster analysis were carried out on TCM in the prescription, and the high-frequent drugs were analyzed. Results(1) General information: A total of 711 children were included, consisting of 522 males (73.42%) and 189 females (26.58%). The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age, and the average age of onset was (4.74 ± 3.48) years old. (2) Clinical treatment plan and use of immunosuppressive agents: Of the 711 children with PNS, 237 were treated with hormone alone (32.33%), and 474 (66.67%) received immunosuppressive agents combined with hormones. In the initial treatment, hormone combined with Tacrolimus (TAC) was the preferred treatment (32.91%). For children with refractory PNS who exhibited poor clinical efficacy, Rituximab (RTX) was mostly used for treatment, with a ratio of up to 23.63%. (3) TCM syndrome and medication rule: In PNS syndrome differentiation, Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases, accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases, accounting for 16.60%. A total of 711 children were included, of which 706 children were treated with TCM. This involved a total of 706 prescriptions, 226 TCM, and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae (81.16%), Radix Astragali (71.81%), Poria (68.84%), Rhizoma Atractylodis Macrocephalae (63.60%), and Fructus Corni (57.37%). The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest, and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children, TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS, RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali, Poria, Rhizoma Atractylodis Macrocephalae, and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.
9.Mechanism of Zuogui Pills in regulating bone metabolism through OXT/OXTR feed-forward loop based on theory of "all marrows dominated by brain".
Yan-Chen FENG ; Ya-Li LIU ; Xue DANG ; Lu SUN ; Jin-Yao LI ; Jia-Bin SONG ; Shun-Zhi YANG ; Fei-Xiang LIU
China Journal of Chinese Materia Medica 2025;50(10):2761-2768
Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals
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Rats, Sprague-Dawley
;
Rats
;
Female
;
Drugs, Chinese Herbal/administration & dosage*
;
Oxytocin/genetics*
;
Receptors, Oxytocin/genetics*
;
Humans
;
Osteoporosis, Postmenopausal/genetics*
;
Bone and Bones/drug effects*
;
Brain/drug effects*
;
Bone Marrow/drug effects*
10.Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix regulates NLRP3 inflammasome to ameliorate inflammatory response in diabetic kidney disease mice through PI3K/Akt/mTOR signaling pathway.
Zi-Jie YAN ; Lin ZHANG ; Xin-Yao HAN ; Tian-Peng MA ; Song-Jing ZHOU
China Journal of Chinese Materia Medica 2025;50(10):2798-2809
This study aims to evaluate the therapeutic effect of Alpiniae Oxyphyllae Fructus-Saposhnikoviae Radix(AOF-SR) in a diabetic kidney disease(DKD) mouse model, explore its potential mechanism in regulating the NOD-like receptor protein 3(NLRP3) inflammasome via phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway, and provide new theoretical support for traditional Chinese medicine(TCM) intervention in DKD. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), the active ingredients and potential targets of AOF-SR were screened and its molecular mechanisms were investigated through molecular docking, molecular dynamics simulations, and experimental validation. The db/db mice were randomly divided into four groups: model group, low-dose AOF-SR group, high-dose AOF-SR group, and canagliflozin group. The db/m mice served as normal group. After one week of acclimatization, the mice underwent drug intervention. Starting from one week after treatment, body weight, blood glucose levels, and 24-hour urinary protein(24hUP) were measured every two weeks. After 13 weeks of administration, tissue collection and indicator detection were performed. Blood glucose, 24hUP, urinary microalbumin(mAlb), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were determined. Pathological changes in kidney tissue were observed using hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum IL-1β, IL-18, and caspase-1, while RT-qPCR was employed to measure the mRNA expression levels of IL-1β, IL-18, caspase-1, and NLRP3. Western blot was used to assess the protein expression levels of NLRP3, PI3K, p-Akt, Akt, p-mTOR, and mTOR. Network pharmacology analysis indicated that wogonin, pinocembrin, hancinol, and kaempferol were the core compounds for drug treatment of the disease. Molecular docking and molecular dynamics simulations showed that core compounds, particularly wogonin, could specifically bind to PIK3R1, thereby regulating the PI3K/Akt/mTOR pathway. The experimental results indicated that both low and high doses of AOF-SR and canagliflozin significantly reduced blood glucose, 24hUP, mAlb, Scr, and BUN levels in db/db mice, while improving kidney pathological damage and inflammatory cell infiltration. Moreover, the treatments reduced the mRNA expression levels of caspase-1, IL-1β, and IL-18 in the kidneys of db/db mice, as well as the secretion of these factors in the serum. The drugs also inhibited the mRNA and protein expression levels of NLRP3 in the kidneys of db/db mice and decreased the protein levels of PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, AOF-SR may improve kidney inflammation in DKD mice by regulating the PI3K/Akt/mTOR signaling pathway and inhibiting NLRP3 inflammasome activation.
Animals
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Mice
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Signal Transduction/drug effects*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
TOR Serine-Threonine Kinases/metabolism*
;
Diabetic Nephropathies/metabolism*
;
Inflammasomes/drug effects*
;
Male
;
Drugs, Chinese Herbal/chemistry*
;
Humans
;
Mice, Inbred C57BL


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