Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
J Ethnopharmacol. 2021 Jul 15;275:114102. doi: 10.1016/j.jep.2021.114102. Epub 2021 Apr 6.
Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi), the root of Aconitum carmichaelii Debx., is a representative medicine for restoring yang and rescuing patient from collapse. However, less studies had been reported on the reproductive toxicity and genotoxicity of Fuzi. According to the principle of reducing toxicity and preserving efficiency, only processed products of Fuzi are commonly applied in clinic, including Baifupian, Heishunpian and Danfupian. However, whether processing could alleviate the reproductive toxicity and genotoxicity of Fuzi had not been revealed.
To assess the effect and possible mechanism of Fuzi and its processed products on reproductive toxicity and genotoxicity in male mice.
Aqueous extracts of Fuzi and its processed products (Baifupian, Heishunpian and Danfupian, 5.85 g/kg) were administrated by gavage once daily for fourteen consecutive days. The reproductive toxicity was evaluated by testis weight, testis ratio, testis histopathology, sperm count, sperm viability rate and sperm deformity rate. The genotoxicity was evaluated by comet assay and micronucleus test in sperm, peripheral blood cell and bone marrow cell. Possible mechanisms of attenuating toxicity by processing were analyzed by detecting the level of testosterone, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase (CAT).
Fuzi significantly caused different degrees of reproductive toxicity and genotoxicity, specifically reducing the weight and testicular coefficient of testis, causing obvious pathological changes in testicular tissue, reducing sperm count and sperm viability rate, increasing sperm deformity rate and DNA damage in sperm/peripheral blood cells/bone marrow cells. Moreover, Fuzi decreased the level of testosterone, SOD, GSH and CAT, while increased the level of MDA in serum. Notably, the reproductive toxicity and genotoxicity induced by the processed products, especially Heishunpian and Danfupian, were significantly lowered compared to Fuzi. Processing could increase the level of testosterone, SOD, GSH, CAT and decrease the level of MDA compared to Fuzi.
Fuzi and its processed products had reproductive toxicity and genotoxicity, but the toxicity of processed products was significantly weakened compared to Fuzi. The protective mechanism of processing to reduce the toxicity of Fuzi might be related to increasing the level of testosterone and decreasing oxidative stress.
制川乌（中药名：附子），是毛茛科植物乌头的子根，是回阳救逆、补火助阳的代表药物。然而，关于附子的生殖毒性和遗传毒性的研究较少。根据减毒增效的原则，临床上仅应用其炮制品，包括白附片、黑顺片和淡附片。但是，炮制是否能减轻附子的生殖毒性和遗传毒性尚未被揭示。
评估附子及其炮制品对雄性小鼠生殖毒性和遗传毒性的影响及可能的机制。
以水提物的形式给予附子及其炮制品（白附片、黑顺片和淡附片，5.85 g/kg）灌胃，连续 14 天，每天一次。通过睾丸重量、睾丸比、睾丸组织病理学、精子计数、精子活力和精子畸形率来评估生殖毒性。通过彗星试验和精子、外周血和骨髓细胞的微核试验来评估遗传毒性。通过检测睾酮、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、丙二醛（MDA）和过氧化氢酶（CAT）的水平来分析炮制减毒的可能机制。
附子可引起不同程度的生殖毒性和遗传毒性，具体表现为睾丸重量和睾丸系数降低，睾丸组织出现明显病理变化，精子计数和精子活力降低，精子畸形率升高，精子/外周血/骨髓细胞的 DNA 损伤增加。此外，附子降低了血清中睾酮、SOD、GSH 和 CAT 的水平，增加了 MDA 的水平。值得注意的是，与附子相比，炮制品，尤其是黑顺片和淡附片，引起的生殖毒性和遗传毒性明显降低。与附子相比，炮制可提高睾酮、SOD、GSH、CAT 的水平，降低 MDA 的水平。
附子及其炮制品具有生殖毒性和遗传毒性，但炮制品的毒性明显低于附子。炮制降低附子毒性的保护机制可能与提高睾酮水平和降低氧化应激有关。
