Improvement Effects of α-lipoic Acid on Glucose Metabolism Disorder of Insulin Resistant HepG 2 Cells / 中国药房

OBJECTIVE：To study the i mprovement effects of α-lipoic acid on glucose metabolism disorder of insulin resistant HepG2 cells. METHODS ：The effects of 25-1 000 µmol/L α-lipoic acid on survival rate of human hepatoma cell HepG2 were determined by MTT assay so as to determine the concentration of α-lipoic acid. Negative control group ，insulin resistance group （1× 10－7 mol/L insulin ），combination resistance group （30 µmol/L sodium arsenite+ 1×10－8 mol/L insulin ），α-lipoic acid low- concentration，medium-concentration and high-concentration groups were set up. HepG 2 cells were treated with α-lipoic acid for 12 h and then cultured with corresponding concentration of sodium arsenite or/and insulin for 24 h. The glucose oxidase method was used to detect the glucose consumption ，colorimetric method was used to detect hexokinase activity and pyruvate kinase activity ， and anthrone method was used to detect glycogen content. Western blot assay was used to detect the protein expression of GLUT 4， p-GSK3β and GSK3β as well as the ratio of p-Akt/Akt and p-GSK3β/GSK3β. RESULTS：25，50，100 µmol/L α-lipoic acid had no significant effect on the survival rates of HepG 2 cells（P＞0.05），and survival rates of H epG2 cells were higher than 96％，so they were used as the low ，medium and high concentration for follow-up study. Compared with negative control group ，glucose consumption，the activities of hexokinase and pyruvate kinase ，glycogen content ，protein expression of GLUT 4 and p-GSK 3β，the ratio of p-Akt/Akt and p-GSK 3β/GSK3β were decreased significantly in insulin resistance group and combined resistance group， while the protein expression of GSK 3β was increased significantly（P＜0.05）. Compared with combination resistance group ，the glucose consumption （except for α-lipoic acid low- concentration group ），the activities of h exokinase（except for α-lipoic acid low-concentration and medium-concentration groups ） andpyruvate kinase （except for α-lipoic acid low-concentration com and medium-concentration groups ）， glycogen contents ， protein expression of GLUT 4 （except for α-lipoic acid mail：bliang163@163.com low-concentration group ）and p-GSK3β，the ratio of p-Akt/ Akt（except for α-lipoic acid low-concentration and medium-concentration groups ）and p-GSK 3β/GSK3β（except for α-lipoic acid low-concentration groups ）were increased significantly in α-lipoic acid groups ，while protein expression of GSK 3β（except for α-lipoic acid low-concentration and medium-concentration groups ） was decreased significantly （P＜0.05）；glycogen content ， protein expression of GLUT 4 and the ratio of p-GSK 3β/GSK3β in α-lipoic acid high-concentration group as well as the protein expression of p-GSK 3β in α-lipoic acid medium-concentration and high-concentration groups were improved significantly （P＜0.05）. CONCLUSIONS：α-lipoic acid can improve the disorder of glucose metabolism in insulin resistant HepG 2 cells，the mechanism of which may be associated with the increase of glucose consumption ，the activities of glucose metabolism related enzymes and glycogen content ，and expression up-regulation of the phosphorylation levels of Akt and GSK 3β protein，the expression of GLUT 4 and p-GSK 3β proteins，down-regulation of the expression of GSK 3β protein.

Pharmacoeconomic Evaluation of α-Lipoic Acid Alone or Combined with Mecobalamin versus Mecobalamin in the Adjunctive Treatment of Diabetic Peripheral Neuropathy / 中国药房

OBJECTIVE： To evaluate the clinical efficacy and economics of α-lipoic acid injection alone or combined with Mecobalamin injection versus Mecobalamin injection in the adjunctive treatment of diabetic peripheral neuropathy （DPN）. METHODS： Retrieved from PubMed， Cochrane Library， Embase， CNKI， VIP， CBM and Wanfang database， using “mecobalamin” “α-lipoic acid” and“diabetic peripheral neuropathy”as Chinese retrieval words， “Thioctic acid” “α-lipoic acid” “Methylcobal” “Mecobalamin” “Diabetic peripheral neuropathy” as English retrieval words， relevant randomized controlled trials （RCTs） were collected during the date of database establishment to Aug. 30th， 2018. Meta-analysis was conducted for total response rate. From the perspective of health care providers， cost-effectiveness analysis was used for economic evaluation and sensitivity analysis was conducted by a 15％ fluctuation of cost and total response rate. RESULTS： Totally 13 RCTs were included， involving 1 131 patients. The results of Meta-analysis showed that the total response rate of two-drug combination therapy in the treatment of DPN was higher than that of mecobalamin alone [RR＝1.41， 95％CI（1.28， 1.55）， P＜0.000 01]； that of α-lipoic acid injection alone in the treatment of DPN was higher than that of mecobalamin injection alone [RR＝1.35， 95％CI（1.25，1.47）， P＜0.000 01]， with statistical significance. Results of cost-effectiveness analysis showed that the cost-effectiveness ratio （CER） of Mecobalamin injection was 211.38 yuan， and CER of two-drug combination and α-lipoic acid injection alone were 1 484.42 and    1 383.49 yuan， respectively. The incremental cost-effectiveness ratio （ICER） were 4 589.52 and 4 638.82 yuan， which were all lower than per capita GDP in 2017. Sensitivity analysis showed that the cost-effectiveness analysis results kept stable. CONCLUSIONS： Compared with Mecobalamin injection， α-lipoic acid injection combined with Mecobalamin injection in the adjunctive treatment of DPN show high total response rate and economics.

Biosynthesis of α-lipoic acid in Gluconobacter oxydans increases the production of vitamin C by one-step fermentation / 生物工程学报

In a one-step fermentation system of vitamin C production with Gluconobacter oxydans and Ketogulonicigenium vulgare, a functional module of α-lipoic acid biosynthesis was constructed in G. oxydans. The engineered G. oxydans was co-cultured with K. vulgare to enhance the growth and 2-keto-L-gulonic acid (2-KGA) production of K. vulgare. This one-step fermentation system alleviated the growth inhibition during the mono-culture of K. vulgare and strengthened the interaction between the two bacteria. Moreover, the yield of vitamin C precursor (2-KGA) increased to 73.34 g/L (the control group was 59.09 g/L), and the conversion of D-sorbitol to 2-KGA increased to 86.0%. This study provides a new idea for further optimizing the one-step fermentation system of vitamin C production.

Immunomodulatory effects of α-Lipoic acid / 中国免疫学杂志

Alpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically.Accumulating evidence suggests that α-lipoic acid might have immunomodulatory effects on either adaptive or innate immune system.This Review focuses on the evidence and potential targets involved of the immunomodulatory effects of α-lipoic acid.It highlights that α-lipoic acid may have beneficial effects in conjunction with the current treatment of autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.

Alpha-lipoic acid alleviates the 6-OHDA-induced SH-SY5Y cell damage by inhibiting autophagy via AMPK/mTOR pathway / 中华老年医学杂志

Objective To investigate the effects of α-lipoic acid(ALA)on 6-hydroxydopamine(6-OHDA)-induced autophagy in human neuroblastoma(SH-SYSY)cells and its possible mechanisms.Methods SH-SYSY cells were divided into 5 groups:blank control group (group A),ALA group (group B),6-OHDA group(group C),ALA+6-OHDA group(group D),and rapamycin(RAPA)group (group E).The cell viability,cell apoptosis,and oxidative stress were assayed and analyzed in A-D group.The expression of autophagy-related proteins LC3-Ⅱ,AMP-activated protein kinase(AMP-K),phosphorylated AMPK (p-AMPK),the mammalian target of rapamycin (mTOR) and p-mTOR were detected by Western blot in A-E group.Results Compared with the blank control group,the 6-OHDA group significantly reduced the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜0.05),and increased the cellular apoptosis rate(P＜0.01),oxidative stress level(P ＜0.01),LC3-Ⅱ protein expression(P＜0.05,with the highest level at 6 h after treatment),and p-AMPK protein expression(P＜＜0.05).There was no significant difference in these indices between ALA group and the blank control group.Compared with 6-OHDA group,ALA+ 6-OHDA group showed that the cell viability(P ＜ 0.01) and p-mTOR protein expression (P ＜ 0.05) were increased,while the cellular apoptosis rate(P＜0.01),oxidative stress level(P＜0.01),LC3-Ⅱ protein expression(P ＜0.05),and p-AMPK protein expression (P ＜ 0.05)were decreased.Conclusions The 6-OHDA can induce oxidative stress and autophagy in SH-SY5Y cells and decrease the cell viability.ALA can alleviate the 6-OHDA-induced cell injury possibly by inhibiting autophagy via AMPK/mTOR pathway.

The inhibitory effect of α-lipoic acid on the high salt-induced hypertension rats / 重庆医学

Objective To investigate whether the excessive production of reactive oxygen species (ROS) in the mitochondria of the rostral ventrolateral medulla (RVLM) can inhibit the high salt-induced hypertension response.Methods A total off 32 male rats were divided into two groups:two groups were given normal salt diet (0.3％ NaCl) for 8 weeks (n=16) and high salt diet (8％ NaCl) for 8 weeks (n=16,induced hypertension model) respectively.The two groups were divided into four groups,two groups were given α-lipoic dissolving in 0.9％ normal saline (60 mg/kg),two groups were fed with saline for 9 weeks.There were ffour groups:the experimental group (n=8,the hypertension model sample fed α-lipoic acid),the model group (n=8,the hypertension model sample fed saline),the control group (n=8,normal salt diet sample fed α-lipoic acid) and the blank control group (n=8,normal salt diet sample ffed saline).Monitored the change of the arterial pressure and detected the expression off superoxide by immunofluorescence at the end of the experiment,measured the expression of NAD(P)H NOX2,NOX4 and Cu/Zn-SOD in RVLM by Western blot;determined the expression differences of oxidative stress related substances such as mitochondrial malondialdehyde(MDA)in RVLM by ELISA.Results The mean arterial pressure (MAP) in the experimental group was lower than that in the model group,the difference was statistically significant (P＜0.05);in the experimental group and the model group the intensities of fluorescent-labled dihydroethidium(DHE) were 60.2±3.1,99.1±3.8;the numbers of positive neurons in Cu/Zn-SOD were 20.8±1.1,6.9 ± 1.2;the numbers of NOX2 positive neurons were 12.3 ± 3.5,25.1 ±5.4;the numbers of NOX4 positive neurons were 10.1±2.2,13.3±4.1,the difference was statistically significant (P＜0.05).Western blot showed that the NOX2 levels of the experimental group and the model group were 78.9 ± 2.0,112.7 ± 3.8;the levels of NOX4 were 63.2± 2.1,99.4 ± 1.7.The levels of Cu/Zn-SOD in RVLM of the experimental group and the model group were 19.7 ±1.6,10.3± 1.2,the difference was statistically significant (P＜0.05);the levels of mitochondrial superoxide dismutase (SOD) were (33.1±3.8),(15.2±1.7)U/mg,the difference was statistically significant (P＜0.05).The levels of mitochondrial glutathione (GSH) in the experimental group and the model group were (5.2±0.9),(2.3±0.5)μmol/g;the levels of norepinephrine (NE) were (325.8 ± 7.3),(467.9 ± 6.1) pg/mL,the difference was statistically significant (P＜0.05).Conclusion α-lipoic acid could decrease the expression of NOX2,NOX4 and the bioenergy of mitochondria enzyme,and increase the intracellular antioxidant ability in the RVLM during the development of hypertension to inhibit the oxidative stress response in the development of hypertension.

Observation on effect of α-lipoic acid combined with lipid microsphere alprostadil in treating elderly early diabetic kidney disease / 重庆医学

Objective To investigate the clinical curative effect of α-lipoic acid combined with lipid microsphere alprostadil in treating elderly early diabetic kidney disease .Methods One hundred and sixty-four cases of early diabetic kidney disease treated in this hospital from January 2014 to January 2016 were selected and randomly divided into the experimental group and the control group according to the random number table method ,82 cases in each group .The control group was given lipid microsphere alpros-tadil ,while on this basis the experimental group was added with α-lipoic acid .The various biochemical indexes ,clinical efficacy and subcutaneous bruising ,fundus event occurrence were compared between the two groups .Results The levels of U-RBP and NAG after treatment in the two groups were significantly decreased compared with before treatment ,the difference was statistically sig-nificant (P<0 .05) .Although other indicators such as serum Scr ,BUN ,CysC andβ2-MG had different degrees of decline ,but the difference was not statistically significant (P>0 .05) .The effective rate in the experimental group was 91 .46% ,which was signifi-cantly higher than 78 .05% in the control group ,the difference was statistically significant (P<0 .05) .Subcutaneous bruising and fundus events in the experiment group had the increasing trend ,but the difference between the two groups had no statistical signifi-cance (P>0 .05) .Conclusion α-lipoic acid combined with lipid microsphere alprostadil in treating elderly early diabetic kidney dis-ease can better improve glomerular and renal tubular function .

Clinical Efficacy of α-Lipoic Acid versus Epalrestat in the Treatment of Diabetic Peripheral Neuropathy:A Systematic Review / 中国药房

OBJECTIVE:To systematically review the efficacy of α-lipoic acid versus epalrestat in the treatment of diabetic pe-ripheral neuropathy(DPN),and provide evidence-based reference for clinic. METHODS:Retrieved from CJFD,CBM,VIP,Wan-fang Database and PubMed,randomized controlled trials(RCT)about α-lipoic acid versus epalrestat in the treatment of DPN were collected,and the study was screened by inclusion and exclusion criteria. Meta-analysis was performed by using Rev Man 5.3 soft-ware after data extraction and quality evaluation by Cochrane software. RESULTS:Totally 6 RCTs were enrolled,involving 408 pa-tients. Results of Meta-analysis showed,compared with epalrestat,there were no significant differences in the total effective rate [RR=0.98,95%Cl(0.84,1.15),P=0.81],motor nerve conduction velocity [median nerve:MD=1.02,95%Cl(-1.10,3.14),P=0.34;common peroneal nerve:MD=0.23,95%Cl(-1.11,1.58),P=0.73] and sensory nerve conduction velocity [median nerve:MD=1.10,95%Cl(-0.39,2.59),P=0.15;common peroneal nerve:MD=0.95,95%Cl(-1.47,3.36),P=0.44] in α-lipoic acid group. CONCLUSIONS:The efficacy of α-lipoic acid is similar to epalrestat in the treatment of DPN,as well as the motor nerve conduction velocity and sensory nerve conduction velocity of median nerve or common peroneal nerve.

EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE / 中国修复重建外科杂志

OBJECTIVE: To investigate the effect of α-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet.

Comparison of R(+)-α-lipoic acid exposure after R(+)-α-lipoic acid 200 mg and 300 mg and thioctic acid 600 mg in healthy Korean male subjects

Alpha-lipoic acid, a physiological form of thioctic acid, is a strong antioxidant that relieves diabetic neuropathic symptoms. R(+)-α-lipoic acid shows superior antioxidative effects to its racemate. We compared the pharmacokinetics (PKs) and tolerability of R(+)- and S(-)-α-lipoic acid after a single oral dose of R(+)-α-lipoic acid, Dexid®, and its racemate, thioctic acid in healthy male subjects. We used an open-label, randomized, single-dose, three-treatment, parallel study design to compare the PK exposure of the active form, R(+)-α-lipoic acid. Thirty subjects completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean±SD) of R(+)-α-lipoic acid after doses of R(+)-α-lipoic acid 200 mg, 300 mg and thioctic acid 600 mg were 4186.8±1956.7, 6985.6±3775.8 and 6498.4±3575.6 µg/L, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC(last)) were 1893.6±759.4, 3575.2±1149.2 and 3790.0±1623.0 µg·h⁻¹·L⁻¹, respectively. The geometric mean ratio and 90% confidence intervals of R(+)-α-lipoic acid 200 mg to thioctic acid 600 mg for the C(max) and AUC(last) were 0.71 (0.43–1.15) and 0.51 (0.37–0.70), respectively. The corresponding R(+)-α-lipoic acid 300 mg to thioctic acid 600 mg values were 1.11 (0.68-1.80) and 0.97 (0.71-1.34), respectively. In conclusion, R(+)-α-lipoic acid 300 mg showed PK characteristics similar to those of thioctic acid 600 mg and both formulations were well tolerated.

Effect analysis of α-lipoic acid combined with alprostadil in patients with diabetic peripheral neuropathy / 中国综合临床

Objective To discuss the effect of α-lipoic acid combined with alprostadil in patients with diabetic peripheral neuropathy (DPN).Methods Eighty-two patients with DPN were divided into the control group(n=41) and research group(n=41) according to the random number table method.The patients of the control group were given alprostadil based on conventional therapy, while the research group were given alpha lipoic acid based on treatment of the control group, the course was two weeks.The bilateral median nerve and sural nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were tested by electromyograph.Disease severity were evaluated by neuropathy symptoms questionnaire (TSS) and pain degree were tested by Visual analogue scales(VAS).The MNCV, SNCV, TSS and VAS of before and after treatment and the clinical effect of the two groups were compared.Results There were no statistically significant difference about MNCV and SNCV of the two groups before treatment (P＞0.05).After treatment, the MNCV and SNCV of nervus medianus and nervus peroneus communis of research group and control group were significantly higher than before treatment, and the differences of research group before and after treatment (MNCV of nervus medianus: (42.5 ± 3.6) m/s vs (47.8± 4.6) m/s, t =-5.752, P ＜ 0.05;SNCV of ervus medianus : (39.6 ±1.6) m/s vs (46.2±4.5) m/s,t =-5.882,P＜0.05;MNCV of nervus peroneus communis: (39.8±3.2) m/s vs (44.5±2.5) m/s,t=-4.263,P＜0.05;SNCV of nervus peroneus communis: (36.5±1.7) m/s vs (48.7± 2.6) m/s, t =-7.526, P ＜ 0.05), significantly obvious than the control group (MNCV of nervus medianus: (42.3 ±4.2) m/s vs (44.5±5.3) m/s,t =-4.627,P＜0.05;SNCV of nervus medianus: (39.8 ±2.4) m/s vs (42.4±2.5) m/s,t =-5.527,P＜0.05;MNCV of nervus peroneus communis: (40.3±1.6) m/s vs (42.2± 1.6) m/s, t =-4.181, P＜ 0.05;SNCV of nervus peroneus communis: (36.4± 2.3) m/s vs (41.2±3.5) m/s,t =-5.928,P＜0.05).Before the treatment,the TSS and VAS of the control group were (11.4±2.5) sore and (5.3±1.6) sore,of the research group were (11.6±1.6) sore and (5.2±1.8) sore,and there was no significant difference between the two groups (P＞0.05).After treatment, the TSS and VAS of the control group were (6.4± 1.3) sore and (3.6± 1.3) sore, of the research group were (4.2± 3.3) sore and (1.7 ±0.9) sore, and compared to before treatment, there was significant difference (P＜0.05), and the research group was significantly lower than the control group, the difference between the two groups was statistically significant (P＜ 0.05).The total effective rate of research group was obviously higher than that of control group, the differences were statistically significant (95.1％ (39/41) vs 65.9％ (27/41), x2 =5.363, P =0.031) .Conclusion The effect of α-lipoic acid combined with alprostadil in patients with diabetic peripheral neuropathy is obviously better than that of using alprostadil only,it is worth popularization and application.

The therapeutic effect and effects on nerve conduction velocity of α-lipoic acid combined with monosialoteterahexosyl ganglioside sodium on diabetic peripheral neuropathy / 中国综合临床

Objective To observe the therapeutic effect and effects on nerve conduction velocity of α-lipoic acid combined with monosialoteterahexosyl ganglioside sodium (GM 1) on diabetic peripheral neuropathy (DPN).Methods Ninety-six cases patients with DPN were randomly divided into the observation group (50 cases) and the control group(46 cases).The control group received GM1 40 mg daily though travenous drip,the observation group received α-lipoic acid 600 mg and daily though travenous drip.The course of treatment was 2 weeks in two groups.The effect was observed after 2 weeks,the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by EMG.Results The total effectiveness of observation group was 94.00％(47/50),higher than that of the control group(71.74％ (33/46),x2=7.0205,P＜ 0.05).After the treatment,MNCV and SNCV of median nerve of observation group and the control group were (47.6813.34)m/s and (43.82±3.10)m/s,(40.23±2.76)m/s,(37.31 ±2.79)m/s,and M NCV and SNCV of common peroneal nerve of observation group and the control group were(42.86±3.16)m/s and (39.47±2.17)m/s,(35.67±2.61) m/s and (32.16±2.50) m/s,all improved compared to before treatment(observation grou:t =7.876,8.428,6.923,7.234;control grou:t =3.572,3.483,3.413,4.182;P＜0.05),and the magnitude of improvement of the observation group was more significant,and the difference was significant compared to control group after six months (t =5.133,3.827,4.634,4.545;P＜0.05).Conclusion α-lipoic acid combined with GM1 in the treatment of DPN can significantly improve the clinical symptoms of patients and improve nerve conduction velocity,is better than the single use of gangliosides,it is worthy of clinical application.

Influence of different dose α-lipoic acid on blood glucose and C-reaction protein in type 2 diabetic patients with macroangiopathy / 中国综合临床

Objective To discuss the influence of different dose α-lipoic acid on blood glucose and C-reaction protein(CRP) in type 2 diabetic patients with macroangiopathy.Methods Seventy-two cases type 2 diabetic patients with macroangiopathy were divided randomly and voluntarily into the conventional dose group(n=36) and high dose group(n=36).The patients of conventional dose group were given conventional dose α-lipoic acid(300 mg/d) based on glucose treatment while high dose group were given high dose α-lipoic acid (600 mg/d) based on glucose treatment,the courses were all 15 d.The fasting blood glucose(FBG),2 h postprandial blood glucose(2 hBG),serum CRP of before and after treatment of between the two groups and safety during the treatment were compared.Results The FBG,2 hBG and CRP of before and after treatment were respcetively (9.24±2.18) mmol/L and (8.18±1.38) mmol/L,(13.26±3.17) mmol/L and (11.26±1.63) mmol/L,(21.52±4.17) mg/L and (14.72±3.73) mg/L;(9.26±2.04) mmol/L and (5.82±1.27)mmol/L,(13.52±2.45) mmoL/L and (8.92±1.04) mmol/L,(22.65±4.67) mg/L and (8.61±1.52) mg/L,all groups decreased obviously,the differences were statistically significant compared to that of before treatment(t=4.265,4.654,4.956 and 5.562,6.254,7.654,P＜0.05),and the high dose group showed more lower (t=5.353,5.783,6.257,P＜0.05).After treatment,ALT ((37.26±9.64) U/L),AST ((38.22±7.04) U/L),BUN((7.25±1.52) mmol/L) and Scr((55.25±11.25) mmol/L) of all groups increased obviously than pretreatment((33.53±6.37) U/L,(33.15±7.16) U/L,(5.43±4.67) mmol/L,(53.15±13.65) mmol/L),but the differences were no statistically significant compared to that of before treatment (t=-2.061,-2.165,-1.455,-0.689,P＜0.05),and there were also no statistical significance between the two groups(t =2.125,3.026,1.235,1.035,P＜0.05).Conclusion α-lipoic acid can obviously decrease the blood glucose and CRP in type 2 diabetic patients with macroangiopathy,which has a significant dose effect relationship,and is safe and worthy of clinical application.

Evaluation of the effect of Boerhavia diffusa on gentamicin‑induced nephrotoxicity in rats.

Background: Ayurvedic literature claims that Boerhavia diffusa possesses rejuvenative properties especially related to the urinary system. Objective: To evaluate effect of aqueous extract of root of Boerhavia diffusa in gentamicin‑induced nephrotoxicity in rats. Materials and Methods: Study was conducted in two parts, using 40 rats in each part. Rats were equally divided into five groups for each part. Group 1: Normal control, Group 2: Disease control and Groups 3, 4, and 5: α‑lipoic acid (ALA) and 200 and 400 mg/kg of B. diffusa, respectively. All groups, except Group 1, concomitantly received gentamicin 150 mg/kg/day for 10 days. Parameters measured in part I were blood urea nitrogen (BUN), serum creatinine, kidney malondialdehyde (MDA), and glutathione (GSH) levels, kidney injury on histopathology; in part II, paraaminohippurate (PAH) clearance. Statistical Analysis: Mean ± SD of body weight, creatinine, BUN, MDA, GSH and PAH clearance were compared using parametric tests. Median histopathology scores were compared using Kruskal–Wallis test. ‘P’ value of < 0.05 was considered significant. Results: High dose of gentamicin caused significant elevation in BUN, serum creatinine and kidney MDA, fall in kidney GSH and histopathological damage in disease control group as compared with normal control (P < 0.05). Treatment with B. diffusa prevented changes in above parameters, comparable to ALA. Effects of both doses of B. diffusa were significantly better than disease control (P < 0.05). B. diffusa did not show significant improvement in PAH clearance, which was reduced due to gentamicin damage. Conclusion: B. diffusa exerted protection against structural and functional damage induced by gentamicin possibly due to its antioxidant properties.

Efficacy ofα-Lipoic Acid Treatment on Sepsis-induced Acute Kidney Injury in Rats and Its Mechanisms / 中国医科大学学报

Objective To investigate the impact ofα?lipoic acid(ALA)treatment on sepsis?induced acute kidney injury in rats and explore the mechanisms. Methods A total of 32 male SD rats were randomized into 4 groups:normal control group(group A),ALA?treated control group (group B),sepsis group(group C)and sepsis with ALA treated group(group D). Group A and B underwent sham operation,while CLP operations were conducted in group C and D. Rats in both group B and group D were then administered with 200 mg/kg ALA by oral gavage immediately after the surgical procedure. Twenty?four hours after the surgical procedure blood samples were obtained for the evaluation of creatinine,BUN,TNF?α,IL?6 and IL?1β. Rat kidneys were rapidly removed for PAS stain. Western blot was employed to determine the expression of NF?κB. Results Pathologi?cal changes of kidney were induced by sepsis and the level of creatinine,BUN,TNF?α,IL?6 and IL?1βwere significantly increased by 178%,66%, 55%,114%and 110%(P<0.01). respectively;simultaneously the phosphorylation and nuclear expression of NF?κB p65 in kidney tissues were significantly increased by 144%and 102%(P<0.01). Sepsis?induced acute kidney injury also significantly reduced the expression of IκBαby 61%(P<0.01). These changes were significantly suppressed by early ALA treatment. Compared with C group,the level of creatinine,BUN,TNF?α,IL?6 and IL?1βwere significantly decreased by 48%,26%,25%,37%and 40%(P<0.05),respectively,and the relative expression of IκBαwas increased by 103%(P<0.05). Conclusion The present study demonstrated that ALA can suppress the activation of NF?κB,thus ameliorat?ing sepsis?related acute kidney injury.

Efficacy of Mecobalamin versus α-Lipoic Acid in the Treatment of Diabetic Peripheral Neuropathy:a Me-ta-analysis / 中国药房

OBJECTIVE:To systematically review the efficacy of mecobalamin versus α-lipoic acid in the treatment of DPN, and to provide evidence-based reference for clinical treatment. METHODS:Retrieved from Medline,EMBase,PubMed,Cochrane Library,CJFD,VIP and Wanfang database,randomized controlled trials (RCT) about mecobalamin (test group) vs. α-lipoic acid (control group)in the treatment of DPN were collected. After quality evaluation and data extraction,Meta-analysis was performed by using Rev Man 5.2 statistics software. RESULTS:A total of 11 RCT were included,involving 940 patients. Results of Me-ta-analysis showed the total effective rate in test group was significantly lower than control group,there were significant difference in 2 group [OR=0.17,95%CI(0.12,0.24),P<0.001]. CONCLUSIONS:The efficacy of α-lipoic acid is better than mecobalamin in the treatment of DPN. Due to the limit of methodological quality and sample size,it remains to be further verified with more rig-orously designed and long-term follow-up of large-scale RCT.

The effect ofα-lipoic acid on the retinal expression level of VEGF in rats with diabetes mellitus and mechanism / 重庆医学

Objective To study the effect of α-lipoic acid on the retinal expression level of VEGF and diabetic retinopathy in rats with diabetes mellitus and mechanism.Methods Totally 72 Wistar rats were divided into 4 groups:12 (control group)in group A,24 in modeling group(group B),24 in group treated withα-LA(group C)and 12 in high-glucose(group D).Group B to group D were given 60 mg/kg STZ through intraperitoneal injection,rats in group C were given 100 mg/kg α-LA and rats in group D were given 5.0% glucose-solution.The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 of 4 groups were compared by statistics.Results After 72 h,the FPG of group A was(4.57 ±0.1 5 )mmol/L,that of group B was (21.72±4.28)mmol/L,that of group C was(21.54±4.96)mmol/L and that of group D was(21.83±4.77)mmol/L,the difference had statistical significance (P 0.05).The body mass,FPG,FINS,HOMA-IR,expression level of VEGF,activity of SOD,GSH and IL-6 among 4 groups at 4 w,8 w and 12 w had statistical difference (P <0.05).After 12 w,the difference of GR stage among group B to group D had statistical significance (P <0.05).Conclusion α-LA can inhibit the expression of VEGF in rats with diabetes mellitus,which is related to its ability to re-duce the oxidative stress and inflammation reaction,as well as to alleviate the insulin resistance.

The influence of α-lipoic acid on nerve conduction velocity in the treatment of type 2 diabetes with peripheral neuropathy / 中国基层医药

Objective To observe the influence of α-lipoic acid on nerve conduction velocity in the treatment of type 2 diabetes with peripheral neuropathy,to provide a theoretical basis for clinical treatment.Methods 90 type 2 diabetes patients with peripheral neuropathy were included in this study.The patients were randomly divided into the observation group and the control group,45 cases in each group.The control group was given conventional therapy,containing hypoglycemic comprehensive intervention and neurotrophic treatment.The observation group was given αt-lipoic acid treatment,600mg/d,21d for a course of treatment.The motor and sensory nerve conduction velocity were measured by EMG after a course,and the peripheral neuropathy symptoms (limb pain,numbness,fever,cold,hypoesthesia) before and after treatment were observed,the clinical efficacy was evaluated.Results The motor nerve conduction velocity (median nerve,tibial nerve,peroneal nerve) and sensory nerve conduction velocity (median nerve,peroneal nerve) of the observation group after treatment were significantly higher than before treatment (t =3.946,4.175,3.887,3.915,4.034,all P ＜ 0.05),but the median nerve sensory conduction velocity of the control group had no significant difference before and after treatment(P ＞ 0.05).The motor nerve conduction velocity (median nerve,tibial nerve,peroneal nerve) and sensory nerve conduction velocity (median nerve,peroneal nerve) of the observation group after treatment were significantly higher than the control group (t =3.488,3.585,3.362,3.246,3.505,all P ＜ 0.05).The efficacy of limb pain,numbness,fever,cold,feeling diminished of the observation group were 71.43％,78.95％,62.5％,61.54％,59.26％,which were significantly higher than 36.36％,43.24％,21.4％,29.17％,28％ of the control group(all P ＜0.05).The total effective rate of the observation group was 84.44％,which was significantly higher than 64.44％ of the control group (x2 =6.925,P ＜ 0.05).Conclusion α-lipoic acid can improve the motor nerve conduction velocity and sensory nerve conduction velocity of type 2 diabetes patients with peripheral neuropathy,significantly relieve the positive symptoms of DPN and improve clinical efticacy,which is worthy of clinical use.

Effects ofα-lipoic acid combined with motilin in treatment of patients with diabetic gastroparesis / 中华内分泌外科杂志

Objective To explore the curative effects and safety of α-lipoic acid combined with motilin in treatment of patients with diabetic gastroparesis and its influence on gastrointestinal dynamics and gastrointesti -nal hormone.Methods 108 patients with diabetic gastroparesis were included and they were divided into the ob -servation group and the control group according to the random indicator method , with 54 cases in each group .All patients were given routine hypoglycemic therapy .On this basis, patients in the control group were given motilin while patients in the observation group were given α-lipoic acid combined with motilin .After 14 days, the cura-tive effects, the rate of gastric emptying, oral-colonic transit time(OCTT), and gastrointestinal hormone including gastric dynamic element ( MTL ) and somatostatin ( SS ) , stomach gastrin-releasing ( GAS ) and adverse reactions during treatment were compared between the 2 groups.Results The total effective rate was 85.19% and 64.81% respectively in the observation group and the control group , and the difference had statistical significance (P0.05).Conclusions The cura-tive effects of α-lipoic acid combined with motilin in treatment of diabetic gastroparesis is distinct .Its mechanism may be related to improving gastrointestinal disorders , and adjusting gastrointestinal hormone .

α-Lipoic acid promotes inhibition of pyrroIidine dithiocarbamic acid on Hep-2 ceII proIiferation / 中国药理学与毒理学杂志

OBJECTIVE To investigate whether α-lipoic acid(α-LA)can promote the anti-prolifera-tion effect of pyrrolidine dithiocarbamic acid(PDTC)in Hep-2 cells. METHODS The laryngeal carcino-ma Hep-2 cells were cultured with α-LA,PDTC or α-LA+PDTC respectively for 12,24 and 48 h. The proliferation of Hep-2 cells was detected by WST-1 assay and soft agar colony formation while apoptosis and cell cycle were analyzed by Hoechst33258 staining and flow cytometry. RESULTS α-LA 5 -500 μmol·L-1 could not inhibit Hep-2 cell proliferation,but PDTC 5 -50 μmol·L-1 could( P ﹤0.05,P ﹤0.01). The cell proliferation inhibitory rate of PDTC 5 μmol·L-1 combined with α-LA 5,10 and 20 μmol·L-1 groups was much higher than in control group(P﹤0.01)and PDTC alone group(P﹤0.05). When α-LA 5 μmol·L-1 was used in combination with PDTC 5 μmol·L-1 for 12-48 h,the cell proliferation was inhibited in a time-dependent manner(r=0.987,P﹤0.05). When the cells were treated for 24 h,the number of soft agar colony formations in combined group was significantly smaller than that of both α-LA alone group(P﹤0.01)and PDTC alone group(P﹤0.05). The result of Hoechst33258 staining and flow cytometry indicated that after combined treatment with PDTC 5 μmol·L-1 and α-LA 5 μmol·L-1 for 24 h,the level of apoptosis and the percentage of cells in G2 / M stage were significantly increased compared with PDTC alone or α-LA alone treatment. CONCLUSION α-LA can enhance the anti-proliferation and pro-apoptosis effect of PDTC in Hep-2 cells.