1.Research progress on immunosuppressive activity of monomers extracted from Chinese medicine.
Shiqin SUN ; Youzhi WANG ; Yabin ZHOU
China Journal of Chinese Materia Medica 2010;35(3):393-396
The clinical or experimental study proves that Chinese medicine such as Tripteryglum wilfordii, Lignum Sappan, Caulis Sinomenii, Radix Trichosanthis and Herba Artemisiae Annuae have good immunosuppressive activity. Further researches on the immunosuppressive active components from Chinese medicine have been the main direction in recent years. The recent researches on immunosuppressive effect and possible mechanisms for the monomers such as triperine, triptolide, bazilein, potosappanin A, sinomenine, trichosanthin and artemisinin extracted from those Chinese medicine are introduced in this review.
Animals
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Artemisinins
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pharmacology
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therapeutic use
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Diterpenes
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pharmacology
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therapeutic use
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Drugs, Chinese Herbal
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pharmacology
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therapeutic use
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Epoxy Compounds
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pharmacology
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therapeutic use
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Humans
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Immunosuppressive Agents
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pharmacology
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therapeutic use
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Morphinans
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pharmacology
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therapeutic use
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Phenanthrenes
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pharmacology
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therapeutic use
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Plants, Medicinal
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chemistry
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Trichosanthin
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pharmacology
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therapeutic use
2.Study on Protective Effect and Its Mechanism of Thymoquinone on Myocardial Fibrosis Induced by Lipopolysaccharide in Rats
Wei CAI ; Jiadan YANG ; Shan GAO ; Shiqin LI ; Shurong WANG
China Pharmacy 2019;30(4):464-469
OBJECTIVE: To investigate the protective effect and its mechanism of thymoquinone (TQ) on myocardial fibrosis (MF) induced by lipopolysaccharide in rats. METHODS: Totally 40 male Wistar rats were randomly divided into control group, model group, TQ low-dose and high-dose groups [5, 10 mg/(kg?d)], with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally, other groups were given LPS intraperitoneally to induce MF model, once a day, for consecutive 3 weeks. Since the first day of modeling, administration group was given relevant medicine intraperitoneally, once a day, for consecutive 3 weeks. After last medication, ELISA method was used to detect the contents of serum inflammation factors (IL-1β, IL-6, TNF-α) in rats. Cardiac mass parameters (HW/BM, LVW/BW) were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators (MDA, SOD) and myocardial collagen indexes (HYP, Col-Ⅰ, Col-Ⅲ) were detected by chemical analysis, xanthine oxidase method or ELISA. mRNA expression of regulation genes (Col-Ⅰ, Col-Ⅲ, MMP-3, MMP-9, TGF-β1 and Smad3) related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS: Compared with control group, there were swollen myocardial cells, disordered nuclei of different sizes and visible fiber hyperplasia in model group; the levels of serum inflammatory factors and LVW/BW, cardiac contents of MDA, HYP, Col-Ⅰand Col-Ⅲ, mRNA expression of Col-Ⅲ, TGF-β1 and Smad3 in model group were increased significantly (P<0.05), while SOD activity was decreased significantly (P<0.05). Compared with model group, the degree of myocardial fibrosis was improved in TQ groups to different extents; serum content of IL-1β and the contents of MDA, HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group, serum contents of IL-1β, IL-6 and TNF-α, LVW/BW and the contents of MDA, HYP, Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ, Col -Ⅲ, TGF-β1 in TQ groups were decreased significantly (P<0.05). The activities of SOD in cardiac tissue were increased significantly in TQ groups (P<0.05). There was no statistical significance in other indexes among groups (P>0.05). CONCLUSIONS: TQ can protect against MF model rats to certain extent, the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction, and down-regulation of mRNA expression of Col-Ⅰ, Col-Ⅲ and TGF-β1.
3.N-terminal truncation of prenyltransferase enhances the biosynthesis of prenylnaringenin.
Chaojie GUO ; Song GAO ; Hongbiao LI ; Yunbin LYU ; Shiqin YU ; Jingwen ZHOU
Chinese Journal of Biotechnology 2022;38(4):1565-1575
8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism*
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Flavonoids/metabolism*
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Molecular Docking Simulation
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Prenylation
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Saccharomyces cerevisiae/metabolism*
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Sophora/metabolism*
4.Effect of Shenling Baizhusan on Alcoholic Liver Injury in Rats by Regulating Ferroptosis Based on Nrf2 Signaling Pathway
Xiangyu ZHOU ; Sufang ZHOU ; Yuru LI ; Shiqin CAI ; Jiajia LIAO ; Zuoyu YE
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):104-113
ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway by regulating ferroptosis in rats with alcoholic liver injury. MethodForty SD rats were randomly divided into model group, polyene phosphatidylcholine group, and high, medium, and low-dose Shenling Baizhusan groups, with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group, polyene phosphatidylcholine group, high, medium, and low-dose Shenling Baizhusan groups were given 10 mL·kg-1 liquor by gavage for modeling, and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration, 143.64 mg·kg-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group, 15, 7.5, 3.75 mg·kg-1 of Shenling Baizhusan were given to Shenling Baizhusan high, medium, and low-dose groups, respectively, and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), total cholesterol (TC), and triglyceride (TG) were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α (TNF-α) and interleukin-β (IL-β) were detected by the enzyme-linked immunosorbent assay (ELISA). The levels of lipopolysaccharide (LPS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and Fe+ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin (HE) staining and oil red O staining. The mRNA expression levels of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and nuclear factor-κB (NF-κB) were detected by Real-time polymerase chain reaction (Real-time PCR). The protein expression levels of Nrf2, HO-1, GPX4, FTH1, p65, and phosphorylation (p)-p65 were detected by Western blot. ResultAs compared with the blank group, the levels of liver function (ALT, AST, and GGT) and blood lipids (TC and TG) in the model group were significantly increased (P<0.05). The liver showed obvious steatosis, with a large number of fat deposition, the oxidative stress and inflammatory factors were significantly increased (P<0.05), and the level of Fe+ was significantly increased in model group (P<0.05). The protein expression levels of Nrf2, HO-1, GPX4, and FTH1 was significantly down-regulated (P<0.05), and those of p65 and p-p65 was significantly up-regulated in the model group (P<0.05). The mRNA expression levels of Nrf2, HO-1, GPX4, and FTH1 were significantly down-regulated (P<0.05), and the mRNA expression level of NF-κB was significantly up-regulated (P<0.05). As compared with the model group, the levels of liver function (ALT, AST, and GGT) and blood lipids (TC and TG) in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased (P<0.05), liver steatosis was significantly improved, fat deposition was significantly reduced, oxidative stress and inflammatory factors were significantly decreased (P<0.05 ), and Fe+ level was significantly decreased (P<0.05). In the high-dose and medium-dose Shenling Baizhusan, the protein expression levels of Nrf2, HO-1, GPX4, and FTH1 were significantly up-regulated (P<0.05), and those of p65, p-p65 were significantly down-regulated (P<0.05). The mRNA expression levels of Nrf2, HO-1, GPX4, and FTH1 were significantly up-regulated (P<0.05), and the mRNA expression level of NF-κB was significantly down-regulated (P<0.05). ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD, regulate steatosis and fat deposition, and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress
5. Molecular mechanism and treatment of pulmonary fibrosis
Shiqin ZHOU ; Yali LUO ; Wen ZHOU ; Xiaofeng QI ; Mengyong XIAO ; Yali LUO
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(10):1133-1147
Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease. The pathogenesis of PF is not yet clear. The two anti fibrosis drugs approved for IPF treatment, nidanib and pirfenidone, have been proved to reduce the decline of pulmonary function of pF, but both have side effects. So far, there is no obvious and effective treatment to prevent the progress of pF. Therefore, this review focuses on the different cells, molecular mechanisms involved in PF and the current treatment progress of PF, so as to provide theoretical support for a better understanding of these cells, molecular mechanisms and drug development and application in PF.
6.Responses of Patients with Disorders of Consciousness to Habit Stimulation: A Quantitative EEG Study.
Jingqi LI ; Jiamin SHEN ; Shiqin LIU ; Maelig CHAUVEL ; Wenwei YANG ; Jian MEI ; Ling LEI ; Li WU ; Jian GAO ; Yong YANG
Neuroscience Bulletin 2018;34(4):691-699
Whether habit stimulation is effective in DOC patient arousal has not been reported. In this paper, we analyzed the responses of DOC patients to habit stimulation. Nineteen DOC patients with alcohol consumption or smoking habits were recruited and 64-channel EEG signals were acquired both at the resting state and at three stimulation states. Wavelet transformation and nonlinear dynamics were used to extract the features of EEG signals and four brain lobes were selected to investigate the degree of EEG response to habit stimulation. Results showed that the highest degree of EEG response was from the call-name stimulation, followed by habit and music stimulations. Significant differences in EEG wavelet energy and response coefficient were found both between habit and music stimulation, and between habit and call-name stimulation. These findings prove that habit stimulation induces relatively more intense EEG responses in DOC patients than music stimulation, suggesting that it may be a relevant additional method for eliciting patient arousal.
Adult
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Alcohol Drinking
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physiopathology
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Brain
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physiopathology
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Consciousness Disorders
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physiopathology
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therapy
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Electroencephalography
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Female
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Habits
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Humans
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Male
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Middle Aged
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Music
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Names
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Nonlinear Dynamics
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Physical Stimulation
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Rest
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Smoking
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physiopathology
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Speech
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Treatment Outcome
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Wavelet Analysis
7. Research progress of lactate dehydrogenase A in digestive system tumors and related drugs
Siyu WANG ; Jiawei LI ; Chenghao LI ; Ling LI ; Qingyang GUO ; Lu QIU ; Shiqin ZHOU ; Yongqi LIU ; Jiawei LI ; Ling LI ; Yongqi LIU ; Jiawei LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):445-454
Malignant tumors of digestive system are highly prevalent malignant tumors that seriously threaten human health around the world. At present, the curative efficacy and prognosis of traditional treatment methods cannot reach the expectation, so it is urgent to find new targets for cancer treatment and realize targeted therapy for tumors. Abnormal energy metabolism in tumor cells is regarded as a hallmark of cancer, and malignant tumor cells absorb glucose through aerobic glycolysis pathway, and obtain a small amount of energy and produce lactate under the catalysis of a series of enzymes. Lactate dehydrogenase A (Lactate dehydrogenase A, LDHA), as a key enzyme in the aerobic glycolysis pathway of tumor cells, plays an important role in the metabolic changes of tumor cells. Studies have demonstrated that LDHA has high expression characteristics in a variety of tumor cells,and its high expression in clinic is often related to the poor prognosis and high metastasis rate of tumors, which is expected to be a new target for cancer therapy. This article reviews the role of LDHA in the development of digestive system tumors and the research progress of related drugs.
8. Research status of dialectical prevention and treatment of acute lung injury based on the theory of "Wei qi and Ying Xue"
Xiaofeng QI ; Yali LUO ; Mengyong XIAO ; Shiqin ZHOU ; Wen ZHOU ; Fangyu AN ; Ben-Jun WEI ; Yongqi LIU ; Yali LUO ; Yongqi LIU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):429-437
Acute lung injury (ALI) is a common clinical critical respiratory disease. At present, the mechanism of the disease has not been fully elucidated, there is a lack of specific drugs in clinical practice and the mortality rate is high, which is a difficult problem in the medical field. In recent years, traditional Chinese medicine has exerted its unique advantages and efficacy in the prevention and treatment of ALI, which has aroused the attention of domestic and foreign scholars. Based on the theory of "Wei Qi Ying Xue", this paper discusses the current research status of prevention and treatment of ALI by traditional Chinese medicine, and analyzes its pathogenesis, clinical manifestations and corresponding analysis with TCM syndrome. According to the angle of "Wei Qi Ying Xue", the progress of syndrome differentiation and treatment is highly consistent with immune response, inflammatory response, oxidative stress and apoptosis, in order to find new ideas and medication for the prevention and treatment of ALI with integrated traditional Chinese and Western medicine.