Background: Nowadays, acute alcoholic intoxication has become the third public problem in China, and the anti-inebriation products mainly aimed at increasing the activity of enzyme involved in the alcohol metabolism, which is a single mechanism that can accelerate alcohol metabolism. Thus, a new formula, Jiujiuguiyi (JJGY) which could protect liver, relieve the abnormal excitability of the center and improve muscle retardation at the same time is designed by us. Methods: The model of acute alcoholic intoxication was established by intragastric administration with 0.12 ml/10g 50% alcohol in mice. JJGY was orally administrated (gavage) once a day for 20 consecutive days before the establishment of acute alcoholic model. Mice were randomly divided into 8 groups with 8 each: blank control group (CON), model group (M), Haiwangjinzun positive control group (HWJZ), experimental groups (AL, AH, BL, BH, AB). Giant, crawling time on the rota-rod, the activities of aspartate amino trans- ferase (AST), alanine amino transferase (ALT) and superoxide dismutase (SOD) in both liver and serum, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), glutathione peroxidase (GSH-PX) in liver as well as the HE staining of liver slices, the formation of malondialdehyde (MDA) in serum were determined after acute alcoholic intoxication. Results: Compared with model group, JJGY significantly decreased the AST and ALT activity in liver and serum and MDA activity in serum. Meanwhile, it enhanced the ADH and ALDH level in liver as well as the hepatic and serous SOD activity, indicating more efficient metabolism of alcohol and less hepatic injury. HE staining results also proved that JJGY could reduce alcoholic liver cell injury, and the effect was more obvious in the group medicated before alcohol administration. Moreover, JJGY significantly prolonged the crawling time on the rota-rod and improved the gait of mice and the effect was proved to be better than the widely used health product Haiwangjinzun. Conclusions: This study suggests that JJGY is able to protect liver, relieve the abnormal excitability of the center and improve muscle retardation after acute alcoholic intoxication. Its liver protection effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.
In the present study, a new compound Chinese herbal medicine formula, Jiujiuguiyi, was designed by using the medicine and food homology theory. The formula aims at protecting liver, relieving the abnormal excitability of the center and improving muscle retardation at the same time. Acute alcoholic intoxication model in mice was built, then the ethology test and biochemical test were conducted to exam the efficacy of the formula in different preparations. The results suggest that JJGY can protect the acute alcoholic intoxication mice through multiple mechanisms, providing a new way to develop antialcoholismic drug homologous food.
Emerging evidence has demonstrated that Tanshinone IIA (Tan IIA) prevents cardiomyocytes injury, cardiac fibroblasts and atherosclerosis. However, the molecular mechanism underlying the effects of Tan IIA is still unclear. To investigate the role of Tan IIA in inflammatory response in a ROS-NLRP3 inflammasome dependent manner, RAW264.7 cells stimulated with LPS were recruited to produce a cell model of inflammatory response. Our results indicated that the production of NO was significantly increased after stimulated by LPS, and Tan IIA treated significantly decreased the level of NO. The mRNA expression of NLRP3, IL-1β and TNF-α was significantly inhibited by Tan IIA compared with LPS treated cells. The protein expression of NLRP3, IKBα, pp65/p65 and pp38/p38 was significantly decreased by Tan IIA, compared with LPS or LPS+ATP stimulated groups. Meanwhile, Tan IIA significantly inhibited the level of ROS induced by LPS+ATP. And NAC, a ROS inhibitor, could also inhibit the protein expression of NLRP3. Based on these findings, it could be speculated that the mechanism underlying the effect of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.
Tan IIA could inhibit the inflammatory response and NLRP3 expression stimulated by LPS or LPS+ATP. Acetylcysteine (N-acetyl-l-cysteine, NAC), a ROS inhibitor, could inhibit LPS+ATP-induced increase in NLRP3 level. The mechanism underlying the effects of Tan IIA may involve the regulation of ROS-NF-κB/ P38-NLRP3 pathway. This study further characterized the molecular mechanism of Tan IIA, and provided new thoughts to its clinical therapy.
In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells （BMNC）was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P < 0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.
Acquired deletions of mtDNA and abnormal mitochondrial function are crucial reasons in some blood disease include aplastic anemia. Angelica sinensis helps in tonifying the blood and promoting its circulation via anti-oxidative and neuroprotective effects. In this paper, we demonstrated that Angelica sinensis polysaccharide can improve improve the mitochondrial ultrastructure, and suppress the downregulation of transmembrane potential and apoptosis of myeloid element to cure bone marrow failure.
Quality marker (Q-marker) of Chinese materia medica (CMM) plays an important role in quality control of CMM products. However, its research strategy and technique remain unclear. Based on the fact that quality standard of CMM should be associated with clinical efficacy, taking Jinqi Jiangtang tablet treating type 2 diabetes as an example, the Q-marker related to activity via the reverse analysis of drug metabolism in clinic and traceability of botanic biosynthetic pathways is discovered and validated. Therefore, we proposed a new research strategy of Q-marker of CMM with "Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", to improve quality control of CMM products.
Highlights: "Discovery of clinical active constituents as guidance, Reverse analysis of metabolic transformations as link, and Traceability of biosynthesis pathways as key", a new research strategy for discovering quality marker of Chinese materia medica (CMM), promotes quality standard of CMM.
Objective: To investigate the effect of Dingjifumai Decoction (DJFM) on Electrocardiogram (ECG) and sodium potassium pump in rats with ventricular arrhythmia. Methods: Forty healthy male SD rats (200 ± 20g) were randomly divided into blank group, model group, Metoprolol group and DJFM group. Ten rats in each group were fed with normal diet and free drinking water. Each group was given gavage, and the amount of gavage in each group was calculated according to body weight. In the model group, 0.001% Aconitine was injected into the tail vein at 30ug/kg. In the Metoprolol group, Metoprolol suspension was given according to the standard of 5.2mg/kg per day. In the DJFM group, DJFM was given at 17.6g/kg per day. After 2 weeks of administration, the biologic experiment system BL-420F was used to monitor the II lead ECG curve, and the ECG changes were observed and recorded. Then, the left ventricle of the rat was taken, and part of the heart tissue sodium potassium pump was detected. Results: (1) The effect of DJFM on ECG of rats with ventricular arrhythmia: After intravenous injection of aconitine, the incidence of Ventricular Premature beat (VP), Ventricular Tachycardia (VT), Ventricular Fibrillation (VF) in the model group was 100%, suggesting that the model building of rats with ventricular arrhythmia was successful. (2) VP, VT, and VF time: Compared with model group, DJFM group and Metoprolol group can significantly delay the VP, VT and VF, the difference was statistically significant (P < 0.05). The effect of DJFM group and Metoprolol group on delaying the appearance of VP, VT and VF was the same, there was no significant difference (P > 0.05). (3) The effect of DJFM on sodium potassium pump in rat ventricular arrhythmia heart tissues: Compared with the blank group, the sodium potassium pump value in the model group was significantly decreased, and the difference was statistically significant (P < 0.05). Compared with the model group, the sodium potassium pump value of the tissues in the Metoprolol group and the DJFM group increased, and the difference was statistically significant (P < 0.05). There was no significant difference in sodium potassium pump between the Metoprolol group and the DJFM group (P > 0.05). Conclusion: 1. The rat model of ventricular arrhythmia can be successfully prepared by intravenous injection of Aconitine. 2. DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. 3. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism.
Highlights In this study, the effects of Dingjifumai Decoction (DJFM) on Electrocardiogram and sodium potassium pump of rats with ventricular arrhythmia were observed, and the effects and mechanism of DJFM on ventricular arrhythmia were discussed. We found that DJFM can prolong the occurrence time of cardiac arrhythmias caused by aconitine in rats, such as VP, VT, VF, et al. The mechanism may be related to fast Na+ channel, and it may prevent and control arrhythmias by inhibiting Na+ influx and reducing the fast response cellular self-discipline. DJFM can protect the myocardial tissue sodium potassium pump, which can protect the myocardial cells and improve the myocardial metabolism
The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.
The research on the dose-effect relationship in Chinese materia medica was delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. However, there are more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. This paper aimed to present the current basic situation.
As a chronic disease that seriously endangers public health, the number of coronary heart disease (CHD) patients in China has increased in recent years. There is great potentiality to integrate traditional Chinese and Western medicine therapies to prevent and treat CHD in clinical practice. However, most of the current integrated therapies still lack sufficient high-quality evidence, and the key links in how to apply are unclear. It is urgent to optimize them through evidence-based research to further improve the effectiveness. Therefore, we propose strategies to conduct evidence-based optimization of integrated traditional Chinese and Western medicine therapies in prevention and treatment of progressive cardiovascular diseases. These are integrated clinical trial design, attention to the key links of taking effect, combination of clinical and basic research. Based on the strategies, we started the national key research and development project "Evidence-based optimization research of TCM therapies in prevention and treatment of CHD (angina pectoris - myocardial infarction - heart failure)", which is expected to be a new paradigm in the field.
Objective: (+)-Clausenamide ((+)-CLA), the active ingredient of wampee, was isolated from the leaves of Clausena lansium (Lour.) Skeels. This study aimed to evaluate the protective potential of (+)-CLA against acetaminophen (APAP)-induced nephrotoxicity in mice. Methods: Mice were divided into control, APAP, high-dose (+)-CLA, and low-dose (+)-CLA groups. Then, mice were preadministered (+)-CLA (50 and 100 mg/kg) for 5 consecutive days. After the last treatment, the animals received a single intraperitoneal injection of APAP (600 mg/kg). Renal histopathology was evaluated by staining with hematoxylin and eosin. The levels of malondialdehyde (MDA) and glutathione (GSH) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined using corresponding kits. Western blotting was used to analyze the expression of apoptosis-related proteins in renal tissue. Results: Administration of APAP increased serum creatinine and blood urea nitrogen levels in comparison with the control group. An increase in renal MDA level, depletion of GSH, and reductions in CAT and SOD activities in renal tissue indicated that APAP-induced kidney injury was mediated by oxidative stress. The expressions of Bax and caspase-3, cleavage of caspase-3, and cytoplasm cytochrome c levels were up-regulated in renal tissue, whereas Bcl-2 expression and mitochondrial cytochrome c levels were down-regulated in the APAP group, which revealed that APAP-induced kidney injury significantly increased cell apoptosis in renal tubules. The histopathology of kidney tissue supported these biochemical mechanisms. (+)-CLA can reverse changes in most of the abovementioned parameters and nearly restore the normal structure of the kidney. Conclusion: Oxidative stress and apoptosis are considered to be the mechanisms underlying APAP-induced nephrotoxicity. (+)-CLA could be a promising antidote for APAP-induced acute renal damage owing to its antioxidative and antiapoptotic effects.
(+)-Clausenamide ((+)-CLA), an acid amide isolated from the leaves of Clausena lansium (Lour.) Skeels, significantly decreases creatinine and blood urea nitrogen levels and increases the antioxidative abilities. The underlying mechanisms of (+)-CLA were involved in improving the antioxidative and antiapoptotic effects. This study provides a basis to clinical application of (+)-CLA.
Objective: Yes Associated Protein (YAP) is a downstream effector that negatively regulated by Hippo kinase LATS1/2. As a transcriptional coactivator, YAP controls the transactivation of variety target genes to promote cell proliferation which is a critical survival input for cancer cells, thus the inhibition of YAP function is a promising strategy to treat cancer patients. The aim of this study was to explore YAP inhibitors derived from natural products using a cell-based YAP-TEADs luciferase reporter assay and investigate the functional activities of the novel inhibitor. Methods: natural compounds were used by 8×GTIIC luciferase reporter assay to screen YAP inhibitor. Phosphorylation of YAP and AMPK were detected by Western Blotting. The target genes of YAP were determined through RT-PCR. Inhibition on HepG2 cells of screened compounds were assessed by the Sulforhodamine B (SRB) assay. Results: we found that Shikonin (derived from the traditional Chinese medical herb Zicao (Lithospermum erythrorhizon)) exerted significant suppression against the transcriptional activity of YAP (inhibition ratio=74.3%), accompanied with increased phosphorylation of YAP protein upon within short-exposure to cancer cells. Shikonin treated on HepG2 induced phosphorylation of AMPK. In HepG2 cell lines, Shikonin exhibited a profound cytotoxicity in a concentration manner. Conclusion: our results indicated that the inhibition activity of Shikonin on YAP function was probably due to the activation of AMPK by phosphorylation. Moreover, Shikonin exhibited potent cytotoxicity on cancer cells. In summary, the present study identifies Shikonin as a novel natural inhibitor of YAP function and could be an anti-cancer drug candidate for cancer treatment.
Aberrant activation of YAP, a transcriptional co-activator, would result in the transactivation of target genes, and ultimately leading to the tumor development and malignance. Thus YAP has been regarded as a promising target for cancer therapy; however it has been challenged by the lack of effective inhibitors against YAP activity, particularly those origins from the natural resources. The current study identifies Shikonin, a natural compound derived from the traditional Chinese medical herb Zicao (Lithospermum erythrorhizon), as a potent inhibitor against YAP pathway so as to exert anti-cancer activities. And the YAP inhibitory effect was probably due to the activation of AMPK pathway.
Objective: To investigate the neuroprotective effect of Bu-Shen-Huo-Xue (BSHX) extract, a polyherbal formula, against High Glucose (HG)-induced neurotoxicity in PC12 cells. Methods: Cell viability assay, Lactate Dehydrogenase (LDH) assay, Reactive Oxygen Species (ROS) detection, Hoechst 33258, Acridine Orange (AO)/Ethidium Bromide (EB) double stain and Mitochondrial Membrane Potential (MMP) assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases (MAPKs) were detected by western blot. Results: BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 MAPKs. Conclusion: BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.
High glucose (HG)-induced neurotoxicity is implicated in the pathology of diabetic encephalopathy (DE). In our study, Bu-Shen-Huo-Xue extract (BSHX), a polyherbal formula, exhibits neuroprotective activity on HG-induced PC12 cells and the possible mechanisms may be associated with the suppression of reactive oxygen species (ROS) generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways. This study provids a promising agent for the treatment of DE in clinical applications.
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