Unveiling differential mechanisms of chuanxiong cortex and pith in the treatment of coronary heart disease using SPME-GC×GC-MS and network pharmacology.

Ligusticum chuanxiong Hort (LCH) is a well-known traditional Chinese medicinal herb for treating coronary heart disease (CHD). This study investigated the differential preventive mechanisms of Rhizome Cortex (RC) and Rhizome Pith (RP) of LCH. Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography-tandem mass spectrometry analysis identified 32 differential components, and network pharmacology revealed 11 active ingredients and 191 gene targets in RC, along with 12 active ingredients and 318 gene targets in RP. Primary active ingredients in RC were carotol, epicubenol, fenipentol, and methylisoeugenol acetate, while 3-undecanone, (E)- 5-decen-1-ol acetate, linalyl acetate, and (E)- 2-Methoxy-4-(prop-1-enyl) phenol were dominant in RP. KEGG mapping analysis associated 27 pathways with RC targets and 116 pathways with RP targets. Molecular docking confirmed the efficient activation of corresponding targets by these active ingredients. This study provides valuable insights into the preventive and therapeutic effects of RC and RP in CHD.

Electroacupuncture pretreatment alleviates myocardial injury through regulating mitochondrial function.

BACKGROUND: Electroacupuncture is well known for its advantageous neuroanalgesic and therapeutic effects on myocardial ischemia-reperfusion injury. The purpose of the present research was to verify whether electroacupuncture can alleviate bupivacaine-induced myocardial injury. METHODS: Specific pathogen-free Wistar rats were used to establish the bupivacaine-induced myocardial injury model. Western blot, PCR, transmission electron microscope and enzyme-linked immunosorbent (ELISA) methods were used to evaluate bupivacaine-induced structure injury and dysfunction of the mitochondria as well as the alleviating effects of lipid emulsion, acupoint injection, and electroacupuncture pre-treatment of the oxidase stress response. RESULTS: Bupivacaine caused structural damage, degradation, and swelling of mitochondria. Furthermore, it reduced adenosine triphosphate (ATP) synthesis and impaired energy metabolism in the mitochondria. Structural and functional impairment of the mitochondria was alleviated via lipid emulsion injection, acupoint injection, and electroacupuncture pre-treatment. Electroacupuncture pre-treatment of PC6 yielded a greater alleviating effect than others approaches. Following electroacupuncture pre-treatment of PC6 point, the number of mitochondria increased; apoptosis was reduced, enzymatic activity of cytochrome C oxidase (COX) and superoxide dismutase and expression of uncoupling protein 2, voltage-dependent anion channel 1, and Bcl 2 were upregulated and SLC25A6, MDA levels were downregulated. Additionally, our findings indicated that electroacupuncture pre-treatment of PC6 point exerted an effect on the mitochondria via the mitochondrial-transcription-factor-A/nuclear-respiratory-factor-1/proliferator-activated-receptor-gamma-coactivator-1 pathway. CONCLUSION: The present study revealed that electroacupuncture pre-treatment of PC6 could effectively alleviate bupivacaine-induced myocardial mitochondrial damage, thereby providing a theoretical basis for clinical studies and applications of this treatment method.

Glycolipid metabolism and liver transcriptomic analysis of the therapeutic effects of pressed degreased walnut meal extracts on type 2 diabetes mellitus rats.

Walnut meal (WM) is rich in polyphenols which exhibit multiple therapeutic effects. The purpose of this study was to investigate the therapeutic effects of walnut meal extracts (WMP) on glycolipid metabolism and liver transcriptomics in T2DM rats. A T2DM rat model was established by using a high-fat diet combined with streptozotocin. A 5-week WMP therapy showed the effects of decreasing water intake, excretion, fasting blood glucose, fasting insulin, and insulin resistance, increasing ß-cell function and insulin sensitivity index; meanwhile regulating dysfunctional lipid metabolism and reducing inflammation; improving body weight, oral glucose tolerance test and insulin sensitivity; and increasing the activities of SOD and CAT while decreasing the MDA levels in the liver and serum of T2DM rats. Moreover, 10 key differentially expressed genes were identified by RNA-seq, including Gck, RT1-Ba, Fasn, Slc13a3, Cd74, Jun, Cyp4a1, Myh7b, Plin3, and Got1, and they were highly potentially related to glycolipid metabolism. Our results suggested that WMP exhibited the anti-diabetic effect and could regulate glycolipid metabolism in T2DM rats. This finding might assist in identifying potential therapeutic targets for T2DM prevention and intervention.

Electroacupuncture pretreatment induces rapid tolerance to bupivacaine cardiotoxicity in rats.

BACKGROUND: Evidence suggests that electroacupuncture (EA) protects against arrhythmia and myocardial injury induced by myocardial ischaemia-reperfusion. However, to our knowledge, it remains unknown whether EA could alleviate bupivacaine-induced cardiotoxicity. Therefore, we aimed to explore the effect of EA pretreatment on bupivacaine-induced cardiac arrest and outcomes of cardiopulmonary resuscitation (CPR) in rats. METHODS: 24 adult male Sprague-Dawley rats were randomly divided into two groups: EA (n=12), and minimal acupuncture (MA) (n=12). Rats in both groups were needled at bilateral PC6, ST36, and ST40. Needles in the EA group were electrically stimulated for 60 min. ECG and invasive arterial blood pressure measurements were recorded. Two hours after EA or MA, 10 mg/kg bupivacaine was infused intravenously at a rate of 5 mg/kg/min in all rats. Rats suffering cardiac arrest were immediately subjected to CPR. At the end of the experiment, arterial blood samples were taken from surviving rats for blood gas analysis. RESULTS: The time from bupivacaine infusion until 20% prolongation of the QRS and QT interval, and the time to cardiac arrest, were notably increased among the rats pretreated with EA. Moreover, EA pretreatment significantly improved mean arterial pressure and heart rate at all monitored points after bupivacaine infusion. The proportion of animals surviving was higher in the EA group (9/12) than the MA group (3/12) at the end of experiment (p=0.039). CONCLUSIONS: Tolerance to bupivacaine-induced cardiotoxicity appeared to be increased following EA pre-treatment. The mechanism of action underlying the effects of EA on bupivacaine-induced cardiotoxicity requires further investigation.

Molecular authentication of Tetrastigma hemsleyanum from its adulterant species using ISSR, CAPS, and ITS2 barcode.

Tetrastigma hemsleyanum is a rare and endangered herb, which is commercialized as the resource of anti-cancer drugs. Wild T. hemsleyanum plants are on the verge of extinction recently, there are increasing numbers of counterfeits on the market. In the present study, inter-simple sequence repeat (ISSR), Cleaved amplified polymorphic sequence (CAPS), and the internal transcribed spacer region II (ITS2) barcode were used for the first time for the authentication of T. hemsleyanum from its commonly counterfeits. ISSR analysis suggested that it was a useful method for distinguishing T. hemsleyanum from its adulterants of different genus. However, it was insufficient to distinguish T. hemsleyanum from those adulterants of the same genus. ITS2 of T. hemsleyanum and the commonly counterfeits were amplified and sequenced. The Neighbor-Joining tree constructed from the ITS2 sequences showed that T. hemsleyanum was clearly differentiated from all counterfeits samples. A mutation site in the ITS2 region of T. hemsleyanum had been found which could be recognized by the restriction endonuclease NcoI. T. hemsleyanum could be readily distinguished from counterfeits as the PCR products from T. hemsleyanum could be digested sufficiently by NcoI, while the PCR products from counterfeits could not be digested. The results indicated that CAPS and ITS2 barcode methods provided effective and accurate identification of T. hemsleyanum from all its adulterants, while ISSR could only distinguish T. hemsleyanum from its adulterants of different genus. The CAPS method developed in the present study will serve as a reliable tool for safe and effective use of T. hemsleyanum in the clinic application. It will also play an important role for the identification, management and conservation of this endangered species.

[Effects of pretreatment of electroacupuncture on bupivacaine poisoning in rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment at different times for heart arrest induced by bupivacaine poisoning in rats. METHODS: With a randomized, blind, control study, 24 SD rats were divided into a control group, a EA for 60 min (EA 60) group and a EA for 30 min (EA 30) group, 8 cases in each one. Rats in the EA 60 group and EA 30 groups were treated with EA at bilateral "Neiguan" (PC 6), "Zusanli" (ST 36) and "Fenglong" (ST 40) for 60 min and 30 min respectively. While no treatment was given in the control group. Then rats were monitored by leadⅡelectrocardiograph; catheters were inserted into the femoral vein to open the vein access and into the carotis to monitor the arterial pressure. Three hours after EA, 10 mg/kg bupivacaine was injected through femoral vein. The mean arterial pressure (MAP) and heart rate (HR) were automatically recorded by PowerLab system. The time points when QRS widened by 20 percent and cardiac arrest and the survival rates were observed. RESULTS: After the injection of bupivacaine, five rats in the EA 60 group caught cardiac arrest,while all the rats in the other two groups caught it. The survival rates were not statistically significant among the three groups (P>0.05). The time of QRS widening by 20 percent in the EA 60 group was (87.4±14.8) s,which was longer than (63.6±14.2) s in the EA 30 group and (51.2±12.4) s in the control group (both P<0.05). From injection of bupivacaine to cardiac arrest, the time of (375.3±23.7) s in the EA 60 group and that of (328.3±47.7)s in the EA 30 group were more than (235.5±91.5) s in the control group (both P<0.05). After the injection, MAP and HR in the EA 60 group were higher than those in the EA 30 group and control group at most time points (all P<0.05). CONCLUSIONS: EA pretreatment apparently decreases the vulnerability of bupivacaine-induced heart arrest, with better protective effect of 60 min pretreatment than that of 30 min.

[Multiple functions of transcutaneous electrical acupoint stimulation in peri-anesthesia period].

Through literature retrieval, the effects of transcutaneous electrical acupoint stimulation (TEAS) in peri-anesthesia period are summarized. It is found out that TEAS can reduce anesthetics consumption, relieve stress reaction of surgery, stabilize patients' hemodynamics, reduce surgical complication and improve immune function and quality of recovery; besides, it has protective function on heart, brain, liver, stomach, intestines and so on. However, except certain analgesic effect, the sham TEAS and transcutaneous electrial nerve stimulation do not have other functions of TEAS. The acupoint selection and stimulation parameter of TEAS in assisting anesthesia are still needed be improved and united.

[Effect of adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants and its action characteristics].

The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.

A platinum(II) complex of liriodenine from traditional Chinese medicine (TCM): Cell cycle arrest, cell apoptosis induction and telomerase inhibition activity via G-quadruplex DNA stabilization.

Liriodenine (L), an antitumor active ingredient from the traditional Chinese medicine (TCM), Zanthoxylum nitidum, afforded a platinum(II) complex (1) of L, cis-[PtCl2(L)(DMSO)], which previously reported for its in vitro antitumor activity and intercalative binding with DNA. In this study, complex 1 was further discussed for its antitumor mechanism and structure-activity relationship, comparing with L and cisplatin. Towards the most sensitive BEL-7404 human hepatoma cells, complex 1 significantly induced cell cycle arrest at both G2/M phase and S phase. It suggests that double helix DNA is not the simplex intracellular target for 1. On the other hand, the BEL-7404 cells incubated with 1 and stained by Hoechst 33258 and AO/EB showed typical cell apoptosis in dose-dependent manner. The BEL-7404 cells incubated with 1 and stained by JC-1 were also characteristic for cell apoptosis on the loss of mitochondrial membrane potential. Furthermore, the G-quadruplex DNA binding property of complex 1 was also investigated by spectroscopic analyses, fluorescent indicator displacement (FID) assay and fluorescence resonance energy transfer (FRET) assay. The results indicated that 1 stabilized the human telomeric G4-HTG21 DNA better than L. The telomerase inhibition ratio of 1 ((62.50±0.03)%), which was examined by telomerase polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), was much higher than L ((21.77±0.01)%). It can be ascribed to the better G4-HTG21 DNA stabilization of 1 than L. The results suggested that the nuclei, mitochondria and telomerase via G-quadruplex DNA stabilization all should be key targets for the antitumor mechanism of 1, in which the central platinum(II) played a key role.

[Observation on therapeutic effect of type II early diabetic nephropathies intervened by acupoint thread embedding].

OBJECTIVE: To observe the therapeutic effect of type II early diabetic nephropathies intervened by acupoint thread embedding for strengthening spleen and benefiting kidney. METHODS: Sixty cases of type II early diabetic nephropathies were randomly divided into an acupoint thread embedding group and a routine therapy group, 30 cases in each group. In routine therapy group, western medicine routine therapy was applied to control blood sugar, blood pressure and blood lipid. In acupoint thread embedding group, besides the western medicine routine therapy, thread embedding intervention was given at Pishu (BL 20), Zusanli (ST 36), Shenshu (BL 23) and Yishu (Extra) on both sides as main acupints, and the treatment course was 3 months. Urinary micro-albumin excretion (UAER), total score of TCM syndrome and monitor control indices (blood sugar, blood pressure, blood lipid, urea nitrogen and serum creatinine) in both groups were observed before and after treatment, and the therapeutic effects in both groups were compared. RESULTS: After treatment, the indices of UAER and total score of TCM syndrome were all reduced (P < 0.001, P < 0.01); the reduction in acupoint thread embedding group was more obvious (P < 0.01, P < 0.05); the total effective rate in acupoint thread embedding group was 76.7% (23/30), superior to that of 63.3% (19/30) in routine therapy group (P < 0.05). The blood sugar, blood pressure and blood lipid in both groups were remarkably improved (all P < 0.001) after treatment; the urea nitrogen and creatinine had no notable variation. CONCLUSION: Acupoint thread embedding combined with western medicine routine therapy can not only reduce the urinary micro-albumin excretion of type II early diabetic nephropathies, but also improve the Chinese medicine symptoms and the therapeutic effect is superior to that of simple western medicine routine therapy.

[Studies on the triterpenoids constituents from Phyllodium elegans].

OBJECTIVE: To study the chemical constituents of Phyllodium elegans. METHODS: The compounds were isolated and purified by extraction, chromatography on silica gel and recrystallization. Their structures were elucidated on the basis of physicochemical properties and spectra analysis. RESULTS: Three triterpenoids were isolated and identified as lupenone (1), lupeol (2), betulin (3). CONCLUSION: Compound 2 is obtained from the genus for the first time, Compounds 1-3 are isolated from this plant for the first time.

Accumulation and distribution of uranium in rats after implantation with depleted uranium fragments.

PURPOSE: The aim of our study was to clarify the accumulation and distribution of uranium in depleted uranium (DU) implanted rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at 3 dose levels (low, medium and high), and biologically inert tantalum (Ta) fragments were used as controls. At 1 day and 7, 30, 90, 180 and 360 days after implantation, the rats were euthanized and tissue samples including serum and urine were collected to analyze the uranium levels by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: At all time points, uranium levels in all the DU implanted groups were higher than that in Ta control group, and uranium concentrations in kidney and bone were significantly greater than that in other tissues. Otherwise, uranium concentrations increased with a close correlation to the implanted DU doses and duration of exposure, with a peak at 90 days post-implantation, after which followed by a decreasing period, but still maintained at a relatively high level even at 360 days post- implantation. The uranium concentrations in bone were 6.92 +/- 0.97 microg U/g, 16.35 +/- 1.67 microg U/g and 21.64 +/- 3.68 microg U/g in the low-, medium- and high-dose group animals, while values in kidney tissues were 10.66 +/- 1.10 microg U/g, 14.06 +/- 1.28 microg U/g and 17.79 +/- 2.87 microg U/g, respectively, at 360 days post-implantation. CONCLUSION: It was concluded that kidney and bone are the primary reservoirs for uranium redistributed from intramuscularly embedded fragments, and the accumulations in kidney, bone and many other tissues suggest the potential for unanticipated physiological consequences of chronic exposure to DU.

Flavonoids and a new polyacetylene from Bidens parviflora Willd.

Fifteen flavonoids, 1-7 and 9-16, and a polyacetylene, 8, were isolated from the ethanol extract of the dried whole plant of Bidens parviflora Willd. by various chromatographic techniques. Their structures have been elucidated on the basis of spectroscopic analyses and chemical studies. Compound 8 is new and was identified as 3-(R),8(E)-decene-4,6-diyne-1,3,10-triol. All the flavonoid compounds were isolated for the first time from this plant species.

[Clinical study on effect of acupoint sticking of chuanfuling in dog-days in preventing and treating children asthma in remission stage].

OBJECTIVE: To explore the effect and mechanism of acupoint sticking of Chuanfuling (CFL) in dog-days (the hottest periods of the year) in preventing and treating children asthma in remission stage. METHODS: Ninety patients were divided into three groups, 30 in each. Patients in the CFL group were treated with CFL sticking, in the Western medicine (WM) group treated with Pulmicort inhalation, and in the control group was untreated. The clinical effect and indexes of humoral immunity (IgE, IgA, IgG) and cellular immunity (Eos, IL-4, IFN-gamma) before and after treatment were observed. RESULTS: After treatment in the CFL group all the immune parameters were significantly improved (P<0.05 or P<0.01), all were better than those in the control group (P<0.05 or P<0.01), and the effect on IgA and IgG was better than that in the WM group. In the WM group after treatment, improvement was shown on the IgE and cellular immune parameters with signifian difference (P<0.05 or P<0.01), better than those in the control group (P<0.05 or P<0.01). Besides, significant difference was shown in comparing IL-4 level between the WM group and the CFL group (P<0.05). CONCLUSION: CFL sticking in dog-days could significantly improve the immune function in children with asthma to alleviate and control the attack.