1.Effect of Shenge Bushen Capsules and Its Polysaccharides and Flavonoids on Precocious Puberty in Young Mice
Hong SUN ; Fan LEI ; Chenggong LI ; Shixian HU ; Weihua WANG ; Bin REN ; Juan HAO ; Rui LUO ; Lijun DU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):95-103
ObjectiveTo explore the effect of Shenge Bushen Capsules (SBC) on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part, mice were divided into four groups: The control group and the low, medium, and high-dose SBC groups (234.7, 469.4, 938.7 mg·kg-1, respectively). In the second part, mice were divided into four groups: Control group, Pseudostellariae Radix polysaccharide (PRP) group, total flavonoids group, and SBC group, all receiving a dose of 469.4 mg·kg-1. After 7 days of administration, the vaginal opening of female mice and the descent of testes and scrotum in male mice, as well as the ovarian and testicular organ indices, were observed. After 4 weeks of administration, female and male mice were housed together for 2 days, and the pregnancy rate of females was monitored. After delivery, the pregnant female mice continued receiving the treatment for 4 weeks, and the sexual development of their offspring, including vaginal opening, testicular descent, and organ indices of ovaries and testes, was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group, there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration, the pregnancy rate in the low-dose group was significantly reduced (P<0.05), but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices, and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC, Pseudostellariae Radix polysaccharide, significantly reduced the vaginal opening in female mice after 7 days of administration (P<0.05). After 4 weeks, the serum estradiol levels of non-pregnant female mice were decreased (P<0.05), but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally, there were no significant effects on precocious puberty indicators, such as vaginal opening and testicular descent, in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice, and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.
2.Design, synthesis and anti-Alzheimer's disease activity evaluation of cinnamyl triazole compounds
Wen-ju LEI ; Zhong-di CAI ; Lin-jie TAN ; Mi-min LIU ; Li ZENG ; Ting SUN ; Hong YI ; Rui LIU ; Zhuo-rong LI
Acta Pharmaceutica Sinica 2025;60(1):150-163
19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound
3.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
4.Effects of quercetin on inflammatory response in allergic rhinitis rats through TLR4/IRAK4/NF-κB signaling pathway
Xixi LEI ; Kebin DENG ; Rui JIANG
China Pharmacy 2025;36(7):832-836
OBJECTIVE To investigate the effects and mechanism of quercetin (QUE) on inflammatory response in allergic rhinitis (AR) model rats based on Toll-like receptor 4/interleukin 1 (IL-1) receptor-associated kinase/nuclear factor κB (TLR4/ IRAK4/NF-κB) signaling pathway. METHODS AR model rats were constructed by ovalbumin sensitization method. A total of 48 successfully constructed rats were randomly divided into AR group, QUE-L and QUE-H groups (i.g administration, 17.5, 35 mg/kg) and QUE-H+TLR4 activator lipopolysaccharide (LPS) group (i.g administration of 35 mg/kg QUE+intravenous administration of 0.4 mg/kg LPS via tail vein), with 12 rats in each group. Another 12 normal healthy rats were selected as control group, once a day, for 21 consecutive days. After the last medication, rhinitis symptoms of rats in each group were scored. The serum levels of immunoglobulin E (IgE), histamine (HIS), and inflammatory factors were all detected. The proportions of regulatory T cells (Treg) and helper T cells 17 (Th17) cells in blood were detected, the Th17/Treg ratio was calculated, and the pathological condition of nasal mucosal tissue was observed. The expressions of TLR4/IRAK4/NF-κB pathway related protein in nasal mucosal tissue were determined. RESULTS Compared with control group, nasal mucosal tissue damage in the AR group was more severe, with partial shedding of epithelial cells, the proliferation of goblet cells, and obvious inflammatory cell infiltration. The rhinitis symptom score, the levels of IgE, HIS and IL-17, Th17 proportion, Th17/Treg ratio,p-IRAK4/IRAK4 and p-NF-κB p65/NF-κB p65 ratios as well as relative expression of TLR4 protein were increased significantly (P<0.05), while IL-10 level and Treg proportion were decreased significantly (P<0.05). Compared with AR group, the pathological injuries of nasal mucosa and the above indexes in QUE-L and QUE-H groups were all improved significantly (P<0.05). LPS treatment could reverse the improvement effects of high-dose QUE on histopathological damage to nasal mucosa tissue and the aforementioned indicators (P< 0.05). CONCLUSIONS QUE can inhibit the inflammatory response in AR rats by inhibiting TLR4/IRAK4/NF- κB signaling pathway.
5.The Mechanism of Exercise Regulating Intestinal Flora in The Prevention and Treatment of Depression
Lei-Zi MIN ; Jing-Tong WANG ; Qing-Yuan WANG ; Yi-Cong CUI ; Rui WANG ; Xin-Dong MA
Progress in Biochemistry and Biophysics 2025;52(6):1418-1434
Depression, a prevalent mental disorder with significant socioeconomic burdens, underscores the urgent need for safe and effective non-pharmacological interventions. Recent advances in microbiome research have revealed the pivotal role of gut microbiota dysbiosis in the pathogenesis of depression. Concurrently, exercise, as a cost-effective and accessible intervention, has demonstrated remarkable efficacy in alleviating depressive symptoms. This comprehensive review synthesizes current evidence on the interplay among exercise, gut microbiota modulation, and depression, elucidating the mechanistic pathways through which exercise ameliorates depressive symptoms via the microbiota-gut-brain (MGB) axis. Depression is characterized by gut microbiota alterations, including reduced alpha and beta diversity, depletion of beneficial taxa (e.g., Bifidobacterium, Lactobacillus, and Coprococcus), and overgrowth of pro-inflammatory and pathogenic bacteria (e.g., Morganella, Klebsiella, and Enterobacteriaceae). Metagenomic analyses reveal disrupted metabolic functions in depressive patients, such as diminished synthesis of short-chain fatty acids (SCFAs), impaired tryptophan metabolism, and dysregulated bile acid conversion. For instance, Bifidobacterium longum deficiency correlates with reduced synthesis of neuroactive metabolites like homovanillic acid, while decreased Coprococcus abundance limits butyrate production, exacerbating neuroinflammation. Furthermore, elevated levels of indole derivatives from Clostridium species inhibit serotonin (5-HT) synthesis, contributing to depressive phenotypes. These dysbiotic profiles disrupt the MGB axis, triggering systemic inflammation, neurotransmitter imbalances, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Exercise exerts profound effects on gut microbiota composition, diversity, and metabolic activity. Longitudinal studies demonstrate that sustained aerobic exercise increases alpha diversity, enriches SCFA-producing genera (e.g., Faecalibacterium prausnitzii, Roseburia, and Akkermansia), and suppresses pathobionts (e.g., Desulfovibrio and Streptococcus). For example, a meta-analysis of 25 trials involving 1 044 participants confirmed that exercise enhances microbial richness and restores the Firmicutes/Bacteroidetes ratio, a biomarker of metabolic health. Notably, endurance training promotes Veillonella proliferation, which converts lactate into propionate, enhancing energy metabolism and delaying fatigue. Exercise also strengthens intestinal barrier integrity by upregulating tight junction proteins (e.g., ZO-1, occludin), thereby reducing lipopolysaccharide (LPS) translocation and systemic inflammation. However, excessive exercise may paradoxically diminish microbial diversity and exacerbate intestinal permeability, highlighting the importance of moderate intensity and duration. Exercise ameliorates depressive symptoms through multifaceted interactions with the gut microbiota, primarily via 4 interconnected pathways. First, exercise mitigates neuroinflammation by elevating anti-inflammatory SCFAs such as butyrate, which suppresses NF-κB signaling to attenuate microglial activation and oxidative stress in the hippocampus. Animal studies demonstrate that voluntary wheel running reduces hippocampal TNF‑α and IL-17 levels in stress-induced depression models, while fecal microbiota transplantation (FMT) from exercised mice reverses depressive behaviors by modulating the TLR4/NF‑κB pathway. Second, exercise regulates neurotransmitter dynamics by enriching GABA-producing Lactobacillus and Bifidobacterium, thereby counteracting neuronal hyperexcitability. Aerobic exercise also enhances the abundance of Lactobacillus plantarum and Streptococcus thermophilus, which facilitate 5-HT and dopamine synthesis. Clinical trials reveal that 12 weeks of moderate exercise increases fecal Coprococcus and Blautia abundance, correlating with improved 5-HT bioavailability and reduced depression scores. Third, exercise normalizes HPA axis hyperactivity by reducing cortisol levels and restoring glucocorticoid receptor sensitivity. In rodent models, chronic stress-induced corticosterone elevation is reversed by probiotic supplementation (e.g., Lactobacillus), which enhances endocannabinoid signaling and hippocampal neurogenesis. Furthermore, exercise upregulates brain-derived neurotrophic factor (BDNF) via microbial metabolites like butyrate, promoting histone acetylation and synaptic plasticity. FMT experiments confirm that exercise-induced microbiota elevates prefrontal BDNF expression, reversing stress-induced neuronal atrophy. Fourth, exercise reshapes microbial metabolic crosstalk, diverting tryptophan metabolism toward 5-HT synthesis instead of neurotoxic kynurenine derivatives. Butyrate inhibits indoleamine 2,3-dioxygenase (IDO), a key enzyme in the kynurenine pathway linked to depression. Concurrently, exercise-induced Akkermansia enrichment enhances mucin production, fortifies the gut barrier, and reduces LPS-driven neuroinflammation. Collectively, these mechanisms underscore exercise as a potent modulator of the microbiota-gut-brain axis, offering a holistic approach to alleviating depression through microbial and neurophysiological synergy. Current evidence supports exercise as a potent adjunct therapy for depression, with personalized regimens (e.g., aerobic, resistance, or yoga) tailored to individual microbiota profiles. However, challenges remain in optimizing exercise prescriptions (intensity, duration, and type) and integrating them with probiotics, prebiotics, or FMT for synergistic effects. Future research should prioritize large-scale randomized controlled trials to validate causality, multi-omics approaches to decipher MGB axis dynamics, and mechanistic studies exploring microbial metabolites as therapeutic targets. The authors advocate for a paradigm shift toward microbiota-centric interventions, emphasizing the bidirectional relationship between physical activity and gut ecosystem resilience in mental health management. In conclusion, this review underscores exercise as a multifaceted modulator of the gut-brain axis, offering novel insights into non-pharmacological strategies for depression. By bridging microbial ecology, neuroimmunology, and exercise physiology, this work lays a foundation for precision medicine approaches targeting the gut microbiota to alleviate depressive disorders.
6.Ectopic thyroid gland in parotid region: a case report and literature review
ZHANG Lei ; CHEN Xibo ; HENG Wei ; WANG Xuefeng ; WANG Yangyang ; LIU Rui
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(8):659-665
Objective:
To explore the clinical characteristics, diagnosis, and treatment of ectopic thyroid gland in the parotid gland area, and to provide clinical ideas for the diagnosis and treatment of ectopic thyroid gland.
Methods:
A case of a normal thyroid gland with ectopic thyroid gland tissue in the parotid gland area in the neck was reported. The male patient was 20 years old. The chief complaint was the discovery of a painless mass gradually increasing under the left earlobe for one month. Clinical examination showed obvious bulging of the tissue under the left earlobe. A strip-shaped mass approximately 3.0 cm long could be palpated. It was soft in texture, with a clear boundary, and located under the skin. The skin was pale red and of normal temperature. The body position movement test was negative. Color Doppler ultrasound of the thyroid gland in the neck showed that the shape and size of the thyroid gland were normal. CT images of the head and neck showed a band-like soft tissue density shadow at the area of the parotid gland behind and below the left earlobe, with a clear boundary. The CT value was approximately 30 HU, and further enhancement yielded no additional findings. The admitting diagnosis was a mass in the left parotid gland area. The tumor was incised using a conventional surgical method for the parotid gland area. During the operation, it was found that the tumor was located under the skin, and the contents were bright-red granulomatous tissue without a capsule and adhesive to the skin tissue. The parotid gland capsule was not involved. After the tumor was completely scraped off, intermittent suturing was performed. The resected tumor was sent for pathological examination. A retrospective analysis of the diagnosis and treatment of this type of case was conducted in combination with a literature review.
Results:
The wound of the patient failed to heal in the first stage after the operation. By applying iodoform gauze for pressurized dressing changed weekly, the wound gradually healed about 2 months later. The postoperative pathological report showed an ectopic thyroid gland in the left parotid gland area. The results of the literature review indicate that ectopic thyroid glands can be partial or complete. In the former, normal thyroid gland tissue exists in the neck, and some thyroid gland tissue appears in other locations, mostly at the base of the tongue and mediastinum. In the latter, the thyroid gland in the neck is absent. Both can present with abnormal thyroid gland function and local compression symptoms, and the symptoms are more obvious in patients with a complete ectopic thyroid gland. Ectopic thyroid glands are mainly diagnosed and differentiated through physical examination and imaging examination. Ectopic thyroid glands occurring subcutaneously in the parotid gland area are extremely rare. Physicians should design personalized treatment plans based on clinical examinations and surgical indications.
Conclusion
A subcutaneous ectopic thyroid gland in the parotid gland area is rare. For ectopic thyroid gland surgery, a reasonable surgical plan should be designed considering the patient's aesthetic needs and prognosis. Puncture biopsy should be performed when necessary to formulate the surgical plan.
7.Research on Regulatory Mechanism of Verbenalin on HCoV-229E-infected Macrophage Injury Based on Mitophagy
Qiyue SUN ; Lei BAO ; Zihan GENG ; Ronghua ZHAO ; Shuran LI ; Xihe CUI ; Jingsheng ZHANG ; Xian LIU ; Rui XIE ; Xiaolan CUI ; Shanshan GUO ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):29-37
ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells (RAW264.7) damaged by human coronavirus (HCoV)-229E infection, thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 (CCK-8) assay for assessing cell proliferation and viability. Cells were randomly divided into four groups: normal control, verbenalin group (125 μmol·L-1), model group (HCoV-229E), and HCoV-229E + verbenalin group (HCoV-229E + 125 μmol·L-1 verbenalin). Cell viability was measured using the CCK-8 assay, and the maximum non-toxic concentration (CC0), half-maximal cytotoxic concentration (CC50), half-maximal effective concentration (EC50), and selectivity index (SI) of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity, and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential (MMP). mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC0 of verbenalin was 125 μmol·L-1. The CC50 was 448.25 μmol·L-1. The EC50 against HCoV-229E-infected cells was 46.28 μmol·L-1, and the SI was 9.68. Compared with the normal group, the model group showed significantly reduced cell survival rate (P<0.01), increased cell death rate (P<0.01), decreased MMP (P<0.01), and suppressed mitophagy (P<0.01). In contrast, verbenalin treatment significantly improved cell survival rate (P<0.01), reduced cell death rate (P<0.01), alleviated MMP loss (P<0.01), and enhanced mitophagy levels (P<0.01) compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy, maintenance of MMP stability, and alleviation of mitochondrial damage.
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.Research on Regulatory Mechanism of Verbenalin on HCoV-229E-infected Macrophage Injury Based on Mitophagy
Qiyue SUN ; Lei BAO ; Zihan GENG ; Ronghua ZHAO ; Shuran LI ; Xihe CUI ; Jingsheng ZHANG ; Xian LIU ; Rui XIE ; Xiaolan CUI ; Shanshan GUO ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):29-37
ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells (RAW264.7) damaged by human coronavirus (HCoV)-229E infection, thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 (CCK-8) assay for assessing cell proliferation and viability. Cells were randomly divided into four groups: normal control, verbenalin group (125 μmol·L-1), model group (HCoV-229E), and HCoV-229E + verbenalin group (HCoV-229E + 125 μmol·L-1 verbenalin). Cell viability was measured using the CCK-8 assay, and the maximum non-toxic concentration (CC0), half-maximal cytotoxic concentration (CC50), half-maximal effective concentration (EC50), and selectivity index (SI) of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity, and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential (MMP). mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC0 of verbenalin was 125 μmol·L-1. The CC50 was 448.25 μmol·L-1. The EC50 against HCoV-229E-infected cells was 46.28 μmol·L-1, and the SI was 9.68. Compared with the normal group, the model group showed significantly reduced cell survival rate (P<0.01), increased cell death rate (P<0.01), decreased MMP (P<0.01), and suppressed mitophagy (P<0.01). In contrast, verbenalin treatment significantly improved cell survival rate (P<0.01), reduced cell death rate (P<0.01), alleviated MMP loss (P<0.01), and enhanced mitophagy levels (P<0.01) compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy, maintenance of MMP stability, and alleviation of mitochondrial damage.
10.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.


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