Integration of pharmacodynamics and metabolomics to reveal rhubarb anthraquinone protection against nonalcoholic fatty liver disease rat model.

OBJECTIVES: The objective of the present study was to investigate the effect of Rhubarb anthraquinone (RA) on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) rat model, and explore potential biomarker and metabolic pathways by using the metabolomics method. MATERIALS AND METHODS: We established HFD rats as the NAFLD model. Forty Sprague-Dawley rats were randomly divided into a control group, model group, RA low-dose group, RA medium-dose group, and RA high-dose group, and evaluated the protective effect of RA on NAFLD by detecting biochemical indicators of serum and pathological changes of liver tissue. Investigating potential biomarkers and metabolic pathways connected with RA's protective effects against NAFLD by UHPLC-Q-TOF-MS untargeted metabolomics. RESULTS: The results showed that RA significantly reversed the increase of TG, TC, ALT, AST, and ALP (P < .05), the decrease of HDL-C (P < .05), and alleviated pathological conditions in NAFLD rats. Based on potential biomarker analysis, RA affected metabolic pathways such as fatty acids biosynthesis, bile acids biosynthesis, and pentose phosphate pathway, delaying the progression of NAFLD. CONCLUSION: RA improved blood lipid levels, liver function, and pathological conditions of NAFLD rats. Meanwhile, affected the metabolic pathways and regulated the synthesis of fatty acids and bile acids in NAFLD rats.

Protective mechanism of Paeonol on central nervous system.

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.

Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats.

BACKGROUND AND OBJECTIVES: Rhubarb anthraquinones contain five main components, that is, rhein, emodin, aloe-emodin, chrysophanol, and physcion, which demonstrate good therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, research on its pharmacokinetics in NAFLD remains lacking. This study aimed to investigate the pharmacokinetic differences of rhubarb anthraquinones in normal and NAFLD rats. METHODS: This study developed an NAFLD rat model by high-fat diet feeding for 6 weeks. Normal and NAFLD groups were orally administered different rhubarb anthraquinones doses (37.5, 75, and 150 mg/kg). The concentration of the rhein, emodin, aloe-emodin, chrysophanol, and physcion in plasma was determined by high-performance liquid chromatography-ultraviolet. RESULTS: The results revealed significant differences in pharmacokinetic behavior between normal and NAFLD rats. Compared with normal rats, NAFLD rats demonstrated significantly increased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0 → ∞) of rhubarb anthraquinones (P < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (Tmax), terminal elimination half-life (t1/2), and mean residence time (MRT) of rhubarb anthraquinones (P < 0.05). CONCLUSIONS: This study indicates significant differences in the pharmacokinetics of rhubarb anthraquinones between the physiological and NAFLD states of rats. Rhubarb anthraquinone demonstrated a longer retention time and slower absorption rate in NAFLD rats and exhibited higher bioavailability and peak concentration. This finding provides important information for guiding the clinical use of rhubarb anthraquinones under pathological conditions.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. AIM OF THE STUDY: The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. METHODS: First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. RESULTS: A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. CONCLUSION: By combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

The protective effect of forsythiaside A on 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestatic liver injury in mice: Based on targeted metabolomics and molecular biology technology.

Cholestasis is a disorder of bile secretion and excretion caused by a variety of etiologies. At present, there is a lack of functional foods or drugs that can be used for intervention. Forsythiaside A (FTA) is a natural phytochemical component isolated from the medicinal plant Forsythia suspensa (Thunb.) Vahl, which has a significant hepatoprotective effect. In this study, we investigated whether FTA could alleviate liver injury induced by cholestasis. In vitro, FTA reversed the decrease in viability of human intrahepatic bile duct epithelial cells, the decrease in antioxidant enzymes (SOD1, CAT and GSH-Px), and cell apoptosis induced by lithocholic acid. In vivo, FTA protected mice from 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury, abnormal serum biochemical indexes, abnormal bile duct hyperplasia, and inflammatory infiltration. Furthermore, FTA treatment alleviated liver fibrosis by inhibiting collagen deposition and HSC activation. The metabonomic results showed that DDC-induced bile acid disorders in the liver and serum were reversed after FTA treatment, which may benefit from the activation of the FXR/BSEP axis. In addition, FTA treatment increased the levels of antioxidant enzymes in the serum and liver. Meanwhile, FTA treatment inhibited ROS and MDA levels and cleaved caspase 3 protein expression, thereby reducing DDC-induced hepatic oxidative stress and apoptosis. Further studies showed that the antioxidant effects of FTA were dependent on the activation of the BRG1/NRF2/HO-1 axis. In a word, FTA has a significant hepatoprotective effect on cholestatic liver injury, and can be further developed as a functional food or drug to prevent and treat cholestatic liver injury.

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking.

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p-NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.

Celastrol as an emerging anticancer agent: Current status, challenges and therapeutic strategies.

Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicine Tripterygium wilfordii Hook F., which has multiple pharmacological activities. In particular, modern pharmacological studies have demonstrated that celastrol exhibits significant broad-spectrum anticancer activities in the treatment of a variety of cancers, including lung cancer, liver cancer, colorectal cancer, hematological malignancies, gastric cancer, prostate cancer, renal carcinoma, breast cancer, bone tumor, brain tumor, cervical cancer, and ovarian cancer. Therefore, by searching the databases of PubMed, Web of Science, ScienceDirect and CNKI, this review comprehensively summarizes the molecular mechanisms of the anticancer effects of celastrol. According to the data, the anticancer effects of celastrol can be mediated by inhibiting tumor cell proliferation, migration and invasion, inducing cell apoptosis, suppressing autophagy, hindering angiogenesis and inhibiting tumor metastasis. More importantly, PI3K/Akt/mTOR, Bcl-2/Bax-caspase 9/3, EGFR, ROS/JNK, NF-κB, STAT3, JNK/Nrf2/HO-1, VEGF, AR/miR-101, HSF1-LKB1-AMPKα-YAP, Wnt/ß-catenin and CIP2A/c-MYC signaling pathways are considered as important molecular targets for the anticancer effects of celastrol. Subsequently, studies of its toxicity and pharmacokinetic properties showed that celastrol has some adverse effects, low oral bioavailability and a narrow therapeutic window. In addition, the current challenges of celastrol and the corresponding therapeutic strategies are also discussed, thus providing a theoretical basis for the development and application of celastrol in the clinic.

Nephroprotective and nephrotoxic effects of Rhubarb and their molecular mechanisms.

Rhubarb, in the form of a traditional Chinese medicine, is used in the treatment of chronic kidney disease (CKD). Previous studies have demonstrated that Rhubarb possesses a good nephroprotective effect, which primarily protects the kidneys from fibrosis, oxidation, inflammation, autophagy, and apoptosis. However, studies have shown that the long-term inappropriate use of Rhubarb may cause damage to renal function. Therefore, how to correctly understand and scientifically evaluate the pharmacodynamics and toxicity of Rhubarb with regard to CKD is a scientific question that urgently needs to be answered. In this review, we explain and illustrate how Rhubarb exerts its nephroprotective effect against CKD. We also describe the mechanisms of action that may cause its nephrotoxicity. Valuable and practical clinical guidance is proposed with regard to methods for mitigating the nephrotoxicity of Rhubarb.

Quercetin alleviates ethanol-induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy.

This study aimed to investigate the therapeutic effect of quercetin on ethanol-induced hepatic steatosis in L02 cells and elucidate the potential mechanism. In brief, L02 cells were pretreated with or without ethanol (3%) for 24 h, then treated quercetin (80, 40, 20 µM) for 24 h. The transfection procedure was performed with transcription factor EB (TFEB) small interfering RNA (siRNA TFEB) for 24 h. Our results showed that quercetin autophagic flux in the L02 cells, via upregulating of microtubule associated protein light chain 3B (LC3-II) and lysosome-associated membrane protein 1 (LAMP1), then downregulating of protein sequestosome 1 (SQSTM1/p62). Mechanistically, quercetin activated TFEB nuclear translocation, contributing to lysosomal biogenesis and autophagic activation. Accordingly, the genetic inhibition of TFEB-dependent autophagy decreased ethanol-induced fat accumulation in L02 cells via regulating fatty acid ß oxidation and lipid synthesis. Subsequently, quercetin-induced TFEB-dependent autophagic activation was also linked to inhibit oxidative stress via suppressing reactive oxygen species (ROS), enhancing activities of antioxidant enzymes, and promoting nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) translocation. Thus, we uncovered a novel protective mechanism against ethanol-induced hepatic steatosis and oxidative stress through TFEB-mediated lysosomal biogenesis and discovered insufficient autophagy as a novel previously unappreciated autophagic flux.

Knowledge about, attitude and acceptance towards, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China: A cross-sectional survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has had a serious impact on health all over the world. Cancer patient, whose immunity is often compromised, faces a huge challenge. Currently, some COVID-19 vaccines are being developed and applied on general population; however, whether cancer patients should take COVID-19 vaccine remains unknown. Our study aimed to explore the knowledge, attitude, acceptance, and predictors of intention to receive the COVID-19 vaccine among cancer patients in Eastern China. METHODS: A cross-sectional study was conducted in Eastern China from June 17th to September 3rd, 2021. Patients were selected using a convenience sampling method. A self-report questionnaire was developed to assess knowledge about the COVID-19 vaccine, attitude towards the vaccine and acceptance of the vaccine; following a review of similar studies previously published in the scientific literature, multivariate logistic regression analysis was used to determine the predictors associated with COVID-19 vaccine acceptance. RESULTS: A total of 2158 cancer patients were enrolled in this study. The rate of vaccine hesitancy was 24.05% (519/2158); further, among the participants of vaccine acceptance, 767 had taken COVID-19 vaccine (35.54%), and 872 were willing to get vaccinated (40.01%). A total of 24 variables including demographic characteristics, clinical status of cancer, impact of COVID-19 pandemic on study participants, patients' knowledge about the COVID-19 vaccine, and attitude towards the vaccine, had significant differences between the "vaccine hesitancy" population and "vaccine acceptance" population. Multivariate logistic regression analysis indicated that parameters including alcohol consumption (odds ratio [OR] = 1.849; 95% confidence interval [CI]: 1.375-2.488; P-reference [P-Ref] < 0.001 vs non-drinkers), income impacted by COVID-19 pandemic (OR = 1.930, 2.037 and 2.688 for mild, moderate, and severe impact, respectively; all P-Ref < 0.01 vs no impact), knowledge of how the vaccine was developed (OR = 1.616; 95% CI: 1.126-2.318; P-Ref = 0.009 vs unknown), believing in the safety of the vaccine (OR = 1.502; 95% CI: 1.024-2.203; P-Ref = 0.038 vs denying the safety of vaccine), willingness to pay for the vaccine (OR = 3.042; 95% CI: 2.376-3.894; P-Ref < 0.001 vs unwilling), and willingness to recommend families and friends to get vaccinated (OR = 2.744; 95% CI: 1.759-4.280; P-Ref < 0.001 vs do not recommend) were contributors to vaccine acceptance. While such as being retired (OR = 0.586; 95% CI: 0.438-0.784; P-Ref < 0.001 vs unemployed), undergoing multiple therapies of cancer (OR = 0.408; 95% CI: 0.221-0.753; P-Ref = 0.004 vs no ongoing treatment), and worrying that the vaccine might deteriorate the prognosis of cancer (OR = 0.393; 95% CI: 0.307-0.504; P-Ref < 0.001 vs might not) were contributors to vaccine hesitancy. CONCLUSION: This study provided preliminary estimates of the rates of vaccine acceptance and vaccine hesitancy among cancer patients in Eastern China. The intention to receive the COVID-19 vaccine was impacted by factors such as patient occupation, alcohol consumption, and some parts of knowledge about and attitude towards COVID-19 vaccine. It is recommended to develop individualized vaccination plans that meet the healthcare needs of cancer patients.

Synthesis of pterodontic acid derivatives and the study of their anti-influenza A virus (H1N1) activity.

Laggera pterodonta (DC.) Benth, a folk herb widely distributes in southwest China, especially in Yunnan Province, demonstrates anti-pathogenic microorganisms, anti-inflammatory, inhibition of Helicobacter pylori activities in vitro et al. Interestingly, previous studies have shown that pterodontic acid (1), a eudesmane-type sesquiterpene isolated from L. pterodonta (DC.), displays excellent selective antiviral activity to H1N1 subtype of influenza A virus. At the same time, our group also discovered that the antiviral activity of 1 was relatively close to that activity of post-marketed ribavirin. Therefore, we consider that the synthesis of pterodontic acid (1) derivatives and evaluation of their anti-influenza A virus (H1N1) activities is of potential clinical significance. In this manuscript, a series of pterodontic acid derivatives were prepared and demonstrated significantly improved anti-influenza A virus (H1N1) activities, providing more opportunities for the treatment of respiratory viral diseases.

Uncaria rhynchophylla ameliorates unpredictable chronic mild stress-induced depression in mice via activating 5-HT1A receptor: Insights from transcriptomics.

BACKGROUND: Depression is a pervasive or persistent mental disorder that causes mood, cognitive and memory deficits. Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history, although its efficacy and potential mechanism are still uncertain. PURPOSE: The present study aimed to investigate anti-depression effect and potential mechanism of U. rhynchophylla extract (URE). STUDY DESIGN AND METHODS: A mouse depression model was established using unpredictable chronic mild stress (UCMS). Effects of URE on depression-like behaviours, neurotransmitters, and neuroendocrine hormones were investigated in UCMS-induced mice. The potential target of URE was analyzed by transcriptomics and bioinformatics methods and validated by RT-PCR and Western blot. The agonistic effect on 5-HT1A receptor was assayed by dual-luciferase reporter system. RESULTS: URE ameliorated depression-like behaviours, and modulated levels of neurotransmitters and neuroendocrine hormones, including 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), corticosterone (CORT), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH), in UCMS-induced mice. Transcriptomics and bioinformatics results indicated that URE could regulate glutamatergic, cholinergic, serotonergic, and GABAergic systems, especially neuroactive ligand-receptor and cAMP signaling pathways, revealing that Htr1a encoding 5-HT1A receptor was a potential target of URE. The expression levels of downstream proteins of 5-HT1A signaling pathway 5-HT1A, CREB, BDNF, and PKA were increased in UCMS-induced mice after URE administration, and URE also displayed an agonistic effect against 5-HT1A receptor with an EC50 value of 17.42 µg/ml. CONCLUSION: U. rhynchophylla ameliorated depression-like behaviours in UCMS-induced mice through activating 5-HT1A receptor.

[Effect of herbal cake-partitioned moxibustion on renal function and expression of renal connective tissue growth factor, integrin-linked kinase and bone morphogenetic protein-7 in chronic renal failure rabbits].

OBJECTIVE: To observe the effect of herbal cake-partitioned moxibustion on renal function and expression of connective tissue growth factor (CTGF), integrin-linked kinase (ILK) and bone morphogenetic protein-7 (BMP-7) in chronic renal failure (CRF) rabbits, so as to reveal its mechanisms underlying improvement of CRF. METHODS: Twenty-four male New Zealand rabbits were randomly divided into control, model, medication and herbal cake-partitioned moxibustion (moxibustion) groups (n=6 rabbits in each group). The CRF model was established by gavage of suspension of Adenine (150 mg·kg-1·d-1) for 21 days. Herbal cake-partitioned moxibustion was applied to "Mingmen"(GV4) and bilateral "Shenshu"(BL23), "Pishu"(BL20) and for 5 moxa-cones every time. Rabbits of the medication group was treated by gavage of Losartan Potassium (2.33 mg·kg-1·d-1). All the treatments were conducted once daily,12 times a course for consecutive 3 courses with a two-day rest after each course of treatment. Serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urine protein contents were detected by using an automatic biochemical analyzer. The expression levels of CTGF, ILK and BMP-7 proteins and mRNA in the kidney tissue were determined by Western blot and quantitative real time-PCR, separately. RESULTS: Following modeling, Scr and BUN and 24 h urine protein contents were significantly increased in the model group in comparison with the control group (P<0.01). After the intervention, Scr and BUN contents were all significantly decreased in both the moxibustion and medication groups relevant to the model group (P<0.01), suggesting an improvement of the renal function. Compared with the control group, the expression levels of ILK and CTGF mRNAs and proteins were obviously up-regulated (P<0.01), and those of BMP-7 mRNA and protein significantly decreased in the model group (P<0.01). In comparison with the model group, the expression levels of ILK and CTGF mRNAs and proteins were significantly down-regulated in the two treatment groups (P<0.01, P<0.05), and those of BMP-7 mRNA and protein markedly increased in the two treatment groups (P<0.01). In comparison with the medication group, the expression level of ILK protein was significantly up-regulated (P<0.01) and BMP-7 protein was significantly down-regulated (P<0.01) in the moxibustion group. No significant differences were found between the medication and moxibustion groups in down-regulating the levels of Scr, BUN and 24 h urine protein and expression of ILK mRNA, CTGF mRNA and protein and BMP-7 mRNA(P>0.05). CONCLUSION: Herbal cake-partitioned moxibustion can improve renal function in CRF rabbits, which may be related to its effects in suppressing the expression of ILK and CTGF, and in up-regulating the expression of BMP-7 in the kidney tissue.

The reproductive toxicity of saponins isolated from Cortex Albiziae in female mice.

Saponin frsom Cortex Albiziae (SCA) are extensively used in the clinical treatment of tumor and depression. However, SCA may cause several adverse effects, including reproductive toxicity. The present study was designed to assess the mechanism by which SCA cause reproductive toxicity in female mice. The general reproductive toxicity testing was accomplished in female Kunming mice. The animals were divided into four groups: three groups that were treated by oral gavage with 135, 270, and 540 mg·kg(-1)·d(-1) of SCA prepared in physiological saline, respectively, and one vehicle control group that was treated with physiological saline only. The gestational toxicity tests were conducted at 540 mg·kg(-1)·d(-1). The general reproductive toxicity results showed that the pregnancy rate of the SCA-treated group decreased with the pregnancy rate being decreased by 70% at 540 mg·kg(-1)·d(-1). SCA elicited maternal toxicity in the ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The rates of implantation in the early, middle, and late pregnancy were all decreased, with stillbirths and maternal deaths being observed. Histopathological changes showed that SCA adversely affected the ovary and the uterus. In conclusion, SCA-induced reproductive toxicity in female mice is most likely caused by its damage to the ovary and the uterus.

Effect of Salvia miltiorrhiza on retinopathy.

OBJECTIVE: To explore the effect of Salvia miltiorrhiza on diabetic retinopathy (DR). METHODS: Diabetic mice of natural incidence type with monogenic inheritance were selected. Alloxan was injected into the caudal vein of mice once to induce DR. The structural changes of retina tissue in normal mice, DR mice and mice with high, medium and low dose of Salvia miltiorrhiza injection were observed under microscope. Then the blood glucose concentration and malonaldehyde (MDA) content were detected. RESULTS: There were some microaneurysms in retina of DR group, number of gangliocyte was decreased significantly, and cells were sparse and in disorder. After modeling, the blood glucose level of high-dose Salvia miltiorrhiza group (SM III group) was significantly different from DR group (P<0.01). Till the tenth week, the blood glucose level of all SM groups was decreased significantly compared with DR group (P<0.01). The effective rates of three SM groups were 93.8%, 76.4% and 50.3%, respectively. After ten weeks, MDA content of DR group was significantly higher than those of the normal control group and SM group (P<0.01), and medium and low dose SM groups had significantly higher MDA than that of normal control group (P<0.01). CONCLUSIONS: Salvia miltiorrhiza had certain protective effect on DR mice through the blood-ocular barrier.

Differentially expressed proteins of MCF-7 human breast cancer cells affected by Zilongjin, a complementary Chinese herbal medicine.

PURPOSE: Zilongjin, a complementary Chinese herbal medicine, has been used to alleviate the adverse effects of chemotherapeutic drugs in cancer therapy. However, the mechanisms of anti-cancer activity of Zilongjin are still largely unkonwn. EXPERIMENTAL DESIGN: First, the proteomic approach of combined 2-DE and ESI-MS/MS was used to investigate the effect of Zilongjin on the protein expression in MCF-7 cells. Then, the differential expression of some proteins was confirmed by Western blot, cytoimmunofluoresecnce, and quantitative real-time RT-PCR analysis. RESULTS: The identified proteins with differential expression, involved in such events as protein translation, cellular signal transduction, cytoskeleton formation and transportation, include seven downregulating proteins, such as Eukaryotic translation initiation factor 3 subunit I, Eukaryotic translation initiation factor 1A Y-chromosomal, Ran-specific GTPase-activating protein, Ubiquitin-conjugating enzyme E2 N, Tropomodulin-3, Macrophage-capping protein, and Tumor protein D52, as well as two upregulating proteins, HSP ß-1 and keratin18. Moreover, the differential expression of three proteins was confirmed. CONCLUSIONS AND CLINICAL RELEVANCE: (i) These results provide a new insight into the molecular mechanisms of Zilongjin on therapy for breast cancer. (ii) The application of the proteomic approaches will result in the more extended appreciation of Chinese medicine than those known at present.

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

BACKGROUND & OBJECTIVE: Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. METHODS: A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. RESULTS: The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). CONCLUSION: Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

[Inspiration to basic researches of traditional Chinese medicine from the 2001 Nobel Prize].

The contributions of the three winners (L Hartwell, RT Hunt and PM Nurse) of the 2001 Nobel Prize for physiology or medicine revealed the mystical veil of cell cycle control. It was of far-reaching significance for exploring new method for cancer treatment. It will also give a good deal of enlightenment to the basic research of traditional Chinese medicine. Their understanding about the cause and development of cancers changed from the static view to dynamic dialectical analysis, from simplex study to comprehensive analysis; they stressed regulation, instead of killing in the treatment of cancer; and they thought that the numerous factors driving the normal process of the cell cycle could be summarized as positive and negative factors. These opinions were similar to some theories of traditional Chinese medicine, such as treatment based on syndrome differentiation, integrative treatment, and keeping the balance between yin and yang, and established a connection between traditional Chinese medicine and the western medicine, which would further widen the research on compound prescriptions of Chinese herbs.

[In vitro effect of zilongjin on prostate cancer cell line LNCaP].

OBJECTIVE: To investigate the effect of Zilongjin (ZLJ) on human androgen-dependent type of prostate cancer cell line LNCaP. METHODS: MTT assay, flow cytometry and fluorescence microscopy were used to observe the effect of ZLJ in anti-proliferation, cell cycle arresting and apoptosis induction. RT-PCR was used to examine the effect of ZLJ on expressions of prostate marker gene (PSA), androgen receptor (AR), apoptosis related genes (bcl-2 and bax), and Western blot assay was used to detect the effect on protein expression of bcl-2 and bax. RESULTS: ZLJ could cause apparent inhibition on proliferation, induce G0/G1 phase arresting and apoptosis in time- and dose-dependent manner on LNCaP cells. The concentration for inhibiting cell growth by 50% (IC50) in 72 hrs was 0.79 mg/ml. ZLJ could down-regulate the expression of PSA, AR, bcl-2 genes and lower bcl-2 protein expression, but showed ineffective on bax protein expression. CONCLUSION: ZLJ displays its anti-tumor effects by way of inhibiting the cell proliferation, arresting the G0/G1 phase, inducing apoptosis, down-regulating PSA, AR, bcl-2 gene expression and lowering bcl-2 protein expressions.

In vitro effect of zilongjin on prostate cancer cell line LNCaP / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Zilongjin (ZLJ) on human androgen-dependent type of prostate cancer cell line LNCaP.</p><p><b>METHODS</b>MTT assay, flow cytometry and fluorescence microscopy were used to observe the effect of ZLJ in anti-proliferation, cell cycle arresting and apoptosis induction. RT-PCR was used to examine the effect of ZLJ on expressions of prostate marker gene (PSA), androgen receptor (AR), apoptosis related genes (bcl-2 and bax), and Western blot assay was used to detect the effect on protein expression of bcl-2 and bax.</p><p><b>RESULTS</b>ZLJ could cause apparent inhibition on proliferation, induce G0/G1 phase arresting and apoptosis in time- and dose-dependent manner on LNCaP cells. The concentration for inhibiting cell growth by 50% (IC50) in 72 hrs was 0.79 mg/ml. ZLJ could down-regulate the expression of PSA, AR, bcl-2 genes and lower bcl-2 protein expression, but showed ineffective on bax protein expression.</p><p><b>CONCLUSION</b>ZLJ displays its anti-tumor effects by way of inhibiting the cell proliferation, arresting the G0/G1 phase, inducing apoptosis, down-regulating PSA, AR, bcl-2 gene expression and lowering bcl-2 protein expressions.</p>