Network Meta-analysis was employed to compare the efficacy of Chinese medicine injections for activating blood and resolving stasis combined with conventional western medicine in the treatment of acute ischemic stroke and the effects on platelet aggregation rate, fibrinogen(FIB), and hypersensitive C-reactive protein(hs-CRP), with a view to providing evidence-based medicine reference for clinical medication. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase were searched for randomized controlled trial(RCT) on the treatment of acute ischemic stroke with Salvia Miltiorrhiza Ligustrazine Injection, Danhong Injection, Shuxuetong Injection, Xueshuantong Injection, Shuxuening Injection, Safflower Yellow Pigment Injection, and Ginkgo Diterpene Lactone Meglumine Injection combined with conventional western medicine. The retrieval time was from database inception to March 18, 2023. The articles were extracted by two researchers and their quality was evaluated. R 4.2.2 was used for network Meta-analysis. A total of 87 RCTs involving 8 580 patients were included. Network Meta-analysis showed that, in terms of reducing National Institutes of Health stroke scale(NIHSS) scores, the surface under the cumulative ranking curve(SUCRA) showed the order of Xueshuantong Injection + conventional western medicine(88.7%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(73.7%) > Shuxuetong Injection + conventional western medicine(69.7%) > Shuxuening Injection + conventional western medicine(51.8%) > Danhong Injection + conventional western medicine(43.7%) > Safflower Yellow Pigment Injection + conventional western medicine(36.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(35.3%) > conventional western medicine(1.7%). In terms of improving clinical total effective rate, SUCRA showed the order of Danhong Injection + conventional western medicine(63.0%) > Shuxuening Injection + conventional western medicine(59.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(58.9%) > Safflower Yellow Pigment Injection + conventional western medicine(57.1%) > Xueshuantong Injection + conventional western medicine(56.8%) > Shuxuetong Injection + conventional western medicine(54.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(50.5%) > conventional western medicine(0.03%). In terms of improving Barthel index, SUCRA showed the order of Danhong Injection + conventional western medicine(84.7%) > Shuxuetong Injection + conventional western medicine(72.4%) > Safflower Yellow Pigment Injection + conventional western medicine(61.6%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(44.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(43.2%) > Shuxuening Injection + conventional western medicine(42.2%) > conventional western medicine(1.4%). In terms of reducing platelet aggregation rate, SUCRA showed the order of Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(82.4%) > Shuxuetong Injection + conventional western medicine(81.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(40.7%) > Danhong Injection + conventional western medicine(37.3%) > conventional western medicine(8.0%). In terms of reducing FIB, SUCRA showed the order of Danhong Injection + conventional western medicine(81.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(71.9%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(70.0%) > Shuxuetong Injection + conventional western medicine(46.7%) > Xueshuantong Injection + conventional western medicine(22.6%) > conventional western medicine(8.7%). In terms of reducing hs-CRP, SUCRA showed the order of Shuxuening Injection + conventional western medicine(89.9%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(78.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(52.4%) > Danhong Injection + conventional western medicine(47.6%) > Xueshuantong Injection + conventional western medicine(43.5%) > Shuxuetong Injection + conventional Western medicine(35.6%) > conventional western medicine(2.3%). The results indicated that Xueshuantong Injection + conventional western medicine, Danhong Injection + conventional western medicine, and Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine ranked the top three. Xueshuantong Injection + conventional western medicine had the best effect on reducing NIHSS scores. Danhong Injection + conventional western medicine showed the best performance of improving clinical total effective rate, improving Barthel index, and reducing FIB in the blood. Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine had the best effect on reducing platelet aggregation rate in the blood. Shuxuening Injection + conventional western medicine had the best effect on reducing hs-CRP. However, more high-quality RCTs are needed for verification in the future to provide more reliable evidence-based medical reference.
Humans ; Medicine, Chinese Traditional ; Ischemic Stroke/drug therapy* ; Network Meta-Analysis ; C-Reactive Protein ; Drugs, Chinese Herbal/therapeutic use* ; Adjuvants, Pharmaceutic ; Diterpenes ; Lactones ; Meglumine

OBJECTIVE: To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells. METHODS: For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting. RESULTS: Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01). CONCLUSIONS Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Diterpenes/therapeutic use* ; Humans ; Mice ; NF-kappa B/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Urinary Bladder Neoplasms/drug therapy*

Danshen, the dried root or rhizome of Salvia miltiorrhiza Bge., is a traditional and folk medicine in Asian countries, especially in China and Japan. In this review, we summarized the recent researches of Danshen in traditional uses and preparations, chemical constituents, pharmacological activities and side effects. A total of 201 compounds from Danshen have been reported, including lipophilic diterpenoids, water-soluble phenolic acids, and other constituents, which have showed various pharmacological activities, such as anti-inflammation, anti-oxidation, anti-tumor, anti-atherogenesis, and anti-diabetes. This article intends to provide novel insight information for further development of Danshen, which could be of great value to its improvement of utilization.
Diterpenes ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Hydroxybenzoates ; chemistry ; Molecular Structure ; Oils, Volatile ; chemistry ; Phytochemicals ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Plant Roots ; chemistry ; Quality Control ; Salvia miltiorrhiza ; chemistry

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cadherins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cytokines ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Vimentin/metabolism

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.
Animals ; Biomarkers ; Chromatography, High Pressure Liquid ; methods ; Diterpenes ; toxicity ; Epoxy Compounds ; toxicity ; Glycyrrhiza ; Male ; Metabolomics ; Phenanthrenes ; toxicity ; Plant Extracts ; therapeutic use ; Principal Component Analysis ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF).

METHODSTotally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis.

RESULTSAfter chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05).

CONCLUSIONT II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up-regulating NGF activities.

Calcitonin Gene-Related Peptide ; blood ; Diterpenes, Abietane ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Nerve Growth Factor ; blood ; Neural Conduction ; drug effects ; Organoplatinum Compounds ; adverse effects ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Up-Regulation

OBJECTIVE: To determine the combined cytotoxic effect and the molecular basis of triptolide and sodium cantharidinate on hepatoma cell line 7721.
 METHODS: After treating the hepatoma cell line 7721 with triptolide(9, 18, or 36 μg/mL) and/or sodium cantharidinate (2, 5, or 10 μg/mL), cell viability assay and apoptosis were examined by MTT and flocytometry, respectively. The protein levels of caspase 3 and nuclear factor κB were analyzed by Western blot.
 RESULTS: Viability of hepatoma cell line 7721 was inhibited by either the therapy of triptolide and/or sodium cantharidinate (P<0.05) in a time- and dose-dependent manner. The combined effects of both drugs were better than those of the single drug (P<0.05). The combined therapy down-regulated the expression of NF-κB p65 (P<0.05) while up-regulated the expression of caspase-3 (P<0.05).
 CONCLUSION Triptolide and sodium cantharidinate exert a synergistic toxic effect on hepatoma cell line 7721, which is related to increasing capase-3 activity and suppression of NF- κB.
Apoptosis ; drug effects ; Cantharidin ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Diterpenes ; pharmacology ; therapeutic use ; Down-Regulation ; Drug Therapy, Combination ; Epoxy Compounds ; pharmacology ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; NF-kappa B ; drug effects ; Phenanthrenes ; pharmacology ; therapeutic use ; Transcription Factor RelA

Cardiovascular diseases, like coronary heart disease and myocardial infarction, are the most common cause of death worldwide. Chinese medicines have demonstrated rich cardioprotective activities for clinical applications. Salvia miltiorrhiza, a very important component of traditional Chinese medicine, can promote blood circulation and relieve blood stasis. Salvia miltiorrhiza is widely used in treatment of cardiovascular and cerebrovascular disease such as coronary heart disease and cerebral infarction ( CI). Tanshinone II(A), the major lipophilic components extracted from the root of S. miltiorrhiza, possesses anti-atherosclerosis, anti-cardiac hypertrophy, anti-oxidant, anti-arrhythmia and so on. This paper discusses current research status of tanshinone II(A) in cardioprotective effects.
Animals ; Cardiovascular Diseases ; drug therapy ; genetics ; metabolism ; physiopathology ; Coronary Vessels ; drug effects ; physiopathology ; Diterpenes, Abietane ; therapeutic use ; Humans

OBJECTIVETo study the role of nuclear factor (NF)-kappaB pathway with p38MAPK in Curcuma wenyujin diterpenoid compound C (CDCC) fighting against inflammation and inducing gastric cancer cell apoptosis by stimulating gastric cell SGC7901 with tumor necrosis factor-alpha (TNF-alpha).

METHODSHuman umbilical vein endothelial cells (HUVECs) and human gastric cancer SGC-7901 cells were in vitro acted by CDCC in different concentrations at different time points. Their growth inhibition ratios were measured by MTT assay. The apoptosis rate of gastric cancer cells was detected by Annexin V-FITC/PI double staining. Nuclear translocation of p65 was detected by cell immunofluorescence. Expression levels of p38MAPK/P-p38MAPK, p65/P-p65, and Caspase 3/P-Caspase 3 were measured by Western blot.

RESULTSCDCC had significant inhibitory effect on the proliferation of SGC-7901. It also could effectively induce the apoptosis of gastric cancer cell SGC-7901. It also could reduce nuclear translocation of p65 in gastric cancer cell SGC-7901. Results of Western blot indicated that expression levels of p38MAPK and p65 were reduced and the expression level of Caspase-3 was elevated along with increased concentrations of CDCC (P<0.05).

CONCLUSIONApoptosis executive protein Caspase 3 activated by regulating p65 via p38MAPK might be one of possible mechanisms for CDCC fighting against inflammation and gastric cancer.

Apoptosis ; Caspase 3 ; Cell Line, Tumor ; Curcuma ; Diterpenes ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; Stomach Neoplasms ; drug therapy ; Tumor Necrosis Factor-alpha

OBJECTIVETo explore the effect of Tanshinone II A on severe acute pancreatitis (SAP) lung injury (ALI) rats and its possible mechanism.

METHODSSD rats were injected with sodium taurocholate to induce SAP group, and then intervened with sodium tanshinone II A sulfonate ( STS group). Simultaneously a sham-operation group (SO group) was set up. There were 24 rats in each group. The survival state and wet-to-dry weight ratio of lung tissues were observed. Activities of myeloperoxidase (MPO) in lung were determined by MPO reagent kit. Pathologic changes of lung tissues were determined by Hofbuaer method. Expression levels of three cytokines, TNF-alpha, IL-1beta, and intercellular cell adhesion molecule-1 (ICAM-1) were detected by ELISA.

RESULTSThe survival state of rats in the SAP group was deteriorated. The wet-to-dry weight ratio, MPO activities, pathologic changes in lung tissues, and expression levels of TNF-alpha, IL-1beta, and ICAM-1 increased significantly more in the SAP group than in the SO group (P < 0.05). Compared with those in the SAP group, the survival state of rats in the STS group was improved; the wet-to-dry weight ratio, MPO activities, pathologic changes in lung tissues, and expression levels of TNF-alpha, IL-1beta, and ICAM-1 obviously decreased in the STS group (P < 0.05).

CONCLUSIONTanshinone II A had remarkable effect on SPA LI rats, which might be associated with changing cytokines levels and attenuating infiltration of lung inflammatory cells.

Acute Lung Injury ; drug therapy ; Animals ; Cytokines ; metabolism ; Diterpenes, Abietane ; pharmacology ; therapeutic use ; Intercellular Adhesion Molecule-1 ; Interleukin-1beta ; Lung ; Pancreatitis ; drug therapy ; Peroxidase ; Rats ; Rats, Sprague-Dawley ; Taurocholic Acid ; Tumor Necrosis Factor-alpha