虫草对肺部疾病治疗的研究进展

肺纤维化、慢性阻塞性肺病和哮喘是人类主要的呼吸系统疾病,它们均以肺部或呼吸道的慢性炎症为特征,当前的治疗方法尚不理想并伴随着很多的副作用,人们迫切需要一种更安全的替代疗法。冬虫夏草是我国传统的名贵药用真菌,被广泛用来治疗多种肺部疾病。近年来,冬虫夏草对肺部疾病治疗作用的研究取得了较大进展,本文综述了冬虫夏草、其无性型中国被毛孢(Hirsutella sinensis或Ophicordyceps sinensis)和其他相关虫草及其提取物对肺纤维化、慢性阻塞性肺病、哮喘等肺部疾病治疗作用的研究进展,并介绍了其作用机制的研究成果。     

冬虫夏草在呼吸系统炎性疾病的药理及临床研究进展

通过近30年国内外相关文献分析,系统总结了冬虫夏草在呼吸系统炎性疾病治疗中的药理和临床研究进展。冬虫夏草及其相关产品在肺部疾病治疗的药理和临床研究广泛,药用历史悠久,总结发现其主要通过调节机体免疫、减少肺部渗出、抑制炎症反应而发挥疗效。为加快冬虫夏草抗呼吸系统炎性疾病的中药新药开发及应用提供了参考资料。     

基于核壳型亲水作用色谱技术同时测定冬虫夏草中核苷和糖醇类成分的含量

核苷和糖醇类成分是冬虫夏草Ophiocordyceps sinensis中两类重要的活性成分,常被作为冬虫夏草质量的评价指标。本研究采用核壳型亲水作用色谱柱技术,建立同时测定冬虫夏草中核苷和糖醇类成分含量的快速液相色谱分析方法。结果表明,在8 min内尿苷、腺苷、肌苷、鸟苷和甘露醇均实现基线分离,且各成分线性关系良好,日内精密度、日间精密度和重复性均小于3%,平均回收率在99.0%~106.1%,供试品溶液在24 h内稳定。20批冬虫夏草的尿苷、腺苷、肌苷、鸟苷和甘露醇含量与文献报道结果基本一致。本研究建立的方法快速、准确、可靠,可用于冬虫夏草核苷和糖醇类成分的同时测定。     

天然冬虫夏草多菌共存生物体分子异质性的检验与讨论

中药冬虫夏草数百年来用于滋补保健、疾病防治和病后康复,但有关冬虫夏草菌的学术争议一直没有停止。中国被毛孢是冬虫夏草菌的无性世代学说较为流行,然而学界尚未获得证实这一学说的直接证据。部分间接证据来自于分子系统学微观和宏观研究。该文回顾了冬虫夏草分子系统学文献,讨论了微观研究和宏观研究的实验方法、数据分析方法及其结果。冬虫夏草分子生物学微观研究不断获得新证据,证明天然冬虫夏草基因组DNA的多元异质性,揭示冬虫夏草中含有的多种真菌和多种突变基因型冬虫夏草菌,证明冬虫夏草是多种真菌与蝙蝠蛾幼虫尸体构成的复杂的菌虫物种复合体。随着冬虫夏草的成熟,在僵虫体和子座中多种菌物的差异存在巨大的、非同步的动态变化。宏观分子系统学研究的丰度加权算法揭示在僵虫体、子座和子囊果中分子标记多态性的高度差异及其在冬虫夏草成熟过程中的动态变化。这些分子系统学研究结果支持冬虫夏草是"一个统一微生态系统"的学说。     

一种冬虫夏草全基因组DNA的提取方法

冬虫夏草是真菌与昆虫形成的复合生物体,本研究建立了一种可同时提取冬虫夏草真菌子座和虫体全部基因组DNA的方法。该方法稳定高效,简便易行,提取纯度高,适用于冬虫夏草多重PCR、Realtime-PCR和DNA指纹图谱等分子水平的研究。     

北冬虫夏草菌丝体吨级液体深层发酵及生理活性物质的研究

我国药用食’周冬虫夏草的历史悠久。近年来通过大量药理实验证明,它具有降脂降压,抑菌抗癌等作用,临床上用于治疗心律失常、肝炎后的肝硬化,对肾功能衰竭、骨癌、肺癌、前列腺癌等也具有较好的疗效。随着冬虫夏草的广泛应用,野生虫草资源已不能满足人们日益增长的需求,人们开始尝试人工培养虫草。但人工培养技术不易掌握。此外,人们还分离虫草真菌进行液体深层发酵生产虫草菌丝体。目前已有报道。传统观点认为冬虫夏草的产地为西藏、青海、四）11等地,但据目前所知东北地区虫草资源也很丰富,尤其北冬虫夏草种类多。本研究为进一步…     

冬虫夏草发酵制剂对实验性糖尿病小鼠血糖水平的调节

糖尿病是现代疾病中的仅次于癌症的第二杀手.中国疾病预防控制中心提供的报告称,中国糖尿病和糖耐量递减的患病率逐年升高,近年增长速度加快,患者绝对数量庞大.据估计,目前中国20岁以上的糖尿病患者超过2 000万人,糖耐量递减病人不低于3 000万人.由于糖尿病及其并发症对人们的身心健康的危害越来越大,因此,我们有必要寻求更好的预防和治疗手段来解决这一世界难题.传统名贵中药冬虫夏草具有补肺、补肾和补虚损的作用,中医临床上将其组方,用于对糖尿病的治疗并获得一定疗效.通过动物实验,研究冬虫夏草制剂对实验性糖尿病小鼠血糖水平的调控作用,将为其临床应用,提供可靠的依据.     

利用CTAB法和子囊孢子破壁法提取冬虫夏草菌DNA

通过CTAB法从冬虫夏草菌株和天然冬虫夏草不同部位提取DNA,并用PCR扩增进行验证,证明了CTAB法适合从冬虫夏草子座、菌核和冬虫夏草菌培养物中提取DNA。首次报道1种将子囊孢子破壁直接进行PCR扩增的方法,并比较了该方法和CTAB法在提取冬虫夏草DNA方面的差异。2种方法获得的DNA用于PCR扩增均能得到较好的结果。     

冬虫夏草生物学及生态学研究中的关键科学问题研究进展

冬虫夏草是一种具有极高药用和食用价值的珍稀菌类,其生物学特性和可持续发展关键技术一直是冬虫夏草研究关注的重点。总结了冬虫夏草生物学及生态学中的几个重要科学问题,包括冬虫夏草菌侵染蝙蝠蛾幼虫的途径及机制、冬虫夏草菌子实体形成及生长过程中的关键调控因子、冬虫夏草菌遗传多样性及基因组学研究、天然冬虫夏草及其微环境中的微生物群落组成、全球变暖背景下未来青藏高原地区的气候变化对冬虫夏草资源的影响等的研究进展,并分析了现有研究中尚未明确和不足之处。未来在冬虫夏草生物学及生态学的研究中,需要利用和研发更加先进的观测设备及试验方法,以实现天然冬虫夏草发生发育的原位观测和机理研究;充分利用冬虫夏草人工培植技术,结合分子生物学研究,从基因水平上揭示冬虫夏草菌生态适应性及侵染蝙蝠蛾幼虫的机理;建立冬虫夏草科学研究基地,开展长期定位观测试验并结合生态学模型构建明确未来气候变化对冬虫夏草资源的影响,以期进一步深入冬虫夏草生物学和生态学研究、推进我国冬虫夏草资源的合理利用及可持续发展的政策制定。     

冬虫夏草繁育品和野生品虫草酸含量比较

为了建立冬虫夏草中虫草酸含量的检测方法,比较冬虫夏草繁育品和野生冬虫夏草中的虫草酸含量,文中采用超声水提法研究了料液比和提取时间对虫草酸含量的影响,筛选出料液比为1∶50、提取时间为5 min时可高效提取冬虫夏草样品中的虫草酸。检测方法经方法学考察,专属性、重复性、准确度、稳定性均符合要求;21批冬虫夏草繁育品样本中的虫草酸含量为9.04%~14.14%;21批野生冬虫夏草虫草酸含量为6.16%~13.94%。通过t检验统计分析显示,冬虫夏草繁育品和野生冬虫夏草的虫草酸含量差异不显著,具有良好一致性。     

Extract of Cassiae semen attenuates diabetic nephropathy via inhibition of advanced glycation end products accumulation in streptozotocin-induced diabetic rats

Chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs), which accelerates the development of diabetic complications. Previous studies have shown that extract of Cassiae semen (CS), the seed of Cassia tora, has inhibitory activity on AGEs formation in vitro and reduces transforming growth factor-beta1 (TGF-β1) and extracellular matrix protein expression via inhibition of AGEs-mediated signaling in glomerular mesangial cells. In this study, to examine the preventive effects of CS extract on the development of diabetic nephropathy in vivo, streptozotocin (STZ)-injected diabetic rats were orally administered CS extract (200 mg/kg body weight/day) for 12 weeks. Serum glucose, triglycerides, and total cholesterol in diabetic rats were significantly higher compared to control rats. CS or aminoguanidine (AG) treatment significantly reduced these factors. Proteinuria and creatinine clearance were also significantly decreased in the CS-treated group compared with the untreated diabetic group. The CS-treated group had significantly inhibited COX-2 mRNA and protein, which mediates the symptoms of inflammation in the renal cortex of diabetic rats. Furthermore, histopathological studies of kidney tissue showed that in diabetic rats, AGEs, the receptor for AGEs, TGF-β1, and collagen IV were suppressed by CS treatment. Our data suggest that oral treatment of CS can inhibit the development of diabetic nephropathy via inhibition of AGEs accumulation in STZ-induced diabetic rats.     

Differential Expression of Specific Dermatan Sulfate Domains in Renal Pathology

Dermatan sulfate (DS), also known as chondroitin sulfate (CS)-B, is a member of the linear polysaccharides called glycosaminoglycans (GAGs). The expression of CS/DS and DS proteoglycans is increased in several fibrotic renal diseases, including interstitial fibrosis, diabetic nephropathy, mesangial sclerosis and nephrosclerosis. Little, however, is known about structural alterations in DS in renal diseases. The aim of this study was to evaluate the renal expression of two different DS domains in renal transplant rejection and glomerular pathologies. DS expression was evaluated in normal renal tissue and in kidney biopsies obtained from patients with acute interstitial or vascular renal allograft rejection, patients with interstitial fibrosis and tubular atrophy (IF/TA), and from patients with focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy (MGP) or systemic lupus erythematosus (SLE), using our unique specific anti-DS antibodies LKN1 and GD3A12. Expression of the 4/2,4-di-O-sulfated DS domain recognized by antibody LKN1 was decreased in the interstitium of transplant kidneys with IF/TA, which was accompanied by an increased expression of type I collagen, decorin and transforming growth factor beta (TGF-β), while its expression was increased in the interstitium in FSGS, MGP and SLE. Importantly, all patients showed glomerular LKN1 staining in contrast to the controls. Expression of the IdoA-Gal-NAc4SDS domain recognized by GD3A12 was similar in controls and patients. Our data suggest a role for the DS domain recognized by antibody LKN1 in renal diseases with early fibrosis. Further research is required to delineate the exact role of different DS domains in renal fibrosis.     

Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats

Cordyceps sinensis (CS) is an entomogenous fungus used as a tonic food and Chinese medicine to replenish health. This study investigated the protective effects of CS in rats post-renal ischemia–reperfusion (I/R) sequence by analyzing the influence on stromal cell-derived factor-1α (SDF-1α and chemokine (C-X-C motif) receptor 4 (CXCR4) expressions and senescence during recovery. Chemokine SDF-1 [now called chemokine C-X-C motif ligand 12 (CXCL12)] and its receptor CXCR4 are crucial in kidney repair after ischemic acute renal failure. CS treatment significantly alleviated I/R-induced renal damage assessed by creatinine levels (p < 0.05) and abated renal tubular damages assessed by periodic acid-Schiff with diastase (PASD) staining. CS induced early SDF-1α expression and increased CXCR4 expression 1–6 h post-reperfusion. Histology studies have revealed that CS induced SDF-1α in squamous cells of Bowman’s capsule, mesangial cells, distal convoluted tubules (DCT), and proximal convoluted tubules (PCT). CS also improved renal repair in I/R-induced injury by increasing Ki-67 staining. I/R induced renal senescence after 3 and 6 h of reperfusion. However, CS alleviated I/R-induced senescence at early stage (1 and 3 h). We conclude that CS protects against I/R injury via the SDF-1/CXCR4-signaling axis and alleviates senescence.     

Chitooligosaccharide inhibits RANKL-induced osteoclastogenesis and ligation-induced periodontitis by suppressing MAPK/ c-fos/NFATC1 signaling

Considering the high rate of osteoclast-related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose-dependently. CS suppressed osteoclast-specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-mediated mitogen-activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c-fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis-induced alveolar bone loss by micro-computerized tomography and histological analysis. Overall, CS inhibited RANKL-induced osteoclastogenesis and ligature-induced rat periodontitis model, probably by suppressing the MAPK/c-fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast-related diseases.     

Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis

Cordyceps sinensis is a herb medicine in China for the treatment of general debility after sickness and for persons of advanced age. In the present study, cordyceps sinensis was extract by phosphate buffer saline (PBS) and dialyzed overnight against PBS using a membrane cut off at 3,500 dalton molecular weight. The resulting macromolecule fraction (defined as CS) was assayed in anesthetized rats for hypotensive effects and in isolated aorta for vasorelaxant effects. Intravenous injection of CS (8,16, 24 and 32 mg/kg, respectively) suppressed significantly the mean arterial pressure (MAP) in a dose-dependent manner. 32 mg/kg of CS induces the maximal hypotensive response with a 58 +/- 4 mm Hg (from 107 +/- 6 to 49 +/- 3 mm Hg) change in MAP and a over 45 min action duration. In aortic rings precontracted with phenylephrine treatment with CS between 0.5 and 500 microg/ml induced dose dependent relaxation. Maximal vasorelaxant response evoked by 150 microg/ml CS was 68.9 +/- 7.3%. Furthermore, CS-induced vasorelaxation is mediated by the endothelium possibly by stimulating the release of the nitric oxide and endothelium-derived hyperpolarizing factor. In conclusion, the present study revealed that presence of a constituent in CS which reduces MAP by relaxing the vascular beds directly. However, the effect may be caused by a single active ingredient or by the combined action of many active agents found in the extract.     

Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11 beta-hydroxysteroid dehydrogenase.

The in vivo effect(s) of carbenoxolone (CS) on renal 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), hepatic 11 beta-OHSD, and 5 beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11 beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11 beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11 beta-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11 beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 microM and 50 microM corticosterone, as was 5 beta-reductase (P < 0.05) using 4 microM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11 beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11 beta-OHSD and 5 beta-reductase with no inhibition of renal 11 beta-OHSD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Asparagus racemosus Willd (Liliaceae) ameliorates early diabetic nephropathy in STZ induced diabetic rats

Diabetic nephropathy is a major "microvascular" complication of diabetes, differs from other causes of chronic kidney diseases in its predictability, with well-defined functional progression from hyperfiltration to micro- to macroalbuminuria to renal failure. The present study was undertaken to investigate the effect of Asparagus racemosus Willd (Liliaceae) on streptozotocin-induced early diabetic nephropathy. Single i.p injection of streptozotocin (55 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats and thereafter treated orally with ethanolic extract of Asparagus racemosus (EEAR) at a dose level of 100 and 250 mg/kg daily for 4 weeks. The efficacy of extract was compared with diabetic control rats. A. racemosus treatment significantly decreased plasma glucose, creatinine, urea nitrogen, total cholesterol and triglyceride levels. Renal hypertrophy, polyuria, hyperfiltration, microalbuminuria and abnormal changes in the renal tissue as well as oxidative stress were effectively attenuated by EEAR treatment. Basement membrane thickening and mesangial proliferation formation without nodules were seen in diabetic rats, whereas these structural changes were reduced in EEAR treated groups. Results of this study suggested that A. racemosus has beneficial effect in the treatment of diabetic     

Vitamin C prevents cigarette smoke induced oxidative damage of proteins and increased proteolysis

Aqueous extract of cigarette smoke (CS) contains some stable oxidants, which oxidize human plasma proteins, bovine serum albumin, amino acid homopolymers, and also cause extensive oxidative degradation of microsomal proteins. Similar observations are made when the aqueous extract of cigarette smoke is replaced by whole phase CS solution or whole phase cigarette smoke. CS-induced microsomal protein degradation is a two step process: (i) oxidation of proteins by the oxidants present in the CS and (ii) rapid proteolytic degradation of the oxidized proteins by proteases present in the microsomes. Using aqueous extract of CS equivalent to that produced from one-twentieth of a cigarette, the observed initial and postcigarette smoke treated values of different parameters of oxidative damage per milligram of microsomal proteins are respectively: 0.24 and 1.74 nmoles for carbonyl formation, 125.4 and 62.8 fluorescence units for tryptophan loss, 10.2 and 33.4 fluorescence units for bityrosine formation, and 58.3 and 12.2 nmoles for loss of protein thiols. When compared with sodium dodecyl sulphate polyacrylamide gel electrophoresis profiles of untreated microsomal proteins, the extent of microsomal protein degradation after treatment with whole phase CS solution or aqueous extract of CS is above 90%. Ascorbate (100 microM) almost completely prevents cigarette smoke-induced protein oxidation and thereby protects the microsomes from subsequent proteolytic degradation. Glutathione is partially effective, but other antioxidants including superoxide dismutase, catalase, vitamin E, probucol, beta-carotene, mannitol, thiourea, and histidine are ineffective. The gas phase cigarette smoke contains unstable reactive oxygen species such as superoxide (O2*-) and hydrogen peroxide (H2O2) that can cause substantial oxidation of pure protein like albumin but is unable to produce significant oxidative damage of microsomal proteins. Gas phase cigarette smoke-induced albumin oxidation is not only inhibited by ascorbate and glutathione but also by superoxide dismutase, catalase and mannitol. The stable oxidants in the cigarette smoke are not present in the tobacco and are apparently produced by the interaction of O2*-/H2O2/OH* of the gas phase with some components of the tar phase during/following the burning of tobacco.     

Pronóstico del paciente tratado de síndrome de Cushing

Cushing syndrome (CS), due to an ACTH-secreting pituitary adenoma, adrenal tumors, or ectopic ACTH secretion, causes hypercortisolism. CS is associated with major morbidity, especially metabolic and cardiovascular complications, osteoporosis, psychiatric changes, and cognitive impairment. Despite biochemical “cure” of hypercortisolism and clinical improvement after effective treatment, these complications are only partially reversible. Exacerbation of prior autoimmune diseases is also seen. All of these lead to quality of life impairment and increased mortality. This review addresses the main comorbidities and long-term consequences of CS despite clinical and biochemical “cure”.