Effect of Preoperative Lifestyle Management and Prehabilitation on Postoperative Capability of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The surgical intervention serves as the paramount and prevalent remedy for individuals afflicted with colorectal malignancies, with the significance of perioperative stewardship and convalescence being indisputable. Prehabilitation coupled with preoperative lifestyle modulation has demonstrated efficacy in patients subjected to certain classifications of abdominal procedures. However, the evidence pertaining to its impact on those battling colorectal cancer remains equivocal. METHODS: A meta-analysis, grounded in pairwise contrast, of randomized controlled trials (RCTs) was orchestrated, coupled with a systematic review, to probe the efficacy of preoperative lifestyle modulation and prehabilitation on patients' postoperative functionality and recuperation. An exhaustive exploration of 8 electronic databases and trial registries was undertaken to encompass all pertinent RCTs disseminated in English or Chinese from January 2012 through December 2022. Employing a random-effects model, we evaluated parameters such as the 6-minute walk test (6 MWT), complications, quality of life (QoL), aggregate and postoperative duration of hospitalization (tLHS and postLHS), and healthcare expenditure (HExp) for postoperative patients. RESULTS: A total of 28 RCTs were incorporated into the systematic review and meta-analysis. Relative to conventional preoperative care, rehabilitation or preoperative lifestyle management was found to enhance postoperative 6MWT (SMD 1.30, 95% CI 0.30 to 2.29) and diminish the complication rate (OR 0.53, 95% CI 0.40 to 0.69). Nonetheless, no significant discrepancies were observed in QoL (SMD 1.81, 95% CI -0.26 to 3.87), tLHS (SMD -0.26, 95% CI -0.68 to 0.15), and postLHS (SMD -1.46, 95% CI -3.12 to 0.20) between the groups. HExp could not be evaluated due to a lack of sufficient data for synthesis. Most pooled outcomes exhibited significant heterogeneity, urging a cautious interpretation. Subgroup analysis revealed that nutritional interventions could mitigate the incidence of complications, and preoperative exercise could improve tLHS and postLHS. A combined approach of physical, nutritional, and psychological intervention or prehabilitation proved superior to any single intervention in enhancing postoperative capabilities. CONCLUSION: This meta-analysis delineated the efficacy of preoperative interventions on postoperative capabilities in patients with colorectal cancer, thereby offering evidence for clinical practice. It was concluded that preoperative interventions are unequivocally beneficial for postoperative functional recovery and the reduction of complication rates in patients with colorectal cancer. Nonetheless, the acquisition of more high-level evidence is still necessitated to further ascertain the effectiveness of this strategy for other patient groups and to establish its best practices. The heterogeneity in the pooled outcomes underlines the need for future studies to be more uniform in their design and reporting, which would facilitate more robust and reliable meta-analyses.

Integration of non-targeted metabolomics with network pharmacology deciphers the anxiolytic mechanisms of Platycladi Semen extracts in CUMS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.

Anxiolytic effects, metabolism and plasma pharmacokinetics of 3, 6' -disinapoylsucrose.

3,6'-disinapoylsucrose (DISS) is a bioactive oligosaccharide ester derived from Polygalae Radix. This study aims to explore the anxiolytic effects of DISS and further reveal the material basis by establishing the pharmacokinetics of DISS and its metabolites. Behavioral experiments such as the open field test (OFT) and elevated plus maze test (EPM) were performed to evaluate the anxiolytic effects of DISS in mice after oral administration. By UPLC-MS/MS analysis, DISS and its metabolites both in blood and cerebrospinal fluid were identified, and the pharmacokinetics of DISS and its metabolites were characterized in SD rats after oral administration of DISS (100 mg·kg-1). Oral DISS could increase the time and frequency of mice entering the central area of the field in OFT and open arm in EPM, which indicated DISS has good anxiolytic effects. We also identified DISS and its metabolites (sinapic acid (SA), 3,4,5-trimethoxycinnamic acid (TMCA), methyl-3,4,5-trimethoxycinnamate (TMCA-CH2), p-Coumaric acid (CA) and p-methoxycinnamic acid (MA)) in rat plasma and cerebrospinal fluid. The pharmacokinetic results showed that DISS was rapidly absorbed after administration and reached its highest concentration at 12 min, SA had the highest exposure level in vivo and was probably the main active form of DISS action, TMCA could maintain at a low concentration for a long time. In brief, we reported the anxiolytic effect of DISS firstly, revealed the cerebrospinal fluid distribution and pharmacokinetics of DISS and its metabolites. Our findings provide the basis for further insight into the mechanisms involved in the anxiolytic effects of DISS.

[Mechanism of hepatotoxicity induced by ethanol extract of Dysosma versipellis based on "quantity-weight-evidence" network toxicology].

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.

Multi modular toxicity assessment of nephrotoxicity in podophyllotoxin exposure rats on account of toxicological evidence chain (TEC) concept.

Early diagnosis of kidney injuries caused by herbs is necessary to enable effective treatments, prevent kidney failure and promote the internationalization and modernization of herbal medicine. Whereas the toxic assessment evidence has not integrated yet, and the evaluation method has not been unanimously agreed. For example, the gold standard assessing toxicity in animals remains to be histopathology, but serum biochemical indexes are the primary measures for monitoring organs dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with toxicological evidence chain (TEC) concept could identify indicators of injury and provide new insights into the mechanisms of nephrotoxicity. Firstly, the objective phenotype of the animals was observed in detail and the toxicity performance was collected after administration. Subsequently, histopathological examination and serum biochemical toxicity evidence were collected. Next, we obtained concurrent measurements of transcriptomic changes in kidneys, and changes along with metabolic profiles in serum, after exposure to PT(Podophyllotoxin) to acquire evidence at the molecular level. Last but not least, the GTEA (Grades of Toxicological Evidence Assessment) based on GRADE(Grading of Recommendations Assessment, Development, and Evaluation) system was used to evaluate toxic evidence which can be assigned to a toxic level. The orally gavaged rats with PT have been confirmed with dose-dependent kidney damage from 5 to 15 mg/kg after 4 d. Our findings suggest that the main pathological changes occurred in Glycerophosphatidylcholine metabolism, Arachidonic acid metabolism, Energy metabolism, Tyrosine metabolism, Tryptophan metabolism and so on.Moreover, the alteration of the potential metabolites lipid (i.e. LPC, palmitic acid) and sulfate could serve as plausible markers of PT-induced kidney injury. Our approach provides a mechanistic framework for the refinement of the grading standard of toxicity evidence, which is applicable to other toxicants originated from herbal medicine based on multi-omics data.

Integrating network pharmacology and non-targeted metabolomics to explore the common mechanism of Coptis Categorized Formula improving T2DM zebrafish.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases. Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. AIM OF THE STUDY: Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. MATERIALS AND METHODS: Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. RESULTS: A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine, baicalin, coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications, mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. CONCLUSION: Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.

Study on potential toxic material base and mechanisms of hepatotoxicity induced by Dysosma versipellis based on toxicological evidence chain (TEC) concept.

Dysosma Versipellis (DV), a traditional Chinese medicine, has the functions of eliminating phlegm, detoxification, dispersing knots . However, its serious toxicity limits its further use. Therefore, it is necessary to conduct a comprehensive toxicity study of DV, screen the basis of potential toxic substances and understand its toxic mechanism. Based on the concept of toxicological evidence chain (TEC), this study utilizes the technologies and means of chemomics, metabolomics, molecular docking and network toxicology flexibly, step by step to find the evidence of potential toxic components in the development of hepatotoxicity induced by DV, evidence of critical toxicity events, evidence of adverse outcomes, thus, a chain of toxicity evidence with reference and directivity can be organized. It further confirmed the toxic damage and potential molecular mechanism of DV. 5 potential toxic components were identified, namely, Podophyllotoxin-4-O-D-glucoside, Podorhizol, Podophyllotoxin, Podophyllotoxone and 3',4'-O,O-Didemethylpophyllotoxin. These chemical constituents affect phenylalanine metabolism, glycerophospholipid metabolism, energy metabolism and other related pathways by regulating PAH, SOD1, SOD2 and other related targets, then it induces oxidative stress, cell apoptosis, inflammatory reaction and energy consumption, which ultimately induces the occurrence of liver injury. The results of this study provide some reference for the follow-up analysis of toxicity mechanism of DV.

Integrated metabolomics and network toxicology to reveal molecular mechanism of celastrol induced cardiotoxicity.

Celastrol (CS), an active triterpene derived from traditional Chinese medicine Tripterygium wilfordii Hook. f, has been used to treat chronic inflammation, arthritis and other diseases. However, it has been reported that CS can trigger cardiotoxicity and the molecular mechanism of heart injury induced by CS is not clear. Considering the wide application of Tripterygium wilfordii Hook. f in clinics, it is necessary to develop an accurate and reliable method to assess the safety of CS, and to elucidate as much as possible the mechanism of cardiotoxicity induced by CS. In this study, Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics revealed clues to the mechanism of CS-induced heart injury. Palmitic acid significantly increased in plasma from CS-treated rats, and this increase resulted in oxidative stress response in vivo. Excessive ROS further activate TNF signaling pathway and caspase family, which were obtained from the KEGG enrichment analysis of network toxicology strategy. Protein expression level of caspase-3, caspase-8, bax were significantly increased by western blot. Q-PCR also showed the similar results as western blot. It means that apoptosis plays a key role in the process of celastrol induced cardiotoxicity. Blocking this signal axis may be a potential way to protect myocardial tissue.

[Research progress in mineral Chinese medicine realgar].

Realgar is a mineral traditional medicine with definite efficacy. The function of realgar is detoxicating, insecticiding, eliminating dampness and phlegm, etc. It is widely applied in clinical practice by compatibility medicines. However, the safety and scientificalness of clinical application are questioned because of the toxic effect caused by arsenic compounds. At present, there are still many problems in the research of realgar, which are mainly manifested in three areas: the expression of main components and effective substances are inconsistent; the anti-tumor mechanism is difficult to explain at the molecular level; the mechanism of compatibility is not clear. As a result, realgar and realgar-containing Chinese patent medicines are frequently prohibited from entering the international market, and the reputation of traditional Chinese medicine is also damaged. This paper would analyze the research status of realgar at home and abroad as well as its problems from its main components, effective substances, anti-tumor mechanism and compatibility mechanism. In view of these difficulties, quantum chemical calculation method is proposed to solve them, so as to make up for the shortcomings and limitations of experimental technology and experimental conditions, reduce the cost of realgar research and improve research efficiency. Moreover, it provides inspiration for research of other mineral medicine.

Anxiolytic effect of a novel 9,10-dihydrophenanthrene, juncuenin H, is associated with metabolic changes in cortical serotonin/dopamine levels in mice.

Two novel phenanthrenoids, juncuenin H (1) and dijuncuenin B (2), together with eight known phenanthrenoids, effusol (3), dehydroeffusol (4), juncusol (5), dehydrojuncusol (6), juncuenin B (7), dehydrojuncuenin B (8), juncuenin A (9), and dehydrojuncuenin A (10), were isolated from the underground parts of Juncus setchuenensis. The structures of the compounds were determined by 1D and 2D NMR and mass spectroscopy. The anxiolytic activities of compounds 1, 6, 9, and 10 were evaluated. In order to explore the mechanisms underlying their anxiolytic activities, the levels of serotonin (5-HT), dopamine (DA), and their metabolites in the cerebral cortex and hippocampus of mice treated with compound 1 were determined by quantitative mass spectrometry. The mice treated with compound 1 had significantly lower levels of 5-HT, 3-methoxytyramine (3-MT), 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA), and 3, 4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex than those of the vehicle control-treated mice. The levels of HVA and 5-HIAA in the hippocampus were also significantly lower in the mice treated with compound 1 than in the control group mice. These results suggest that the metabolic changes, reflected in the levels of DA and/or 5-HT, may contribute to the anxiolytic activity of the phenanthrenoids studied herein.

[Effects of tannins in Galla Chinensis on pharmacokinetics of rifampicin in vivo and in vitro].

This study was aimed to explore the effects of tannins in Galla Chinensis on rifampicin in vivo. In the experiment in vitro, UV spectrophotometry and high performance liquid chromatography (HPLC) were used to investigate the solubility of rifampin in pH 1.3, 6.8, artificial gastric juice environment and artificial intestinal fluid environment as well as the effects of tannins on solubility of rifampin in the above conditions. In the experiment in vivo, the process of rifampicin was studied after intragastric administration of rifampicin and rifampicin+ tannins in Galla Chinensis, and then the pharmacokinetic parameters were calculated. The results showed that rifampicin was constantly precipitated in the artificial gastric juice environment over time, and nearly 85% of the rifampicin was precipitated after 6 hours; it showed a good solubility in the artificial intestinal juice environment. After adding the said tannins, the concentration of rifampicin was decreased significantly in both environments, and the concentration of rifampicin in artificial intestinal juice remained relatively stable, while that in artificial gastric juice remained the original downward trend. The pharmacokinetic parameters displayed that as compared with rifampicin alone, AUC0-t and Cmax were decreased significantly, MRT0-t slowed down significantly, Tmax doubled to 7.0 h and the bioavailability was only 31.65% in rifampicin + tannins in Galla Chinensis group. The experiment indicated rifampicin had a poor solubility in acidic environment and the decrease of bioavailability of rifampicin when in combination with tannin was mainly due to the reduction of rifampicin solubility in intestinal tract by complexation of rifampicin with tannin, thus affecting its absorption in intestinal tract. Therefore, rifampicin and the Chinese herbal medicines or Chinese patent medicines rich in tannin should not be taken simultaneously.

Metabolic profile of danshen in rats by HPLC-LTQ-Orbitrap mass spectrometry.

Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the traditional Chinese medicines (TCMs) most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, little is known about the chemical and metabolic profiles of danshen in vitro or in vivo. In particular, more information is needed in relation to the 50% ethanol extracts usually used in danshen formulations such as Fufang Xueshuantong Capsules and Fufang Danshen tablets. High-performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer (HPLC-LTQ-Orbitrap) provides a sensitive and accurate method for analyzing the composition of samples. This method was used to determine the in vitro and in vivo chemical and metabolic profiles of danshen. Sixty-nine components of danshen extract and 118 components of danshen in rat plasma, urine, feces, and bile were unambiguously or tentatively identified. These results not only revealed the material composition of danshen, but also provided a comprehensive research approach for the identification of multi-constituents in TCMs.

Support for Natural Small-Molecule Phenols as Anxiolytics.

Natural small-molecule phenols (NSMPs) share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were assayed with the elevated plus maze (EPM) test in mice. The oral doses were 5, 10 and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10 mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl group in 4-hydroxycinnamic acid (4-OH CA) was essential for the anxiolytic activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl CA). The in vivo spike recording of rats' hippocampal neurons also showed significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal spike recording results converged to indicate the hippocampal CA1 region might be a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides further experimental data supporting NSMPs sharing anxiolytic activity, which may have general implications for phytotherapy because small phenols occur extensively in herbal medicines.

[Review on anxiolytic effect of natural small-molecule phenols].

Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor, anti-bacterial, and anti-inflammatory activities. Recent literatures have demonstrated that flavonoids have a significant anti-anxiety effect on the central nervous system. In addition, studies showed that flavonoids acted as pro-drugs, which were transformed into smaller phenols through intestinal microflora. The small phenolic metabolites were crucial for the anxiolytic effects of these flavonoids, indicating that natural small-molecule phenols(NSMP) generally have anxiolytic activities. In this paper, the supporting evidences (before June 2016) from SciFinder database have been summarized. Furthermore, NSMPs were classified according to chemical structures; their anxiolytic effects, mechanisms, and the structure-activity relationships were also discussed.

[Toxicity of mineral Chinese medicines containing mercury element].

Mineral Chinese medicine is the distinctive part of the Chinese traditional medicine. The mineral Chinese medicines containing mercury elements such as cinnabaris, calomelas and hydrargyri oxydum rubrum are widely applied in the clinical conditions because of their efficacy of sedative, sterilization, removing necrotic tissue and promoting granulation. However, the rationality and security of clinical application are questioned because of the toxic effect caused by mercury compounds. This paper would summarize the efficacy of the mineral Chinese medicines containing mercury element, as well as their hepatotoxicity, nephrotoxicity, embryotoxicity, and neurotoxicity effect and mechanisms. Improper usage or high dose of the mineral Chinese medicines containing mercury element would cause acute hepatotoxicity. Cinnabaris, calomelas and hydrargyri oxydum rubrum may lead to chronic hepatotoxicity, nephrotoxicity, embryotoxicity and neurotoxicity when they were applied externally to the skin for long-term use. In addition to the accumulation of mercury elements in the tissues and organs, the species and forms of mercury compounds absorbed into the body in different ways, should be also studied in order to understand the toxicity of the mineral Chinese medicines containing mercury element. Meanwhile the dose and period of treatment shall be also considered in order to provide the references for rational and safe clinical application of the mineral Chinese medicines containing mercury element.

Effect of compatible herbs on the pharmacokinetics of effective components of Panax notoginseng in Fufang Xueshuantong Capsule.

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC0-t), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC0-t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.

Protective Effects of Panax notoginseng Saponins against High Glucose-Induced Oxidative Injury in Rat Retinal Capillary Endothelial Cells.

Diabetic retinopathy, a leading cause of visual loss and blindness, is characterized by microvascular dysfunction. Hyperglycemia is considered the major pathogenic factor for diabetic retinopathy and is associated with increased oxidative stress in the retina. In this study, we investigated the potential protective effects of Panax notoginseng Saponins (PNS) in retinal capillary endothelial cells (RCECs) exposed to high glucose conditions. We found a pronounced increase in cell viability in rat RCECs incubated with both PNS and high glucose (30 mM) for 48 h or 72 h. The increased viability was accompanied by reduced intracellular hydrogen peroxide (H2O2) and superoxide (O2 (-)), decreased mitochondrial reactive oxygen species (ROS), and lowered malondialdehyde (MDA) levels. PNS also increased the activities of total superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione peroxidase (GSH-PX). The glutathione (GSH) content also increased after PNS treatment. Furthermore, PNS reduced NADPH oxidase 4 (Nox4) expression. These results indicate that PNS exerts a protective effect against high glucose-induced injury in RCECs, which may be partially attributed to its antioxidative function.

A combination of the main constituents of Fufang Xueshuantong Capsules shows protective effects against streptozotocin-induced retinal lesions in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Xueshuantong Capsule, an herbal formula licensed for clinical use in China, which is composed of Panax notoginseng (Burkill) F.H. Chen, Salvia miltiorrhiza Bunge, Astragalus membranaceus (Fisch.) Bunge, and Scrophularia ningpoensis Hemsl, has proven effective for the treatment of diabetic retinopathy. However, its bioactive constituents are still ambiguous. In this study, the therapeutic effects of a combination of the main constituents of Fufang Xueshuantong Capsule (cFXT) were evaluated in streptozotocin (STZ)-induced retinal lesions to identify the bioactive constituents. METHODS: Sprague-Dawley rats, except for those in the control group (vehicle+vehicle), were administered a single injection of 60mg/kg STZ. One-week later, STZ-treated rats were randomly divided into three groups-one STZ group (STZ+vehicle) and two cFXT treatment groups (STZ+cFXT). The rats in the latter two groups received cFXT 44.8mg/kg or cFXT 22.4mg/kg by intragastric gavage once per day, for 24 consecutive weeks. The rats in the control and STZ groups received the vehicle in the same way. Body weights and fasting blood glucose levels were recorded every four weeks. After treatment, hemorheological tests were performed to record the erythrocyte aggregation indexes, blood viscosity, and plasma viscosity. The trypsin digestion method was used to observe pericyte and acellular capillary counts in the retina. Ultraviolet spectrophotometry was utilized to measure the activity of aldose reductase (AR) by measuring the nicotinamide adenine dinucleotide phosphate (NADPH) consumption at 340nm. An immunohistochemical assay was used to observe the expressions of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the retina. The expression levels of intercellular adhesion molecule-1 (ICAM-1), endothelin-1 (RT-1),and occludin in the retina were tested by the western blot assay. RESULTS: cFXT is composed of 991.44mg/g saponins of Panax notoginseng, 1.62mg/g harpagoside, 0.70mg/g cryptotanshinone, 0.74mg/g tanshinone I, and 5.50mg/g astragaloside A. Although it showed no effects on the increased body weight and blood glucose levels induced by STZ in rats. However, it showed a tendency to attenuate the increase in erythrocyte aggregation, plasma viscosity, and acellular vessel and pericyte loss, paralleled with a reversal of the hyper-activation of AR, the hyper-expression of VEGF, ICAM-1, and ET-1, and the hypo-expression of PEDF and occludin in the retinas of STZ-treated rats. CONCLUSION: The saponins of Panax notoginseng, harpagoside, cryptotanshinone, tanshinone I, and astragaloside A are the main bioactive constituents of Fufang Xueshuantong Capsule and contribute to the attenuation of STZ-induced retinal lesions in rats. These constituents can be used as the base to optimize a new drug for the treatment of diabetic retinopathy, and can be selected for quality control of Fufang Xueshuantong Capsules.

[Distribution of chemical compounds of Fufang Xueshuantong capsule in eyes and kidney of beagle dogs].

Diabetic retinopathy(DR) and diabetic nephropathy(DN) are the most common complications of diabetes, and the main causes of death and disability of diabetes. Clinical reports showed that Fufang Xueshuantong capsule(FXT) had effective curative effect on DR and DN, but there was no report on the distribution of chemical compounds of FXT in beagle dog eyes and kidneys. In this study, FXT was given by gavage administration in Beagle dogs for 3 days, and then their eyeballs and kidneys were taken. The chemical compounds in beagle dog eyes and kidneys were detected by HPLC LTQ-Orbitrap technology. Furthermore, by comparing with the data from retrieving literature and references, the chemical compounds were identified by the accurate mass, retention time (tR), and MS/MS. Fourteen and 19 types of notoginsenosides were respectively identified in eyeballs and kidneys in this study, and these results could lay foundation for clarifying the effective ingredients of FXT in treatment of DR and DN.

[Impacts on physical and mental health of patients with polycystic ovary syndrome treated with electroacupuncture:a randomized controlled trial].

OBJECTIVE: To explore the impacts on physical and mental health of the patients with polycystic ovary syndrome (PCOS) treated with electroacupuncture (EA) or Diane 35. METHODS: Seventy-two patients of PCOS were randomized into an acupuncture group and a western medication group, 36 cases in each group. In the acupuncture group, acupuncture was applied to relieving liver stagnation and regulating qi activity at Ganshu (BL 18), Danzhong (CV 17), Qimen (LR 14), Zhongwan (CV 4), Tianshu (ST 25), Guanyuan (CV 4), Zigong (EX-CA 1), Sanyinjiao (SP 6), Zusanli (ST 36) and Taichong (LR 3). After qi arrival, the electric stimulation was added for 30 min. Acupuncture treatment was given 3 times a week. In the western medication group, Diane 35 was taken since the 5th day of menstruation and lasted for 21 days. The cycle of treatment was 3 months in the two groups. Before treatment and at the end of treatment, the symptom scores were evaluated and the self-report symptom inventory, symptom checklist-90 (SCL-90) was used for the mental health evaluation and the comparison was made between the two groups. RESULTS: Compared with those before treatment in the same group, the symptom scores were reduced significantly after treatment in the two groups (both P<0.01). After treatment, the symptom scores in the acupuncture group were reduced significantly as compared with those in the western medicationgroup (P<0.01). After treatment, the scores of somatization, interpersonal sensitivity, depression, anxiety and hostility were reduced significantly as compared with those before treatment in the acupuncture group (all P<0.05). After treatment, the scores of somatization, interpersonal sensitivity, depression, anxiety, hostility and phobic factor were lower significantly than those in the western medication group (all P<0.05). CONCLUSIONS: EA with relieving liver stagnation and regulating qi activity reduces the symptom scores of PCOS and SCL-90 scores, acting on regulating both physical and mental conditions. The effects achieved with acupuncture are better than those with Diane 35.