天然植物来源的3,4-二羟基苯甲醛改善雄性小鼠生殖损伤的作用

doi:10.5246/jcps.2022.06.037

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (6): 429-440.DOI: 10.5246/jcps.2022.06.037

天然植物来源的3,4-二羟基苯甲醛改善雄性小鼠生殖损伤的作用

张宏宁¹, 韩淑英², 蒲小平³, 安春娜²^,^*()

1. 首都医科大学基础医学院药理学系, 北京 100069
2. 华北理工大学基础医学院药理学系, 河北唐山 063210
3. 北京大学药学院分子与细胞药理学系, 北京 100191

收稿日期:2022-01-27 修回日期:2022-03-15 接受日期:2022-03-26 出版日期:2022-06-30 发布日期:2022-06-30
通讯作者: 安春娜
作者简介:
+ Tel.: +86-315-8805210, E-mail: ancna@126.com
基金资助:
Science and Technology Program of the Beijing Municipal Education Commission (Grant No. KM201810025002), National Natural Science Foundation of China (Grant No. 81801522), and Natural Science Foundation of Hebei Province (Grant No. H2018209342).

Natural plant-derived 3,4-dihydroxybenzaldehyde ameliorates reproductive damage of male mice

Hongning Zhang¹, Shuying Han², Xiaoping Pu³, Chunna An²^,^*()

1 Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
2 Department of Pharmacology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China
3 Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Received:2022-01-27 Revised:2022-03-15 Accepted:2022-03-26 Online:2022-06-30 Published:2022-06-30
Contact: Chunna An

摘要/Abstract

摘要：

我们研究了来自丹参的3,4-二羟基苯甲醛对体外小鼠精子存活和精子细胞膜完整性的影响, 以及对环磷酰胺在体内诱导的小鼠生殖损伤的影响。3,4-二羟基苯甲醛(0.01, 0.1和1 mg/mL)可提高分离的小鼠精子存活率和精子细胞膜完整性(均P < 0.05)。在环磷酰胺处理的雄性小鼠(腹腔注射60 mg/kg/d, 共5天)中, 3,4-二羟基苯甲醛(灌胃40 mg/kg/d, 共35天)增加睾丸指数、附睾指数和精子核成熟度(均P < 0.05)。3,4-二羟基苯甲醛还改善了睾丸形态, 其特征是生精细胞层排列有序, 腔内精子数量增多, 间质细胞正常, 生精小管排列紧密。3,4-二羟基苯甲醛还增加了睾丸超氧化物歧化酶(SOD)活性并提高了DJ-1表达。此外, 它还降低了ICAM-1的表达并增加了VCAM-1、PEDF、VEGF和PPARγ的表达。这些结果表明, 3,4-二羟基苯甲醛在体外可增加小鼠精子存活率和精子细胞膜完整性, 并在体内通过DJ-1和其他靶点减少环磷酰胺对小鼠睾丸的损伤。因此, 3,4-二羟基苯甲醛可用于治疗男性生殖损伤和抗肿瘤药环磷酰胺引起的生殖毒性。

关键词: 天然化合物, 3,4-二羟基苯甲醛, 生殖损伤

Abstract:

In the present study, we studied the effects of 3,4-dihydroxybenzaldehyde, derived from Salvia miltiorrhiza Bunge, on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo. 3,4-Dihydroxybenzaldehyde (0.01, 0.1, and 1 mg/mL) improved sperm survival rate and sperm membrane integrity in separated mouse sperm (all P < 0.05). In cyclophosphamide-treated male mice (60 mg/kg/d through intraperitoneal injection for 5 d), 3,4-dihydroxybenzaldehyde (40 mg/kg/d through intragastric gavage for 35 d) increased the testis index, epididymis index, and sperm nuclear maturity (all P < 0.05). 3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells, numbers of sperm in the lumen, normal mesenchymal cells, and close and tidy arrangement of the seminiferous tubules. 3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression. In addition, it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1, PEDF, VEGF, and PPARγ. These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo. 3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.

Key words: Natural plants, 3,4-Dihydroxybenzaldehyde, Reproductive damage

Supporting:

张宏宁, 韩淑英, 蒲小平, 安春娜. 天然植物来源的3,4-二羟基苯甲醛改善雄性小鼠生殖损伤的作用[J]. 中国药学(英文版), 2022, 31(6): 429-440.

Hongning Zhang, Shuying Han, Xiaoping Pu, Chunna An. Natural plant-derived 3,4-dihydroxybenzaldehyde ameliorates reproductive damage of male mice[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(6): 429-440.

图/表 9

Figure 1. Chemical structure of PAL.

Table 1. PAL (0.01, 0.1, and 1 mg/mL) significantly improves mouse sperm survival rate and sperm membrane integrity in vitro.

Table 2. PAL (40 mg/kg) increases testis index, epididymis index, sperm nuclear maturity, and testicular SOD activity in CYP-treated male mice.

Figure 2. PAL improves testis morphology in CYP-treated male mice. The results were representatives of three independent replications. The images were captured using an IX83 microscope (400 ×). (a) Control group; (b) Model group; (c) 10 mg/kg PAL group; (d) 40 mg/kg PAL group.

Figure 3. PAL increases DJ-1 expression of testis in CYP-treated male mice by Western blotting. The images were representatives of three independent replications. Data were expressed as mean ± SD. ##P < 0.01 versus control mice. **P < 0.01 versus CYP only mice. △P < 0.05 versus 10 mg/kg PAL mice.

Figure 4. PAL reduces ICAM-1 expression and enhances VCAM-1 expression of testis in CYP-treated male mice by Western blotting. The images were representatives of three independent replications. Data were expressed as mean ± SD. ##P < 0.01 versus control mice. **P < 0.01 versus CYP only mice. △P < 0.05 versus 10 mg/kg PAL mice.

Figure 5. PAL increases PEDF and VEGF expressions of testis in CYP-treated male mice by Western blotting. The images were representatives of three independent replications. Data were expressed as mean ± SD. ##P < 0.01 versus control mice. *P < 0.05, **P < 0.01 versus CYP only mice. △P < 0.05, △△P < 0.01 versus 10 mg/kg PAL mice.

Figure 6. PAL increases PPARγ expression of testis in CYP-treated male mice by Western blotting. The images were representatives of three independent replications. Data were expressed as mean ± SD. ##P < 0.01 versus control mice. *P < 0.05 versus CYP only mice. △P < 0.05 versus 10 mg/kg PAL mice.

Figure 7. Proposed mechanism by which PAL protects male mouse reproductive damage.

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天然植物来源的3,4-二羟基苯甲醛改善雄性小鼠生殖损伤的作用

Natural plant-derived 3,4-dihydroxybenzaldehyde ameliorates reproductive damage of male mice

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