[Development of needle-thread integrative embedding needle].

The needle-thread integrative embedding needle consists of needle handle, needle core, thread, locker and needle guard. The thread is fixed in the core by the locker. With the needle inserted into acupoint, the locker is separated from the thread, while the thread is embedded directly into acupoint, to achieve one acupoint with one needle. This type of thread embedding needle is operated simply and safely without cross infection occurrence, easy to carry.

[International standard ISO 22236 Traditional Chinese medicine-Thread-embedding acupuncture needle for single use: experience and recommendation].

The ISO 22236 Traditional Chinese medicine-Thread-embedding acupuncture needle for single use, as the first international standard (IS) in acupoint thread-embedding field, has been officially published by International Organization for Standardization (ISO) in 2020. The background of its development, difficulties and countermeasures in the process of development were reviewed, and the experience of standard development was summarized, aiming to provide methods and references for future IS development of acupuncture and moxibustion instruments. It is suggested that strengthening the discourse power in the process of IS development, increasing the compound talents cultivation for IS, valuing the importance of enterprises in the development of IS, and creating an advantageous environment for the development of IS are the keys to improve the level of standardization of acupuncture and moxibustion instruments and play a more important role in the IS development.

A Urinary Metabolomics Analysis Based on UPLC-MS and Effects of Moxibustion in APP/PS1 Mice.

OBJECTIVE: Alzheimer's disease (AD) is a common neurodegenerative disorder with the symptoms of cognitive impairment and decreased learning and memory abilities. Metabolomics can reflect the related functional status and physiological and pathological changes in the process of AD. Moxibustion is a unique method in traditional Chinese medicine, which has been used in the treatment and prevention of diseases for thousands of years. METHODS: A total of 32 APP/PS1 mice were randomly divided into the model group, moxibustion group, moxa smoke group and smoke-free moxibustion group (n=8/group), using the random number table method, while eight C57BL/6 mice were used as the control group. The five groups were measured for 20 min/day, 6 days/week, for 4 weeks. After 4 weeks' experiment, all the mice were placed in metabolic cages to collect urine continuously for 24 hours, for UPLC-MS analysis. RESULTS: Principal component analysis (PCA) was used to identify the different metabolites among the five groups, and partial least squares discriminant analysis (PLS-DA) was performed to reveal the effects on the metabolic variance. Sixteen potential biomarkers were identified among the five groups, primarily related to amino acid metabolism, starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, and aminoacyl biosynthesis. There were 17 differences in the potential metabolites between the control and model groups, involving the metabolism of amino acid, purine, pyrimidine, nicotinic acid and nicotinamide, and biosynthesis of pantothenate and coenzyme A. Fifteen potential biomarkers were identified between the model and moxibustion groups, related to starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, glyoxylate, dicarboxylate anions and some amino acid metabolism. CONCLUSION: Moxibustion can regulate the metabolism of substance and energy by improving the synthesis and decomposition of carbohydrates and amino acids in APP/PS1 transgenic AD model mice.

Curcumin Suppresses Aldosterone-Induced CRP Generation in Rat Vascular Smooth Muscle Cells via Interfering with the ROS-ERK1/2 Signaling Pathway.

Aldosterone regulates the initiation and development of atherosclerosis which is identified as a chronic inflammatory disease by promoting the generation of C-reactive protein in vascular smooth muscle cells. Curcumin is the most active ingredient of turmeric with anti-inflammation and antioxidation effects. Here, the effect of curcumin on aldosterone-induced C-reactive protein generation in vascular smooth muscle and the molecular mechanisms involved were explored. Primary rat vascular smooth muscle cells and hyperaldosteronism model rats were used in this study. The amount of C-reactive protein, reactive oxygen species, and the signaling pathway-related molecules generated were estimated. We found that curcumin inhibited aldosterone-induced C-reactive protein generation in vascular smooth muscle cells by interfering with the reactive oxygen species-ERK1/2 signal pathway. The results provide new evidence for the potential anti-inflammatory and cardiovascular protective effects of curcumin.

Moxibustion at CV4 alleviates atherosclerotic lesions through activation of the LXRα/ABCA1 pathway in apolipoprotein-E-deficient mice.

OBJECTIVES: To investigate the anti-atherogenic effect of moxibustion and whether it is mediated through the reverse cholesterol transport process. METHODS: 8-week-old male apolipoprotein E deficient (ApoE-/- knockout) mice were randomly divided into two groups (n=10 per group): atherosclerosis (AS) and AS plus moxibustion (AS+M). C57BL/6J mice of the same background (n=10) were selected as controls. Mice in the AS+M group received indirect moxibustion with an ignited moxa stick held over CV4. Mice of the AS and control groups were restrained in the same holder with an unlit moxa stick held over CV4. All treatments were performed for 20 min per day, 6 days per week for 12 weeks. After the treatment, the mice were euthanased and their serum lipids were measured. The aortic roots and thoracic aortas were collected for haematoxylin and eosin and red oil O staining, respectively, to analyse the atherosclerotic lesions. Expression of adenosine triphosphate binding cassette (ABCA)A1/G1 and liver X receptor α (LXRα) in the thoracic aorta were examined with Western blotting. RESULTS: The moxibustion-treated (AS+M) mice showed a significantly lower plaque area percentage in the aortic root and thoracic aorta, and higher expression of LXRα and ABCA1 in the thoracic aorta compared with the AS mice. No significant differences were found in average lipid area percentage in the thoracic aorta, or ABCG1 expression in the thoracic aorta, between mice in the AS+M and AS groups. CONCLUSION: Moxibustion treatment at CV4 suppressed the progression of atherosclerotic lesions in ApoE-/- mice. The anti-atherogenic effect of moxibustion may be achieved by: (1) regulation of lipid metabolism, and thus prevention of lipid accumulation; and (2) upregulation of LXRα- and ABCA1-mediated cholesterol efflux in the lesion area.

Lung Function Decline after 24 Weeks of Moxa Smoke Exposure in Rats.

OBJECTIVE: Moxibustion is a complementary therapy that has been used for thousands of years. Burning moxa produces smoke and inhalable particulates. Recent research has indicated that smoke inhalation is associated with negative lung effects. This study aimed to evaluate the lung function of rats after moxa smoke exposure at different concentrations. METHODS: Using a randomised block experiment design, 28 male Wistar rats were randomly divided into three moxa smoke groups (opacity) (n=7): low concentration (27.45 mg/m3), medium concentration (168.76 mg/m3), and high concentration (384.67 mg/m3) with a control group. Rats in the moxa smoke groups were exposed in an automatic dynamic exposure device separately with different concentrations for 20 min/d, 6d/week, for 24 weeks. Rats in the control group were exposed in the same space without moxa smoke. Lung function was evaluated by the AniRes 2005 animal pulmonary function analysing system. Statistical Product and Service Solutions 18.0 software was used for data analysis. RESULTS: In the study, no deaths were found in any group. There was no difference of forced expiratory volume in one second/forced vital capacity percentage (FEV1/FVC%), inspiratory resistance (Ri), and expiratory resistance (Re) among each group after 24 weeks of moxa smoke exposure (P>0.05). Compared with the control group (0.33 ml/cmH20), dynamic compliance (Cdyn) was reduced in the medium (0.29 ml/cmH20) and high (0.25 ml/cmH20) concentration groups (P<0.05); however, Cdyn in the low concentration group (0.29 ml/cmH20) was not significantly affected. CONCLUSION: Moxa smoke exposure at low concentrations did not affect the rat's lung function. Moxa smoke of medium and high concentrations destroyed the lung function represented by decreased Cdyn. However, moxa smoke of low concentrations (27.45 mg/m3) is much higher than the concentration in a regular moxibustion clinic (3.54 mg/m3). Moxa smoke at higher concentrations might destroy the lung function. The safety evaluation of moxa smoke requires further research.

Twelve-week study of moxa smoke: occupational exposure in female rats.

OBJECTIVE: To assess the toxicity of moxa smoke in rats. METHODS: Forty-eight female Wister rats were randomly divided into 4 groups (n = 12/group) to simulate moxa smoke exposure in Chinese medicine clinics (CMCs): the control group, and three moxa-smoke exposed groups of PM10 mass concentrations 3-5, 7-9 and 27-30 mg/m3 , respectively. These concentrations were 1 × , 2-3 × , and 7-9 × fold the concentrations found in CMCs. Exposures continued for 12 weeks (200 min/d, 5 d/week). RESULTS: No deaths were noted. After the exposure, the body weights, ratios of organ weight to body weight, urinary parameters, hematological parameters, clinical chemistry parameters and microscopic examinations revealed no obvious toxicity. CONCLUSION: Moxa smoke did not induce toxic effects in female rats in the study. These findings provide new evidence to the toxicity of moxa smoke.

Moxibustion in Early Chinese Medicine and Its Relation to the Origin of Meridians: A Study on the Unearthed Literatures.

Moxibustion is an integral part of Traditional Chinese Medicine (TCM). It achieved higher level of recognition and had more general application in ancient times than in contemporary life. As the vital historical sources, the records of unearthed literatures offered precious insights to Chinese social life pattern and medical practice in Qin and Han dynasties (221 BC-220 AD). There was no surprise that the bamboo and silk documents excavated from Mawangdui () tomb, Hantanpo () tomb, and other relics had a large amount of texts relevant to moxibustion. This research sorted moxibustion recordings from seven unearthed literatures and discovered that moxibustion had been developed into different modalities and utilized to treat many diseases at that time. In addition, the indications, contraindications of moxibustion, and the method of postmoxibustion care were also discussed. On this basis, some hints were provided to support the hypothesis that the practice of moxibustion led to the discovery of meridians. All our preliminary results in the research have drawn attention for this old therapy and given a new source for its application in clinic and scientific research.

A new flavonoid glycoside (APG) isolated from Clematis tangutica attenuates myocardial ischemia/reperfusion injury via activating PKCε signaling.

Clematis tangutica has been shown to be beneficial for the heart; however, the mechanism of this effectremains unknown. Apigenin-7-O-ß-D-(-6″-p-coumaroyl)-glucopyranoside (APG) is a new flavonoid glycoside isolated from Clematis tangutica. This study investigates the effects of APG on myocardial ischemia/reperfusion (IR) injury (IRI). An IRI model of primary myocardial cells and mice was used in this study. Compared with the IR group, APG preconditioning is protective against IRI in primary myocardial cells and in mice hearts in a dose-dependent manner. The cardioprotective mechanisms of APG may involve a significant PKCε translocation into the mitochondria and an activation of the Nrf2/HO-1 pathway, which respectively suppressesmitochondrial oxidative stress and inhibits apoptosis. In addition, PKCε-targeted siRNA and a PKCε specialized inhibitor (ε-V1-2) were used to inhibit PKCε expression and activity. The inhibition of PKCε reversed the cardioprotective effect of APG, with an inhibition of Nrf2/HO-1 activation and increased mitochondrial oxidative stress and cardiomyocyte apoptosis. In conclusion, PKCε activation plays an important role in the cardioprotective effects of APG. PKCε activation induced by APG preconditioning reduces mitochondrial oxidative stress and promotes Nrf2/HO-1-mediated anti-apoptosis signaling.

[Micronucleus in vitro induced by inhalable particulate matters in moxa smoke].

OBJECTIVE: To investigate whether inhalable particulate matters can cause the damage of chromosome or mitotic apparatus to produce micronucleus, and to evaluate genetic toxicology of moxa smoke on chromosome. METHODS: By MTT method, the 24 h half maximal inhibitory concentration (IC50) of moxa smoke condensation (MSC) on Chinese hamster ovary (CHO) cells was 0.087 mg/mL. CHO cells, which were cultured in vitro, were divided into a solvent control group, a positive control group (cyclophosphamide as solvent), a low concentration group, a moderate concentration group and a high concentration group. The low concentration group, moderate concentration group and high concentration group were set approximately 1/8, 1/4, 1/2 of IC50, respectively. Whether micronucleus had dose-effect response induced by the damage of chromosome or mitotic apparatus was observed after CHO cells were contaminated by MSC in the low concentration group, moderate concentration group and high concentration group. RESULTS: The rate of micronucleus induced by MSC in the low concentration group, moderate concentration group and high concentration group was higher than that in the solvent control group (all P < 0.05), which presented dosage-effect response. The experiment was repeated 3 times, indicating it was repeatable with statistical significance. CONCLUSION: High concentration of MSC shows toxicity to induce chromosome damage, which disappears at low concentration. The genetic toxicology is also dependent on concentration, and the concentration of moxa smoke is essential. In clinical treatment, it is noted to control the level of moxa smoke, while the clinical safety standard of moxa smoke concentration is in need of further study.

The selective estrogen receptor modulators in breast cancer prevention.

BACKGROUNDS: Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). METHODS: Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. RESULTS: To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. CONCLUSION: A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

[Effects of moxa smoke with different concentrations on expression of SOD and MDA in lung and serum of rats].

OBJECTIVE: To observe the effects of intervention of moxa smoke with different concentrations on superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and lung of male rats, so as to explore the safety concentration of moxa smoke. METHODS: A total of 32 Wistar male rats were randomly divided into a control group, a low-concentration group, a moderate-concentration group and a high-concentration group, 8 rats in each one. All the rats were exposed in the full-automatic toxicant exposure cabinet, and the overshadow of moxa smoke was set at 0%, 10%, 40% and 70%, respectively. Each rat was exposed for 20 min per day. After 26 weeks, the activities of SOD and content of MDA in serum, lung organ and bronchoalveolar lavage fluid were tested. RESULTS: Compared with the control group, the activities of serum SOD in the high-concentration group were reduced (P< 0. 05), but those in the low-concentration group and moderate-concentration group were not significantly different (both P>0. 05). Compared with the control group, the content of serum MDA in the low-concentration group, moderate-concentration group and high-concentration group was increased insignificantly (all P>0. 05). There were no significant differences regarding activities of SOD and content of MDA in lung organ and bronchoalveolar lavage fluid among each moxa smoke group (all P>0. 05). CONCLUSION: There is no obvious toxic reaction in the low-concentration group and moderate-concentration group; in the high-concentration group the antioxidant ability is damaged due to long-term exposure.

Effects of shenque moxibustion on behavioral changes and brain oxidative state in apolipoprotein e-deficient mice.

Purpose. To determine whether moxibustion influences the learning and memory behavior of ApoE-/- male mice, and investigate the mechanism of moxibustion on the alteration of oxidized proteins (glial fibrillary acidic protein, ß-amyloid) in hippocampus. Methods. Thirty-three ApoE-/- mice were randomly divided into 3 groups (n = 11/group): moxibustion, sham moxibustion, and no treatment control. Wild-type C57BL/6 mice (n = 13) were used for normal control. Moxibustion was performed with Shenque (RN8) moxibustion for 20 minutes per day, 6 days/week for 12 weeks. In sham control, the procedure was similar except burning of the moxa stick. Behavioral tests (step-down test and Morris water maze task) were conducted in the 13th week. The mice were then sacrificed and the tissues were harvested for immune-histochemical staining. Results. In the step-down test, the moxibustion group had shorter reaction time in training record and committed less mistakes compared to sham control. In immune-histochemical study, the moxibustion group expressed lower level of GFAP and less aggregation of ß-amyloid in the hippocampus than the sham control. Conclusion. Our findings suggest that moxibustion may enhance learning capability of ApoE-/- mice. The mechanism may be via inhibiting oxidized proteins (GFAP and ß-amyloid) in astrocytes.

Use of the Layer Analysis Method of the Yellow Emperor's Inner Classic in modern society.

This article introduces the Layer Analysis Method of the Yellow Emperor's Inner Classic text to revive its use in modern acupuncture and medicine. This is a crucial concept, especially for the diagnosis and treatment of diseases by acupuncture. First, the rise and decline of this method is explored. Second, the differentiation of this method is described by symptoms, the affected organs, and the stage of the disease. Third, the treatment method is summarized into four categories: (1) equipment, (2) technique, (3) acupoint, and (4) pathology. The resemblance of the Layer Analysis Method to modern clinical applications is worth examining. The sinew layer is especially fascinating with its similarity to the Anatomy Trains' track. The skin, vessel, muscle, and bone layers have their respective resemblances to their counterparts in modern medicine. The holism concept of traditional Chinese medicine (TCM) is demonstrated throughout the Layer Analysis Method theory. In addition, the Layer Analysis Method of the Yellow Emperor's Inner Classic should be reconsidered and complemented by channel-collateral pattern differentiation for acupuncturists to achieve better clinical results. Future research on acupuncture should consider this theory with the channel-collateral pattern differentiation theory.

[Effects of controllable dynamic inhaled exposure of moxa smoke on LDL-r, ICAM-1 and morphology of heart tissue in rats].

OBJECTIVE: To observe the change of lipid metabolism and vascular endothelium as well as morphology of heart tissue in rats who were long-time exposed to moxa smoke with different concentrations in order to provide reference for safety assessment of moxa smoke on cardiovascular system. METHODS: One hundred and sixty-eighty Wistar rats were randomly divided into a control group, a low-concentration group, a median-concentration group and a high-concentration group, 42 rats in each one. The rats were exposed to moxa smoke with concentration of 0%, 10%, 40% and 70%, respectively, for 20 min per day. After continuous intervention for six months, enzyme-linked immunosorbent assay (ELISA) was applied to measure the level of low density lipoprotein-receptor (LDL-r) and intercellular adhesion molecule-1 (ICAM-1) in blood serum in each group; the slices of heart tissue were stained with hematoxylin-eosin staining method to observe morphology change of heart tissue. RESULTS: (1) After the intervention of moxa smoke, the levels of LDL-r and ICAM-1 in the low-concentration group were not statistically different from those in the control group (both P > 0.05); the level of LDL-r in the median-concentration group was significantly increased, which was statistically different from that in the control group [(3.87 +/- 0.27) mg/mL vs (2.12 +/- 0.13) mg/mL, P < 0.01], however, the content of ICAM-1 was not obviously changed; although the level of LDL-r in the high-concentration group was presented with an escalating trend, it was not statistically different from that in the control group (P > 0.05) while the level of ICAM-1 was obviously increased (P < 0.01). (2) Under the light microscope, the abnormalities of cardiac muscle fibers and myocardial cell in each group were not been observed. CONCLUSION: The long-time intervention of low-concentration moxa smoke has no significant effects on lipid metabolism and vascular endothelium of rats, indicating that clinical application of low-concentration moxa smoke is relatively safe. The long-time intervention of moderate-concentration moxa smoke could significantly increase the clearance rate of cholesterol, implying the beneficial regulation of moxa smoke on lipid metabolism. The high-concentration moxa smoke could induce certain damage to vascular endothelium but its mechanism is in need of further research. The pathologic change of heart tissue could not be induced by moxa smoke with any concentration.

[Adenoid cystic carcinoma of the breast:report of 25 cases].

OBJECTIVE: To explore the clinical features, management approach and treatment outcomes for adenoid cystic carcinoma (ACC) of the breast. METHODS: The clinicopathological data of 25 patients with breasts ACC treated in our hospital from years 1990 to 2012 were retrospectively reviewed and their prognosis was analyzed. RESULTS: The median age of these 25 patients was 53 years (ranged from 31 to 81 years). With the exception of one male case, all patients were female including 17 cases of postmenopausal women. The most frequent presenting symptom is breast lumps, most (48.0%) were in the upper outer quadrant and areola area of the breast. Core needle biopsy was performed in five patients. The specimen finding were adenoids in three and invasive carcinoma in two cases. Axillary lymph node dissection was performed in 23 patients. Only two patients had histologically positive lymph nodes (3 of 14 and 2 of 20). Expression of ER and PR in 14 cases was detected by immunohistochemistry, showing one PR-positive and three ER-positive cases. The median follow-up of the 25 cases was 118 months (ranged from 12 to 244 months). Two patients died of lung metastases at 3 and 10 years after the surgery, respectively. CONCLUSIONS: Due to the complexity of the histology of ACC, adequate sampling of specimens is essential for accurate diagnosis. ACC of the breast is a rare disease with a relatively good prognosis. The low incidence of axillary lymph node metastasis suggests that axillary node dissection is not recommended as a routine procedure. Breast ACC are often with negative ER and PR expression, and the value of adjuvant therapy needs to be further investigated.

[Effect of Qufeng Tongluo Recipe on expression of desmin and CD2AP proteins in adriamycin-induced nephropathy rats: an experimental research].

OBJECTIVE: To investigate the effect of Qufeng Tongluo Recipe (QTR) on the expression of desmin and CD2-associated protein (CD2AP) in adriamycin-induced nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was induced by a disposable intravenous injection of adriamycin. The model was successfully established after 3 weeks. Rats were then randomly divided into the blank control group (Group A, n =12), the model control group (Group B, n = 8), the small, medium, large dose QTR group (Group C, n = 8; Group D, n = 8; Group E, n = 8), and the positive control group (Group F, n = 8). From the fourth week normal saline was given to rats in Group A and Group B, QTR 1.0 g/mL, 2.1 g/mL, and 4.2 g/mL was respectively administered to those in Group C, D, and E. Prednisone 25 mg/kg was given to rats in Group F. All medication was performed by gastrogavage at 10 mL/kg, once daily, for 28 successive days. 24-h urinary protein excretion and sera biochemical indices were determined during medication. At the end of the experiment, ultrastructure was observed, mRNA expression of desmin, mRNA and protein of CD2AP were detected by Real-time PCR and Western blot. RESULTS: (1) Compared with Group B, 24-h urinary protein excretion significantly decreased in Group C, D, E, and F (P < 0.05). (2) Compared with Group B, Alb in Group C, D, and E increased (P < 0.05) and TC significantly decreased (P < 0.05). TG significantly increased in Group F (P < 0.05). (3) Results of electron microscope showed, compared with Group B, the morphology of foot cells was improved to various degrees in Groups D, E, and F, especially the foot process structure and the number of foot processes were significantly improved, which was more obviously shown in Group D and Group E. (4) mRNA expression of desmin, mRNA and protein of CD2AP increased in adriamycin-induced nephropathy rats (P < 0.05). After intervention, when compared with Group B, mRNA expression of desmin and CD2AP were significantly lower in Group C, D, E, and F (P < 0.05). (5) Compared with Group A, expression of desmin and CD2AP significantly increased (P < 0.05). Compared with Group B, the expression of desmin protein were obviously lower in Group C, D, E, and F, and the protein expression of desmin obviously decreased in Group D, E, and F (P < 0.05). The protein expression of desmin and CD2AP gradually decreased in Group C, D, and E (P < 0.05). Compared with Group F, the expression of CD2AP protein obviously increased in Group C and D (P < 0.05); the expression of CD2AP protein obviously decreased in Group E (P < 0.05); the expression of desmin protein was higher in Group C, D, and E (P < 0.05). CONCLUSION: QTR's therapeutic effect on adriamycin-induced nephropathy rats might be achieved through altered expression of desmin and CD2AP.

Influence of the gastrointestinal microflora and efflux transporters on the absorption of scutellarin and scutellarein.

Scutellarin (SG) and its aglycone, Scutellarein (S), are flavonoids of therapeutic cardiocerebrovascular disease. SG was hydrolyzed by bacterial enzyme into S which was absorbed in the intestine. The aim of this study was to determine the effects of the microflora in the intestinal lumen and the efflux transporter of intestinal epithelial cells on the absorption process of SG and S. After oral administration of antibiotics in Sprague-Dawley rats, the reduced bacterial enzyme formation significantly hinders the absorption of SG, whereas scarcely that of S. The absorption study in situ single-pass intestinal perfusion revealed that S could be absorbed throughout the intestine of rats. The effective intestinal permeability of S in the jejunum was much lower than in the other sections of the GI tract. The efflux transporter promoted SG secretion into lumen from enterocytes, which hindered the absorption of both SG and S into the bloodstream. The efflux transporter protein inhibitor (verapamil, probenecid and reserpine) remarkably enhanced the absorption of S and the bioconversion of S into SG in both the rat intestine and Caco-2-monolayer models.

Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal slit diaphragm proteins in adriamycin-induced rat nephropathy.

AIMS: Centella asiatica has been used to treat kidney diseases in Chinese traditional medicine. Asiaticoside (an extraction of C. asiatica) exerts a variety of pharmacological effects including immunomodulatory and anti-inflammatory functions. However, the mechanism of asiaticoside in the treatment of renal diseases remains largely unknown. This study investigated the molecular mechanism of asiaticoside in treating adriamycin-induced nephropathy of rats. MAIN METHODS: Sixty-two SD male rats were randomly divided into normal control group (n=12) and nephropathy group (n=50). Except for the normal control group, rats were injected with adriamycin (6mg/kg) via the tail vein to induce nephropathy. Adriamycin induced nephropathic rats were divided into untreated group, prednisone group (25mg/kg), and asiaticoside groups with various dosages (8, 16 and 32mg/kg). Samples of urine and serum, tissue of kidney were collected for analysis after treatments for four weeks. Morphological changes were evaluated under light microscope and electron microscope. Synaptopodin, desmin, nephrin and podocin mRNA and protein were determined by RT-PCR and Western blotting. KEY FINDINGS: Compared to the untreated nephropathy group, asiaticoside treatment mitigated histological damages, decreased 24-hour urine protein excretion and total cholesterol, increased serum albumin. Asiaticoside treatment increased the mRNA and protein levels of synaptopodin, nephrin and podocin in a dose-dependent manner. Furthermore, asiaticoside treatment decreased the mRNA and protein levels of desmin. SIGNIFICANCE: Asiaticoside can mitigate adriamycin-induced nephropathy in rats, which is associated with the increase in synaptopodin, nephrin and podocin gene expression, and the decrease in desmin gene expression.

Effects and mechanisms of the functional parts of Dahuang Zhechong pill containing serum on platelet-derived growth factor-stimulated proliferation of vascular smooth muscle cells.

OBJECTIVE: To investigate and compare the effects and mechanisms of three functional parts of Dahuang Zhechong Pill (DHZCP), including drugs with the function of removing blood stasis and promoting blood circulation (FP-I), drugs with the function of expelling heat and moistening dryness (FP-II), and drugs with the function of nourishing yin and replenishing blood (FP-III) of DHZCP, on platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs) proliferation with the method of serum pharmacology. METHODS: VSMCs proliferation of rat was assayed by measuring the cell viability with the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) method. DNA synthesis in VSMCs was examined by detecting 5'-bromo-2'-deoxyuridine incorporation with the immunocytochemical method. Cycle of VSMCs was evaluated with flow cytometry. Expression of cyclin D1, p27, PKCα, and phosphorylated extracellular signal regulated kinase 1/2 (ERK1/2) was quantified by the Western blotting method. RESULTS: The FP-I and FP-III containing serum was capable of inhibiting PDGF-stimulated proliferation and DNA synthesis of VSMCs, arrested VSMCs in G phase, downregulated cyclin D1, and upregulated p27 expression (P <0.01 or P <0.05). The FP-I and FP-III containing serum also inhibited the PDGF-induced phosphorylation of tyrosine of ERK1/2 and PKCα expression (P <0.01 or P <0.05). CONCLUSIONS: FP-I and FP-III of DHZCP are able to inhibit VSMCs proliferation via interrupting PKCα-ERK1/2 signaling, modulating the expression of cell cycle proteins to result in arresting the cells in G phase. The inhibitory effect is mainly related to the function of removing blood stasis and promoting blood circulation, slightly to the function of nourishing yin and replenishing blood, but not to the function of expelling heat and moistening dryness.