川芎嗪又称四甲基吡嗪,是提取自伞形科藁本属植物川芎根茎的一种中药单体成分,属于酰胺类生物碱.川芎嗪除了具有传统的活血祛瘀、抑制血小板聚集、扩张血管、改善血液循环、缓解疼痛等作用外,随着研究的不断深入,发现川芎嗪还具有心脑血管疾病预防与治疗、多器官如心脏、脑组织和肾脏等的缺血再灌注损伤修复、血管内皮保护、肿瘤抑制、哮喘病人气道重塑、钙超载抑制和免疫调节等作用.现从川芎嗪在心血管疾病、脑疾病、肾损伤、肿瘤等疾病中的应用,对近几年川芎嗪最新研究进展进行综述,以期为川芎嗪的临床应用提供参考.
Age-related macular degeneration(ARMD)is one of the main causes of irreversible visual impairment in the middle-aged and elderly people, which severely impacts the patient's life quality and poses a substantial health economic burden on society. There are two types of late ARMD in clinic: wet ARMD and dry ARMD. Anti-vascular endothelial growth factor drugs, as first-line clinical drugs for wet ARMD, achieved remarkable efficacy. For dry ARMD, however, effective therapies are in the air. This review focuses on the potential drugs, biological therapies and traditional Chinese medicines that made significant progresses in clinical trials for dry ARMD, including anti-inflammatory drugs(doxycycline and FHTR2163), anti-oxidants(risuteganib and elamipretide), complement inhibitors(APL-2 and zimura), visual cycle modulators(ALK-001), neuroprotective agents(brimonidine), stem cell transplantation(MA09-hRPE and BMMF), gene therapy(HMR59), and traditional Chinese medicine(saffron, curcumin, quercetin and resveratrol). The new drugs exhibited favorable clinical efficacy and broad application prospects, which would foster hope for improvement and treatment of ARMD.
Malignant tumors seriously threaten people’s health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development.
Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.
心脑血管疾病是全球人类首要致死因素,动脉粥样硬化(As)是其主要病理基础.As发病机制复杂,临床使用的化学药物疗效单一,价格昂贵,不良反应较大.作用靶点多、不良反应少、价廉易得的中草药已成为防治心脑血管疾病的研究热点,丹参作为代表药物在As防治方面具有独特作用.该文章从中医与As关系以及丹参主要有效组分抗As活性方面,综述了丹参抗As的药理学研究进展,重点介绍了其水溶性组分丹酚酸B和丹酚酸A、脂溶性组分丹参酮ⅡA和隐丹参酮抗As活性与作用机制,以期为丹参抗As应用提供参考.
Diabetic retinopathy(DR)is a common chronic complication of diabetes mellitus, which cause irreversible damage of microvessels in the retina. DR is a leading blindness eye disease among diabetes mellitus. The pathogenesis of DR is mainly related to oxidative stress, inflammation and neovascularization. DR patients are treated with laser photocoagulation, vitrectomy and medicine in clinical trials. The traditional Chinese medicine and Chinese herb monomers have unique efficacy in the treatment of DR, especially in retinal protection, which provides valuable supplement. The paper summarized application practice and mechanism of representative Chinese herbal formulas and Chinese herb monomers in the treatment of DR, which would provide references for the clinical treatment and new drug development of DR.
Background Vascular calcification is a closely linked to cardiovascular diseases, such as atherosclerosis, chronic kidney disease, diabetes, hypertension and aging. The extent of vascular calcification is closely correlate with adverse clinical events and cardiovascular all-cause mortality. The role of autophagy in vascular calcification is complex with many mechanistic unknowns. Methods In this review, we analyze the current known mechanisms of autophagy in vascular calcification and discuss the theoretical advantages of targeting autophagy as an intervention against vascular calcification. Results Here we summarize the functional link between vascular calcification and autophagy in both animal models of and human cardiovascular disease. Firstly, autophagy can reduce calcification by inhibiting the osteogenic differentiation of VSMCs related to ANCR, ERα, β-catenin, HIF-1a/PDK4, p62, miR-30b, BECN1, mTOR, SOX9, GHSR/ERK, and AMPK signaling. Conversely, autophagy can induce osteoblast differentiation and calcification as mediated by CREB, degradation of elastin, and lncRNA H19 and DUSP5 mediated ERK signaling. Secondly, autophagy also links apoptosis and vascular calcification through AMPK/mTOR/ULK1, Wnt/β-catenin and GAS6/AXL synthesis, as apoptotic cells become the nidus for calcium-phosphate crystal deposition. The failure of mitophagy can activate Drp1, BNIP3, and NR4A1/DNA‑PKcs/p53 mediated intrinsic apoptotic pathways, which have been closely linked to the formation of vascular calcification. Additionally, autophagy also plays a role in osteogenesis by regulating vascular calcification, which in turn regulates expression of proteins related to bone development, such as osteocalcin, osteonectin, etc. and regulated by mTOR, EphrinB2 and RhoA. Furthermore, autophagy also promotes vitamin K2-induced MC3T3 E1 osteoblast differentiation and FGFR4/FGF18- and JNK/complex VPS34–beclin-1-related bone mineralization via vascular calcification. Conclusion The interaction between autophagy and vascular calcification are complicated, with their interaction affected by the disease process, anatomical location, and the surrounding microenvironment. Autophagy activation in existent cellular damage is considered protective, while defective autophagy in normal cells result in apoptotic activation. Identifying and maintaining cells at the delicate line between these two states may hold the key to reducing vascular calcification, in which autophagy associated clinical strategy could be developed.
心房纤颤(AF)是常见室上性快速心律失常,可单独发病,亦可与心力衰竭、心肌梗死等伴发.胺碘酮与多非利特等临床常用药物,仅能减少AF发作次数与时间,很难使其恢复正常窦性节律,且因其选择性差,可诱发严重室性心律失常.因此,研发新型抗AF药物十分迫切.Kv1.5钾离子通道仅在心房肌表达,选择性强,可望成为抗AF药物设计的高选择性靶标.现综述Kv1.5钾离子通道抑制剂抗AF的应用与作用机制,以期为抗AF药物研发与临床应用提供参考.
心脑血管疾病为全球人类首要死因,动脉粥样硬化(As)是其主要病理基础.As发病机制复杂,与高血脂、高血糖、炎症、内皮损伤等密切相关.白藜芦醇(Res)是多酚类中药单体,具有良好的抗As活性,长期大量使用副作用较小.现综述Res的理化性质、提取、合成方法,重点介绍了Res通过改善血脂、抑制炎症、抗氧化、抑制血小板凝聚、降糖等途径改善As的作用,以期为Res的临床应用提供参考.
Glaucoma is an eye disease characterized by progressiveretinal nerve damage and impaired vision, which is the top one irreversible blinding eye disease. The pathologic intraocular pressure elevation is its key risk. At present, the clinical medicine with intraocular pressure reducing and retinal nerve protection effects focused on symptomatic therapy with unsatisfied effects. Chinese herb monomers have advantages of both Chinese herbs and chemical drugs. Chinese herbs and Chinese herb monomers have favorable effects on glaucoma therapy, especially on retinal nerve protection, which provides a vast room for new drug development. The paper summarized applications and mechanism of representative anti-glaucoma Chinese herbal formulas, Chinese herbs and especially Chinese herb monomers, which would provide references for clinical therapy and new drug development for glaucoma.