[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.

Dendrobium offificinale polysaccharides prevents glucocorticoids-induced osteoporosis by destabilizing KEAP1-NRF2 interaction.

Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale (D. officinale) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale, on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo, respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.

Pharmacokinetic study of deufruquintinibs in rats by HPLC-MS/MS after oral administration.

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method was established to quantitatively determine the pharmacokinetics of fruquintinib (HMPL-013) and its derivatives [deufruquintinib-3D (HMPL-013-3D), deufruquintinib-6D (HMPL-013-6D) and deufruquintinib-9D (HMPL-013-9D)] in rats. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The method established in this assay was successfully applied to a pharmacokinetic study of HMPL-013 and HMPL-013-Ds after oral administration. These results showed that HMPL-013-Ds had longer half-life and larger area under the plasma concentration-time curve than HMPL-013, especially HMPL-013-6D, which provides a significant basis for innovative ideas for drug structure transformation to reduce drug administration frequency and dosage.

Application of Acupuncture to Attenuate Immune Responses and Oxidative Stress in Postoperative Cognitive Dysfunction: What Do We Know So Far?

Postoperative cognitive dysfunction (POCD) is a common sequela following surgery and hospitalization. The prevention and management of POCD are important during clinical practice. POCD more commonly affects elderly patients who have undergone major surgery and can result in major decline in quality of life for both patients and their families. Acupuncture has been suggested as an effective intervention for many neurological disorders. In recent years, there are increasing interest in the use of acupuncture to prevent and treat POCD. In this review, we summarized the clinical and preclinical evidence of acupuncture on POCD using a narrative approach and discussed the potential mechanisms involved. The experimental details and findings of studies were summarized in tables and analyzed. Most of the clinical studies suggested that acupuncture before surgery could reduce the incidence of POCD and reduce the levels of systematic inflammatory markers. However, their reliability is limited by methodological flaws. Animal studies showed that acupuncture reduced cognitive impairment and the associated pathology after various types of surgery. It is possible that acupuncture modulates inflammation, oxidative stress, synaptic changes, and other cellular events to mitigate POCD. In conclusion, acupuncture is a potential intervention for POCD. More clinical studies with good research design are required to confirm its effectiveness. At the same time, findings from animal studies will help reveal the protective mechanisms, in which systematic inflammation is likely to play a major role.

Effect of Hispolon from Phellinus lonicerinus (Agaricomycetes) on Estrogen Receptors, Aromatase, and Cyclooxygenase II in MCF-7 Breast Cancer Cells.

Phytoestrogen has previously been proposed as an alternative to hormone replacement therapy. Hispolon has been found to have phytoestrogenic properties. However, the possible effects of hispolon on estrogen receptors and other related molecules remain to be determined. This study was performed mainly to confirm the estrogenic function of hispolon as it relates to estrogen receptors, aromatase, and cyclooxygenase 2 (COX-2). Hispolon was shown to increase the serum 17ß-estradiol in vivo. Immunohistochemical staining methods showed that hispolon exhibited a biphasic effect on ERα/ß and aromatase expression in MCF-7 cells. Hispolon could also significantly inhibit aromatase activity, assessed using the enzyme-linked immunosorbent assay. Western blotting showed that COX-2 and aromatase could be inhibited by hispolon. These results further prove the phytoestrogenic features of hispolon and explore some pharmacological mechanisms that suggest that hispolon could be useful in the treatment of breast cancers or other gynecologic diseases.

Two new steroidal glycosides with unique structural feature of 14α-hydroxy-5ß-steroids from Reineckia carnea.

Two new steroidal glycosides (1-2) were isolated from the roots of Reineckia carnea, together with three known compounds (3-5). Their structures were determined on the basis of chemical methods and spectral data. Compounds 1-2 were the unique steroidal glycosides possessing structural feature of 14α-hydroxy-5ß-steroids, and compounds 4-5 were isolated from R. carnea for the first time. The isolated compounds (1-5) were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, the compounds 2 and 3 showed cytotoxicity against Caski cancer cell line with IC50 values of 34.4 and 3.7µM, respectively.

Hyperbaric oxygen therapy for postoperative spinal dural arterio-venous fistula patients: An observational cohort study.

Spinal dural arterio-venous fistula (SDAVF) is a common type of spinal vascular malformation. Surgical obliteration of the fistula can cure SDAVF anatomically, but the functional outcome is unsatisfactory.The aim of the study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on the functional recovery of postoperative SDAVF patients.This prospective cohort study included postoperative SDAVF patients. Patients were divided into control and HBOT groups. Patients in control group received conventional treatment, whereas those in the HBOT group received conventional treatment plus HBOT (2.0 atmospheric pressure absolute, 14 days). Follow-up was done at 1, 3, 6, 12, and 24 months after surgery for evaluation, including symptoms. To assess the effectiveness of HBOT on SDAVF patients, we compared the postoperative magnetic resonance imaging and neurological outcomes of each group with respect to modified Aminoff-Lougue scale and modified Denis Pain and Numbness Scale.From September 1, 2013 to January 31, 2014, 33 SDAVF patients (27 male) treated by microsurgery were included in this study. Sixteen patients were in the HBOT group and 17 patients were in the control group. At 24 months follow-up, the improvement of mDPNS for the HBOT group was significantly larger than those of the control group (2.25 vs 0.88; P = 0.005). In the HBOT group, the average length of hypersignal in magnetic resonance imaging T2 image decrease at 3 months after surgery was 3.25 compared with 2.29 in the control group (P = 0.009). No major adverse effects were reported for all 16 patients who received HBOT.The current findings suggest that HBOT is an effective and safe treatment to relieve lower body pain and numbness for postoperative SDAVF patients.

Acupuncture for refractory epilepsy: role of thalamus.

Neurostimulation procedures like vagus nerve stimulation (VNS) and deep brain stimulation have been used to treat refractory epilepsy and other neurological disorders. While holding promise, they are invasive interventions with serious complications and adverse effects. Moreover, their efficacies are modest with less seizure free. Acupuncture is a simple, safe, and effective traditional healing modality for a wide range of diseases including pain and epilepsy. Thalamus takes critical role in sensory transmission and is highly involved in epilepsy genesis particularly the absence epilepsy. Considering thalamus serves as a convergent structure for both acupuncture and VNS and the thalamic neuronal activities can be modulated by acupuncture, we propose that acupuncture could be a promising therapy or at least a screening tool to select suitable candidates for those invasive modalities in the management of refractory epilepsy.

A nutrient mixture reduces the expression of matrix metalloproteinases in an animal model of spinal cord injury by modulating matrix metalloproteinase-2 and matrix metalloproteinase-9 promoter activities.

This study aimed to determine whether a novel nutrient mixture (NM), composed of lysine, ascorbic acid, proline, green tea extracts and other micronutrients, attenuates impairments induced by spinal cord injury (SCI) and to investigate the related molecular mechanisms. A mouse model of SCI was established. Thirty-two mice were divided into four groups. The sham group received vehicle only. The SCI groups were treated orally with saline (saline group), a low dose (500 µg 3 times/day) of NM (NM-LD group) or a high dose (2,000 µg 3 times/day) of NM (NM-HD group). The levels of mouse hindlimb movement were determined every day in the first week post-surgery. The protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Wild-type and mutant MMP-2- and MMP-9-directed luciferase constructs were generated and their luciferase activities were determined. NM significantly facilitated the recovery of hindlimb movement of the mice in comparison to that in the saline group. The expression levels of MMP-2 in the NM-LD and NM-HD groups were decreased by ~50% compared with the saline group as indicated by western blotting results. The expression levels of MMP-9 in the NM-LD and NM-HD groups were decreased to ~25 and ~10%, respectively. These results suggest that NM significantly inhibits the expression of MMP-2 and MMP-9 proteins. Reverse transcription quantitative polymerase chain reaction results indicated that NM reduced the levels of MMP-2 and MMP-9 mRNA. Furthermore, the luciferase results indicated that site-directed mutagenesis comprising a -1306 C to T (C/T) base change in the MMP-2 promoter and a -1562 C/T base change in the MMP-9 promoter abolished the inhibitory effects of NM on MMP-2 and MMP-9 promoters. These results suggest that NM attenuates SCI-induced impairments in mice movement by negatively affecting the promoter activity of MMP-2 and MMP-9 genes and thus decreasing the expression of MMP-2 and MMP-9 proteins.

Triptolide downregulates Treg cells and the level of IL-10, TGF-ß, and VEGF in melanoma-bearing mice.

Regulatory T cells play a key role in suppressing tumor immunity. Triptolide, a major active component isolated from the Chinese medicinal herb Tripterygium wilfordii, has been proven to possess multiple antitumor activities. Here, we investigated the effect of triptolide on regulatory T cells and on the level of IL-10, transforming growth factor-ß, and vascular endothelial growth factor in tumor-bearing mice. Fifty male C57BL/6 mice were randomly grouped as follows: normal control group, model group with B16-F10 cells implanted, and three treatment groups with cyclophosphamide, triptolide-high dose, triptolide-low dose. The proportion of regulatory T cells in the spleen and axillary lymph nodes was evaluated by flow cytometric analysis. Production of cytokines IL-10, transforming growth factor-ß, and vascular endothelial growth factor in serum was measured using enzyme-labeled immunosorbent assay kits. The mRNA levels of Foxp3, IL-10, and transforming growth factor-ß in the spleen and vascular endothelial growth factor in tumor tissue were detected by real-time PCR. The results showed that triptolide significantly decreased the proportion of regulatory T cells and lowered the Foxp3 level in the spleen and axillary lymph nodes of tumor-bearing mice. Production of IL-10 and transforming growth factor-ß in peripheral blood, and the mRNA level of IL-10 and transforming growth factor-ß in the spleen were also decreased. Additionally, triptolide could remarkably inhibit production of vascular endothelial growth factor in tumor-bearing mice. In conclusion, our study demonstrated that triptolide might inhibit tumor growth by inhibiting regulatory T cells and some cytokines such as IL-10 and transforming growth factor-ß, as well as production of vascular endothelial growth factor.

Tupisteroide A-C, three new polyhydroxylated steroidal constituents from the roots of Tupistra chinensis.

Three new steroidal compounds with polyhydroxy groups, tupisteroide A-C (1-3), were obtained from the roots of Tupistra chinensis, together with one known compound (4) that was isolated from this plant for the first time. The structures of tupisteroide A-C were determined on the basis of one- and two-dimensional NMR spectroscopy, including (1) H-(1) H Correlation Spectroscopy, Heteronuclear Multiple Bond Correlation, and Heteronuclear Single Quantum Coherence experiments. The isolated compounds were evaluated for their cytotoxic activities against A549, HepG2, and CaSki cancer cell lines in vitro. Among them, compounds 1, 2, and 4 did not show significant inhibitory activity, but compound 3 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 25.0 µM.

Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae (Gusuibu).

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese traditional medicine Rhizoma drynariae (Gusuibu) is widely used for clinically treating osteoporosis and bone non-union. Naringin and its active metabolite naringenin are the main active ingredients of Rhizoma drynariae total flavonoids. AIM OF THE STUDY: The purpose of this paper is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin, and provide the basic data to further study for the dose-effect relationship and the mechanism for Rhizoma drynariae in treatment of osteoporosis and other estrogen deficiency-related diseases. MATERIALS AND METHODS: Naringin was extracted from Rhizoma drynariae. Naringin and its metabolin naringenin were tested estrogenic and anti-estrogenic activities through the experiment of cell proliferation and uterus weight gain in mice. Their estrogen-receptor binding abilities were tested by yeast two-hybrid experiment and nuclear receptor cofactor assays (RCAS) experiment, and their possible binding sites for ERß were performed by computer aided molecular docking technology. RESULTS: Naringin and naringenin showed significant effects on the proliferation of estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased proliferation as the drug concentration, and the strongest proliferation appeared at a concentration of 8.6×10(-5)M. When estradiol (10(-10)M) and the different concentrations of naringin or naringenin were treated at the same time, naringin and naringenin could result in antagonistic effects on estradiol-induced MCF-7 cell proliferation, but they did not significantly affect proliferation of estrogen-insensitive ER(-) MDA-MB-231 cells. Naringin and naringenin exhibited higher binding capacity to estrogen receptor ß (ERß) than estrogen receptor α (ERα) in yeast two-hybrid experiments and nuclear receptor cofactor assays (RCAS) experiment. Docking simulation between naringin/naringenin and ERß were performed, and the corresponding binding free energies of naringin-receptor and naringenin-receptor docked complexes were -7.95 and -10.45kcal/mol. Hydrogen bonds were found between naringin and the amino acid residues Lys304 and His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and there may be hydrophobic space interactions between phenyl group (C13-C18) of naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and Leu380. CONCLUSIONS: Naringin and naringenin revealed a double directional adjusting function of estrogenic and anti-estrogenic activities. Both of them showed estrogenic agonist activity at low concentration or lack of endogenous estrogen. On the other hand, they also acted as estrogenic antagonists at high concentrations or too much endogenous estrogen. They produced estrogenic and anti-estrogenic effects primarily through selectively binding with ERß, which could prevent and treat osteoporosis with the mechanism of estrogenic receptor agitation. This paper confirmed the estrogenic and anti-estrogenic activity of naringin and naringenin, and further studies were still essential to study their dose-effect relationship and the anti-osteoporosis mechanism for Rhizoma drynariae in the treatment of osteoporosis and other estrogen deficiency-related diseases.

[Chemical constituents from leaves of Boehmeria nivea].

OBJECTIVE: To study the chemical constituents from the leaves of Boehmeria nivea. METHOD: The leaves were extracted by 95% EtOH at room temprature, the chemical leaves were isolated and purified by repeated silica gel column chromatography, Sephadex LH-20 column chromatography and semipreparative HPLC, and their structures were identified by physical and chemical properties and spectroscpoic methods. RESULT: One compound isolated from n-butanol fraction, four compounds were obtained from ethyl acetate fraction and three compounds from petroleum ether fraction. Their structures were elucidated as kiwiionoside (1), eugenyl beta-rutinoside (2), uracil (3), beta-sitosterol glucoside (4), 3-hydroxy-4-methoxy-benzoic acid (5), cholesterol (6), alpha-amyrin (7). nonacosanol (8). CONCLUSION: Compounds 1-3, 5-8 were isolated from the genus Boehmeria for the first time.

Tongxinluo inhibits oxidized low-density lipoprotein-induced maturation of human dendritic cells via activating peroxisome proliferator-activated receptor gamma pathway.

TongXinLuo (TXL) is a traditional Chinese herbal medicine with multiple vasoprotective activities. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TXL on oxidized low-density lipoprotein (OX-LDL)-induced maturation and immune function of DCs. Human monocyte-derived DCs were incubated with TXL or ciglitazone and were subsequently stimulated with OX-LDL to induce maturation. Similar to ciglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, TXL could significantly reduce the maturation-associated markers induced by OX-LDL, such as CD40, CD86, CD1a, and human leukocyte antigen-DR; improved the endocytotic function; and decreased secretions of cytokine interleukin-12 and tumor necrosis factor alpha. These inhibitory effects of TXL could be partly reversed by silencing the expression of PPAR gamma in DCs. In conclusion, TXL could inhibit OX-LDL-induced maturation of DCs through activating PPAR gamma pathway.

Inhibiting effects of total saponins of panax ginseng on immune maturation of dendritic cells induced by oxidized-low density lipoprotein.

Total saponins of panax ginseng (TSPG) are the major active components in panax ginseng. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TSPG on the maturation and immune function of DCs. Compared with those untreated, the DCs pre-treated with TSPG and then induced by oxidized-LDL exhibited a significantly lower expression of the maturation-associated markers of CD40, CD86, HLA-DR, and CD1a, together with an increased endocytosic function as well as decreased secretions of cytokine. However, silencing the expression of PPARgamma in DCs, the inhibitory effect of TSPG on the maturation DCs was significantly reduced. In conclusion, TSPG could inhibit the maturation of DCs induced by oxidized-LDL which suggests beneficial effects on atherosclerosis and this effect was partly dependent on the PPARgamma pathway at least.

Effect of electroacupuncture on thalamic neuronal response to visceral nociception.

The thalamus has been shown to play an important role in somatovisceral integration. This study set out to examine thalamic neuronal responses to visceral nociception when electrical stimulation was applied to the skin receptive field (RF) or to ST(36), an acupoint most frequently used for abdominal pain conventionally. Single neuronal recordings were carried out extracellularly in the thalamic ventrobasal nucleus of anaesthetized rats. Among numerous neurons responding to tactile stimulation, 72 units were found responsive not only to innocuous stimulation on skin RF (60 activated, 12 inhibited) but also to noxious colorectal distension (CRD). Electrical stimulation (2 Hz, 1 mA) of the neuronal somatic receptive field center reduced the subsequent neuronal responses to CRD in 40 neurons tested. High frequency stimulation (100 Hz) produced stronger inhibition than low frequency (2 Hz) stimulation at RF. The inhibition on visceral nociceptive response occurred immediately after the stimulation. In comparison with the effect of RF stimulation, the inhibitory effect was less at either ipsilateral or contralateral ST(36). Our data suggest that, at single thalamic neuron level, stimulation at conventional acupoint is not necessarily as effective as stimulation at neuronal skin receptive field, and high frequency is more effective than low frequency stimulation for the inhibition of visceral nociception.

[Protective effect of tongxinluo superfines on angiotensin II caused renal injury in rat].

OBJECTIVE: To explore the renal protective effect of Tongxinluo (TXL) and its mechanism of action. METHODS: Eight-week old SD rats were divided into the sham-operated group (A), the model group (B) and the TXL group, 6 rats in each group. Angiotensin II (Ang II) was administered slowly (200 ng/kg per min) to rats in group B and C via subcutaneously embedded osmotic pump to make them stimulative model of renal injury, while to rats in group A, pump embedding with saline infusion. After modeling, TXL was given to group C by gastric perfusion in dosage of 0.8 g/kg per day. And the following indexes were observed 14 days later: configuration of renal arterial endothelium by transmission electron microscope; pathologic figure of kidney with HE stain; renal apoptosis by TUNEL; expression of p53 and p22phox by RT-PCR;and level of reactive oxygen species (ROS) in kidney. RESULTS: Different degree of congestion, swelling, denudation of endothelial cell in renal arterial endothelial cell; glomerular matrix proliferation and partial glomerular atrophy with tendency of fibrosis; increased renal parenchymal apoptosis; enhanced expression of p53 and p22phox; and elevated ROS were found in model animals. All the above-mentioned abnormalities, including glomerular injury, renal cell apoptosis, as well as the increased p53, p22phox expressions and ROS production were all alleviated in group C after TXL treatment. CONCLUSION: TXL could protect renal against Ang II injury, and it may be realized by inhibiting NADPH-ROS/p53 pathways and suppressing cell apoptosis in renal parenchyma.

Antiepileptic effect of electroacupuncture vs. vagus nerve stimulation in the rat thalamus.

Our previous study has shown that both electroacupuncture (EA) and vagus nerve stimulation (VNS) can inhibit cortical epileptiform activities induced by pentylenetetrazole (PTZ). The current study compared the effects of EA and VNS on thalamic neuronal responses to PTZ-induced epileptiform activities. Under general anesthesia, extracellular single unit recordings were made from 49 single neurons in the rat ventrobasal (VB) thalamus. The left vagus nerve was stimulated at 30 Hz, 1 or 3 mA for 5 min. For EA, "Dazhui" acupoint (GV14) was stimulated with the same parameters. It was found that (1) the VB thalamic neurons showed epileptiform activities after PTZ injection; (2) VNS and EA could predominantly inhibit the PTZ-induced epileptiform activities in the thalamic neurons. The higher intensity stimulation (3 mA) in either VNS or EA was, however, not associated with a greater inhibition. Our study suggests that both EA and VNS reduce epileptiform activities at the thalamic level, and EA may be an alternative to VNS.

Antiepileptic effects of electroacupuncture vs vagus nerve stimulation on cortical epileptiform activities.

Introduced about two decades ago, vagus nerve stimulation (VNS) therapy has been increasingly used for the treatment of refractory epilepsy recently. This study was set out to compare the effects between VNS and electroacupuncture (EA) on pentylenetetrazole (PTZ) induced epileptiform activities in the rat cerebral cortex. Under general anesthesia, the parietal cortex of the rat (n=20) was exposed to record the cortical epileptiform activities. The left vagus nerve was stimulated at 30 Hz, 1 mA or 3 mA for 5 min. For EA, "Dazhui" acupoint (GV14) was stimulated with a pair of acupuncture needles with the same parameters. The results show that both VNS and EA at either 1 mA or 3 mA could inhibit the PTZ-induced cortical epileptiform activities, and higher stimulation (3 mA) was not associated with a greater inhibition. In the cases that showed inhibitory responses, there were no statistically significant differences between the two modalities, implying that EA could be comparable to VNS in the treatment of epilepsy. Thus, under current experimental settings, the antiepileptic effect induced by electrical stimulation appeared not vagal specific, and EA could be a good alternative to VNS in the management of epilepsy.

Chinese medicine formula DSQRL versus glucocorticoids for the treatment of experimental pulmonary fibrosis.

Pulmonary fibrosis (PF) is a devastating interstitial lung disease that may develop idiopathically or as a complication of many other diseases. The outcome of the current main treatment by glucocorticoids is by no means satisfactory. This study has tested a new Chinese medicine Decoction for Strengthening Qi and Replenishing Lung (DSQRL) for the treatment of experimental PF in comparison with prednisolone. Eighty-five rats with PF induced by CCl(4) were randomly divided into 4 groups to undertake treatment either by (a) high dose of prednisolone; (b) Chinese medicine formula DSQRL; (c) combined treatment of the above two; or (d) sham feeding of water in equal volume. At the end of 60 days treatment, the DSQRL treatment achieved a significantly better outcome than prednisolone in terms of general behavior, histological examination, hydroxyproline content of the lung and inflammatory cell counts in bronchoalveolar lavage fluid. Thus, the newly proposed Chinese medicinal formula DSQRL appears to be a better and promising option for PF than glucocorticoids for the treatment of PF.