1.Herbal Textual Research on Arcae Concha in Famous Classical Formulas
Yiqin ZHANG ; Yixue ZHUANG ; Yinan LU ; Yanning CHEN ; Yichong CHEN ; Shuiyu XU ; Zhilai ZHAN ; Chengzi YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):208-218
In this paper, the name, origin, producing area, harvesting, processing and functional indications of Arcae Concha were systematically combed and verified by consulting the ancient and modern literature, in order to provide a basis for the development of famous classical formulas containing Arcae Concha. Arcae Concha was first recorded in the name of Han in Bencao Shiyi, but later, due to the influence of LI Shizhen's error of combining Han item with Kuiha in the Ming dynasty, there were aliases such as Kuilu and Fulao, and Yizong Bidu began to include Walengzi as its correct name and has been used ever since. The textual descriptions and illustrations of the medicinal materials of Arcae Concha contained in the materia medica of the past generations were consistent with the modern Arca inflata, A. subcrenata and A. granosa. In ancient times, there were medicinal records of two parts of shell and meat, but now the shell is used as medicine, and the meat is mostly edible. In ancient times, Zhejiang, Shandong, Guangdong and Guangxi were the main producing areas, and Zhejiang was the best. It is now believed that A. inflata is mostly distributed in the northern part of the Huanghai Sea, A. granosa is mostly distributed in the coastal areas south of Shandong Peninsula in China, and A. subcrenata is widely distributed in the coastal areas of China. Its quality is better in a complete, white, no residual meat and sand. In ancient times, there was no clear harvesting period, and the processing was mainly based on vinegar quenching after calcination or powdering of calcined shell, but now the harvesting period is autumn and winter. After harvesting, it is directly washed and crushed for raw use or processed by calcined method. The records of the medicinal materials in the past dynasties on the properties of Arcae Concha were mainly warm, sweet, salty and mild, and it is now believed that Arcae Concha is salty in taste and mild in nature. In ancient times, it was believed that Arcae Concha were mainly used for coldness in the heart and abdomen, coldness in the waist and spine, benefiting the five internal organs, strengthening the stomach. Nowadays, it is believed that Arcae Concha can eliminate phlegm and remove blood stasis, soften the hardness and dissipate the lumps, produce acid and relieve pain. It can be used in the treatment of stubborn phlegm, gall tumor, scrofula and other symptoms. In conclusion, it is suggested that for the famous classical formulas containing Arcae Concha, the corresponding methods should be selected according to the processing requirements of the drug in the formulas, while those without processing requirements can be determined according to the functional position of the products.
2.Hei Xiaoyaosan Modulates Oxidative Stress and Apoptosis to Exert Neuroprotective Effect in Alzheimer's Disease Rats
Yiqin CHEN ; Jiao YANG ; Wenli PEI ; Yumei HAN ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):99-107
ObjectiveTo explore the role and mechanism of Hei Xiaoyaosan in regulating the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in cascade modulation of oxidative stress and apoptosis for preventing and treating Alzheimer's disease (AD). MethodsNinety male SD rats of 4 months old were randomly assigned into a control group (n=10), a sham group (with injection of 1 μL normal saline into bilateral hippocampi, n=10), and a modeling group (with injection of 1 μL beta-amyloid 1-42 solution into bilateral hippocampi to induce AD, n=70). One week after modeling, 50 successfully modeled rats were selected and randomly allocated into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs once daily for six consecutive weeks. The Morris water maze was used to assess the learning and memory abilities of rats. Hematoxylin-eosin (HE) staining was performed to reveal hippocampal morphological changes in AD rats. Apoptosis in the hippocampal CA3 region was detected by terminal-deoxynucleotidyl transferase-mediated Nick end labeling. Immunofluorescence was used to visualize the expression of neuronal nuclear antigen (NeuN) in the CA1 region. Additionally, enzyme-linked immunosorbent assay was performed to assess the activities of glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase (CAT) in the hippocampus. Real-time PCR was conducted to measure the mRNA levels of Akt, GSK-3β, Nrf2, and HO-1, while Western blot was employed to determine the protein levels of phosphorylated Akt (p-Akt)/Akt, phosphorylated GSK-3β (p-GSK-3β)/GSK-3β, Nrf2, and HO-1. ResultsCompared with the control group, the model group on day 5 showed an increase in total swimming distance (P<0.01), a reduction in the percentage of time spent in the target quadrant (P<0.01), reduced and disarranged neurons, nuclear condensation, varying degrees of cellular damage, increased apoptosis of hippocampal neurons (P<0.01), decreased NeuN content (P<0.01), weakend activities of GSH-Px, GST, and CAT (P<0.01), and down-regulated mRNA levels of Nrf2 and HO-1 (P<0.01) and protein levels of p-Akt/Akt, p-GSK-3β/GSK-3β, Nrf2, and HO-1 (P<0.01) in the hippocampus. Compared with the model group, donepezil hydrochloride and high, medium, and low doses of Hei Xiaoyaosan shortened the total swimming distance on day 5 (P<0.05, P<0.01), increased the percentage of time spent in the target quadrant (P<0.05, P<0.01), improved the arrangement and morphology of neurons, reduced nuclear condensation and the apoptosis rate of hippocampal neurons (P<0.01), increased the NeuN content (P<0.01), enhanced the activities of GSH-Px, GST, and CAT (P<0.05, P<0.01), and up-regulated the mRNA levels of Nrf2 and HO-1 (P<0.05, P<0.01) and the protein levels of p-Akt/Akt, p-GSK-3β/GSK-3β, Nrf2, and HO-1 (P<0.05, P<0.01) in the hippocampus. ConclusionHei Xiaoyaosan can regulate the Akt/GSK-3β/Nrf2/HO-1 pathway to enhance the antioxidant stress capacity and inhibit neuron apoptosis to exert the neuroprotective effect, thereby ameliorating the cognitive dysfunction and pathological damage in AD rats.
3.Hei Xiaoyaosan Improves Learning and Memory Abilities in Alzheimer's Disease Rats by Regulating Cell Apoptosis
Huping WANG ; Jiao YANG ; Yiqin CHEN ; Zhipeng MENG ; Yujie LYU ; Yunyun HU ; Wenli PEI ; Yumei HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):108-115
ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease (AD) from cell apoptosis mediated by the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa B (NF-κB) signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group, a sham group, a model group, a donepezil hydrochloride (0.45 mg·kg-1) group, and high-, medium-, and low-dose (15.30, 7.65, and 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups, with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline, while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 (Aβ1-42) solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). Western blot was employed to determine the protein levels of PI3K, Akt, and NF-κB. A cell model of AD was established by co-culturing Aβ1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 (CCK-8) assay and flow cytometry (FC), respectively. ResultsAnimal experiments showed that compared with the blank group, the model group had a prolonged escape latency (P<0.01), a reduced number of crossing platforms (P<0.01), disarrangement and a reduced number of hippocampal neurons, up-regulated expression of Bax and Caspase-3, down-regulated expression of Bcl-2 (P<0.01), decreased p-PI3K/PI3K and p-Akt/Akt levels, and an increased p-NF-κB/NF-κB level (P<0.01). Compared with the model group, donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms (P<0.05, P<0.01), improved the arrangement and increased the number of hippocampal neurons, down-regulated the expression levels of Bax and Caspase-3, up-reguated the expression level of Bcl-2 (P<0.05, P<0.01), increased the p-PI3K/PI3K and p-Akt/Akt levels (P<0.05, P<0.01), and reduced the p-NF-κB/NF-κB level (P<0.05, P<0.01). Cell experiments showed that compared with the blank group, the model group exhibited an increased apoptosis rate (P<0.01). Compared with the model group, the serum containing Hei Xiaoyaosan at various doses improved the cell viability (P<0.01), and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis (P<0.01). ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis, while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.
4.Hei Xiaoyaosan Inhibits Ferroptosis by Regulating SIRT1/p53/SLC7A11 Signaling Pathway to Ameliorate Cognitive Dysfunction in Rat Model of Alzheimer's Disease
Jiao YANG ; Yiqin CHEN ; Wenli PEI ; Yumei HAN ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):116-123
ObjectiveTo investigate the effects of Hei Xiaoyaosan on cognitive impairment and the histone deacetylase sirtuin-1 (SIRT1)/tumor suppressor p53/solute carrier family 7 member 11 (SLC7A11) signaling pathway in the rat model of Alzheimer's disease (AD). MethodsA total of 90 16-week-old SPF-grade SD male rats were randomly assigned in a blank group (n=10), a sham group (n=10, with injection of 1 μL normal saline into the bilateral hippocampi), and an AD modeling group (n=70, with injection of 1 μL β amyloid 1-42 solution into the bilateral hippocampi). According to the random number table method, fifty successfully modeled rats were assigned into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, and 3.82 g·kg-1, respectively) Hei Xiaoyaosan groups, and they were administrated with corresponding agents via gavage once a day for 42 consecutive days. Morris water maze test was carried out to examine the cognitive function of rats. Nissl staining was employed to observe the morphology of hippocampal neurons in each group, and Prussian blue staining was used to detect iron deposition in the hippocampal tissue. Biochemical kits were used to measure the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and iron ion (Fe2+) in the hippocampal tissue. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to determine the protein and mRNA levels, respectively, of SIRT1, p53, SLC7A11, glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the hippocampus. ResultsCompared with the blank group, the model group showed reductions in target quadrant movement distance (P<0.01) and target quadrant residence time (P<0.05), disarrangement of hippocampal neurons, increased ferroptosis deposition in the hippocampus, a lowered level of SOD, risen levels of MDA and Fe2+ (P<0.05, P<0.01), down-regulated protein and mRNA levels of SIRT1, SLC7A11, and GPX4 (P<0.05, P<0.01), up-regulated protein and mRNA levels of p53 and ACSL4 (P<0.01), and aggravated pathological process of AD. Compared with the model group, donepezil hydrochloride extended the target quadrant residence time and the target quadrant movement distance (P<0.05, P<0.01). High- and medium- doses of Hei Xiaoyaosan extended the target quadrant residence time and the target quadrant movement distance (P<0.05, P<0.01), improved the neuron arrangement and reduced the ferroptosis deposition in the hippocampus, elevated the SOD level, lowered the MDA and Fe2+ levels (P<0.05, P<0.01), up-regulated the protein and mRNA levels of SIRT1, SLC7A11, and GPX4 (P<0.01, P<0.05), and down-regulated the protein and mRNA levels of p53 and ACSL4 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan can regulate the SIRT1/p53/SLC7A11 signaling pathway to mitigate oxidative stress and inhibit ferroptosis, thereby ameliorating the cognitive dysfunction in AD rats.
5.Herbal Textual Research on Bruceae Fructus in Famous Classical Formulas
Shuiyu XU ; Yixue ZHUANG ; Yiqin ZHANG ; Yichong CHEN ; Yanning CHEN ; Zhilai ZHAN ; Chengzi YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):11-19
Through consulting the ancient herbal books and modern literature, this paper has carried out the textual research on the name, origin, place of origin, harvesting and processing, and other contents of Bruceae Fructus, combed its ancient and modern medicinal history, so as to provide reference for the development of famous classical formulas containing Bruceae Fructus. Through the herbal textual research, It can be verified that, since the Qing dynasty, Bruceae Fructus has been recorded in the materia medica, most of the materia medica in previous dynasties took Bruceae Fructus as its proper name, and Laoyadan, Kushenzi and Yadanzi as the aliases. The main origin of Bruceae Fructus is Brucea javanica, its medicinal part is the fruit, which is harvested from August to October every year, the fruit can be harvested when it is ripe. Bruceae Fructus was first distributed in Fujian, Guangdong and Guangxi, and gradually expanded to the south of China with the change of time. The traditional processing method of Bruceae Fructus is mainly to remove the shell and kernel, and remove the oil by frosting. The 2020 edition of Chinese Pharmacopoeia stipulates that its processing method is to remove the shell and impurities. Based on the research results, it is suggested that the dried mature fruit of B. javanica should be selected for the development of famous classical formulas containing this herb, and the raw products can be used if the original formula does not specify the processing requirements.
6.Construction of a quality evaluation index system for specialty care of knee ligament injuries based on a three-dimensional quality structure model
Yiqin YANG ; Sanlian HU ; Xiaomei WEI ; Dan HE ; Weihua HOU ; Haiyan WANG ; Tangyu CHEN ; Qi LIANG
Chinese Journal of Practical Nursing 2024;40(9):692-700
Objective:To construct a nursing quality evaluation index system for knee ligament injury to provide a basis for standardizing the nursing practice and improving the nursing quality of knee ligament injury.Methods:Based on the three-dimensional quality structure model of "structure-process-outcome" proposed by Donabedian, the quality evaluation index system for knee ligament injury specialties was constructed through literature review, brainstorming, and Delphi expert consultation from April to June 2023.Results:Sixteen experts were included in the inquiry. The effective recovery rate of the two rounds of expert correspondence questionnaires was 16/16, the expert authority coefficient was 0.95, and the Kendell harmony coefficients of the expert correspondence were 0.116 and 0.122, respectively (both P<0.05). The final constructed knee ligament injury specialty care quality evaluation index system contained 3 primary indicators (structural quality, process quality and outcome quality), 16 secondary indicators, and 69 tertiary indicators.Conclusions:The specialized nursing quality evaluation index system for knee ligament injury constructed in this study is scientific and reliable, which can provide a basis for the evaluation and assessment of the nursing quality of knee ligament injury specialties and promote the continuous improvement of their nursing quality.
7.Investigation on the effect of decocting gypsum into medicine on calcium content of Xiao'er Magan granules
Yiqin FEI ; Tao JIANG ; Pan LÜ ; Ping YANG ; Fangling ZHAN ; Ling XU
Drug Standards of China 2024;25(2):187-194
Objective:To establish a microwave digestion and inductively coupled plasma mass spectrometry(ICP-MS)for determination on calcium content of Xiao'er Magan granules and discuss the effect of decocting gypsum into medicine on calcium content.Methods:ICP-MS was adopted to determine the calcium content in the preparation,and the difference of calcium content in the small preparation and Xiao'er Magan granules prepared by different pul-verization degree gypsum and different alcohol precipitation processes were compared.Results:The consistency of calcium content between different enterprises and batches of the same enterprise was poor.The results showed that the larger the particles,the lower the calcium transfer rate.The smaller the particles,the higher the calcium trans-fer rate.Conclusion:The transfer rate of gypsum decocted calcium is related to its degree of comminution to ensure consistency of preparation quality.It is suggested to unify the comminution degree of gypsum.The method can pro-vide guidance for the optimization on preparation technology of Xiao'er Magan granules.
8.Quality analysis of Xiao'er Magan granules based on chemometrics combined with quantitative analysis of different components
Yiqin FEI ; Pan LYU ; Ping YANG ; Fangling ZHAN ; Ling XU
China Pharmacist 2024;27(6):937-950
Objective To analyse the quality of Xiao'er Magan granules by the combination of chemometrics and difference analysis of component content.Methods The ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UPLC-Q-TOF/MS)method was used to study the characteristic spectrum of basic components.The partial least squares discriminant analysis was used to quantify and screen the markers of quality difference,the methods of muti-component quantification for differential components and fingerprint were established,and the principal component analysis was used to calculate the comprehensive scores of principal components.Results The 12 common peaks were identified by the characteristic spectrum,which were attributed to 6 medicinal herbs,namely Rhizome,Mulberry bark,Bitter almond,Licorice,Perilla seed and Scutellaria.Taking the variable importance projection value>1 as the criterion,4 characteristic components of quality differences(mulberry A,amygdalin,rosmarinic acid and baicalin)were screened out.The fingerprints similarity of 45 batches of samples were 0.867-0.997.14 components were calibrated,and 8 components were identified,which were mulberroside A,L-amygdalin,amygdalin,rosmarinic acid,baicalin,oroxindin,baicalein and wogonin.The scores of principal component 1 of each enterprise were as follows:G>H>A>C>E>D>F>I>B.The scores of principal component 2 were as follows:F>G>H>B>E>D>C>A>I.The ranking of the comprehensive scores was as follows:G>H>C>A>E>F>D>I>B.Conclusion The preparation quality of enterprise G and H is the best.The established fingerprint and quantitative method of quality differential components are accurate and reliable,which can provide reference for the quality analysis of Xiaoer Magan granules.
9.Study on relationship between spicy diet and uremia pruritus in maintenance hemodialysis patients
Xiaoxin BAI ; Ling YANG ; Yan HE ; Chunjing XIANG ; Yuting ZHANG ; Yiqin WANG ; Moqi LI
Chongqing Medicine 2024;53(21):3289-3294
Objective To investigate the relationship between spicy diet and uremic pruritus(UP)in the patients with maintenance haemodialysis(MHD).Methods A total of 403 patients receiving the treat-ment in the blood purification center of this hospital from December 2023 to February 2024 were selected as the study subjects and grouped by the sum of the scores of frequency and degree of pepper intake.The visual analogue rating scale(VAS)was used to conduct the preliminary pruritus score in all patients,and the pa-tients with the score>0 point conducted the multidimensional evaluation by the 14-item uremic skin pruritus scale.The blood routine and itch-related blood biochemical indexes levels of all patients were measured.Results There were 65 cases in the bland diet group,119 cases in the mild spicy diet group and 219 cases in the spicy diet group,and there was no significant difference in the number of genders between the groups(P>0.05).There were statistically significant differences in age,dialysis age and lymphocyte count among the groups(P<0.05).There was no statistically significant difference in the degree of pruritus among the groups(Z=9.301,P=0.157),but it was seen that the proportion of moderate and severe pruritus in the mild spicy diet group and the spicy diet group was decreased,and the proportions of no pruritus and mild pruritus showed the increasing trend.The itching score of the bland diet group was higher than that of the mildly spicy diet group and spicy diet group,and the difference was statistically significant(P<0.05),but there was no statistically significant difference between the mild spicy diet group and spicy diet group(P>0.05).There was a statistically significant difference in the itch score of the patients aged 40-60 years in each group(P<0.05),and there was no statistically significant difference in the itch score between the patients aged>60 years old and<40 years old in each group(P>0.05).There was no statistically significant difference in the itch-related blood biochemical indexes among the groups(P>0.05).Conclusion The spicy diet may reduce the degree of pruritus in patients with MHD,moreover which is not affected by the age and other factors,and may be associated with lymphocyte level decrease in the patients.
10.Hei Xiaoyaosan Regulates Fas/FasL/Caspase-8/Caspase-3 Signaling Pathway to Inhibit Neuronal Apoptosis in AD Rats
Huping WANG ; Yiqin CHEN ; Jiao YANG ; Yunyun HU ; Yujie LYU ; Zhipeng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):18-26
ObjectiveTo explore the effect and mechanism of Hei Xiaoyaosan in regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/Fas ligand (FasL)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to intervene in neuronal apoptosis and prevent Alzheimer's disease (AD). MethodNinety SPF-grade SD male rats of 4 months old were selected and randomly grouped as follows: 10 rats in the blank group, 10 rats in the sham group (bilateral hippocampus injected with 1 μL normal saline), and 70 rats in the modeling group [bilater hippocampus injected with 1 μL amyloid-beta protein 1-42 (Aβ1-42) solution for the modeling of AD]. Fifty successfully modeled rats were selected and randomly assigned into model, donepezil hydrochloride (0.45 mg·kg-1), and high-, medium-, and low-dose (15.30, 7.65, 3.82 g·kg-1) Hei Xiaoyaosan groups. Rats were administrated with corresponding agents by gavage once a day for 42 days. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the cortex and hippocampus, and immunohistochemistry (IHC) was used to detect the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of Fas, FasL, and Fas-associated protein with death domain (Fadd). Western blot was used to determine the protein levels of Fas, FasL, Fadd, Caspase-3, cleved Caspase-3, Caspase-8, and cleved Caspase-8. ResultCompared with the blank group and sham group, the model group showed increased apoptosis rate in the cortex and hippocampus (P<0.01), elevated Bax level (P<0.01), lowered Bcl-2 level (P<0.01), up-regulated mRNA levels of Fas, FasL, and Fadd in the hippocampus (P<0.01), and up-regulated protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.01). Compared with the model group, donepezil hydrochloride and Hei Xiaoyaosan at high and medium doses decreased the apoptosis rate in the cortex and hippocampus (P<0.05, P<0.01), lowered the Bax level (P<0.01), elevated the Bcl-2 level (P<0.01), and down-regulated the mRNA levels of Fas, FasL, and Fadd and the protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.05, P<0.01) in the hippocampus. Low-dose Hei Xiaoyaosan decreased the apoptosis rate in the cortex and hippocampus (P<0.05, P<0.01), lowered the Bcl-2 level (P<0.01), and down-regulated the mRNA levels of FasL and Fadd (P<0.05) and the protein levels of Fas, FasL, Fadd, cleaved Caspase-3, and cleaved Caspase-8 (P<0.05) in the hippocampus. ConclusionHei Xiaoyaosan can protect neurons in the cortex and hippocampus of AD rats by inhibiting the apoptosis mediated by the Fas/FasL/Caspase-8/Caspase-3 signaling pathway.

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