1.Xuefu Zhuyutang in Malignant Tumor Disease: A Review
Jiaqi JI ; Xiaoqing HU ; Yihan ZHAO ; Xuhang SUN ; Dandan WEI ; Junwen PEI ; Shiqing JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):321-330
Cancer has become a significant global public health issue, severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates, drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine (TCM) has demonstrated significant clinical efficacy in cancer treatment and small side effects, making it widely applied in the field of oncology. Xuefu Zhuyutang, derived from Yilin Gaicuo, is known for its abilities to invigorate blood circulation, dispel blood stasis, promote Qi flow, and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang, when combined with conventional Western medications, produces significant effects in the treatment of malignant tumors such as liver cancer, lung cancer, and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments, including radiation esophagitis, radiation encephalopathy, radiation-induced oral mucositis, and edema. Additionally, it alleviates cancer-related pain and fever, blood hypercoagulability, and associated complications such as depression and anxiety, and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms, including the inhibition of Wnt/β-catenin signaling pathway activation, suppression of mitogen-activated protein kinase (MAPK) pathway activation, and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration, induce tumor cell apoptosis, suppress tumor angiogenesis, enhance the cytotoxicity of natural killer cells against tumors, improve the tumor microenvironment, and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects: theoretical exploration, clinical studies, mechanisms of action, and pharmacological basis, aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.
2.Xuefu Zhuyutang in Malignant Tumor Disease: A Review
Jiaqi JI ; Xiaoqing HU ; Yihan ZHAO ; Xuhang SUN ; Dandan WEI ; Junwen PEI ; Shiqing JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):321-330
Cancer has become a significant global public health issue, severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates, drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine (TCM) has demonstrated significant clinical efficacy in cancer treatment and small side effects, making it widely applied in the field of oncology. Xuefu Zhuyutang, derived from Yilin Gaicuo, is known for its abilities to invigorate blood circulation, dispel blood stasis, promote Qi flow, and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang, when combined with conventional Western medications, produces significant effects in the treatment of malignant tumors such as liver cancer, lung cancer, and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments, including radiation esophagitis, radiation encephalopathy, radiation-induced oral mucositis, and edema. Additionally, it alleviates cancer-related pain and fever, blood hypercoagulability, and associated complications such as depression and anxiety, and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms, including the inhibition of Wnt/β-catenin signaling pathway activation, suppression of mitogen-activated protein kinase (MAPK) pathway activation, and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration, induce tumor cell apoptosis, suppress tumor angiogenesis, enhance the cytotoxicity of natural killer cells against tumors, improve the tumor microenvironment, and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects: theoretical exploration, clinical studies, mechanisms of action, and pharmacological basis, aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.
3.Effect of Wenyang Huazhuo Formula (温阳化浊方) on Reproductive Aging,Ovarian Mechanical Micro-environment,and Offspring Reproductive Potential in Aged Model Mice
Jiaqi XU ; Xiaoli ZHAO ; Nan JIANG ; Kaixi LI ; Yafei DING ; Zimu WEN ; Yingying JIA ; Mengjun JIANG ; Tian XIA
Journal of Traditional Chinese Medicine 2025;66(6):612-620
ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula (温阳化浊方, WHF) in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups, 3-month group (20 female mice at 3 months of age), 6-month group (20 female mice at 6 months of age), 6-month + WHF group (20 female mice at 5 months of age treated with WHF), 9-month group (20 female mice at 9 months of age), and 9-month + WHF group (20 female mice at 8 months of age treated with WHF). The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/(kg·d) once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid (HA) content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained, as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group, the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), decreased ovarian collagen content, and reduced numbers of primordial and secondary follicles. In contrast, the numbers of primary follicles, antral follicles, and atretic follicles increased. The levels of anti-Müllerian hormone (AMH), ovarian HA content, and the fertilization rate, cleavage rate, and blastocyst formation rate of oocytes from offspring were significantly lower (P<0.05). Compared with the 6-month group, the 6-month + WHF group showed significantly reduced serum levels of GnRH, FSH, and LH, with a significant decrease in primary follicles, antral follicles, and atretic follicles as well as increase of AMH levels, ovarian HA content, number of primordial and secondary follicle, egg count, and offspring birth weight (P<0.05). Compared with the 9-month group, the 9-month + WHF group exhibited reduced GnRH, FSH, and collagen fiber content, as well as reduced number of primary follicles, antral follicles, and atretic follicles. However, AMH levels, ovarian HA content, number of primordial and secondary follicle, egg count, offspring numbers, birth weight, fertilization rate, cleavage rate, and blastocyst formation rate of oocytes from offspring all significantly increased (P<0.05). ConclusionWHF can significantly improve the ovarian reserve, fertility, and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover, the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.
4.Research progress on the mechanism of traditional Chinese medicine monomers acting on myelosuppression after chemotherapy based on the four properties theory
Sihan ZHANG ; Tingting WANG ; Zhifen ZHAO ; Hanyu KANG ; Jiaqi JI ; Ziqiang GUO ; Tong LIU ; Shiqing JIANG
China Pharmacy 2025;36(18):2341-2347
Chemotherapy is an important treatment for tumors, but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine (TCM) has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors, such as cold-natured (e.g. Scutellaria baicalensis, Rhus chinensis), cool-natured (e.g. Ligustrum lucidum, Ophiopogon japonicus), warm-natured (e.g. Panax ginseng, Epimedium brevicornu, Curcuma longa, Angelica sinensis), hot-natured (e.g. Cinnamomum cassia, Aconitum carmichaeli), and neutral-natured (e. g. donkey-hide gelatin, Lycium barbarum, Rhodiola rosea, fungi), can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells, improving the bone marrow hematopoietic microenvironment, inhibiting the oxidative stress response, regulating signaling pathways, so as to ultimately repaire inflammatory damage and improve hematopoietic function, thereby playing an anti-myelosuppressive role.
5.Effect and mechanism of LncRNA EFRL on homocysteine-induced atherosclerosis in macrophage efferocytosis.
Jiaqi YANG ; Zhenghao ZHANG ; Fang MA ; Tongtong XIA ; Honglin LIU ; Jiantuan XIONG ; Shengchao MA ; Yideng JIANG ; Yinju HAO
Chinese Journal of Cellular and Molecular Immunology 2025;41(7):577-584
Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology*
;
Animals
;
Homocysteine
;
Mice
;
Macrophages/drug effects*
;
Humans
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RAW 264.7 Cells
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Atherosclerosis/chemically induced*
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Apoptosis/genetics*
;
Phagocytosis/genetics*
;
Jurkat Cells
;
Interleukin-1beta/genetics*
;
Efferocytosis
6.Syndrome Differentiation and Treatment of Alopecia Areata Based on the Turbid Toxin Theory from the Perspectives of the Liver,Spleen,and Kidney
Jiaqi LI ; Wenzhao HAN ; Qian YANG ; Yuhang LIU ; Yuxin ZHANG ; Nan JIANG ; Weiye LI ; Xiang LIU
Journal of Traditional Chinese Medicine 2025;66(23):2494-2498
Alopecia areata (AA) is a common hair loss disorder, and the core pathogenesis is the internal gene-ration of turbid toxin caused by qi movement disorder in the liver, spleen, and kidney. Turbid toxin serves as both a pivotal etiological trigger and a pathological driver of disease exacerbation. Clinically, AA can be classified into four principal patterns, including liver constraint with spleen deficiency, internal accumulation of damp-heat, liver-kidney depletion, and qi-blood depletion. Therapeutic strategies prioritize clearing and resolving turbid toxin while regulating the qi movement of the liver, spleen, and kidney. Accordingly, different formulas were applied. Self-formulated Shugan Jianpi Huazhuo Formula (疏肝健脾化浊方) is suggested to drain dampness, resolve turbidity, and unblock qi movement. Self-formulated Sanjiao Fenxiao Jiedu Formula (三焦分消解毒方) can be used to clear heat, drain dampness and resolve toxin. Self-formulated Zishen Yanggan Toudu Decoction (滋肾养肝透毒汤) can clear and vent latent toxins, while Self-formulated Guiqi Shengfa Didu Formula (归芪生发涤毒方) is employed to tonify qi and blood, purge toxins, and regenerate vitality. By differentiating and treating AA based on the functional patterns of the liver, spleen, and kidney, this approach expands the application scope of the turbid toxin theory and provides valuable insights for treatment of AA.
7.Progress of interruption of schistosomiasis transmission and prospects in Yunnan Province
Yun ZHANG ; Lifang WANG ; Xiguang FENG ; Mingshou WU ; Meifen SHEN ; Hua JIANG ; Jing SONG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Zongya ZHANG ; Jihua ZHOU ; Yi DONG ; Chunhong DU
Chinese Journal of Schistosomiasis Control 2024;36(4):422-427
Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.
8.Association between dietary pattern and frailty among people aged 50 years and over in Shanghai
Anli JIANG ; Ye RUAN ; Yanfei GUO ; Shuangyuan SUN ; Yujun DONG ; Jiaqi WANG ; Yan SHI ; Fan WU
Chinese Journal of Epidemiology 2024;45(2):257-264
Objective:To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty.Methods:Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty.Results:A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR=0.743, 95% CI: 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR=0.509, 95% CI: 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions:Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.
9.Association between vitamin D level and grip strength in adults aged 50 and older in Shanghai
Yujun DONG ; Yanfei GUO ; Ye RUAN ; Shuangyuan SUN ; Anli JIANG ; Jiaqi WANG ; Yan SHI ; Fan WU
Chinese Journal of Epidemiology 2024;45(3):393-400
Objective:To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai.Methods:Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength.Results:A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR=1.41, 95% CI: 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR=1.67, 95% CI: 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR=1.30, 95% CI: 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR=1.57, 95% CI: 1.05-2.35; OR=2.40, 95% CI: 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P>0.05). Conclusions:This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.
10.Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway
Hongqing ZHAO ; Qingrui MOU ; Jiaqi JIANG ; Xuan ZHU ; Zhuo LIU ; Yuhong WANG
Digital Chinese Medicine 2024;7(2):195-208
Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway. Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with de-pression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The effi-cacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assess-ments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hema-toxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the ex-pression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological ef-fects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Ex-cept for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were ob-served using HE staining,Nissl staining,TUNEL staining,and transmission electron mi-croscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed. Results(i)ZJJF significantly reduced the high blood glucose,insulin,and glycated he-moglobin levels in model rats(P<0.01).It increased autonomous activity and decreased de-spair-like behaviors(P<0.01),improved the pathological damage of hippocampal neurons,increased the number of neuronal nuclei(P<0.01),and reduced the number of mechanocytes,vacuolar cells,and apoptotic neurons(P<0.05,P<0.01,and P<0.01,respec-tively).ZJJF down-regulated the expression levels of pro-apoptotic proteins Bax and caspase-3(P<0.01),up-regulated the anti-apoptotic protein Bcl-2(P<0.01),and significantly inhibit-ed the overexpression of phosphorylated JNK(p-JNK),Elk-1,and c-fos(P<0.01).(ii)SP6 in-creased autonomous activity and reduced despair time in model rats(P<0.05),although it had no significant effects on sucrose preference(P>0.05).It increased the number of Nissl bodies in hippocampal neurons(P<0.01),reduced the protein expression levels of Bax(P<0.01)and caspase-3(P<0.05),and decreased the number of apoptotic neurons(P<0.05).SP6 also increased the expression level of Bcl-2(P<0.01),and inhibited the high expression levels of p-JNK,Elk-1,and c-fos(P<0.01,P<0.01,and P<0.05,respectively),suggesting that hip-pocampal neuronal apoptosis in diabetic rats with depression is associated with abnormal ac-tivation of JNK signaling pathway.Compared with ZJJF group,ZJJF+Aniso group showed a decrease in sucrose preference(P<0.05)and an increase in despair time(P<0.01)with more notable hippocampal neuronal damage.This group also exhibited a decrease in expression level(P<0.01)Bcl-2 and an increase in expression levels of Bax,caspase-3,p-JNK,Elk-1,and c-fos(P<0.01,P<0.05,P<0.05,P<0.01,and P<0.05,respectively),indicating that the antidepressant effects of ZJJF,its improvement of neuronal apoptosis,and regulation of JNK signaling molecules could all be reversed by a specific JNK agonist. Conclusion ZJJF exerts a significant hypoglycemic effect and ameliorates the apoptosis of hippocampal neurons by inhibiting the activation of JNK signaling pathway,which is a promising formula for the treatment of diabetic depression in clinical settings.

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