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Effects of onion extract on the growth of fibroblasts in pathological scar through MAPK/ERK pathway

The Chinese Journal of Clinical Pharmacology.2024;40(21):3092-3096. doi:10.13699/j.cnki.1001-6821.2024.21.006

Objective To investigate the effect of onion extract on the growth of fibroblasts in pathological scar and its mechanism.Methods The isolated fibroblasts were randomly divided into blank group(normal cultured),experimental-L group(10 μmol·L-1 onion extract),experimental-M group(20 μmol·L-1 onion extract),experimental-H group(40 μmol·L-1 onion extract),anisomycin group[40 μmol·L-1 onion extract+10 μmoL·L-1 mitogen activated protein kinase(MAPK)signaling pathway activator anisomycin].Cell proliferation was detected by clonogenesis assay,cell apoptosis was detected by flow cytometry,cell migration was detected by wound healing assay,and relative expression levels of related proteins was detected by Western blot assay.Results The colonies number of blank group,experimental-L group,experimental-M group,experimental-H group and anisomycin group was 176.89±12.92,147.22±5.03,102.56±8.42,71.56±6.85 and 124.78±10.70,respectively;the apoptosis rates were(4.19±0.29)％,(8.67±0.75)％,(17.59±1.32)％,(25.75±2.10)％and(10.88±1.06)％,respectively;the migration rates were(0.60±0.05)％,(0.43±0.04)％,(0.31±0.02)％,(0.18±0.03)％and(0.51±0.04)％,respectively;the relative expression levels of phosphorylation-MAPK(p-MAPK)protein were 0.82±0.12,0.53±0.08,0.43±0.05,0.37±0.05 and 0.62±0.07,respectively;the relative expression levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)protein were 0.93±0.10,0.73±0.07,0.60±0.07,0.47±0.07 and 0.76±0.07,respectively;the relative expression levels of alpha smooth muscle actin(α-SMA)protein were 0.80±0.09,0.60±0.04,0.33±0.03,0.21±0.02 and 0.77±0.08,respectively;the relative expression levels of collagen Ⅰ were 0.82±0.08,0.63±0.07,0.43±0.03,0.31±0.02 and 0.69±0.06,respectively.The above indexes in experimental-L,-M,-H groups were compared with those in blank group,and the differences were statistically significant(all P＜0.05);the above indexes in anisomycin group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Onion extract may inhibit fibroblast growth,cell migration,fibrosis and extracellular matrix deposition by inhibiting MAPK/ERK pathway,induce cell apoptosis and alleviate the formation of pathological scar.

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Research of lactate inhibiting the fibrotic phenotype of cardiac fibroblasts

Kai-yin CHEN ; Tao OU ; Yi LI ; Yi-hong WEN ; Jin-feng SU ; Ya WANG ; Heng-li ZHAO ; Zhi-xin SHAN

The Chinese Journal of Clinical Pharmacology.2024;40(21):3102-3107. doi:10.13699/j.cnki.1001-6821.2024.21.008

Objective To investigate the regulatory effect and possible mechanism of lactic acid on the fibrotic phenotype of cardiac fibroblasts.Methods Mouse cardiac fibroblasts(mCFs)were divided into control group(conventional culture),experimental-L group(4 mmol·L-1 L-lactic acid),experimental-M group(8 mmol·L-1 L-lactic acid),experimental-H group(12 mmol·L-1 L-lactic acid),transforming growth factor-β1(TGF-β1)group(10 ng·mL-1 TGF-β1),combined group(10 ng·mL-1 TGF-β1+12 mmol·L-1 L-lactic acid)and monocarboxylate transporter inhibitor(CHC)group(3 mmol·L-1 CHC).Western blot was used to detect the expression of fibrosis-related proteins and pan-lactate modification(Pan Kla)and H3 histone K18 lactate modification;cell scratch assay was used to detect cell migration ability.Results The cell migration rates of the control group,TGF-β1 group,experimental-H group and combined group were(40.56±0.03)％,(61.61±0.04)％,(26.59±0.05)％and(38.33±0.06)％,respectively.Compared with the control group,TGF-β1 group and experimental-H group,TGF-β1 group and combined group,the differences were statistically significant(all P＜0.01).The relative expression levels of collagen type Ⅰ alpha 1(COL1A1)protein in the control group,TGF-β1 group,experimental-H group and TGF-β1+experimental-H group were 0.76±0.09,1.10±0.07,0.40±0.04 and 0.68±0.10,respectively;the relative expression levels of COL3A1 protein were 0.87±0.05,1.15±0.07,0.32±0.07 and 0.73±0.06,respectively;the relative expression levels of α-smooth muscle actin(α-SMA)protein were 0.86±0.04,1.24±0.09,0.30±0.05 and 0.74±0.08,respectively.Compared with the control group,the above indexes of the TGF-β1 group and the experimental-H group were significantly different from those of the control group,and the above indexes of the TGF-β1 group were significantly different from those of the combined group(all P＜0.01).The cell migration rates of mCFs in the control group,experimental-H group and CHC group were(62.60±6.50)％,(28.00±8.15)％and(39.40±4.50)％,respectively;the relative expression levels of COL1A1 protein were 1.10±0.07,0.49±0.04 and 0.34±0.06,respectively;the relative expression levels of COL3A1 protein were 1.04±0.10,0.60±0.20 and 0.37±0.03,respectively;the relative expression levels of α-SMA protein were 1.20±0.11,0.67±0.20 and 0.48±0.18,respectively;the modification levels of Pan Kla were 1.06±0.07,1.54±0.09 and 1.53±0.12,respectively;the modification levels of H3K18la protein were 0.67±0.06,1.23±0.06 and 1.14±0.08,respectively.The above indexes of CHC group and experimental-H group were significantly different from those of control group(all P＜0.01).Conclusion L-lactic acid may play a role in inhibiting the fibrosis phenotype of mCFs by increasing non-histone lactic acid modification and H3K18la modification.

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Protective effects of HMS5552 on pancreatic β cell injury in diabetic rats

Ke-xin ZHOU ; Meng-jiao WANG ; Yu-zheng LÜ ; Miao-miao LIU ; Shou-min XI

The Chinese Journal of Clinical Pharmacology.2024;40(21):3108-3112. doi:10.13699/j.cnki.1001-6821.2024.21.009

Objective To investigate the protective effect of HMS5552 on pancreatic islet β-cell injury in diabetic rats and study the mechanism.Methods A total of 40 SD rats were fed with high-sugar and high-fat diet for 8 weeks combined with intraperitoneal injection of streptozotocin(STZ)to induce type 2 diabetic rat models.The successful model rats were divided into model group(0.9％NaCl by gavage)and experimental group(30 mg·kg-1 HMS5552 by gavage).The other 20 normal rats served as the normal group(0.9％NaCl was given by gavage).Hematoxylin-eosin(HE)staining was used to detect the pathological changes of pancreatic islets.The INS-1 cells were divided into blank group(normal cultured),model group(high-sugar and high-fat culture medium)and experimental-L,-M,-H groups(high-sugar and high-fat culture medium+0.3,3.0 and 30.0 μmol·L-1 HMS5552).The viability of INS-1 cells was detected by cell counting kit-8(CCK-8)method,the apoptosis of INS-1 cells was detected by Annexin V/PI method,the mRNA expression level of B cell lymphocytoma 2(Bcl-2)was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)method;the expression level of phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway and apoptosis protein was detected by western blotting.Results HE staining showed that the pathological damage of pancreas in the experimental group rats was significantly less than that in the model group.The cell viability of the blank group,model group and experimental-L,-M,-H groups were(99.67±2.40)％,(48.18±4.18)％,(61.74±4.78)％,(70.74±6.36)％and(78.30±4.68)％,respectively;apoptosis rates were(10.40±4.66)％,(48.60±3.27)％,(35.90±4.45)％,(28.07±5.35)％and(18.30±3.04)％,respectively;the relative expression levels of Bcl-2 mRNA were 1.00±0.03,0.32±0.04,0.59±0.05,0.62±0.04 and 0.72±0.12,respectively;phosphorylated PI3K(p-PI3K)/PI3K ratios were 1.00±0.00,0.34±0.05,0.46±0.02,0.64±0.01 and 0.81±0.01,respectively;phosphorylated AKT(p-AKT)/AKT ratios were 1.00±0.00,0.28±0.12,0.63±0.02,0.74±0.06 and 0.87±0.09,respectively.The above indexes in the model group compared with the blank group,the differences between the above indexes of the experimental-L,-M,-H groups and the model group were statistically significant(P＜0.05,P＜0.01).Conclusion HMS5552 can improve glucose metabolism in diabetic rats and protect pancreatic β-cells by regulating the expression of PI3K/AKT signaling pathway.

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Research status of hydrogen sulfide in the prevention and treatment of gastrointestinal ischemia-reperfusion injury

Si-yu WU ; Xu-tao SUN ; Shuo CAO ; Cai-yun MAO ; Qi ZHOU ; Yun-jia SONG

The Chinese Journal of Clinical Pharmacology.2024;40(21):3171-3175. doi:10.13699/j.cnki.1001-6821.2024.21.021

Gastrointestinal ischemia reperfusion(I/R)injury is a major cause of high morbidity and mortality in patients with surgical trauma.At present,there are few studies on gastrointestinal I/R injury,so it is particularly important to find treatment methods for gastrointestinal I/R injury.As the third gas signaling molecule,H2S plays an important physiological and pathological role in the human gastrointestinal system.Recently,a variety of novel H2S donors such as ATB-344 and AP39 have shown therapeutic value for gastrointestinal I/R injury.Therefore,this article reviewed the treatment of gastrointestinal I/R injury by H2S donors and its mechanism of action,aiming to provide a new treatment method for gastrointestinal I/R injury,in order to provide a reference for clinical medication of gastrointestinal I/R injury.

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Research status of clinical application of Zhengan Xifeng decoction in the treatment of hypertension

Mei-long SI ; Hua JIN ; Zhi-jun LIU ; Shuang-fang LIU

The Chinese Journal of Clinical Pharmacology.2024;40(21):3176-3180. doi:10.13699/j.cnki.1001-6821.2024.21.022

Hypertension is a cardiovascular syndrome characterized by increased systemic arterial blood pressure,which seriously affects human health and quality of life.At present,Chinese medicine has attracted much attention in the prevention and treatment of hypertension due to its multi-target and multi-pathway treatment advantages.Zhengan Xifeng decoction which has the effects of calming the liver and extinguishing wind,nourishing yin and suppressing yang.Zhengan Xifeng decoction has a good effect on hypertension,and its mechanism of action may be related to the regulation of intestinal flora,modulation of gastrointestinal hormones,blockade of renin-angiotensin-aldosterone system,inhibition of vascular remodeling,and improvement of insulin resistance.This paper systematically reviews the relevant research on Zhengan Xifeng decoction for the treatment of hypertension in recent years,in order to provide a reference for the further application of this prescription and subsequent related research.

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Discussion on food impact during oral drug development though case studies

Fei-fei LIU ; Jian LI ; Yi-lin LIU ; Li-li GAO ; Rui-rui HE

The Chinese Journal of Clinical Pharmacology.2024;40(21):3206-3210. doi:10.13699/j.cnki.1001-6821.2024.21.028

Co-administration of an orally administered drug with food can increase the systemic exposure of the drug,to have a significant impact on the safety and efficacy of orally administered drug products.Food-effect studies is very important in drug development.Food exerts its effects on the mechanisms of drug action and physiological environment of the body,to have a significant impact on the safety and efficacy of drugs,including the drug development process,post market clinical application of drugs,and patient compliance.The effect of food is different across meals with different fat or caloric contents.This article discusses orally administered drug products,combining drug development cases,according to relevant regulations and guidelines,starting from the approach of food-effect studies in drug development,to analyze the key role of food-effect studies in the drug development process,to elucidate the clinical pharmacology and food-effect characteristics,to clarify the actual usage and dosage,to provide reference for the design of food-effect studies in drug development.

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Research status of circulating tumor DNA in colorectal cancer

Shao-bo MO ; Yun FENG ; Jun-jie PENG ; Hai ZOU

The Chinese Journal of Clinical Pharmacology.2024;40(21):3186-3190. doi:10.13699/j.cnki.1001-6821.2024.21.024

Circulating tumor DNA(ctDNA)is emerging as a pivotal technology in the diagnosis and therapeutic management of colorectal cancer(CRC).Serving as a liquid biopsy biomarker,ctDNA offers genetic insights into tumors,encompassing mutations,methylation patterns,and more,thereby holding significant promise for early detection,treatment response monitoring,and prognostic evaluation.This review comprehensively outlines the research strides in ctDNA pertaining to CRC,encompassing early-stage screening and diagnosis,minimal residual disease surveillance,treatment response tracking and prognostic status.

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Clinical trial of empagliflozin in the traetment of patients with heart failure after acute myocardial infarction

Xiao-xing HU ; Jing SUN

The Chinese Journal of Clinical Pharmacology.2024;40(21):3067-3070. doi:10.13699/j.cnki.1001-6821.2024.21.001

Objective To observe the clinical efficacy and safety of empagliflozin tablets in the treatment of patients with heart failure after acute myocardial infarction(AMI).Methods The patients with heart failure after AMI were randomly divided into control and treatment groups.The control group was given conventional anti-heart failure treatment.The treatment group was given empagliflozin 10 mg per time,once a day,orally,on the basis of control group.The clinical efficacy,cardiac function indexes,scores of minnesota living with heart failure questionnair(MLHFQ)and safety were compared between the two groups.Results Treatment group were enrolled 56 cases,1 case dropped out,and 55 cases were finally included in the statistical analysis.Control group were enrolled 58 cases,3 cases dropped out,and 55 cases were finally included in the statistical analysis.After treatment,the total effective rates of treatment and control groups were 83.64％(46 cases/55 cases)and 56.36％(31 cases/55 cases)with significant difference(P＜0.05).After treatment,the N-terminal B-type brain natriuretic peptide levels of treatment and control groups were(833.12±112.73)and(1 210.93±98.92)pg·mL-1,the interleukin-6 levels were(6.07±2.25)and(11.06±3.03)ng·L-1,the hypersensitive C-reactive protein levels were(6.82±2.17)and(13.20±3.18)mg·L-1,the 6 min walking distances were(345.15±51.96)and(246.72±57.90)m,the left ventricular ejection fractions were(53.11±5.97)％and(49.65±5.20)％,the MLHFQ scores were(49.38±9.08)and(60.05±10.07)points,respectively.The differences of above indexes were statistically significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were loss of appetite and dizziness,which those in control group were abdominal bloating.The total incidences of treatment and control groups were 5.45％and 1.82％without significant difference(P＞0.05).Conclusion Empagliflozin tablets can significantly improve the clinical efficacy of patients with heart failure after AMI,improve the cardiac function and quality of life,without increasing the incidence of adverse drug reactions.

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Clinical trial of sacubactril valsartan combined with dapagliflozin in the treatment of patients with type Ⅱ cardio-renal syndrome

Yan LI ; Juan ZHANG ; Xiao-tong AN ; Wen GAO ; Yang HOU ; Ling SUN

The Chinese Journal of Clinical Pharmacology.2024;40(21):3071-3075. doi:10.13699/j.cnki.1001-6821.2024.21.002

Objective To observe the clinical efficacy and safety of sacubactril valsartan tablets combined with dapagliflozin tablets in the treatment of patients with type Ⅱ cardio-renal syndrome(CRS).Methods The patients with type Ⅱ CRS were divided into control group and treatment group according to cohort method.Control group was given dapagliflozin 10 mg per time,qd,orally.On the basis of control group,treatment group was given sacubactril valsartan sodium tablets 50 mg per time,bid,orally,and doubled every 2 to 4 weeks until 200 mg per time,bid.Two groups were treated for 3 months.The clinical efficacy,cardiac and renal function and safety were compared between the two groups.Results There were 89 cases in the control group and 87 cases in the treatment group.After treatment,the total effective rates of treatment and control groups were 91.95％(80 cases/87 cases)and 80.90％(72 cases/89 cases),and the difference was statistically significant(P＜0.05).After treatment,the cardiac output of treatment group and control group were(4.36±0.48)and(4.05±0.41)L·min-1,the left ventricular ejection fraction were(48.62±5.02)％and(43.21±4.51)％,the serum creatinine levels were(84.01±10.36)and(95.26±12.65)pmol·L-1,the blood urea nitrogen levels were(6.23±1.12)and(8.04±1.41)mmol·L-1,the urinary protein excretion rates were(79.03±8.27)and(86.05±10.32)μg·min-1,the urinary albumin/creatinine ratios were(90.04±15.13)and(102.16±17.26)mg·g-1,and the differences were statistically significant(all P＜0.05).The adverse drug reactions of treatment group were gastrointestinal reaction,hypotension and hypoglycemia,while those in the control group were hypoglycemia,gastrointestinal reaction and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.05％and 6.74％without significant difference(P＞0.05).Conclusion Sacubatrol valsartan tablets combined with dapagliflozin tablets have a definitive clinical efficacy in the treatment of type Ⅱ CRS,which can improve patients'cardiac and renal function,without increasing the incidence of adverse drug reactions.

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Clinical trial of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk HPV infection-related cervical lesions

Xue BAI ; Shu-wei HAO ; Wei LÜ ; Ya-wen DING ; Nai-yi DU

The Chinese Journal of Clinical Pharmacology.2024;40(21):3082-3086. doi:10.13699/j.cnki.1001-6821.2024.21.004

Objective To observe the therapeutic effect of thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets in the treatment of patients with high-risk human papillomavirus(HPV)infection-related cervical lesions and the impact on T lymphocyte subsets.Methods The patients with high-risk HPV infection-related cervical lesions were divided into the treatment group and the control group according to the cohort method.The control group was given human interferon α2b vaginal effervescent tablets 5 × 105 U,once daily,for 2 months.On this basis,the treatment group was treated with thymopeptide enteric-coated capsules at a dose of 30 mg·time-1,three times a day,for 2 months.Therapeutic effects,cervical vaginal microecology indicators[pH values of vaginal secretions,Nugent scores and white blood cell count],T lymphocyte subsets,cytokines[interleukin-4(IL-4),IL-6,IL-10,tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)]were compared between the two groups,and the safety were evaluated.Results Seventy cases in the treatment group and 72 cases in the control group.After treatment,the total effective rate of the treatment group was 94.29％(66 cases/70 cases),which was higher than the control group's 80.56％(58 cases/72 cases),the differences were statistically significant(P＜0.05).After treatment,pH values of vaginal secretions in treatment group and control group were 4.26±0.19 and 4.38±0.17;Nugent scores were(2.53±0.36)and(2.79±0.40)scores;Blood cell count were 5.12±1.14 and 6.03±1.21;CD3+were(69.32±8.10)％and(66.54±7.03)％;CD4+were(37.25±5.03)％and(34.67±4.82)％;CD4+/CD8+were 1.50±0.35 and 1.42±0.33;serum IL-4 levels were(7.49±1.64)and(9.20±2.18)pg·mL-1;serum IL-6 levels were(20.95±5.03)and(26.64±6.22)pg·mL-1;serum IL-10 levels were(11.72±2.46)and(13.43±2.97)pg·mL-1;serum TNF-α levels were(16.48±3.75)and(13.25±2.03)pg·mL-1;serum IFN-γ levels were(13.35±2.11)and(10.93±2.86)pg·mL-1;the differences were statistically significant(all P＜0.05).Adverse drug reactions in the treatment group included nausea,fever,vaginal itching and pain;which in the control group included vaginal itching and pain.The total incidence rates of adverse reactions in the treatment group and the control group were 8.57％(6 cases/70 cases)and 5.56％(4 cases/72 cases),without statistically significant difference(P＞0.05).Conclusion Thymopeptide enteric-coated capsules combined with human interferon α2b vaginal effervescent tablets can improve immune function,reduce inflammatory reactions,and improve cervical and vaginal micro-ecological environment in patients with high-risk HPV infection-related cervical lesions.

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