ABSTRACT
OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS: Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.
Subject(s)
Acupuncture Therapy , Gastrointestinal Microbiome , Irritable Bowel Syndrome , Moxibustion , Thioctic Acid , Rats , Male , Animals , Irritable Bowel Syndrome/genetics , Irritable Bowel Syndrome/therapy , Moxibustion/methods , Rats, Sprague-Dawley , Lipopolysaccharides , Ubiquinone , Zeatin , Diarrhea/genetics , Diarrhea/therapy , Terpenes , Water , Folic Acid , Acupuncture PointsABSTRACT
Pks13 was identified as a key enzyme involved in the final step of mycolic acid biosynthesis. We previously identified antitubercular coumestans that targeted Pks13-TE, and these compounds exhibited high potency both in vitro and in vivo. However, lead compound 8 presented potential safety concerns because it inhibits the hERG potassium channel in electrophysiology patch-clamp assays (IC50 = 0.52 µM). By comparing the Pks13-TE-compound 8 complex and the ligand-binding pocket of the hERG ion channel, fluoro-substituted and oxazine-containing coumestans were designed and synthesized. Fluoro-substituted compound 23 and oxazine-containing coumestan 32 showed excellent antitubercular activity against both drug-susceptible and drug-resistant Mtb strains (MIC = 0.0039-0.0078 µg/mL) and exhibited limited hERG inhibition (IC50 ≥ 25 µM). Moreover, 32 exhibited improved metabolic stability relative to parent compound 8 while showing favorable bioavailability in mouse models via serum inhibition titration assays.
Subject(s)
Mycobacterium Infections , Mycobacterium tuberculosis , Animals , Antitubercular Agents/chemistry , Coumarins , Ligands , Mice , Microbial Sensitivity Tests , Mycolic Acids/metabolism , Oxazines/metabolism , Polyketide Synthases , Potassium Channels/metabolismABSTRACT
AIMS: To investigate the status of spiritual care competencies among clinical nurses and their relationships with psychological capital. BACKGROUND: Limited knowledge is about the influence of positive personal characteristics on nurses' spiritual care competencies. METHODS: A multicentre cross-sectional study. A total of 1717 nurses were recruited from nine separate Chinese hospitals. Online questionnaires were delivered through a local nursing association to assess socio-demographics, spiritual care competencies and psychological capital of nurses. RESULTS: Nurses had mild-to-moderate levels of spiritual care competencies and moderate levels of psychological capital. Psychological capital and its two metrics (self-efficacy and hope), spiritual care education, professional qualification and shift work were the main predictors of spiritual care competencies (each p < .05). CONCLUSION: The findings of the study show a positive relationship between psychological capital and spiritual care competencies of clinical nurses. Strengthening nurses' psychological capital could improve their spiritual care competencies. IMPLICATIONS FOR NURSING MANAGERS: Nurse managers and hospital administrators should better understand the value of psychological capital for nurses' capacity development. Effective interventions need to be implemented separately or combined with spiritual care education programmes to improve nurses' psychological capital and spiritual care competencies.
Subject(s)
Nurse Administrators , Spiritual Therapies , Cross-Sectional Studies , Humans , Spirituality , Surveys and QuestionnairesABSTRACT
Cisplatin, a commonly used chemotherapy drug, can increase the survival rate of cancer patients. However, it often causes various side effects, including neuronal deficit-induced cognitive impairment. Considering that curcumin is effective in neuronal protection, the action of curcumin on cognitive improvement was evaluated in cisplatin-treated C57BL/6 mice in the present study. Our results first showed that curcumin restored impaired cognitive behaviors. Consistent with this, neurogenesis and synaptogenesis were improved by curcumin. In addition, cisplatin-induced dysfunction of apoptosis-related proteins was partly reversed by curcumin. Moreover, cisplatin-induced autophagy was enhanced by curcumin. Our results also indicated that cisplatin induced autophagy through the endoplasmic reticulum (ER) stress-mediated ATF4-Akt-mTOR signaling pathway. Curcumin activated AMPK-JNK signaling, which mediated both mTOR inhibition and Bcl-2 upregulation and in turn enhanced autophagy and suppressed apoptosis, respectively. In contrast, pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) completely abolished the effects of curcumin on cognitive improvement and improved neurogenesis, synaptogenesis and autophagy. Our results show that cognitive improvement induced by curcumin during chemotherapy is mediated by the enhancement of hippocampal autophagy.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/toxicity , Autophagy/drug effects , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Curcumin/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Autophagy/physiology , Cisplatin/toxicity , Cognitive Dysfunction/pathology , Curcumin/pharmacology , Hippocampus/drug effects , Hippocampus/pathology , Male , Maze Learning/drug effects , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Random AllocationABSTRACT
OBJECTIVE: To evaluate efficacy of traditional Chinese medicine (TCM) for gastric precancerous lesion (GPL). METHOD: Literature retrieval was conducted in seven databases from their inception through Dec. 24th, 2018. The Cochrane collaboration, Review Manager (RevMan5.3) and GRADE profiler software were conducted for this meta-analysis. RESULTS: In primary outcomes, results of meta-analysis showed that TCM had superior to current routine pharmacotherapy (RP) in clinical efficacy, Helicobacter pylori (Hp) eradication rate, efficacy under endoscopy, and TCM syndrome efficacy. Meanwhile, no potential publication bias was detected by Begg's and Egger's tests. In secondary outcomes, compared with control groups, experimental groups were more positive effects on improvement of stomach distention, stomachache, and heartburn. CONCLUSION: Our findings indicated that TCM could have positive effects on GPL. However, further standardized RCTs of rigorous design should be required to obtain more forceful evidence.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Precancerous Conditions/drug therapy , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Chaihu Shugan San (CSS), a traditional Chinese medicine formula, has been used to treat depression for hundreds of years. Recently, the antidepressant-like mechanism of CSS has been increasingly evaluated and demonstrated. However, there are few studies focused on the involvement of the neurotrophic system in mediating the antidepressant-like effects of CSS. Considering the high prevalence of perimenopausal depression around the world, the goal of the present study was to determine whether brain-derived neurotrophic factor (BDNF) signaling is required for the antidepressant-like effects of CSS in perimenopausal depressive-like rats. The results indicate that CSS reverses depressive-like behaviors and attenuates the downregulation of BDNF in the hippocampus of perimenopausal rats exposed to chronic unpredictable mild stress (CUMS). We found that the TrkB antagonist K252 not only blocks the effects of CSS on behavioral improvement but also abolishes the activation of CSS in BDNF-TrkB signaling. As a result, the downstream targets of BDNF signaling, such as the ERK and Akt pathways, are significantly inhibited by K252a. Furthermore, CSS increases hippocampal neurogenesis, while K252a fully prevents this action. In conclusion, the present results demonstrate that the activation of the hippocampal BDNF-TrkB-ERK/Akt signaling pathway is required for the antidepressant-like effects of CSS on the depressive-like state during perimenopause. Additionally, this study also demonstrates that neurogenesis is required for the effects of antidepressants in aging perimenopausal animals and provides fundamental evidence for the clinical application of CSS.
Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Estrous Cycle , Hippocampus/drug effects , Plant Extracts/therapeutic use , Signal Transduction/drug effects , Animals , Brain-Derived Neurotrophic Factor/metabolism , Depression/metabolism , Disease Models, Animal , Female , Hippocampus/metabolism , MAP Kinase Signaling System/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats, Wistar , Receptor, trkB/metabolism , Stress, Psychological/drug therapy , Stress, Psychological/metabolismABSTRACT
AIM: To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS: In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress (WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry (GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS: WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS (days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A (CoA) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways. CONCLUSION: The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism.
Subject(s)
Gastrointestinal Microbiome/physiology , Irritable Bowel Syndrome/metabolism , Metabolome/physiology , Metabolomics/methods , Probiotics/therapeutic use , Animals , Chromatography, Gas/methods , Clostridium butyricum/physiology , Disease Models, Animal , Disease Progression , Feces/chemistry , Female , Humans , Irritable Bowel Syndrome/etiology , Irritable Bowel Syndrome/microbiology , Irritable Bowel Syndrome/therapy , Mass Spectrometry/methods , Mice , Mice, Inbred C57BL , Reproducibility of Results , Sensitivity and Specificity , Stress, Psychological/complications , WaterABSTRACT
Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.
Subject(s)
Antidepressive Agents/pharmacology , Depression/drug therapy , MicroRNAs/antagonists & inhibitors , Animals , Behavior, Animal/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Corticosterone/pharmacology , Depression/metabolism , Disease Models, Animal , Gynostemma , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Mice, Inbred C57BL , Plant Extracts/pharmacology , Protein-Tyrosine Kinases/metabolism , Receptors, Glucocorticoid/metabolism , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Swimming/physiologyABSTRACT
Teng-Long-Bu-Zhong-Tang (TLBZT) is a Chinese herbal formula for colorectal carcinoma treatment. TLBZT effectively induces cell senescence in colorectal carcinoma, accompanied by p21 upregulation. In this study, we further explored the role of p21 in TLBZT-induced cell senescence, as well as the mechanism by which TLBZT upregulates p21. Specific knockdown of p21 expression by small interfering RNA significantly attenuated TLBZT-induced cell senescence in human colorectal carcinoma LS174T cells. Silencing of p53 by small interfering RNA did not affect TLBZT-induced p21 upregulation. Meanwhile, TLBZT inhibited histone deacetylase activity. Furthermore, TLBZT increased acetylation levels of histone H3 and H4, enhancing their binding to the p21 promoter. These data suggested that TLBZT induces cell senescence in LS174T cells through a mechanism involving p21 upregulation via histone H3 and H4 acetylation. This study provides new insights into the application of TLBZT for colorectal carcinoma treatment.
ABSTRACT
Metastasis is one of the primary obstacles to the successful treatment of colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal formula that may be useful in the treatment of metastatic colorectal cancer. The present study evaluated the effects of TLBZT on lung metastasis in human RKO colon carcinoma cells injected into mice via the tail vein. The results demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia-inducible factor 1α. TLBZT also inhibited the expression of integrins αV and ß3 and the phosphorylation of focal adhesion kinase. These results indicate that TLBZT inhibits the lung metastasis of RKO colon carcinoma by regulating the expression of multiple genes. The results of the present study provide a new basis for the management of colorectal cancer metastasis using treatments derived from Chinese herbs.
ABSTRACT
RATIONALE: Gypenosides have been reported to produce neuroprotective effects and increase monoamine neurotransmitter levels in the brain. OBJECTIVE: Considering that depression is involved in monoamine reduction, this study evaluated the antidepressant-like effects of gypenosides in mice exposed to chronic unpredictable mild stress (CUMS). METHODS: The sucrose preference test and forced swimming test were performed after administration of gypenosides (at 25, 50, or 100 mg/kg) for 4 weeks. Hippocampal brain-derived neurotrophic factor (BDNF) and its downstream targets were analyzed by western blot. Additionally, hippocampal neuronal proliferation was measured by immunohistochemistry. RESULTS: Four-week treatment with fluoxetine (20 mg/kg) and gypenosides (at either 50 or 100 mg/kg) increased sucrose preference and decreased the immobility time in mice exposed to CUMS. In addition, gypenosides (at either 50 or 100 mg/kg) also increased BDNF expression and neuronal proliferation in the hippocampus of CUMS animals. Further, we showed that treating CUMS mice with K252a, which is an inhibitor of the BDNF receptor TrkB, blocked the effects of gypenosides (100 mg/kg), including behavioral improvements, neuronal proliferation, and up-regulation of p-TrkB, p-ERK, and p-Akt proteins. CONCLUSIONS: This study demonstrates that gypenosides exhibit antidepressant-like effects in mice, which may be mediated by activation of the BDNF-ERK/Akt signaling pathway in the hippocampus.
Subject(s)
Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/drug effects , Hippocampus/drug effects , Stress, Psychological/metabolism , Animals , Brain-Derived Neurotrophic Factor/metabolism , Carbazoles/pharmacology , Depression , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Extracellular Signal-Regulated MAP Kinases/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Fluoxetine/pharmacology , Gynostemma , Hippocampus/metabolism , Indole Alkaloids/pharmacology , Male , Mice , Phosphorylation/drug effects , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Receptor, trkB/antagonists & inhibitors , Receptor, trkB/drug effects , Receptor, trkB/metabolism , Signal Transduction/drug effects , Stress, Psychological/psychology , Sucrose/administration & dosage , Sweetening Agents/administration & dosage , Swimming , Up-Regulation/drug effectsABSTRACT
Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Drugs, Chinese Herbal/therapeutic use , Liver Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Apoptosis , Autophagy , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cellular Senescence , Drugs, Chinese Herbal/chemistry , Epithelial-Mesenchymal Transition/drug effects , HumansABSTRACT
Traditional Chinese medicine (TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency and other TCM syndromes (Zheng). Modern treatments such as surgery, transarterial chemoembolization (TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma.
ABSTRACT
The concentration alteration of cytosolic-free calcium ([Ca(2+) ]cyt ) is a well-known secondary messenger in plants and plays important roles during pollen grain germination and tube elongation. Here we demonstrate that CML25, a member of calmodulin-like proteins, has Ca(2+) -binding activity and plays a role in pollen grain germination, tube elongation and seed setting. CML25 transcript was abundant in mature pollen grains and pollen tubes, and its product CML25 protein was primarily directed to the cytoplasm. Two independent CML25 loss-of-function T-DNA insertion mutants suffered a major reduction in both the rate of pollen germination and the elongation of the pollen tube. Also, pollen grains of cml25 mutants were less sensitive to the external K(+) and Ca(2+) concentration than wild-type pollen. The disruption of CML25 increased the [Ca(2+) ]cyt in both the pollen grain and the pollen tube, which in turn impaired the Ca(2+) -dependent inhibition of whole-cell inward K(+) currents in protoplasts prepared from these materials (pollen grain and pollen tube). Complementation of cml25-1 mutant resulted in the recovery of wild-type phenotype. Our findings indicate that CML25 is an important transducer in the Ca(2+) -mediated regulation of K(+) influx during pollen germination and tube elongation.
Subject(s)
Arabidopsis Proteins/physiology , Arabidopsis/metabolism , Calcium-Binding Proteins/physiology , Calcium/metabolism , Potassium/metabolism , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Biological Transport , Calcium Signaling , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Calmodulin/genetics , Calmodulin/metabolism , Calmodulin/physiology , Germination , Pollen/growth & development , Pollen/metabolism , Pollen Tube/growth & development , Pollen Tube/metabolismABSTRACT
Nü-zhen-zi, the fruit of Ligustrum lucidum Ait., is one of the most frequently used liver Yin tonifying Chinese herbs for the treatment of liver cancer. However, the effect of Ligustrum lucidum fruit on hepatocarcinoma cells remains unknown. In the present study, we evaluated the effects of a Ligustrum lucidum fruit extract (LLFE) on human hepatocellular carcinoma Bel-7402 cells. The results showed that LLFE inhibited the proliferation of the Bel-7402 cells in a dose- and time-dependent manner. LLFE induced apoptosis in Bel-7402 cells accompanied by activation of caspase-3, -8 and -9. LLFE-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. LLFE treatment also caused a large and flat morphologic cellular change, positive SA-ß-gal staining, and G0/G1 phase cell cycle arrest in the Bel-7402 cells, accompanied by upregulation of p21 and downregulation of RB phosphorylation. Specific knockdown of p21 expression by RNA interference partially abrogated LLFE-induced apoptosis, and significantly abrogated LLFE-induced cell senescence. These observations suggest that Nü-zhen-zi is a potential anticancer herb and support the traditional use of Nü-zhen-zi for hepatocarcinoma treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/genetics , Ligustrum/chemistry , Liver Neoplasms/genetics , Plant Extracts/pharmacology , Amino Acid Chloromethyl Ketones/pharmacology , Apoptosis/drug effects , Caspase Inhibitors/pharmacology , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p21/genetics , HumansABSTRACT
OBJECTIVE: To observe effects of cold- and hot-property herbs and effects of hot and cold constitutions on the tumor growth of tumor bearing rats, and to observe the effect of Cinobufacini Injection (CI) on the tumor growth of tumor bearing rats of different constitutions. METHODS: Eighty healthy male Wistar rats were randomly divided into eight groups, i.e., the tumor bearing control group, the tumor bearing heat syndrome group, the tumor bearing cold syndrome group, the heat syndrome tumor bearing group, the cold syndrome tumor bearing group, the tumor bearing CI group, the heat syndrome tumor bearing CI group, and the cold syndrome tumor bearing CI group, respectively. The weight and volume of rats' subcutaneous tumor were measured 14 days after tumor inoculation. RESULTS: The weight and volume of tumor in the heat syndrome tumor bearing CI group [(3.55 +/- 1.12) g, (2864.44 +/- 1430.51) mm3] and the tumor bearing CI group [(4.29 +/- 1.14) g, (3397.19 +/- 1701.13) mm3] were significantly lower than those of the tumor bearing control group [(6.01 +/- 2.45) g, (6218.91 +/- 3837.64) mm3] and the cold syndrome tumor bearing CI group [(6.90 +/- 1.57) g, (6168.42 +/- 2457.03) mm3], showing statistical difference (P<0.05). There was insignificant difference among other groups. CONCLUSIONS: CI showed better tumor inhibition effects on tumor bearing rats of heat syndrome constitution, which indicated CI was of cold property. It might be possibly used in tumor bearing rats of heat syndrome constitution.
Subject(s)
Bufanolides/pharmacology , Neoplasms, Experimental/pathology , Animals , Bufanolides/therapeutic use , Injections , Male , Neoplasms, Experimental/drug therapy , Rats , Rats, WistarABSTRACT
OBJECTIVE: To observe the effects of cinobufacini injection on serum levels of thyroid-stimulating hormone (TSH) and adrenaline (ADR) in rats, and to speculate the property (cold or heat) of the drug. METHODS: Thirty-two male Wistar rats were randomly divided into normal control group, cinobufacini injection group, cold syndrome group and heat syndrome group. The rats in the four groups were administered with normal saline, cinobufacini injection, and compound of traditional Chinese drugs with heat or cold property. The weights, and the serum TSH and ADR levels of the rats were measured before and after the interventions. RESULTS: The weights of the rats in heat syndrome group markedly decreased after 14-day administration when compared with the normal control group (P < 0.05). There were no significant differences among the normal control group, heat syndrome group and the cinobufacini injection group. Although no statistical difference was noted, the serum TSH levels of the cold syndrome group and cinobufacini injection group were slightly lower than that in the normal control group after 14-day administration, and the heat syndrome group showed a slightly higher serum TSH level. After administration, the serum ADR levels of the cold syndrome group and cinobufacini injection group were significantly lower than that in the normal control group (P < 0.05), and the serum ADR level in the heat syndrome group was higher than that in the normal control group (P < 0.05). CONCLUSION: Cinobufacini injection seemed to be able to suppress the thyrotrophin-releasing hormone-TSH-thyroxine system and sympathetic nervous system, matching up with the characteristics of the Chinese herbs of cold property. And the study provided initial experiment evidence for the conclusion that the property of cinobufacini might be cold.