1.Asymmetric Morita-Baylis-Hillman Reaction of Conjugated Nitroalkene with Activated Aldehyde Catalyzed by Cinchona Alkaloids
Lingyu SUN ; Da LI ; Zhongjing HE ; Wei YAO ; Ru JIANG
China Pharmacist 2017;20(2):216-220
Objective:To develop a catalytic system for the asymmetric Morita-Baylis-Hillman ( MBH) reaction of conjugated ni-troalkene with activated aldehyde, and screen out the chiral catalysts with high activity and enantioselectivity. Methods: Totally 21 chiral organocatalysts were applied in the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and the ee value was deter-mined by chiral HPLC. The effects of temperature, solvent and substrate ratio on the catalytic reaction were investigated. Results: In the presence of cinchona alkaloid catalyst (DHQ)2AQN, β-nitrostyrene reacted with ethyl glyoxylate in toluene at 0℃ affording the MBH adduct in 60% yield with good enantioselectivity (up to 56.9% ee). Conclusion: The bis-cinchona alkaloids with aromatic bridging group are the efficient catalysts for the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and moderate isolated yield and enantioselectivity are obtained.
2.Try to discuss on double regulative and therapeutic actions of acupoints.
Chinese Acupuncture & Moxibustion 2006;26(1):27-28
OBJECTIVETo explore double regulative and therapeutic actions of acupoints, and clinically exert and use these actions.
METHODSDiscuss functions of points, reinforcing and reducing amount of reinforcing and reducing manipulation, combination of acupoints, and application of prescription of acupoints.
CONCLUSIONThe double regulative and therapeutic actions of acupoints are carried out by means of different acupuncture reinforcing and reducing manipulation under different pathological states of the organism.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Humans
3. Research progress on Q-biomarker of Chinese materia medica
Chinese Traditional and Herbal Drugs 2019;50(19):4556-4561
Quality marker (Q-marker) is one of the new directions in the research of quality control of Chinese materia medica. The Q-marker can be either quality chemomarker (Q-chemomarker) or quality biomarker (Q-biomarker). The establishment of a good Q-biomarker can improve the linkage of Chinese medicine quality control methods and standards with clinical safety and effectiveness, at the same time considering the operability of quality control. At present, the FDA of China and the United States have adopted biological evaluation methods as an important part of quality control of Chinese medicines and botanicals medicines. Many companies and researchers are also actively exploring and developing methods for the evaluation of quality of Chinese materia medica. This paper further enlarges and expands the methods and indicators of biological evaluation of Chinese materia medica, and summarizes and analyzes relevant research examples from the perspective of Q-biomarker. We hope that it would promote the richness and development of the theoretical system of Chinese medicine quality markers, so as to provide a reference to solve the practical problems for the quality control and evaluation of Chinese materia medica.
4. Regulatory effects of Cannabis Fructus oil on gut microecology in D-galactose- induced aging mice
Chinese Traditional and Herbal Drugs 2020;51(13):3509-3517
Objective: To investigate the effects of Cannabis Fructus oil on the regulation of gut microecology in D-galactose-induced aging mice. Methods: The Kunming mice were divided into control group, model group, positive control group (Jin Shuangqi group), Cannabis Fructus oil (12.0, 6.0, 3.0 mL/kg) group with six males and six females in each group. In the control group, normal saline was injected subcutaneously into the back of the neck every day. The other five groups were injected subcutaneously with 1% D-galactose aqueous solution, and the volume was 10 mL/kg. After 1 h, the control group was given normal saline by intragastric administration. The other groups were intragastrically administered with different doses of Cannabis Fructus oil for 42 d, and the dosage volume was 20 mL/kg. After the end of the administration, the change in body weight was analyzed; The proximal intestinal tissue of the ileocecal area and the feces in the cecum and colon were retained. Gram staining was used for the detection of Gram-positive bacilli (G+b), Gram-negative bacilli (G-b), Gram-positive cocci (G+c) and Gram-negative cocci (G-c); The ileal mucosa changes were observed by HE staining; The pH value of the colon feces was determined by pH meter; And the content of short-chain fatty acids (SCFA) in feces was determined by gas chromatography. Results: The results showed that Cannabis Fructus oil increased the ratio of bacillus, reduced the ratio of cocci and the cecal coefficient, decreased the pH value of the colon, significantly improved the colon pathological changes of the model animals with unbroken membrane skin, regular glands and rich cup cells and fluff rich, increased the content of SCFAs in the intestine of mice, and significantly increased (P < 0.01) the content of acetic acid, propionic acid, butyric acid, isobutyric acid, and significantly reduced (P < 0.01) the content of isovaleric acid. Conclusion: It could conclude that Cannabis Fructus oil can up-regulate the ratio of D-galactose-induced mice intestinal bacteria structure, improve the intestinal microecology, so as to provide theoretical support for clinical application and product development of Cannabis Fructus oil.
5.Study on the mechanism of Wenyang huazhuo tongluo formula contained serum inhibiting the proliferation of Th17 cells in scleroderma patients
Kelei GUO ; Yingli LI ; Bo BIAN ; Li HAN ; Kai LI ; Hong ZHANG ; Hua BIAN
China Pharmacy 2022;33(15):1820-1824
OBJECTIVE To study the effects of Wenyang huazhuo tongluo formula conta ined serum on the expression and methylation of retinoic acid related nuclear orphan receptor (RORγt),and to explore the mechanism of its regulation of Th 17 cell proliferation in the treatment of scleroderma. METHODS Wistar rats were given 15,30,60 g/(kg·d)Wenyang huazhuo tongluo formula intragastrically to prepare different doses of drug-contained serum ,and peripheral blood of scleroderma patients were collected to sort Th 17 cells. Using blank serum as blank control ,methyltransferase inhibitor decitabine (DCA)as positive control , Th17 cells were treated with different concentrations of drug-contained serum ,and then the proliferation of Th 17 cells was detected by CCK- 8;mRNA expressions of RORγt and IL-17 were detected by qRT-PCR ,and the protein expression of RORγt was detected by Western blot assay ;the protein expression of IL- 17 in the cell supernatant was detected by ELISA ,and the methylation level of RORγt gene promoter was detected by methylation-specific PCR. The transcriptional activity of RORγt gene promoter was detected by dual-luciferase assay. RESULTS Compared with blank control ,Wenyang huazhuo tongluo formula contained serum and DCA could inhibit the proliferation of Th 17 cells(P<0.05),reduced the mRNA and protein expressions of RORγt and IL-17,enhanced the methylation level of RORγt gene promoter and attenuated , the transcription activity of RORγt gene promoter. Except for mRNA expression of Th 17 and the methylation level of RORγt gene promoter in drug-contained serum low-dose group ,there were statistical significance in above indexes of other groups(P<0.05). CONCLUSIONS Wenyang huazhuo tongluo formula can promote the methylation lev el of RORγt gene,and inhibit the expression of RORγt and the secretion of IL-17,so as to inhibit the proliferation of Th 17 cells.
6.The mechanisms of paeonol reversing multidrug resistance in ovarian cancer SKOV3/DDP cells
Li HAN ; Xiao-juan GUO ; Zhong CHEN ; Hua BIAN ; Chao-yun ZHANG ; Wen-hua ZANG ; Qian WANG ; Jiu-lue HU
Acta Pharmaceutica Sinica 2018;53(9):1511-1517
The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.
7.Chaihu Shugansan Combined with Ferulic Acid Regulates BDNF/TrkB Signaling Pathway and Monoamine Neurotransmitters in Frontal Cortex of Rat Model of CUMS
Yuexin LI ; Zhijing ZHANG ; Ziyi GUO ; Di YAN ; Xueyan HU ; Jianping YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):28-37
ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress (CUMS) and explore the mechanism from the histomorphology of frontal cortex, expression of key molecules in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway, and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups (n=10): blank control, depression model, Chaihu Shugansan (3.3 g·kg-1·d-1), ferulic acid (50 mg·kg-1·d-1), Chaihu Shugansan (3.3 g·kg-1·d-1) + ferulic acid (50 mg·kg-1·d-1), and fluoxetine (2.1 mg·kg-1·d-1). Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used, including fasting with free access to water for 24 h, water deprivation with free access to food for 24 h, wetting the bedding with water in the cage, restraint for 3 h, tail clamping for 1 min, swimming in ice water at 4 ℃, and day and night reversal. Each stimulus was used 1 to 3 times, and the modeling lasted for a total of 21 days. At the same time of stimulation, rats in each medication group were treated with corresponding agents by gavage, while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test, sucrose preference test, and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium, and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF, TrkB, and cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group, the depression model group showed reduced body mass (P<0.05, P<0.01), decreased number of crossings and rearings in the open field test and sucrose preference (P<0.01), prolonged time of immobility in the forced swimming test (P<0.01), reduced neuronal cells, increased necrotic cells, and darkening cell staining in the frontal cortex, down-regulated mRNA and protein levels of BDNF, TrkB, CREB, and lowered levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Compared with the depression model group, each intervention group showed improved general state, increased body mass (P<0.05), increased number of crossings (P<0.05), shortened immobility time in the forced swimming test (P<0.01), increased neuronal cells, reduced necrotic cells, and lightened cellular staining in the frontal cortex, up-regulated mRNA and protein levels of BDNF, TrkB and CREB, and elevated levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Moreover, the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex (P<0.05). The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex (P<0.05), and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test, up-regulating the mRNA levels of BDNF, TrkB, and CREB and the protein levels of BDNF and CREB in the frontal cortex, and increasing the DA content in the frontal cortex (P<0.05). ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover, the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.
8.Research on Preparation Process and Quality Evaluation of Traditional Chinese Medicine Dispensing Granules and Its Consistency with Traditional Decoction: A Review
Henian YANG ; Jincheng ZHANG ; Suhui WU ; Hanbing LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):266-274
Traditional Chinese medicine dispensing granules(TCMDGs)is the new type of decoction pieces with the development of modernization of TCM, which has received mixed opinions since its practical application. In 2021, the national departments issued Announcement on Ending the Pilot Work of TCMDGs, marking the end of the 28-year pilot work of TCMDGs, and eligible TCM enterprises can produce TCMDGs after filing. However, this does not mean that the preparation process, quality standard and efficacy research of TCMDGs have been developed and matured, on the contrary, there are still some problems that need to be solved and gradually improved. For example, in the production process, there are problems such as unclear, unified and non-standardized preparation parameters. In terms of quality control, there are some problems such as lack of producing area regulation, variety selection and processing specification. In terms of consistency evaluation with traditional decoction, there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore, in view of some prominent problems of TCMDGs at present, this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia, Publicity of the Unified Standard on the Varieties of TCMDGs, Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs, the origin and variety of raw materials, the processing of decoction pieces, the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining, data analysis and list comparison. Based on the analysis results, the following suggestions were made. In terms of preparation process, the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation, attention should be paid to the relationship between the authenticity, variety, processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction, the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine, quality marker(Q-Marker) theory and physicochemical characterization, so as to provide reference for the application and development of TCMDGs.
9.Gardeniae Fructus and Its Prescriptions in Treatment of Depression: A Review
Lei TIAN ; Yucheng LI ; Ming BAI ; Baoying WANG ; Erping XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):239-247
Depression is a mental disorder characterized by persistent low mood and belongs to the category of "stagnation syndrome" in traditional Chinese medicine (TCM), with the characteristics of high prevalence, high disability rate, high suicide rate, and high recurrence rate. The pathogenesis of depression is extremely complex and involves factors such as genetics, psychology, and social environment. Currently, clinical antidepressant drugs such as tricyclic and tetracyclic antidepressants, and selective serotonin reuptake inhibitors, have slow onset of action and significant adverse effects with long-term application. Furthermore, clinical statistics show that about one-third of patients do not respond to these types of medications. Enhancing the effectiveness of depression treatment has become a major challenge in the medical field. TCM, based on the holistic view and treatment based on syndrome differentiation, has unique advantages in the prevention and treatment of depression, including stable therapeutic effects, low recurrence rate, minimal side effects, and good patient compliance. As one of the heat-clearing drugs, Gardeniae Fructus has the effects of clearing heat, purging fire, cooling blood, and relieving restlessness, which makes it effective in treating patients with "stagnation syndrome". Literature studies have found that active components of Gardeniae Fructus, such as geniposide, genipin, and crocin, as well as drug pairs such as Gardeniae Fructus-Chuanxiong Rhizoma, Gardeniae Fructus-Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis, and Gardeniae Fructus-Lycii Fructus, and prescriptions such as Zhizichi Tang, Yuejuwan, Zhizi Houpotang, Danzhi Xiaoyaosan, and Jieyu Anshen Granules, have shown significant antidepressant effects. The mechanism of action may be related to regulating the hypothalamic-pituitary-adrenal (HPA) axis, modulating neurotransmitters such as serotonin (5-HT) and dopamine (DA), increasing brain-derived neurotrophic factor (BDNF) in the hippocampus, enhancing neurogenesis in the hippocampus, and regulating the nuclear factor-kappa B (NF-κB) signaling pathway to inhibit neuroinflammation. This article summarized the research progress on the active components of Gardeniae Fructus, drug pairs, and Chinse medicinal prescriptions containing Gardeniae Fructus, providing references for further promoting the clinical application of Gardeniae Fructus and its prescriptions in the treatment of depression.
10.Guizhi Fuling Wan reverses drug resistance by regulating PTEN and MTDH in ovarian cancer SKOV3/DDP Cells
Xiao-Juan GUO ; Li HAN ; Wen-Hua ZANG ; Qian WANG ; Hua BIAN ; Jiu-Lue HU ; Chao-Yun ZHANG
Chinese Journal of Pharmacology and Toxicology 2018;32(4):284-284
OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.