Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+-induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH). Additionally, the ACH-induced precontraction was partly reduced by pyrazole-3 (Pyr3), a selective blocker of TRPC3 and stromal interaction molecule (STIM)/Orai channels. These channel-mediated currents were inhibited by the compounds present in P. aviculare extracts, suggesting that this inhibition was mediated by LVDCCs, TRPC3 and/or STIM/Orai channels. Moreover, these channel-mediated currents were inhibited by quercetin, which is present in P. aviculare extracts. Furthermore, quercetin inhibited ACH-induced precontraction in ASM. Overall, our data indicate that the ethyl acetate fraction of P. aviculare and quercetin can inhibit Ca2+-permeant LVDCCs, TRPC3 and STIM/Orai channels, which inhibits the precontraction of ASM. These findings suggest that P. aviculare could be used to develop new bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease.

Objective. To evaluate the effectiveness of astragalus injection (a traditional Chinese patent medicine) for patients with renal damage induced by hypertension according to the available evidence. Methods. We searched MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese VIP Information, China Biology Medicine (CBM), and Chinese Medical Citation Index (CMCI), and the date of search starts from the first of database to August 2011. No language restriction was applied. We included randomized controlled trials testing astragalus injection against placebo or astragalus injection plus antihypertensive drugs against antihypertensive drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane review standards. Results. 5 randomized trials (involving 429 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that astragalus injection was more effective in lowering β 2-microglobulin (β 2-MG), microalbuminuria (mAlb) compared with placebo, and it was also superior to prostaglandin in lowering blood urea nitrogen (BUN), creatinine clearance rate (Ccr). There were no adverse effects reported in the trials from astragalus injection. Conclusions. Astragalus injection showed protective effects in hypertensive renal damage patients, although available studies are not adequate to draw a definite conclusion due to low quality of included trials. More rigorous clinical trials with high quality are warranted to give high level of evidence.

Background/Aims: Tetraethylammonium chloride (TEA) induces oscillatory contractions in mouse airway smooth muscle (ASM); however, the generation and maintenance of oscillatory contractions and their role in ASM are unclear. Methods: In this study, oscillations of ASM contraction and intracellular Ca²⁺ were measured using force measuring and Ca²⁺ imaging technique, respectively. TEA, nifedipine, niflumic acid, acetylcholine chloride, lithium chloride, KB-R7943, ouabain, 2-Aminoethoxydiphenyl borate, thapsigargin, tetrodotoxin, and ryanodine were used to assess the mechanism of oscillatory contractions. Results: TEA induced depolarization, resulting in activation of L-type voltage-dependent Ca²⁺ channels (LVDCCs) and voltage-dependent Na⁺ (V_Na) channels. The former mediated Ca²⁺ influx to trigger a contraction and the latter mediated Na⁺ entry to enhance the contraction via activating LVDCCs. Meanwhile, increased Ca²⁺-activated Cl^- channels, inducing depolarization that resulted in contraction through LVDCCs. In addition, the contraction was enhanced by intracellular Ca²⁺ release from Ca²⁺ stores mediated by inositol (1,4,5)-trisphosphate receptors (IP₃Rs). These pathways together produce the contractile phase of the oscillatory contractions. Furthermore, the increased Ca²⁺ activated the Na⁺-Ca²⁺ exchanger (NCX), which transferred Ca²⁺ out of and Na⁺ into the cells. The former induced relaxation and the latter activated Na⁺/K⁺-ATPase that induced hypopolarization to inactivate LVDCCs causing further relaxation. This can also explain the relaxant phase of the oscillatory contractions. Moreover, the depolarization induced by V_Na channels and NCX might be greater than the hypopolarization caused by Na⁺/K⁺-ATPase alone, inducing LVDCC activation and resulting in further contraction. Conclusions: These data indicate that the TEA-induced oscillatory contractions were cooperatively produced by LVDCCs, V_Na channels, Ca²⁺-activated Cl^- channels, NCX, Na⁺/K⁺ ATPase, IP₃Rs-mediated Ca²⁺ release, and extracellular Ca²⁺.

β2-adrenoceptor agonists are commonly used as bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, they induce severe side effects. Therefore, developing new bronchodilators is essential. Herbal plants were extracted and the extracts’ effect on airway smooth muscle (ASM) precontraction was assessed. The ethyl alcohol extract of semen cassiae (EESC) was extracted from Semen cassia. The effects of EESC on the ACh- and 80 mM K+-induced sustained precontraction in mouse and human ASM were evaluated. Ca2+ permeant ion channel currents and intracellular Ca2+ concentration were measured. HPLC analysis was employed to determine which compound was responsible for the EESC-induced relaxation. The EESC reversibly inhibited the ACh- and 80 mM K+-induced precontraction. The sustained precontraction depends on Ca2+ influx, and it was mediated by voltage-dependent L-type Ca2+ channels (LVDCCs), store-operated channels (SOCs), TRPC3/STIM/Orai channels. These channels were inhibited by aurantio-obtusin, one component of EESC. When aurantio-obtusin removed, EESC’s action disappeared. In addition, aurantio-obtusin inhibited the precontraction of mouse and human ASM and intracellular Ca2+ increases. These results indicate that Semen cassia-contained aurantio-obtusin inhibits sustained precontraction of ASM via inhibiting Ca2+-permeant ion channels, thereby, which could be used to develop new bronchodilators.

This study aimed to compare the effects of polypropylene (PP), lightweight PP (UP) and expanded polytetrafluorethylene (e-PTFE) hernia mesh on the reproductive function of adult male Sprague-Dawley (SD) rats following open tension-free hernioplasty. Forty adult SD rats were obtained and divided into five groups: A sham-operated (FO) group, an e-PTFE mesh group, a PP mesh group, the UP mesh group and a normal control (NC) group (without any surgical manipulation). Ninety days following open tension-free hernioplasty, hematoxylin and eosin staining and immunhistochemistry were used to observe the pathological changes of the testicular tissue and to compare the expression of hypoxia-inducible factor-1α (HIF‑1α) in the rat testis, respectively. ELISA was used to analyze the serum concentration of antisperm antibodies (AsAbs) and routine semen testing was conducted to measure the percentage of grade a+b sperm from the epididymis. More than 50% of mesh adherence to the spermatic cord was observed in the PP and UP groups, and mild or no adhesion was observed in the NC, FO and e-PTFE groups. In the UP and PP groups, marked congestion of necrotic tissue was observed in the seminiferous tubule cavity, a significant reduction in the percentage of grade a+b sperm and a significant increase in the expression levels of AsAbs and HIF-α. It was concluded that the e-PTFE mesh exhibited a marginal effect on the reproductive function of rats compared with that of the PP and UP mesh and is more suitable for tension-free hernioplasty. The clinical significance of these results requires further elucidation with a multi-centered prospective study.