黄连解毒汤治疗新型冠状病毒肺炎(COVID-19)重型气营两燔证的中医方证关系及药理研究进展

自新型冠状病毒肺炎(COVID-19)疫情暴发以来,国家卫生健康委员会及各地相关单位陆续发布多个诊疗方案,其中重症期治疗推荐方剂中黄连解毒汤的中医证侯与《新型冠状病毒肺炎诊疗方案(试运行第七版)》中重型气营两燔证相应,可用于治疗气营两燔证。气营两燔证津液营阴耗损、正不敌邪,气营热毒炽盛,黄连解毒汤清热解毒,可通过祛邪达到扶正护阴的治疗目的。现代药理研究表明黄连解毒汤在治疗COVID-19重型气营两燔证中具有潜在的抗炎解热、抗病毒、抗氧化、调节机体免疫力、保护脏器组织等作用。通过对COVID-19重型气营两燔证的病机演变、黄连解毒汤的方证关系及现代药理作用进行梳理,分析黄连解毒汤治疗重型气营两燔证的中医方证关系及现代药理学基础,以期为黄连解毒汤用于COVID-19重型气营两燔证的有效治疗提供依据。     

含功能性油的水飞蓟宾超饱和自纳米乳的制备与体外评价

目的制备含功能性油的水飞蓟宾超饱和自纳米乳(SLB-S-SNEDDS),并对其进行表征及体外评价研究,以提高难溶性药物水飞蓟宾的生物利用度。方法铁氢化钾还原力与1,1-二苯基-2-苦肼基(DPPH)自由基清除实验筛选功能性油脂;伪三元相图考察乳化剂乳化能力;测定粒径、多分散指数(PDI)、Zeta电位等考察混合油相比例与载药量;相容性与溶出度实验筛选促过饱和物质并考察其质量浓度;从外观、粒径分布、自乳化效率、形态学等方面表征SLB-S-SNEDDS,并进行溶出度、抗氧化能力、细胞毒性等体外评价。结果所得SLB-S-SNEDDS处方为(1)小麦胚芽油/Capryol 90-Cremophor ELP-Transcutol HP与(2)沙棘籽油/Capryol 90-Cremophor ELP-Transcutol HP,1 g基质(包含0.043 g小麦胚芽油或沙棘籽油、0.387 g Capryol 90、0.380 g Cremophor ELP、0.190 g Transcutol HP),水飞蓟宾的添加量为各组分平衡溶解度之和的20%,Soluplus的添加量为上述总质量的0.1%。小麦胚芽油、沙棘籽油体系分别为淡黄色、亮黄色透明状均一液体,2种体系自乳化分散后均呈近球形白色扁平乳滴,粒径约为50 nm,乳化时间均为65 s。与药物原料及SLB-SNEDDS相比,SLB-S-SNEDDS中水飞蓟宾的累积溶出率8h内均维持在85%～110%,表明该体系能够显著提高药物的溶出度。SLB-S-SNEDDS与铁氰化钾反应后的吸光度(A值0.452～0.782,0.488～0.765)以及DPPH自由基清除率(39.09%～96.02%,30.54%～89.20%)均高于相应质量浓度下水飞蓟宾原料的A值与清除率(0.411～0.760,22.89%～63.21%),表明2种处方体系均能提高水飞蓟宾的抗氧化能力。细胞毒性实验结果显示,在5、10μmol/L药物浓度下,水飞蓟宾原料组、水飞蓟宾S-SNEDDS组及其相应的空白S-SNEDDS组细胞生存率均90%,说明SLB-S-SNEDDS及其所用辅料对人克隆结肠腺癌细胞(Caco-2)毒性较小、安全性较好。结论制备的含功能性油SLB-S-SNEDDS在提高水飞蓟宾累积溶出率的同时,增强了其抗氧化能力,为将超饱和自纳米乳(S-SNEDDS)用于改善难溶性药物水溶性及其生物活性提供有益参考。     

苓桂术甘汤中多糖结构组成及其抗氧化活性考察

目的:研究苓桂术甘汤中多糖的结构,包括单糖组成以及官能团检测,并对其抗氧化能力进行评估,为体外生物测定法运用于苓桂术甘汤的质量评价提供基础。方法:利用高效凝胶色谱对全方多糖分子量进行研究;进一步采用气相色谱-质谱(GC-MS)柱前衍生化法及红外光谱扫描分析全方多糖结构组成;采用1,1-二苯基-2-三硝基苯肼(DPPH)及羟基自由基测定全方粗多糖及精多糖的抗氧化能力。结果:全方多糖由单一峰组成,且相对分子质量为3 689 Da,主要由阿拉伯糖、甘露糖、葡萄糖、半乳糖、果糖组成,摩尔比为6. 85∶1. 00∶109. 21∶1. 04∶21. 82,其中葡萄糖和果糖为主要组成成分;红外结果显示聚糖结构中存在吡喃糖及糖醛酸,并且糖苷键存在2种立体异构(α-糖苷键及β-糖苷键);抗氧化研究发现全方多糖有一定清除DPPH自由基及羟基自由基的能力,粗多糖的活性优于精多糖。进一步采用LC-Q-TOF-MS对粗多糖中的其他成分进行定性分析,提示这与甘草中五环三萜类成分的吸附有关。结论:苓桂术甘汤中多糖及五环三萜类物质均是苓桂术甘汤抗氧化作用的物质基础,利用体外生物测定法测定抗氧化活性可作为全面控制苓桂术甘汤质量的评价指标。     

益心舒胶囊治疗病毒性心肌炎气阴两虚证的抗氧化、抗炎作用观察

目的:探讨益心舒胶囊治疗病毒性心肌炎(VMC)气阴两虚证的临床疗效及抗氧化、抗炎的作用。方法:将132例亚急性期VMC患者,采用随机按数字表法分为对照组和观察组各66例。两组均注射用磷酸肌酸钠,1 g/次,1次/d,静脉滴注,连续治疗14 d;辅酶Q10胶囊,1粒/次,3次/d,饭后服用;盐酸曲美他嗪片,1片/次,3次/d,三餐时服用;重症患者,给予地塞米松磷酸钠注射液,10～20 mg/次,1次/d,静脉滴注,连续治疗14 d。对照组口服稳心颗粒,每次1袋,3次/d。观察组口服益心舒胶囊,3粒/次,3次/d。两组疗程均连续治疗8周。监测血清肌钙蛋白I(cTnI)和心肌肌酸磷酸激酶(CK-MB),记录治疗后cTnI,CK-MB的复常率;进行治疗前后心电图检查,记录心电图复常率;进行治疗前后气阴两虚证评分;检测治疗前后肌酸磷酸激酶(CPK),羟丁酸脱氢酶(HBDH),乳酸脱氢酶(LDH)和天门冬氨酸氨基转移酶(AST)水平;进行治疗前后超声心动图检查,记录治疗前后左心室射血分数(LVEF),心脏指数(CI)和舒张早期/舒张晚期最大血流速度(E/A);检测治疗前后超氧化物歧化酶(SOD),丙二醛(MDA),谷胱甘肽过氧化物酶(GSH-Px),干扰素-γ(IFN-γ),白细胞介素-10(IL-10),IL-17和IL-35水平。结果:采用秩和检验分析两组临床疗效,观察组优于对照组(Z=2. 151,P0. 05);观察组cTnI,CK-MB和心电图复常率分别为82. 26%(51/62),90. 32%(56/62)和80. 65%(50/62)分别高于对照组的65. 00%(39/60),73. 33%(44/60)和63. 33%(38/60)(P0. 05);观察组患者血清cTnI,CK-MB,CPK,HBDH,LDH和AST水平均低于对照组(P0. 01);观察组患者LVEF,CI和E/A均高于对照组(P0. 01);观察组SOD和GSH-Px水平均高于对照组(P0. 01),MDA水平低于对照组(P0. 01);观察组IL-10和IL-35水平均高于对照组(P0. 01),IFN-γ和IL-17水平均低于对照组(P0. 01)。结论:在西医常规治疗的基础上,加用益心舒胶囊治疗亚急性期VMC气阴两虚证患者,可通过抗炎和抗氧化作用而保护心肌,临床能起到降低心肌酶,促进心电图、心酶等恢复,改善心功能,提高临床治疗的效果。     

A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology,toxicology, and some pharmaceutical aspects

Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa‐sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.     

In situ antioxidant activity of a dermo‐cosmetic product: A randomized controlled clinical study

Ultraviolet light enhances the generation of reactive oxygen species that are responsible for skin photoageing. The aim of this randomized, vehicle‐ and active‐controlled double‐blind, intra‐individual monocentric study was to evaluate in situ the antioxidant activity of a dermo‐cosmetic product in photoaged skin. Twenty healthy volunteers had defined skin areas randomized to receive a topical product containing 3 antioxidants (pre‐tocopheryl^®, retinaldehyde and glycylglycine ole‐amide), its vehicle and a positive antioxidant control cream. The products were applied daily for 30‐day period. The skin areas were exposed to a controlled dose of UVA rays, and the skin oxidative status was evaluated 4 and 24 hours post‐UVA exposure at D0 (basal value) and after 15 and 30 days of product application. Skin layers were collected by stripping, and antioxidant capacity was measured using the ferric reducing ability of a plasma assay. Lipid peroxidation (LPO) was assessed using the malonyldialdehyde test. The tested product significantly improved the skin antioxidant capacity after 15 and 30 days and significantly decreased the basal level of the skin LPO. The skin LPO level significantly decreased 4 and 24 hours after UVA exposure at 15 and 30 days. These findings were comparable to positive control treated sites and were significantly different from the vehicle and untreated sites. This minimally invasive methodology enabled a quantitative evaluation of potent antioxidant activity in situ in the stratum corneum reflecting real‐life skin conditions and confirming the benefits of the topical application of a product containing 3 antioxidants in the prevention of UVA‐induced oxidative damage.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.