Liang-Ge Decoction Ameliorates Coagulation Dysfunction in Cecal Ligation and Puncture-Induced Sepsis Model Rats through Inhibiting PAD4-Dependent Neutrophil Extracellular Trap Formation.

Liang-Ge (LG) decoction could ameliorate coagulation dysfunction in septic model rats. However, the mechanism of LG in treating sepsis still needs to be clarified. Our current study established a septic rat model to evaluate the effect of LG on coagulation dysfunction in septic rats first. Second, we investigated the effect of LG on NET formation in septic rats. Finally, NETs and PAD4 inhibitors were further used to clarify if LG could improve the mechanism of sepsis coagulation dysfunction by inhibiting NET formation. Our findings indicated that treatment with LG improved the survival rate, reduced inflammatory factor levels, enhanced hepatic and renal function, and reduced pathological changes in rats with sepsis. LG could also alleviate coagulation dysfunction in septic model rats. Besides, LG treatment reduced NETs formation and decreased PAD4 expression in neutrophiles. In addition, LG treatment showed a similar result in comparison to the treatment with either NET inhibitors or PAD4 inhibitors alone. In conclusion, this study confirmed that LG has therapeutic effects on septic rats. Furthermore, the improvement of coagulation dysfunction in septic rats by LG was achieved through inhibiting PAD4-mediated NET formation.

[Therapeutic effect of electric-balance stimulation with scalp acupuncture for motor aphasia after cerebral infarction].

OBJECTIVE: To compare the clinical efficacy between scalp acupuncture electrical stimulation and routine scalp acupuncture for motor aphasia in subacute stage of cerebral infarction. METHODS: A total of 54 patients with motor aphasia in subacute stage of cerebral infarction were randomly divided into an observation group (27 cases, 1 case dropped off) and a control group (27 cases, 2 cases dropped off ). Both groups were treated with routine medication and language training. In the observation group, scalp acupuncture was given at bilateral lower 2/5 of the parietal and temporal anterior oblique line and temporal frontline; after the arrival of qi, the electrical stimulation with disperse-dense wave was given at the affected side and continuous wave was given at healthy side. The control group was treated with routine scalp acupuncture at lower 2/5 of the parietal and temporal anterior oblique line and temporal frontline of the affected side, once a day, five times as a course, totaling two courses of treatment. The aphasia battery of Chinese (ABC) score and Boston diagnostic aphasia examination (BDAE) grade were observed before and after treatment. The levels of oxygenated hemoglobin (HbO2), deoxyhemoglobin (D-Hb) and total hemoglobin (T-Hb) in local cerebral cortex of the two groups were measured in real time using functional near-infrared spectroscopy (fNIRS) before and after treatment. The clinical efficacy of the two groups was compared. RESULTS: After treatment, the scores of listening comprehension, retelling, naming, spontaneous conversation and BDAE grade in the two groups were improved compared with those before treatment (P<0.01, P<0.05), and those in the observation group were better than the control group (P<0.05). Compared before treatment, the levels of HbO2 and T-Hb were increased (P<0.01), and the levels of D-Hb were decreased (P<0.01) after treatment in the two groups. The levels of HbO2 and T-Hb in the observation group were higher than those in the control group (P<0.05), and the level of D-Hb was lower than that in the control group (P<0.05). The total effective rate was 92.3% (24/26) in the observation group, which was higher than 84.0% (21/25) in the control group (P<0.05). CONCLUSION: The scalp acupuncture electrical stimulation could improve cerebral circulation, activate specific functional areas of cerebral cortex, and promote the reconstruction and recovery of brain language function. Its curative effect is better than conventional scalp acupuncture.

Traditional Chinese herbal medicine Astragalus Radix and its effects on intestinal absorption of aconite alkaloids in rats.

Objective: Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the "Wei's Family Prescription". However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods: Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results: The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion: These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Therapeutic effect of electric-balance stimulation with scalp acupuncture for motor aphasia after cerebral infarction / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between scalp acupuncture electrical stimulation and routine scalp acupuncture for motor aphasia in subacute stage of cerebral infarction.@*METHODS@#A total of 54 patients with motor aphasia in subacute stage of cerebral infarction were randomly divided into an observation group (27 cases, 1 case dropped off) and a control group (27 cases, 2 cases dropped off ). Both groups were treated with routine medication and language training. In the observation group, scalp acupuncture was given at bilateral lower 2/5 of the parietal and temporal anterior oblique line and temporal frontline; after the arrival of @*RESULTS@#After treatment, the scores of listening comprehension, retelling, naming, spontaneous conversation and BDAE grade in the two groups were improved compared with those before treatment (@*CONCLUSION@#The scalp acupuncture electrical stimulation could improve cerebral circulation, activate specific functional areas of cerebral cortex, and promote the reconstruction and recovery of brain language function. Its curative effect is better than conventional scalp acupuncture.

Traditional Chinese herbal medicine Astragalus Radix and its effects on intestinal absorption of aconite alkaloids in rats / 中草药·英文版

Objective: Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the “Wei's Family Prescription”. However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods: Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results: The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion: These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Ultrasound-Enhanced Subcritical Fluid Extraction of Essential Oil from Nymphaea alba var and Its Antioxidant Activity.

Background: The essential oil content of the water lily is extremely low; thus, finding a new method that can extract essential oil from water lilies with a high extraction rate and no residual organic solvents is essential. Objective: The optimal processing conditions for the ultrasound-enhanced subcritical fluid extraction of essential oil from Nymphaea alba var (red water lily) and the antioxidant activity of the essential oil in vitro are investigated to provide theoretical bases for identification and development. Methods: Single-factor experiments and orthogonal designs are performed to determine the effects of extraction conditions on essential oil yields. The chemical composition of essential oil is analyzed using GC-MS. Results: The optimum extraction parameters are established as follows: extraction temperature, 35°C; extraction time, 30 min/time for four times; ratio of material to liquid, 1:3; ultrasound power, 250 W/L; and ultrasonic frequency, 20 kHz. The extraction rate of essential oil is 0.315% under these conditions. Eleven components comprise more than 1% content. The main chemical constituents are 8-hexadecyne (31.04%) and 2,6,10-trimethyl-tetradecane (3.95%). The essential oil from N. alba var has an antioxidant activity in vitro; however, its antioxidant activity is weaker than that of butylated hydroxytoluene. Conclusions: Subcritical fluid is suitable for the extraction of essential oil from N. alba var, and the essential oil has a good antioxidant activity. Highlights: The essential oil content of N. alba var is 0.315%. Forty-seven chemical constituents are identified and isolated from N. alba var and analyzed by GC-MS.

Pollen-mediated gene flow ensures connectivity among spatially discrete sub-populations of Phalaenopsis pulcherrima, a tropical food-deceptive orchid.

BACKGROUND: Gene flow in plants via pollen and seeds is asymmetrical at different geographic scales. Orchid seeds are adapted to long-distance wind dispersal but pollinium transfer is often influenced by pollinator behavior. We combined field studies with an analysis of genetic diversity among 155 physically mapped adults and 1105 F1 seedlings to evaluate the relative contribution of pollen and seed dispersal to overall gene flow among three sub-populations of the food-deceptive orchid Phalaenopsis pulcherrima on Hainan Island, China. RESULTS: Phalaenopsis pulcherrima is self-sterile and predominantly outcrossing, resulting in high population-level genetic diversity, but plants are clumped and exhibit fine-scale genetic structuring. Even so, we detected low differentiation among sub-populations, with polynomial regression analysis suggesting gene flow via seed to be more restricted than that via pollen. Paternity analysis confirmed capsules of P. pulcherrima to each be sired by a single pollen donor, probably in part facilitated by post-pollination stigma obfuscation, with a mean pollen flow distance of 272.7 m. Despite limited sampling, we detected no loss of genetic diversity from one generation to the next. CONCLUSIONS: Outcrossing mediated by deceptive pollination and self-sterility promote high genetic diversity in P. pulcherrima. Long-range pollinia transfer ensures connectivity among sub-populations, offsetting the risk of genetic erosion at local scales.

[Protective effect of Fuzheng Yanggan Mixture on drug-induced liver injury].

The model of drug-induced liver injury (DILI) induced by acetaminophen (APAP) in mice was established to investigate the anti-oxidation and anti-ferroptosis mechanisms of Fuzheng Yanggan Mixture on DILI. C57BL/6 mice were randomly divided into five groups: control group, model group, positive group, and low and high-dose Fuzheng Yanggan Mixture groups (0.12, 0.24 g·kg⁻¹). Mice were intragastrically administration with Fuzheng Yanggan Mixture (0.12, 0.24 g·kg⁻¹) once per day for 21 consecutive days, and at the same time, mice were weighted every day. The mice were injected intraperitoneally with 600 mg·kg⁻¹ of APAP to establish a mouse model of acute DILI after 16 h from the last administration of Fuzheng Yanggan Mixture. After 6 h from APAP challenge, the experimental animals were weighted and sacrificed to collect blood and liver tissue samples. And then, the effect of Fuzheng Yanggan Mixture on liver weight and the liver weight ratio of mice were examined; the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and the level of malondialdehyde (MDA), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in the liver tissue were measured. Prostaglandinendoperoxide synthase 2(ptgs2) mRNA level in liver tissues was detected by Q-PCR, and protein expression levels of SLC7A11 and GPX4 in liver tissues were detected by Western blot. Moreover, HE staining, immunohistochemical assay and TUNEL staining were used to observe pathological changes of the liver tissue sections. It is found that Fuzheng Yanggan Mixture could relieve APAP-induced liver enlargement and inhibit hepatic weight ratio increase. Compared with model group, the mice in Fuzheng Yanggan Mixture groups showed decreases in the content of ALT, AST and MDA, and increases in the content of GSH and NADPH. What is more, Fuzheng Yanggan Mixture could down-regulate ptgs2 mRNA level and up-regulate SLC7A11 and GPX4 protein levels. All of the results lead to a conclusion that Fuzheng Yanggan Mixture plays a protective effect on DILI in mice, which may be associated with the inhibition of ferroptosis.

2-(2-Phenylethyl)chromone derivatives in artificial agarwood from Aquilaria sinensis.

Seven new 2-(2-phenylethyl)chromone derivatives (1-7) including a chlorinated one (4), together with eight known ones (8-15), were isolated from the EtOAc extract of artificial agarwood originating from Aquilaria sinensis (Lour.) Gilg. All structures including the absolute configurations were unambiguously elucidated by spectroscopic (NMR, UV, IR, MS) methods, Mosher's method, and comparison with reported data in the literatures. Among those, compounds 8, 12, and 14 exhibited significant inhibition against α-glucosidase in vitro with IC50 values of 0.15, 0.05, and 0.09 mM, respectively (with acarbose as the positive control; IC50: 0.98 mM). In addition, compounds 3, 9, 11, and 14 showed weak inhibitory activity against AChE; and compounds 12 and 13 displayed weak cytotoxicity against human gastric cell line (SGC-7901) among three types of tested human cancer cell lines (BEL-7402, K562, and SGC-7901).

Strong Manual Acupuncture Manipulation Could Better Inhibit Spike Frequency of the Dorsal Horn Neurons in Rats with Acute Visceral Nociception.

Afferent impulses from visceral nociception can be regulated by acupuncture at spinal cord level; however, the effects of different manual acupuncture (MA) manipulations on the afferent impulses are still unknown. Here, we analyzed the spike frequency of excitatory gastric-related wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) following acute gastric distension (GD) in rats and compared their responses to MA manipulations with four different frequencies (0.5, 1, 2, and 3 Hz) at Zusanli (ST36). Results indicated that the spike frequency was increased by acute GD stimulation. Under acute GD circumstances, the spike frequency was further activated by weak MA stimulation (0.5 and 1 Hz), while being significantly inhibited by strong MA stimulation (2 and 3 Hz). After 10 minutes of the strong MA stimulation, same intensity of acute GD caused less spike frequency. Our previous researches had demonstrated that different MA manipulations could increase spike frequency in an intensity-dependent manner in normal rats; these findings suggest that acupuncture may have different modulatory effects depending on the state of the stomach. Since neuronal spike frequency was related to the level of nociception, the results suggest that strong MA manipulation may have better effect on acute visceral nociception.

Efficacy and safety of transcutaneous electrical acupoint stimulation to treat muscle spasticity following brain injury: a double-blinded, multicenter, randomized controlled trial.

OBJECTIVE: This study was aimed at evaluating the clinical efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) to treat muscle spasticity after brain injury (Chinese Clinical Trial Registry: ChiCTR-TRC-11001310). METHODS: A total of 60 patients with muscle spasticity after brain injury were randomized to the following 3 groups: 100, 2, and 0 Hz (sham) TEAS. The acupoints Hegu (LI4)--Yuji (LU10) and Zusanli (ST36)--Chengshan (BL57) on the injured side were stimulated at 0, 2, or 100 Hz, 5 times per week for 4 weeks. The patients were followed up for 1 and 2 months after the treatments. The effects of the treatments on muscle spasticity at the wrist, thumb, the other 4 fingers, elbow, shoulder, knee, and ankle were evaluated by the Modified Ashworth Scale, and the effects on disability were assessed by the Disability Assessment Scale. The walking capability was evaluated by the Holden functional ambulation classification score. The overall performance was assessed by the Global Assessment Scale score and the improved Barthel Index. The safety of the treatments administered was also monitored. RESULTS: The wrist spasticity was significantly reduced from baseline at weeks 2, 3, and 4 of treatment and at the 1- and 2-month follow-up visits in the 100 Hz group (P < 0.01). Compared with 2 Hz or sham TEAS, 100 Hz TEAS decreased wrist spasticity at weeks 2, 3, and 4 of treatment and 1 month after treatment (P < 0.001). The other endpoints were not affected by the treatments. No treatment-emergent adverse events were reported during treatments and follow-up visits. CONCLUSIONS: TEAS appears to be a safe and effective therapy to relieve muscle spasticity after brain injury, although large-scale studies are required to further verify the findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-11001310 http://www.chictr.org.

[Microbial transformation of glycyrrhetinic acid by Cunninghamella blakesleeana].

A study on the microbial transformation of glycyrrhetinic acid (GA) was conducted by a fungus, Cunninghamella blakesleeana CGMCC 3.970 systematically. After incubation with the cell cultures of C. blakesleeana CGMCC 3.970 at 25 degrees C for 7 days on a rotary shaker operating at 135 r x min(-1), GA was converted into one major product and five minor products. The products were extracted and purified by solvent extraction, macroporous adsorbent resin, silica gel column chromatography, and semi-preparative RP-HPLC chromatography. Their structures were identified as 3-oxo-15α-hydroxy-18ß-glycyrrhetinic acid(1), 3-oxo-15ß-hydroxy-18ß-glycyrrhetinic acid (2), 7ß,15α-dihydroxy-18ß-glycyrrhetinic acid (3), 3-oxo-7ß, 15α-dihydroxy-18ß-glycyrrhetinic acid (4), 7ß-hydroxy-18ß-glycyrrhetinic acid(5) and 15α-hydroxy-18ß-glycyrrhetinic acid(6) by the analyses of MS, 1H-NMR and 13C-NMR spectroscopic data respectively. Among them, 2 was a new compound. These results suggest that C. blakesleeana CGMCC 3.970 has the capability of selective ketonization and hydroxylation for GA. [Key words] glycyrrhetinic acid; Cunninghamella blakesleeana CGMCC 3. 970; microbial transformation

Two new Diels-Alder-type adducts from the stem barks of Morus yunanensis.

Two new Diels-Alder adducts, yunanensins B and D (1 and 2), were isolated from the stem bark of Morus yunanensis. Their structures were determined by spectroscopic analysis. Compounds 1 and 2 showed moderate antioxidant effects on liver microsomal lipid peroxidation induced by Fe(2+)-Cys system, with inhibitory ratios of 57.1% and 67.9% at a concentration of 10(-5) mol/l.

[Toll-like receptor 4 in regional acupoints and initiation of acupuncture signals].

It has been well documented that acupuncture effect is produced through suitable manipulation stimulation of the inserted acupuncture needle, and subsequent activation of the body' s inherent nerve-endocrine-immune regulating network. As a physical stimulus, the acupuncture stimulation exerted onto the local acupoint needs being converted into biological signal first, further reaching favorable regulation in the body. Toll-like receptor 4 (TLR 4), an important molecular pattern recognition receptor, can not only recognize the exogenous pathogen-associated molecular patterns but also identify endogenous damage-associated molecular patterns, leading to activation of innate immunity. What's more, TLR 4 has a close relationship with nervous and immune system of the body. In the present paper, the authors make a discussion on the correlation between TLR 4 and acupuncture intervention from 1) TLR 4 and acupuncture signal conversion, 2) TLR 4 and acupuncture clinical phenomenon, and 3) TLR 4 and related mechanisms of acupuncture intervention. Moreover, the authors also think that TLR 4 in the acupoint area may participate in the initiation process of acupuncture stimulation information.

Natural products chemistry research: progress in China in 2011.

This article reviews the progress made by Chinese scientists in the field of natural products chemistry in 2011. Selected compounds with unique structural features and/or promising bioactivities are described herein on the basis of structural types.

Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, part I: transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors.

We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition.

Discovery of potent selective bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model. Part II: optimization studies and demonstration of in vivo efficacy.

Selective phosphodiesterase 2 (PDE2) inhibitors are shown to have efficacy in a rat model of osteoarthritis (OA) pain. We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of phosphodiesterase 4 (PDE4) inhibitors, while minimizing PDE4 inhibitory activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like binding mode orthogonal to the cAMP-like binding mode found in PDE4. Extensive structure activity relationship studies ultimately led to identification of pyrazolodiazepinone, 22, which was >1000-fold selective for PDE2 over recombinant, full length PDEs 1B, 3A, 3B, 4A, 4B, 4C, 7A, 7B, 8A, 8B, 9, 10 and 11. Compound 22 also retained excellent PDE2 selectivity (241-fold to 419-fold) over the remaining recombinant, full length PDEs, 1A, 4D, 5, and 6. Compound 22 exhibited good pharmacokinetic properties and excellent oral bioavailability (F=78%, rat). In an in vivo rat model of OA pain, compound 22 had significant analgesic activity 1 and 3h after a single, 10 mg/kg, subcutaneous dose.

Natural products chemistry research: progress in China in 2011 / 中国天然药物

This article reviews the progress made by Chinese scientists in the field of natural products chemistry in 2011. Selected compounds with unique structural features and/or promising bioactivities are described herein on the basis of structural types.

Adverse events following acupuncture: a systematic review of the Chinese literature for the years 1956-2010.

OBJECTIVES: The objective of this study was to make non-Chinese readers better informed about the current safety situation of acupuncture in China. METHODS: Four (4) major Chinese comprehensive databases were searched: Chinese Journal Full-text Database (1949-2010), China Biomedical Literature Database (1978-2010), Chinese Technology Journal Database (1989-2010), and Wanfang (1998-2010). Case reports of adverse events related to acupuncture therapy were included. Literature reviews, case-control study, translations, duplicate literatures in various databases, and duplicate published articles with duplicate data were excluded. RESULTS: One hundred and sixty-seven (167) articles were included with 1038 cases, among which 35 patients died. The most frequent adverse events were syncope (468 cases), pneumothorax (307 cases), and subarachnoid hemorrhage (64 cases). CONCLUSIONS: Acupuncture-related adverse events were mainly caused by mental tension of the patient, improper operation by the doctor, and incompleteness of sterilization. Most of them can be avoided by standardizing teaching and clinical practices. Making the corresponding safety standards can greatly lower the risk of adverse events and protect patient safety to the greatest extent.

Natural products chemistry research 2010's progress in China.

This article reviews the progresses made by Chinese scientists in the field of natural products chemistry in 2010. Selected compounds with unique structural features and/or promising bioactivities were described herein on the basis of structural types.