1.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
2.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
3.Clinical efficacy of escitalopram combined with transcutaneous cervical vagus nerve stimulation therapy for patients with major depressive disorder and its effect on plasma IL-6 and IL-10 levels
Jin LI ; Jinbo SUN ; Di WU ; Wenjun WU ; Runzhu SUN ; Shanshan XUE ; Yapeng CUI ; Huaning WANG ; Yihuan CHEN
Sichuan Mental Health 2025;38(1):7-13
BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression, which may contribute to the anti-inflammatory properties of vagus nerve stimulation (VNS), whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation (tcVNS) in treating major depressive disorder (MDD) and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression, anxiety and sleep quality as well as the plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in MDD patients, in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21, 2019 to April 17, 2024, 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group (n=23) and control group (n=22) using random number table method. All patients were treated with escitalopram. On this basis, study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation, and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment, Hamilton Depression Scale-17 item (HAMD-17) was used to assess depressive symptoms, and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score, anxiety/somatization subfactor score and insomnia subfactor score in both groups (Wald χ2=315.226, 495.481, 82.420, P<0.01). After 4 weeks of treatment, HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group, with statistically significant differences (Wald χ2=4.967, 32.543, P<0.05 or 0.01), while no statistically significant difference was found in the insomnia subfactor score between two groups (Wald χ2=0.819, P=0.366). Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups (Wald χ2=21.792, 5.242, P<0.05 or 0.01). Compared with baseline data, a reduction in plasma IL-6 levels was detected in both groups (Wald χ2=22.015, 6.803, P<0.01), and an increase in plasma IL-10 levels was reported in study group (Wald χ2=5.118, P=0.024) after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms, anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally, it helps reduce plasma IL-6 levels and increase IL-10 levels. [Funded by Shaanxi Provincial Key Research and Development Program-General Project (number, 2023-YBSF-185), www.clinicaltrials.gov number, NCT04037111]
4.Effect of target characteristics on prospective memory in patients with depressive disorder
Min CHEN ; Dongsheng LYU ; Zheng WANG ; You HOU
Sichuan Mental Health 2025;38(1):14-21
BackgroundMany studies have shown that patients with depressive disorder show impairments in prospective memory, while it is deemed necessary for facilitating their social reintegration, and the current research findings are inconsistent regarding the factors affecting prospective memory of patients with depressive disorder. ObjectiveTo explore the impact of target characteristics (emotional valence and salience) on prospective memory in patients with depressive disorder, so as to provide references for the training and recovery of prospective memory function in these patients. MethodsFrom January to December 2022, 53 patients with depressive disorder were recruited from the outpatient department of Inner Mongolia Autonomous Mental Health Center. Meanwhile, 45 healthy individuals were concurrently recruited from surrounding communities as control group. An experiment with a 2 (participant type: depressive disorder, healthy control) ×2 (target salience: salient, non-salient) ×3 (emotional valence: positive, neutral, negative) factorial design was conducted. The positive/neutral/negative emotional pictures from Chinese Affective Picture System (CAPS) were used for emotional stimulation. A dual-task experimental paradigm was adopted, and the response time and accuracy in prospective memory task and ongoing task were recorded for participants with different target characteristics. Results①In the prospective memory task, the main effect of participant type was statistically significant, with the depressive group showing lower accuracy (F=14.892, P<0.01) and longer response time (F=10.642, P=0.002) compared with control group. ② The main effect of target emotional valence on accuracy (F=7.575, P=0.001) and response time (F=3.196, P=0.044) in the prospective memory task was statistically significant. Simple effect analysis revealed that depressive group yielded a shorter response time and higher accuracy rate under negative conditions compared with positive and neutral conditions (P<0.05 or 0.01). ③ The main effect of target salience on accuracy (F=6.659, P=0.012) and response time (F=10.106, P=0.002) in the prospective memory task was also statistically significant, with higher accuracy and shorter response time for salient targets compared with non-salient targets. ConclusionPatients with depressive disorder demonstrate preferential attention to and processing of negative stimuli in prospective memory tasks, while increasing target salience may facilitate spontaneous processing of prospective memory task in patients with depressive disorder. [Funded by Inner Mongolia Health Commission Medical Health Science and Technology Project (number, 202202104)]
5.Decision-making behavior in patients with depressive disorder and its relationship with depressive and anxiety symptoms
Yuxiang WANG ; Luoya ZHANG ; Maomao ZHANG ; Juan DENG ; Yanjie PENG ; Xiaotong CHENG ; Kezhi LIU ; Wei LEI ; Jing CHEN
Sichuan Mental Health 2025;38(1):22-27
BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However, the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder, and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently, 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used for assessment, and decision-making behavior was evaluated using Probabilistic Reversal Learning (PRL) task. Indicators assessed included the number of trials to criterion, perseverative errors, win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group (t=3.684, P<0.01). There were no statistically significant differences between two groups in trials to criterion, perseverative errors and win-stay rate (t=0.329, 0.132, 0.609, P>0.05). In depression group, BDI and BAI scores were positively correlated with the win-stay rate(r=0.450, 0.398, P<0.01). ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore, the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. [Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University (number, 2019LZXNYDJ39]
6.Connotation and Prevention Strategies of Traditional Chinese Medicine for Panvascular Diseases
Jie WANG ; Jun LI ; Yan DONG ; Cong CHEN ; Yongmei LIU ; Chao LIU ; Lanchun LIU ; Xuan SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):1-14
Panvascular disease, with vascular diseases as the common pathological feature, is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart, brain, kidney, and limbs. It is one of the leading causes of death for Chinese residents at present. Previously, due to the narrow branches of disciplines, too much attention was paid to local lesions, resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies, makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine (TCM). It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel'', ''meridians'', ''visceral manifestation'', and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover, those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm, stasis, stagnation, and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm'', and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis, cerebral atherosclerosis, and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM, and the TCM treatment mainly invigorates Qi and promotes blood circulation, which can inhibit venous thrombosis, improve venous ulcers, and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM, and the treatment mainly promotes Qi and dredges collaterals, which has a good effect on coronary microvascular lesions, diabetic microvascular lesions, pulmonary microvascular lesions, and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion, which can promote lymphangiogenesis and enhance lymphatic reflux. In addition, the combination of TCM and modern technology, especially the application of artificial intelligence, can improve the efficiency of early identification and personalized treatment, resulting in early screening and comprehensive management of panvascular diseases. Therefore, TCM will play a vital role in the prevention and treatment of panvascular diseases.
7.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
8.Protective Effect of Taohong Siwutang on Cerebral Ischemia-reperfusion Injury Based on A1/A2 Phenotype Transformation of Astrocytes Mediated by JAK2/STAT3 Pathway
Huifang WANG ; Xinru CHEN ; Mengyuan CHEN ; Xian ZHOU ; Lan HAN ; Weidong CHEN ; Zhaojie JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):25-34
ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion (CIRI) injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups: A sham operation group, a model group, Taohong Siwutang treatment groups (low dose, medium dose, and high dose), ligustrazine phosphate tablet (LPT) group, and AG490 group. All groups, except for the sham operation group, underwent middle cerebral artery occlusion/reperfusion (MCAO/R) modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 (C3), S100 calcium-binding protein A10 (S100A10), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3). Additionally, protein expression levels of vascular endothelial growth factor-A (VEGF-A) were assessed, and the mRNA expression levels of inflammatory factors, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), were evaluated. Glial fibrillary acidic protein (GFAP) and C3, S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly, VEGF expression levels were measured using enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham operation group, the model group showed a significant increase in cerebral infarction volume and neurological impairment (P<0.01). C3 protein levels were elevated, while S100A10 levels were decreased. Pathway-related markers were significantly upregulated (P<0.05, P<0.01), and VEGF-A protein levels were significantly reduced (P<0.01). The mRNA expression of inflammatory factors was significantly upregulated (P<0.01). Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity (P<0.01) and greatly decreased GFAP and S100A10 fluorescence intensity (P<0.01). Additionally, VEGF content was significantly elevated (P<0.01). Compared with the model group, medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment (P<0.01). Groups treated with low, medium, and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels (P<0.01). In the high-dose Taohong Siwutang and AG490 groups, both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated (P<0.05, P<0.01), while S100A10 expression and VEGF-A protein levels were significantly increased (P<0.01). Additionally, the mRNA expression levels of inflammatory factors were significantly reduced (P<0.01). The co-localization fluorescence intensity of GFAP and C3 significantly decreased (P<0.01), while that of GFAP and S100A10 greatly increased (P<0.01). Furthermore, VEGF content exhibited a marked elevation (P<0.01). ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway, promotion of A2-type astrocyte polarization, reduction of inflammatory factor release, and enhancement of VEGF production.
9.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
10.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.

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