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1.
Article in Chinese | WPRIM | ID: wpr-1016852

ABSTRACT

Neurological diseases are common and frequent in clinical practices, which are the main reasons that affect the quality of life and physical and mental health of patients seriously. Tianma Goutengyin (TGY) is from the New Significance of Patterns and Treatment in Miscellaneous Diseases, which was compiled by a famous doctor, HU Guangci. TGY is widely used in clinical practice and has the effects of calming the liver and calming the wind, clearing heat and activating the blood, tranquilization, and nourishing the liver and kidneys. Clinical studies have confirmed that modified TGY can be used either alone or in combination with acupuncture or western medicine to treat dementia, headache, vertigo, hypertension, insomnia, Parkinson's disease, stroke, epilepsy, and other common neurological diseases, with significant curative effect, few side effects, and high safety. The main active constituents of single flavor drugs in the composition of TGY mainly include gastrodin, gastrodia elata blume polysaccharides, p-hydroxybenzyl alcohol, rhynchophylline, baicalein, leonurine, stachydrine, geniposide, 2,3,5,4,-tetrahydroxystilbene-2-Ο-β-D-glucoside, pinoresinol diglucoside, pachymic acid, β-ecdysteroid, avicularin, etc. It has been found that TGY and these constituents have the effects of ferroptosis inhibition, anti-apoptosis, anti-inflammation, and oxidation resistance, and they can regulate neurotransmitters and autophagy, reduce cerebral edema reduction, lower blood lipid and blood pressure, and improve blood circulation through multiple targets and pathways. This paper reviewed the clinical application of and the mechanism of the whole prescription and single flavor drugs of TGY in the treatment of neurological diseases, so as to provide a theoretical basis for the clinical application of TGY and offer ideas for the follow-up mechanism research of this prescription.

2.
Acta Pharmaceutica Sinica ; (12): 1475-1483, 2023.
Article in Chinese | WPRIM | ID: wpr-978707

ABSTRACT

Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.

3.
Acta Pharmaceutica Sinica ; (12): 1412-1421, 2023.
Article in Chinese | WPRIM | ID: wpr-978709

ABSTRACT

Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.

4.
Chinese Herbal Medicines ; (4): 169-180, 2023.
Article in English | WPRIM | ID: wpr-982507

ABSTRACT

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

5.
Article in Chinese | WPRIM | ID: wpr-970524

ABSTRACT

At present, new concepts, new technologies, and new methods are emerging in the field of medical research, breaking through the inherent thinking patterns and research models, and promoting the transformation of the research paradigm of traditional Chinese medicine(TCM). This paper gave a case study of clinical research in Danhong Injection in the treatment of chronic stable angina, and based on the background of the study, index evaluation model, experimental design method, blind implementation of placebo, data management system, and exploration of clinical efficacy mechanism of traditional Chinese medicine compounds under the framework of modular pharmacology, the scientific idea of "proving efficacy, conforming standard, and exploring mechanism" was used as the guideline to discuss the research model of reevaluation of the effectiveness of post-marketing TCM varieties. This paper drew a target network map of Danhong Injection in the treatment of chronic stable angina for the first time, which was composed of targeted functional modules. By combining evidence-based clinical research with modular pharmacology framework, changes in the pharmacolo-gical mechanism were finally associated with changes in clinical efficacy, and the advantages of phenotypic correlation of efficacy were explored. This study is expected to provide references for the post-marketing effectiveness evaluation and new ideas for the phenotypic pharmacological mechanism study of multi-target TCM compounds and precise treatment, thereby promoting the innovative development of TCM.


Subject(s)
Humans , Medicine, Chinese Traditional , Angina, Stable/drug therapy , Drugs, Chinese Herbal/therapeutic use , Treatment Outcome
6.
Article in Chinese | WPRIM | ID: wpr-970632

ABSTRACT

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.


Subject(s)
Rats , Male , Animals , Rats, Sprague-Dawley , Ferroptosis , Signal Transduction , Brain Ischemia/metabolism , Cyclooxygenase 2/metabolism , RNA, Messenger , Cerebral Infarction , Reperfusion Injury/metabolism , Malondialdehyde , Infarction, Middle Cerebral Artery
7.
Chinese Pharmacological Bulletin ; (12): 580-587, 2023.
Article in Chinese | WPRIM | ID: wpr-1013842

ABSTRACT

Aim To study the hypnotic effect and safety of compound anshen essential oil. Methods Gas chromatograph-mass spectrometer (GC-MS) was used to analyze the main active components of compound anshen essential oil. The mouse model of insomnia was established by intraperitoneal injection of para-chloro-phenyl alanine ( PC PA ) , combined with pentobarbital sodium sleep experiment and EEG characteristic monitoring in rats to study the hypnotic effect and mechanism. The safety of compound anshen essential oil was evaluated by acute toxicity test, skin irritation/allergy test and 90-day repeated administration toxicity test. The clinical effect and safety were evaluated by using the sleep monitoring technology for micro-motion sensitive mattress. Results Four components, including Atractylone (34.61%), (+) -Limonene (17.80%) , Linalool (11.63%), and Ocimene (11.67%) , were detected as the main active components of compound anshen essential oil. Compound anshen essential oil in-halation administration for seven days could effectively reduce the autonomic activity of insomnia mice, shorten the sleep latency (P <0.05) , improve the sleep duration, increase of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and -γ-aminobutyric acid (GABA) in brain of mice with insomnia, and the medium dose group had better hypnotic effect. There was no death or adverse reaction in the safety evaluation test. The sleep balance index of 10 subjects with difficulty in falling a-sleep significantly increased (P <0.05), sleep latency was significantly shortened (P <0.05) , total sleep duration and sleep efficiency were improved, and no ad¬verse reactions were found after using the compound anshen essential oil for two days. Conclusions The compound anshen essential oil developed by the research team is safe and effective in relieving sleep disorders, which may be closely related to the co-regulation of the levels of neurotransmitters such as 5-HT and GABA by the four main active components.

8.
Article in Chinese | WPRIM | ID: wpr-1014685

ABSTRACT

Meloxicam is a long-acting non-steroidal anti-inflammatory drug, which is mainly used in the treatment of chronic osteoarthritis and postoperative analgesia. Recent studies have found that the drug has great therapeutic potential in anti-tumor, improving cognitive impairment in Alzheimerls disease, mobilizing hematopoietic stem cells and so on. This paper reviewed the pharmacological mechanism of meloxicam, the adverse reactions in gastrointestinal tract, kidney, liver and cardiovascular aspects, summarized various forms of clinical application from the perspective of preparation, and summarized the current clinical treatment strategy of combining with Western medicine and Chinese medicine respectively.

9.
Article in Chinese | WPRIM | ID: wpr-940134

ABSTRACT

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex, which is closely related to neurotransmitter regulation, oxidative stress response, inflammatory factors, neuroglial cell, and abnormal gene expression. Western medicine mainly uses phenobarbital, phenytoin sodium, carbamazepine, and other drugs, but long-term use also produces certain toxic and side effects. Traditional Chinese medicine (TCM) believes that the pathogenesis of epilepsy is related to wind, fire, phlegm, and blood stasis, which leads to dysfunction of viscera, disorder of Qi movement, and finally uncontrolled spirit. In recent years, TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug, Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm, awakening spirit and benefiting intelligence, and removing dampness and opening stomach, which has been widely used in clinic. In this paper, the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level, antioxidant stress response, scavenging oxygen free radicals, regulating the expression of c-fos gene, reducing the level of inflammatory mediators, resisting neuronal apoptosis, and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy, and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

10.
Article in Chinese | WPRIM | ID: wpr-940231

ABSTRACT

Epilepsy is a recurrent neurological disease with synchronous abnormal high discharge of neurons in the brain. The pathogenesis of this disease is extremely complex, which is closely related to neurotransmitter regulation, oxidative stress response, inflammatory factors, neuroglial cell, and abnormal gene expression. Western medicine mainly uses phenobarbital, phenytoin sodium, carbamazepine, and other drugs, but long-term use also produces certain toxic and side effects. Traditional Chinese medicine (TCM) believes that the pathogenesis of epilepsy is related to wind, fire, phlegm, and blood stasis, which leads to dysfunction of viscera, disorder of Qi movement, and finally uncontrolled spirit. In recent years, TCM has achieved certain curative effects on the treatment of epilepsy. As a high-frequency antiepileptic drug, Acori Tatarinowii Rhizoma has the effects of opening orifices and eliminating phlegm, awakening spirit and benefiting intelligence, and removing dampness and opening stomach, which has been widely used in clinic. In this paper, the pathogenesis of epilepsy and the pharmacological mechanism of Acori Tatarinowii Rhizoma extract and chemical components in the treatment of epilepsy were expounded by referring to relevant pharmacological studies and animal experiments. It was found that Acori Tatarinowii Rhizoma played a role in regulating the neurotransmitter level, antioxidant stress response, scavenging oxygen free radicals, regulating the expression of c-fos gene, reducing the level of inflammatory mediators, resisting neuronal apoptosis, and regulating the neuroglial cells and the permeability of blood-brain barrier. This paper summarizes the positive effects of Acori Tatarinowii Rhizoma on the treatment of epilepsy, and provides a scientific basis for the popularization and application of Acori Tatarinowii Rhizoma in the prevention and treatment of epilepsy.

11.
Article in Chinese | WPRIM | ID: wpr-940445

ABSTRACT

Post-stroke depression, a common mental complication after stroke, seriously affects the quality of life and even endangers the life safety of patients. It is difficult to be cured due to the complex and diverse pathogenesis. At present, the widely accepted pathogenesis mechanisms include inflammatory mechanism, neurotransmitter mechanism, and endocrine mechanism. According to the theory of Chinese medicine, Qi stagnation, blood stasis, and phlegm turbidity lead to the occurrence of mental diseases after stroke. Curcumae Radix, as a commonly used Chinese herbal medicine, can activate blood circulation for relieving pain, regulate Qi, and relieve depression. The summary of the medication rules of DENG Tie-tao, ZHANG Xue-wen and other Chinese medical physicians showcases that Curcumae Radix is frequently used in the clinical treatment of depression, stroke, and post-stroke depression. Modern pharmacological studies have demonstrated that Curcumae Radix contains β-sitosterol, curdione, curcumin and other medicinal ingredients. This study reviewed the pharmacological effects of effective components in Curcumae Radix and the pharmacological mechanism in the treatment of post-stroke depression and summarized the processing methods of Curcumae Radix, aiming to clarify the important role and determine the optimal processing method of Curcumae Radix in the treatment of post-stroke depression. The results indicate that Curcumae Radix has the effects of regulating neurotransmitters, inhibiting neuroinflammation, protecting neurons, regulating neuroendocrine and antithrombosis, which can prevent and treat post-stroke depression through multiple components, targets, and pathways. The wine-processed Curcuma longa has the best effect.

12.
Article in Chinese | WPRIM | ID: wpr-940576

ABSTRACT

Malignant tumors are currently seriously endangering human health and life, which has become one of the main causes of death in China. In modern Western medicine, they are mainly tackled by surgery, chemotherapy, and radiotherapy, but the death toll continues to rise year by year. At present, most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects, affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance, making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine (TCM), it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore, the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors, and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan, a classic heat-clearing prescription, is composed of Calculus Bovis, Moschus, Olibanum, and Myrrh and has the effects of clearing away heat, removing toxin, eliminating edema, and dissipating mass, which is mainly used to treat carbuncle, pustule, scrofula, multiple abscess, and cancer caused by heat-toxin obstruction. In modern clinical practice, it has been employed in patients with lung cancer, breast cancer, gastric cancer, liver cancer, colorectal cancer, and other malignant tumors, especially during the advanced stage, as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids (such as masticinic acids), volatile oils, steroids (like porcine deoxycholic acid), and bilirubin, which have been proved effective in anti-tumor. This paper reviewed the prescription source, pharmaceutical research, clinical anti-tumor research, and pharmacological mechanisms of Xihuangwan, which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.

13.
Article in Chinese | WPRIM | ID: wpr-940809

ABSTRACT

ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules (JWZX) based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology,the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study,the average degree (AD) of the nodes in the modules was used as an index to screen the main modules of the disease,and the intervention of the sovereign drugs,minister drugs,and assistant drugs on the main modules was explored. Finally,the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment,JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor (P<0.05,P<0.01). The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor (TNF),epidermal growth factor receptor (EGFR),vascular endothelial growth factor A (VEGFA),transcription factor (JUN),tumor protein p53 (TP53),and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8,and the minister drugs such as Centipeda Herba jointly intervened in modules 1,3,5,8,10,and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3,5,10,and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules,and the pathway functions involved 12 categories including cancer,signal transduction,immune system,endocrine system,and amino acid metabolism. The functions of the four major modules involved cancer,signal transduction,and immune system. According to the results of literature verification,the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and hypoxia-inducible factor-1 (HIF-1) signaling pathways,reduction of the immunosuppressive effect in the tumor microenvironment,and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer,and the therapeutic efficacy was achieved through the multiple targets,multiple modules,and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer,which provides a new idea for interpreting the complex mechanism of prescription compatibility.

14.
Article in Chinese | WPRIM | ID: wpr-940811

ABSTRACT

ObjectiveTo explore the mechanism of hypericin against liver cancer using network pharmacology. MethodThe traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), Drug Gene Interaction Database (DGIdb), Comparative Toxicogenomics Database (CTD) and SwissTargetPrediction were used to predict the targets of hypericin. Five databases including GeneCards and Online Mendelian Inheritance in Man (OMIM) were employed to obtain liver cancer-related targets. The intersection was performed to obtain the targets of hypericin against liver cancer. The Database for Annotation, Visualization and Integrated Discovery (DAVID) v2021q4 was used for Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network of the targets was constructed by Cytoscape 3.6.1 to screen the core targets,and the affinity between hypericin and the core targets was verified by molecular docking. The effects of hypericin on liver cancer and the migration of liver cancer cells were observed by cell viability assay and would healing assay, respectively, and its effects on the mRNA and protein expression of key targets cysteinyl aspartate-specific protease-3(Caspase-3) and mitogen-activated protein kinase 3 (MAPK3) were detected by real-time polymerase chain reaction(Real-time PCR) and Western blot, respectively. ResultA total of 45 genes related to the anti-liver cancer effect of hypericin were obtained, and six core target genes were screened. The signal pathways enriched by KEGG pathway analysis included apoptosis,tumor necrosis factor (TNF) and cancer signal pathways. Molecular docking showed that the core target genes Caspase-3,TNF,estrogen receptor 1 (ESR1),MAPK3,catalase (CAT) and cyclooxygenase 2 (PTGS2) had good affinity with hypericin,especially Caspase-3 and MAPK3. In addition,compared with the conditions in control group, cell experiments demonstrated that hypericin could reduce the viability of liver cancer cells (P<0.05),inhibit their migration,increase the mRNA expression of Caspase-3 (P<0.05) and decrease that of MAPK3 (P<0.05). ConclusionHypericin exerted the anti-liver cancer effect by affecting the core targets such as Caspase-3,TNF,ESR1,MAPK3,CAT and PTGS2 and jointly interfering with apoptosis,TNF and cancer signal pathways.

15.
Article in Chinese | WPRIM | ID: wpr-928175

ABSTRACT

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cistanche , Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Tandem Mass Spectrometry/methods
16.
Chinese Pharmacological Bulletin ; (12): 430-436, 2021.
Article in Chinese | WPRIM | ID: wpr-1014354

ABSTRACT

Aim To investigate the pharmacological mechanism of Weimaining in the treatment of lung ade¬nocarcinoma ( LUAD) , using a network pharmacology and molecular docking approach. Methods The active components and potential targets of Weimanin ( Rhizo- ma Fagopyri Cymosi) were screened out through TCM- SP, TCMID, BATMAN-TCM and ETCM data plat-form, and supplemented with literature. The gene ex¬pression data of LUAD were obtained from the Gen Ex¬pression Omnibus database(GEO) , and the differenti¬ally expressed genes were determined using R software. A protein-protein interaction( PPI) network of intersec¬tion targets was constructed by STRING and visualized by Cytoscape software, and GO functional annotation and KEGG pathway enrichment analysis were per¬formed by Metascape platform. Finally, molecular doc¬king studies were carried out to verify the binding of core components and targets. Results Selecting the OB and DL as filter condition, 16 active ingredients and 353 potential targets were involved. MMP-9, MMP-1, CAT and other targets were closely related to LUAD. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Fluid shear stress and athero¬sclerosis, Pathways in cancer, AGE-RAGE signaling pathway, p53 signaling pathway, etc. Conclusions The present study investigates the main active compo¬nents, targets and related pathways of Weimaining in the treatment of LUAD, which provides the theoretical basis and ideas for further research.

17.
Article in Chinese | WPRIM | ID: wpr-872812

ABSTRACT

Hypertension is one of the most common chronic diseases, also an important risk factor for a series of cardio-and cerebra-vascular diseases. Due to its polygenic, multi-factorial nature and heterogeneity, the underlying cause has not been fully elucidated, satisfied therapeutic effect hasn't been totally achieved either. Metabolomics is used to evaluate metabolic changes of organisms from a holistic perspective, associating with biological processes to reveal the whole situation of the body. In recent years, researchers have used metabolomics to study the pathogenesis of hypertension, potential biomarkers, effects of lifestyle interventions, and mechanisms of antihypertensive drugs. Targeted or untargeted ways are applied to study metabolites form blood, urine, or tissues of human or animals. Metabolic pathways of gut microflora, oxidative stress, fatty acids, and amino acids have drawn more attention, and the discovered metabolites may become potential biomarkers, further the diagnostic biomarkers and treatment targets. In addition, traditional Chinese medicine (TCM) is an integrated complex system in syndrome diagnosis and treatment, and metabolomics coincides well with the concepts of it. TCM researchers also use this method to study the biological basis of syndromes in hypertension and the mechanism of antihypertensive Chinese medicine. There are significant differences in the metabolites between different syndromes. TCM treatments can restore the metabolite disturbance caused by high pressure, which is probably one of the pharmacological pathways of antihypertensive Chinese medicine. Metabolomic studies in hypertension have achieved great progress, but there're still challenges in data analysis, integration with other metabolomic studies and other omic studies and causal relationship in further study.

18.
Article in Chinese | WPRIM | ID: wpr-873072

ABSTRACT

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.

19.
Article in Chinese | WPRIM | ID: wpr-873171

ABSTRACT

Objective:To explore the pharmacological mechanism of Danhong injection (DHI) in the treatment of coronary heart disease with angina pectoris from the level of functional modules by modular pharmacological analysis framework. Method:The targets of drug components in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the angina-related genes in DisGeNET, OMIM and CTD databases were combined to construct the target network of DHI for the treatment of coronary angina pectoris by STRING version 11.0. Functional modules were identified by the molecular complex detection (MCODE), Markov cluster (MCL) and GLay algorithms, and the results were optimized by the minimum network structure entropy algorithm. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was performed on the modules by DAVID version 6.8 bioinformatics analysis platform. Result:By integrating 262 genes related to DHI and 192 genes related to angina pectoris, the target network of DHI for angina pectoris was constructed, including 414 nodes and 6 621 edges. After optimization of the minimum network structure entropy, 12 functional modules (number of nodes>3) were identified by MCODE algorithm, of which the largest module (module 1) has 47 nodes and 962 edges, MCODE score=41.826. KEGG pathway enrichment analysis was conducted on the gene network of DHI for angina pectoris and the modules divided by MCODE, and 37 and 58 KEGG signaling pathways were obtained respectively, with the coverage rate of 86.5%. The pathways enriched by the modules could be roughly divided into 11 categories, among which human diseases (45%), signal transduction (17%), and amino acid metabolism (14%) were involved in a large proportion. Module 1 was enriched into 39 pathways, which was signal transduction-related module. Module 3 was amino acid metabolism-related module. Conclusion:The therapeutic effect of DHI on coronary heart disease with angina pectoris is achieved through multiple modules, multiple pathways and multiple functions, mainly by regulating modules related to signal transduction, amino acid metabolism, neuroactive ligand-receptor interaction, Ca2+ and p53 signaling.

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Article in Chinese | WPRIM | ID: wpr-873352

ABSTRACT

Objective:To study the protective effect of Tongxinluo capsule on cerebral ischemia-reperfusion injury, and explore the mechanism of Tongxinluo capsule in treating cerebral ischemia through network pharmacology. Method:The C57BL/6 mouse middle cerebral artery occlusion(MCAO) model was established by improved suture method and divided into sham operation group, model group, low, medium and high-dose Tongxinluo groups (crude drug 1,2,4 g·kg-1, intragastric administration), Aspirin group (2.055 g·L-1, intraperitoneal injection). Then, neurological function score and 2,3,5-triphenyltetrazole chloride(TTC) staining method were used to determine the infarct size of mice at 24, 48, 72 h by cerebral ischemia-reperfusion. First, chemical constituents of Tongxinluo capsule were screened from the BATMAN-TCM database, and the targets were analyzed. Then, gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed, and traditional Chinese medicine(TCM)-active ingredient-target network was constructed. Finally, the multi-dimensional pharmacological mechanism of Tongxinluo capsule in the treatment of cerebral ischemia was predicted. Result:Longa score, HE staining and TTC staining all suggested that Tongxinluo capsule could alleviate brain injury in mice after cerebral ischemia and reperfusion, and the improvement degree of Tongxinluo capsule on brain injury was gradually enhanced with the increase of Tongxinluo capsule dose. A total of 132 active components and 240 intersection targets, including cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha (PRKACA), adenylate cyclase 1(ADCY1), serine/threonine kinase 1 (Akt1), dopamine receptor D2 (DRD2) and discs large homolog 4 (DLG4) were screened from 12 TCM in Tongxinluo capsule. GO was enriched in cationic channel activity, ion gated channel activity, gate channel activity, neurotransmitter receptor activity, ion channel activity, etc. KEGG was enriched in cAMP signaling pathway, calcium signaling pathway, neuroactive ligand-receptor interaction, cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG) signaling pathway and dopaminergic synaptic signaling pathway. Conclusion:Tongxinluo capsule can alleviate brain damage in mice with cerebral ischemia-reperfusion, and achieve brain protection through multiple targets and multiple links. Network pharmacology reveals effective components,targets and pathway of Tongxinluo capsule in the treatment of cerebral ischemia, which provides theoretical support for the mechanism of Tongxinluo capsule in the treatment of cerebral ischemia.

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