赶黄草醇提物和赶黄草总黄酮对小鼠亚急性酒精性肝损伤保护作用的比较研究

九红; 付满玲; 刘洪盛; 张世波; 侯筱芳; 姚吉强; 袁叶飞

doi:10.13386/j.issn1002-0306.2022030254

赶黄草醇提物和赶黄草总黄酮对小鼠亚急性酒精性肝损伤保护作用的比较研究

doi: 10.13386/j.issn1002-0306.2022030254

1.
西南医科大学药学院，四川泸州 646000
2.
西南医科大学科技处，四川泸州 646000
3.
泸州市中医医院药剂科，四川泸州 646000
4.
泸州飞翔医药科技有限公司，四川泸州 646000

基金项目: 四川省重点研发计划（2022YFS0436）；四川省自然科学基金（2022NSFSC1738）；四川省中医药管理局中医药科研专项课题（2020CP0029）；泸州市人民政府-西南医科大学科技战略合作重点项目（2019LZXNYDZ14）；西南医科大学-泸州市中医医院基地项目（2019-LH003）；精细化工应用技术泸州市重点实验室开放课题（HYJY-2106-B）。

详细信息

作者简介:
九红（1994−），女，硕士，研究方向：中药化学与中药药理，E-mail：2632799134@qq.com

通讯作者:
袁叶飞（1973−），男，博士，教授，研究方向：中药化学与中药药理，E-mail：570204691@qq.com

中图分类号: TS201.4
计量
- 文章访问数: 73
- HTML全文浏览量: 22
- PDF下载量: 15
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-22
- 网络出版日期: 2022-12-16
- 刊出日期: 2023-01-17

Comparative Study on Hepatoprotective Effects of Alcohol Extract and Total Flavonoids of Penthorum chinense Pursh against Alcohol-induced Subacute Liver Injury in Mice

1.
Pharmacy College, Southwest Medical University, Luzhou 646000, China
2.
Science and Technology Department, Southwest Medical University, Luzhou 646000, China
3.
Department of Pharmacy, Luzhou Hospital of Traditional Chinese Medicine, Luzhou 646000, China
4.
Luzhou Feixiang Pharmaceutical Technology Co., Ltd., Luzhou 646000, China

摘要

摘要: 目的：比较赶黄草醇提物和赶黄草总黄酮对小鼠亚急性酒精性肝损伤的保护作用。方法：将昆明小鼠随机分为正常组、模型组、阳性组（联苯双酯，150 mg/kg）、赶黄草醇提物3个不同剂量处理组（400、800和1600 mg/kg）及赶黄草总黄酮3个不同剂量处理组（100、200和400 mg/kg）；应用酒精灌胃方法建立亚急性酒精性肝损伤小鼠模型，检测各组小鼠肝脏系数、肝组织病理变化和血清生化指标。结果：与模型组比较，赶黄草醇提物和赶黄草总黄酮高、中剂量组小鼠肝脏系数均显著降低（P<0.05），肝组织损伤和脂肪变性明显减轻，小鼠血清谷丙转氨酶（alanine transaminase，ALT）、谷草转氨酶（aspartate transaminase，AST）、碱性磷酸酶（alkaline phospha-tase，ALP）、乳酸脱氢酶（lactic dehydrogenase，LDH）活性及总胆红素（total bilirubin，TBIL）、总胆固醇（total cholesterol，TC）、甘油三酯（triglycerides，TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）含量均显著降低（P<0.05，P<0.01）。与等生药剂量的赶黄草醇提物组比较，赶黄草总黄酮组小鼠血清ALT、AST、ALP、LDH活性及TBIL、TC、TG和LDL-C含量均显著降低（P<0.05，P<0.01）。结论：赶黄草醇提物和赶黄草总黄酮对亚急性酒精性肝损伤均具有保护作用，赶黄草总黄酮优于赶黄草醇提物，赶黄草总黄酮是赶黄草抗酒精性肝损伤的主要功效成分。
- 赶黄草总黄酮 /
- 赶黄草 /
- 亚急性酒精性肝损伤 /
- 保护作用
Abstract: Object: To compare the hepatoprotective effects of alcohol extract and total flavonoids of Penthorum chinense Pursh on alcohol-induced subacute liver injury in mice. Methods: The mice were randomized into the normal group, model group, positive group (bifendate, 150 mg/kg), ethanol extract of Penthorum chinense Pursh with three different dose treatment groups (400, 800 and 1600 mg/kg), and total flavonoids of Penthorum chinense Pursh with three different dose treatment groups (100, 200 and 400 mg/kg). The model of subacute alcoholic liver injury in mouse was set up by intragastric administration of alcohol. The liver index, pathological changes of liver tissue and serum biochemical indexes were measured in each group. Results: Compared with mice in the model group, the hepatic index was decreased significantly (P<0.05), the liver injury pathological state was ameliorated, the activities of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactic dehydrogenase (LDH) and the content of total bilirubin (TBIL), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) were decreased significantly (P<0.05, P<0.01) in the high and medium treatment groups of alcohol extract and total flavonoids of Penthorum chinense Pursh. The activities of serum ALT, AST, ALP, LDH as well as the content of TBIL, TC, TG and LDL-C in the total flavonoids group were significantly lower than those in the alcohol extract group with the same crude drug dose (P<0.05, P<0.01). Conclusion: Both alcohol extract and total flavonoids of Penthorum chinense Pursh can protect subacute alcoholic liver injury, but total flavonoids does better than alcohol extract. The total flavonoids is a main functional component of Penthorum chinese Pursh to protect alcoholic liver injury.
- Penthorum chinense Pursh total flavonoids /
- Penthorum chinense Pursh /
- subacute alcoholic liver injury /
- protective effect

HTML全文

图 1 赶黄草醇提物和赶黄草总黄酮对亚急性酒精性肝损伤小鼠体重的影响（$\overline{\rm x} $±s，n=10）

Figure 1. Effects of alcohol extract and total flavonoids of Penthorum chinense Pursh on body weight of mice with subacute alcoholic live injury ($ \overline{\rm x}$±s, n=10)

注：与正常组（N）比较，##：差异极显著，P<0.01；与模型组（M）比较，*：差异显著，P<0.05，**：差异极显著，P<0.01。

下载: 全尺寸图片幻灯片

图 2 赶黄草醇提物和赶黄草总黄酮对亚急性酒精性肝损伤肝脏系数的影响（$\overline{\rm x} $±s，n=10）

Figure 2. Effects of alcohol extract and total flavonoids of Penthorum chinense Pursh on liver indexes of mice with subacute alcoholic live injury ($\overline{\rm x} $±s, n=10)

注：与正常组（N）比较，##：差异极显著，P<0.01；与模型组（M）比较，*：差异显著，P<0.05，**：差异极显著，P<0.01；与等生药剂量赶黄草醇提物比较，$：差异显著，P<0.05。

下载: 全尺寸图片幻灯片

图 3 赶黄草醇提物和赶黄草总黄酮对小鼠肝组织病理学的影响（HE染色，400×）

Figure 3. Effects of the alcohol extract and total flavonoids of Penthorum chinense Pursh on liver histopathology of mice (HE staining, 400×)

下载: 全尺寸图片幻灯片

表 1 亚急性酒精性肝损伤小鼠模型成模的判定（$\overline{\rm x} $±s，n=10）

Table 1. Judgment of the successful model of subacute alcoholic live injury in mice ($\overline{\rm x} $±s, n=10)

组别	TC （mmol/L）	LDL-C （mmol/L）	TBIL （mmol/L）	肝组织病变总分（分）
正常组（N）	2.67±0.48	0.323±0.03	1.705±0.325	0.68±0.19
模型组（M）	4.68±0.91^##	0.615±0.15^##	2.803±0.502^##	2.71±1.01^##
注：与正常组（N）比较，##：差异极显著，P<0.01。

下载: 导出CSV

表 2 赶黄草醇提物和赶黄草总黄酮对小鼠肝细胞病变分数的影响（$\overline{\rm x} $±s，n=10）

Table 2. Effects of the alcohol extract and total flavonoids of Penthorum chinense Pursh on pathologic score in the liver cell of mice ($\overline{\rm x} $±s, n=10)

组别	肝细胞变性				炎性改变	细胞坏死	病变总分（分）
组别	水样变性	气球变性	脂肪变性	胞浆凝聚	炎性改变	细胞坏死	病变总分（分）
N	0.25±0.06	0.12±0.04	0±0	0.22±0.07	0.09±0.03	0±0	0.68±0.19
M	0.41±0.12	0.42±0.11	0.53±0.11	0.33±0.12	0.42±0.14	0.30±0.10	2.71±1.01^##
Bif	0.21±0.07	0.23±0.08	0.21±0.08	0.30±0.13	0.15±0.03	0.15±0.04	1.40±0.35^**
GZG	0.23±0.07	0.12±0.07	0.31±0.10	0.28±0.08	0.17±0.04	0.16±0.05	1.33±0.40^**$
GZZ	0.25±0.08	0.19±0.08	0.40±0.13	0.30±0.11	0.22±0.06	0.18±0.06	1.72±0.51^*$
GZD	0.34±0.09	0.25±0.07	0.48±0.11	0.33±0.13	0.33±0.13	0.25±0.05	2.23±0.65
GCG	0.24±0.08	0.15±0.04	0.36±0.07	0.25±0.08	0.25±0.08	0.22±0.07	1.69±0.48^**
GCZ	0.31±0.10	0.28±0.10	0.39±0.12	0.31±0.12	0.35±0.13	0.25±0.06	2.14±0.62^*
GCD	0.36±0.09	0.37±0.11	0.45±0.14	0.31±0.15	0.41±0.15	0.25±0.07	2.40±0.61
注：与正常组（N）比较，##：差异极显著，P<0.01；与模型组（M）比较，：差异显著，P<0.05，*：差异极显著，P<0.01；与等生药剂量赶黄草醇提物组比较，$：差异显著，P<0.05；表3~表4同。

下载: 导出CSV

表 3 赶黄草醇提物和赶黄草总黄酮对小鼠血清肝功能指标的影响（$\overline{\rm x} $±s，n=10）

Table 3. Effects of alcohol extract and total flavonoids of Penthorum chinense Pursh on serum liver function levels in mice ($\overline{\rm x} $±s, n=10)

组别	ALT（U/L）	AST（U/L）	ALP（U/L）	LDH（U/L）	TBIL（mmol/L）
N	36.30±4.03	107.90±12.76	102.00±25.96	1101.50±107.86	1.705±0.325
M	69.60±8.45^##	199.10±29.36^##	193.00±29.29^##	1977.81±247.15^##	2.803±0.502^##
Bif	39.90±3.54^**	114.70±17.41^**	148.30±43.91^**	1175.00±428.66^**	1.885±0.411^**
GZG	40.60±6.79^**$	114.70±19.75^**$	124.50±34.77^**$	1095.90±172.70^**$	1.903±0.398^**$
GZZ	45.70±7.67^**$	123.00±25.30^**$	136.40±39.96^**$	1138.40±149.59^**$	2.108±0.401^**$
GZD	58.70±6.85	157.50±22.60^*$	170.25±42.56	1592.35±198.62	2.689±0.689
GCG	46.00±5.41^*	158.60±29.16^*	141.00±43.83^**	1495.70±315.23^**	2.401±0.326^*
GCZ	52.00±4.27^*	165.00±37.46	157.77±34.68^*	1540.30±255.73^*	2.501±0.502^*
GCD	60.61±5.15	190.00±27.25	180.05±38.55	1782.00±302.73	2.702±0.702

下载: 导出CSV

表 4 赶黄草醇提物和赶黄草总黄酮对亚急性酒精性肝损伤小鼠血脂的影响（$\overline{\rm x} $±s，n=10）

Table 4. Effects of alcohol extract and total flavonoids of Penthorum chinense Pursh on serum lipid levels of mice ($\overline{\rm x} $±s, n=10)

组别	TG（mmol/L）	TC（mmol/L）	LDL-C（mmol/L）
N	1.23±0.24	2.67±0.48	0.323±0.03
M	3.22±1.33^##	4.68±0.91^##	0.615±0.15^##
Bif	1.27±0.58^**	2.85±0.91^**	0.401±0.09^**
GZG	1.54±0.32^**$	2.91±0.60^**$	0.405±0.12^**$
GZZ	1.89±0.38^*	3.55±0.88^*	0.485±0.18^*
GZD	2.58±1.38	4.20±0.85	0.543±0.20
GCG	1.91±0.42^*	3.32±0.54^*	0.491±0.19^*
GCZ	2.21±0.71^*	3.85±0.96^*	0.521±0.13^*
GCD	2.92±0.82	4.51±0.96	0.585±0.21

下载: 导出CSV

参考文献(30)

[1]	付双楠, 朱平生, 高达. 中医药防治化学性肝损伤的研究进展[J]. 中医学报,2017,32(3):449−454. [FU S N, ZHU P S, GAO D. Progress of TCM studies in TCM treatment of liver injury due to chemical factors[J]. Acta Chinese Medicine,2017,32(3):449−454. doi: 10.16368/j.issn.1674-8999.2017.03.116
[2]	刘袆帆, 朱珍, 苏敏璇, 等. 多糖对酒精性肝损伤干预作用的研究进展[J]. 现代食品科技,2020,36(8):379−393. [LIU H F, ZHU Z, SU M X, et al. Efficacy of polysaccharides as alcoholic liver disease therapeutics: A review[J]. Modern Food Science and Technology,2020,36(8):379−393. doi: 10.13982/j.mfst.1673-9078.2020.8.0185
[3]	SALEEM T S M, CHETTY C M, RAMKANTH S, et al. Hepatoprotective herbs-A review[J]. International Journal of Research in Pharmaceutical Sciences,2010,1(5):1−5.
[4]	唐川, 李志, 王升贵, 等. 霍山石斛多糖的制备、功能和产品开发的研究进展[J]. 食品工业科技,2019,40(3):313−320. [TANG C, LI Z, WANG S G, et al. Research progress on preparation, function and product development of polysaccharide of Dendrobium huoshanense[J]. Science and Technology of Food Industry,2019,40(3):313−320. doi: 10.13386/j.issn1002-0306.2019.03.050
[5]	李志满, 邵紫君, 李珊珊, 等. 人参枳子提取物对小鼠酒精性肝损伤的保护作用[J]. 食品工业科技,2019,40(14):302−306, 313. [LI Z M, SHAO Z J, LI S S, et al. Protective effect of extract from Panax ginsen and Hovenia dulcis Thunb against alcohol-induced liver injury in mice[J]. Science and Technology of Food Industry,2019,40(14):302−306, 313.
[6]	孟海涛, 汪鹤, 查学强, 等. 霍山石斛不同提取物抗小鼠亚急性酒精性肝损伤活性的比较研究[J]. 食品科学,2015,36(13):229−234. [MENG H T, WANG H, ZHA X Q, et al. Comparison of hepatoprotective effects of different extracts from Dendrobium huoshanense against alcohol-induced subacute liver injury in mice[J]. Food Science,2015,36(13):229−234. doi: 10.7506/spkx1002-6630-201513042
[7]	LOGGE W B, MORLEY K C, HABER P S, et al. Executive function moderates responses to appetitive cues: A study in severe alcohol use disorder and alcoholic liver disease[J]. Alcohol and Alcoholism,2019,54(1):38−46. doi: 10.1093/alcalc/agy083
[8]	刘畅, 成玉梁, 郭亚辉, 等. 芦荟多糖联合茶多酚对小鼠酒精性肝损伤的预防作用[J]. 食品工业科技,2019,40(22):300−305. [LIU C, CHENG Y L, GUO Y H, et al. Preventive effect of aloe polysaccharide combined with tea polyphenol on alcoholic liver injury in mice[J]. Science and Technology of Food Industry,2019,40(22):300−305. doi: 10.13386/j.issn1002-0306.2019.22.052
[9]	牛佳卉, 袁静, 张慧芳, 等. 王浆酸对小鼠酒精性肝损伤的保护作用[J]. 食品工业科技,2020,41(3):291−296. [LIU J H, YUAN J, ZHANG H F, et al. Protective effect of royal jelly acid on the alcoholliver injury in mice[J]. Science and Technology of Food Industry,2020,41(3):291−296. doi: 10.13386/j.issn1002-0306.2020.03.048
[10]	SHEN T, LIU Y, SHANG J, et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology,2019,156(8):1−12. doi: 10.1053/j.gastro.2019.01.006
[11]	白路平, 乔向宇, 吉日木图, 等. 骆驼乳对小鼠酒精性肝损伤的保护作用[J]. 中国食品学报,2022,22(2):140−149. [BAI L P, QIAO X Y, JIRIMUTU, et al. Protective effect of camel milk on alcoholic liver injury in mice[J]. Journal of Chinese Institute of Food Science and Technology,2022,22(2):140−149. doi: 10.16429/j.1009-7848.2022.02.016
[12]	LIU Y S, YUAN M H, ZHANG C Y, et al. Puerariae lobatae radix flavonoids and puerarin alleviatealcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism[J]. BiomedicineI & Pharmcotherapy,2021,134:111121−111128.
[13]	DING Q C, JIN Z, DONG J H, et al. Bioactivity evaluation of pinocembrin derivatives from Penthorum chinense Pursh stems[J]. Natural Product Communications,2019,14(9):1−9.
[14]	WANG A Q, LI M X, HUANG M, et al. A review of Penthorum chinense Pursh for hepatoprotection: Traditional use, phytochemistry, pharmacology, toxicology and clinical trials[J]. Journal of Ethnopharmacol,2020,251(6):26−32.
[15]	HUANG D D, JIANG Y, CHEN W S, et al. Polyphenols with anti-proliferative activities from Penthorum chinense Pursh[J]. Molecules,2014,19(8):11045−11055. doi: 10.3390/molecules190811045
[16]	张剑, 伍淑明, 杨肖, 等. 赶黄草中化学成分研究进展[J]. 中草药,2017,48(21):4571−4577. [ZHANG J, WU S M, YANG X, et al. Advances in chemical constituents of Penthorum chinense Pursh[J]. Chinese Traditional and Herbal Drugs,2017,48(21):4571−4577. doi: 10.7501/j.issn.0253-2670.2017.21.033
[17]	SUN X L, WU A G, BETTY Y K L, et al. The active components derived from Penthorum chinense Pursh protect against oxidative-stress-induced vascular injury via autophagy induction[J]. Free Radical Biology and Medicine,2020,146:160−180. doi: 10.1016/j.freeradbiomed.2019.10.417
[18]	袁叶飞, 白雪. 赶黄草总黄酮制备方法: 中国, 201811373488.7[P]. 2019-01-25 YUAN Y F, BAI X. Preparation method of total flavone of Penthorum chinense Pursh: China, 201811373488.7[P]. 2019-01-25.
[19]	付满玲, 九红, 袁叶飞. 赶黄草总黄酮对四氯化碳所致小鼠急性化学性肝损伤的保护作用[J]. 现代食品科技,2021,37(6):50−56. [FU M L, JIU H, YUAN Y F. Protective effect of total flavonoids of Penthorum chinense Pursh on acute chemical liver injury induced by carbon tetrachloride in mice[J]. Modern Food Science and Technology,2021,37(6):50−56. doi: 10.13982/j.mfst.1673-9078.2021.6.1054
[20]	王爽, 徐清华, 史保银, 等. 葛白复配颗粒对大鼠亚急性酒精性肝损伤的保护作用[J]. 毒理学杂志,2019,33(1):48−50. [WANG S, XU Q H, SHI B Y, et al. Protective effects of Gebai formulation granule on alcohol-induced hepatic injury in rats[J]. Journal of Toxicology,2019,33(1):48−50. doi: 10.16421/j.cnki.1002-3127.2019.01.008
[21]	苏林梁, 黄业宇, 冯丁山, 等. 槟榔花茶对大鼠亚急性酒精性肝损伤的保护作用[J]. 现代食品科技,2017,33(6):15−19. [SU L L, HUANG Y Y, FENG D S, et al. Protective effects of areca inflorescence tea on alcohol-induced hepatic injury in rats[J]. Modern Food Science and Technology,2017,33(6):15−19. doi: 10.13982/j.mfst.1673-9078.2017.6.003
[22]	QIAO J Y, LI H W, LIU F G, et al. Effects of Portulaca oleracea extract on acute alcoholic liver injury of rats[J]. Molecules,2019,24(16):2887−2910. doi: 10.3390/molecules24162887
[23]	叶文斌, 樊亮, 王昱, 等. 黄果槲寄生果实多糖对急性酒精肝损伤小鼠的保护作用[J]. 安徽农业大学学报,2017,44(2):218−223. [YE W B, FAN L WANG Y, et al. The protectionmechanism of Viscum coloratum (Kom.) Nakai f. lutescens Kitag fruit polysaccharides on acute alcoholic liver injury in mice[J]. Journal of Anhui Agricultural University,2017,44(2):218−223. doi: 10.13610/j.cnki.1672-352x.20170419.021
[24]	易宏伟, 朱笑笑, 黄小莉, 等. 富硒长双歧杆菌抑制乙醇诱导的小鼠肝损伤[J]. 中国药学杂志,2019,54(22):1859−1864. [YI H W, ZHU X X, HUANG X L, et al. Inhibition effect of selenium enriched Bifidobacterium longum on alcohol induced liver damage in mice[J]. Journal of Chinese Pharmaceutical Sciences,2019,54(22):1859−1864.
[25]	JIANG Z, CHEN C, WANG J, et al. Purple potato (Solanum tuberosum L.) anthocyaanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense[J]. Journal of Natural Medicines,2016,70(1):45−53. doi: 10.1007/s11418-015-0935-3
[26]	NIE G, ZHANG Y, ZHOU Z H, et al. Dynamic evaluation of the protective effect of Dendrobium officinale polysaccharide on acute alcoholic liver injury mice in vitro and in vivo by NIR fluorescence imaging[J]. Analytical and Bioanalytical Chemistry,2021,413(23):5715−5724. doi: 10.1007/s00216-021-03546-7
[27]	GOVINDAN S H, JAYABAL A G, SHANMUGAM J K, et al. Antioxidant and hepatoprotective effectsof Hypsizygus ulmarius polysaccharide on alcoholic liver injury in rats[J]. Food Science and Human Wellness,2021,10(4):523−535. doi: 10.1016/j.fshw.2021.04.015
[28]	GAO B, XU M J, BERTOLA A, et al. Animal models of alcoholic liver disease: Pathogenesis and clinical relevance[J]. Gene Express,2017,17(3):173−186. doi: 10.3727/105221617X695519
[29]	JAYARAMAN J, NAMASIVAYAM N. Naringenin modulates circulatory lipid peroxidation, antioxidant status and hepatic alcohol metabolizing enzymes in rats with ethanol induced liver injury[J]. Fundamental and Clinical Pharmacology,2011,25(6):682−689. doi: 10.1111/j.1472-8206.2010.00899.x
[30]	FANG C, ZHOU Q W, LIU Q Y, et al. Crosstalk between gut microbiota and host lipid metabolism in a mouse model of alcoholic liver injury by chronic Baijiu or ethanol feeding[J]. Food & Function,2022,13(2):596−608.