Clinical applications and pharmacological research progress of Lianhua Qingwen capsules/granules

Lianhua Qingwen capsule/granule is an innovative Chinese medicine developed under the guidance of the traditional Chinese medicine(TCM)collateral disease theory.It has the effect of“clearing heat and removing toxin,ventilating the lungs and discharging heat”.In 2003,it was approved as a new drug by the China National Medical Products Administration,through expedited approval during severe acute respiratory syndrome,and now,it has become a representative proprietary Chinese medicine for the treatment of infectious diseases of the respiratory system.Pharmacodynamic studies have revealed that Lianhua Qingwen has broad-spectrum antiviral,antibacterial and anti-inflammatory,antipyretic,coughrelieving,and immunoregulation effects.Clinically it has been used in the treatment of communicable and infectious respiratory diseases such as Coronavirus Disease 2019,influenza,colds,pulmonary infections,etc.and has achieved remarkable curative effects,showing the important clinical guidance of the TCM collateral disease theory.

Therapeutic Effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with Acupoint Application on Chronic Lumbar Muscle Strain and the Recovery of Lumbar Strength

Objective:To study the therapeutic effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application on chronic lumbar muscle strain and the recovery of lumbar strength.Methods:From August 2018 to August 2019,100 patients with chronic lumbar muscle strain admitted to our hospital were selected and randomly divided into an acupoint application group and a combined group of 50 cases each.The acupoint application group was treated by acupoint application,and the combined group was treated with Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)based on acupoint application.The indexes scores,VAS scores,ADL scores,ODI scores,lumbar endurance,TCM syndrome scores and the treatment effects of the two groups before and after treatment were statistically analyzed,and TNF-αand TXB2 levels were detected.Results:After treatment,the scores of indexes,VAS,ODI,TCM syndrome,TNF-αand TXB2 in the combined group were lower than those in the acupoint application group,and the ADL score,lumbar endurance and treatment efficiency were higher than those in the acupoint application group,with a statistical difference(P<0.05).Conclusion:Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application can effectively reduce pain,improve lumbar function,restore lumbar strength,effectively relieve inflammation,with significant effects.

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in mice.Methods A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min.According to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)group.The day after modeling,TXL and BNPL were administered by gavage.Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks.Echocardiography was used to measure cardiac function in mice.Masson staining was used to evaluate the degree of myocardial fibrosis in mice.Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,respectively.The protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western blot.Results TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P<0.05 or P<0.01).TXL significantly increased the protein expressions of PI3K and p-AKT(P<0.05 or P<0.01).There was no significant difference between TXL and BNPL group(P>0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of TXL.Conclusion TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

Protective Effects and Potential Mechanism of Tongxinluo on Mice with Thromboangiitis Obliterans Induced by Sodium Laurate

Objective To investigate the effects of Tongxinluo(TXL)on thromboangiitis obliterans(TAO)and the underlying mechanisms.Methods Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table:the sham group,TAO model group,Compound Danshen Tablet(CDT)group,and the high-,medium-,and low-dose TXL groups.All mice except the sham group were injected with sodium laurate(0.1 mL,5 mg/mL)in the femoral artery to establish TAO mouse model.After modeling,mice in the sham and TAO model groups were intragastrically administered 0.5%(w/v)sodium carboxymethylcellulose,mice in the CDT group were intragastrically administered 0.52 g/kg CDT,and mice in the TXL-H,TXL-M,and TXL-L groups were intragastrically administered 1.5,0.75,and 0.38 g/kg TXL,respectively.After 4 weeks of gavage,the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging.The pathological changes and thrombosis of the femoral artery were observed by morphological examination.The expressions of tumor necrosis factorα(TNF-α)and inducible nitric oxide synthase(iNOS)in the femoral artery wall were detected by HE staining.Levels of thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-keto-PGF1α),endothelin-1(ET-1),interleukin(IL)-1βand IL-6 were measured using enzyme-linked immunosorbent assay(ELISA).Levels of activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT)and fibrinogen(FIB)were detected by a fully automated biochemical analyzer.Results TXL promoted the restoration of blood flow in the lower limbs,reduced the area of thrombosis in the femoral artery,and alleviated the pathological changes in the femoral artery wall.Moreover,the levels of TXB2,ET-1,IL-6,IL-1β,TNF-αand iNOS were significantly lower in the TXL groups compared with the model group(P<0.05 or P<0.01),while the level of 6-keto-PGF1αwas significantly higher(P<0.01).In addition,APTT,PT,and TT were significantly prolonged in TXL groups compared with the model group(P<0.05 or P<0.01),and FIB levels were significantly decreased compared with the model group(P<0.01).Conclusions TXL had a protective effect on TAO mice,and the mechanism may involve inhibition of thrombosis and inflammatory responses.TXL may be a potential drug for the treatment of TAO.

艾灸神阙穴抗长期运动疲劳作用的实验研究（英文）

目的:探讨艾灸神阙穴对长期力竭大鼠抗疲劳性运动作用的影响。方法:将30只Sprague-Dawley(SD)雄性大鼠随机分为空白组、模型组和艾灸组,每组10只。除空白组外,其余大鼠采用反复游泳实验制造长期力竭模型。造模成功后,艾灸组大鼠温和灸神阕穴15 min,隔日1次,共治疗10次。模型组和空白组大鼠不接受治疗。治疗结束后比较各组大鼠的力竭时间及实验前后的体质量,并采用全自动分析仪检测力竭运动24 h后血清中丙二醛(MDA)、血尿素氮(BUN)浓度及天门冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和乳酸脱氢酶(LDH)活性。结果:第10次游泳时间比较,艾灸组明显较模型组长(P<0.01)。艾灸组大鼠第7次、第10次力竭运动前体质量增长速度慢于同期模型组(P<0.05,P<0.01)。模型组大鼠血清MDA和BUN含量及AST、ALT和LDH活性均较空白组升高(均P<0.01)。艾灸组大鼠血清MDA和BUN含量及AST、ALT和LDH活性均较模型组降低(P<0.01)。结论:艾灸神阙穴可以降低长期疲劳大鼠血清中的MDA和BUN含量及AST、ALT和LDH活性,改善疲劳症状。

头针久留配合互动式训练治疗脑卒中后上肢功能障碍疗效观察

目的:观察头针久留针配合互动式训练改善脑卒中患者上肢功能障碍的疗效.方法:将95例脑卒中后上肢功能障碍患者随机分为2组,治疗组48例,对照组47例.两组均进行常规内科基础治疗.两组头针均选取病灶同侧(偏瘫肢体对侧)顶颞前斜线中2/5、顶颞后斜线中2/5.治疗组头针留针7 h并配合互动式训练,对照组仅留针7 h,不进行互动式训练.两组均于治疗前、治疗2周和4周后进行香港版偏瘫上肢功能测试(FTHUE-HK)和简化Fugl-Meyer上肢运动功能评定量表(FMA-UE)评分.结果:治疗组总有效率为97.9%,对照组为74.5%,治疗组总有效率高于对照组(P<0.01).两组治疗2周和4周后的FTHUE-HK评分均高于本组治疗前,组内差异均有统计学意义(均P<0.001);两组治疗4周后的FTHUE-HK评分均高于本组治疗2周后,组内差异均具有统计学意义(均P<0.001).治疗组治疗2周和4周后的FTHUE-HK评分均高于同时间点对照组,组间差异均具有统计学意义(均P<0.05).治疗组在整个治疗期间FTHUE-HK评分虽高于对照组,但两组在治疗2周内的差异趋势无统计学意义(P>0.05),在治疗4周后的差异趋势,具有统计学意义(P<0.05).两组治疗2周和4周后FMA-UE评分均高于本组治疗前,组内差异均具有统计学意义(均P<0.001),且两组治疗4周后FMA-UE评分均高于本组治疗2周后,组内差异均具有统计学意义(均P<0.001).治疗组在治疗2周和4周后的FMA-UE评分均高于同时间点对照组,组间差异均具有统计学意义(均P<0.01).随着治疗次数的增加,两组的FMA-UE评分均逐渐升高,两组FMA-UE评分在治疗2周和4周后的差异趋势,均具有统计学意义(均P<0.05).结论:头针久留针配合互动式训练在改善脑卒中后上肢功能障碍方面疗效优于单纯头针久留针,且持续治疗2周以上时,疗效优势更明显.

Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function

Background： Our previous studies have shown that Tongxinluo （TXL）, a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density （MVD） in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. Methods： After intragastric administration of TXL （0.1 ml/10 g body weight） to C57BL/6J wild-type mice （n = 8） and ApoE-/- mice （n=8）, total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein （VLDL）-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate （HR）, lelt ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and let1 ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity （PSV）, end diastolic flow velocity, and mean flow velocity （MFV） were measured. The pulsatility index （PI） and resistant index were calculated in order to evaluate the vascular elasticity and resistance. Tile endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor （VEGF）. lnamunohistochenaical detection was perlbrmed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P 〈 0.05 was considered statistically significant. Results： Although there was no significant decrease of cholesterol level （F = 2.300, P = 0.240）, TXL inhibited the level of triglyceride and VLDL （F- 9.209, P- 0.024 and F = 9.786, P ： 0.020, respectively） in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS （all P 〈 0.05）. TXL enhanced aortic PSV and MFV （F = 10.774, P = 0.024 and F = 11.354, P - 0.020, respectively） and reduced PI of ApoE-/- mice （1.41 ± 0.17 vs. 1.60 ± 0.17; P= 0.037）. After incubation with 10μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% - 3%, significantly higher than control group mice （F = 9.280, P = 0.040）. TXL also restrain the angiogenesis of ApoE-/- mice aorta （F = 21.223, P = 0.010）. Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice （54.0 ± 3.0/mm2 vs. 75.0 ± 2.0/mm2; F = 16.054, P - 0.010）. However, TXL could significantly enhance MVD （65.0 ± 5.0/mm2 vs. 54.0 ±3.0/mm2; F- 11.929, P = 0.020） in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot （F = 20.247, P = 0.004）. Conclusions： TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat tolessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity： improves endothelium-dependent vasodilatation： restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.