School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
Yujing Technology Shanghai Co., Ltd, Shanghai, 200131, PR China.
J Ethnopharmacol. 2024 Nov 15;334:118539. doi: 10.1016/j.jep.2024.118539. Epub 2024 Jul 8.
Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct.
This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective.
Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway.
The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway.
In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment.
基于代谢组学的研究
基于代谢组学的研究
知母（Anemarrhena asphodeloides Bunge）和黄柏（Phellodendron chinense C. K. Schneid）是传统中药中的经典药对，常用于改善良性前列腺增生（BPH）的症状。然而，其作用机制尚不清楚。
本研究旨在从代谢角度阐明该药对对 BPH 的潜在治疗机制。
建立丙酸睾酮诱导的 BPH 大鼠模型，通过前列腺参数、组织病理学和血清中二氢睾酮（DHT）和睾酮（T）水平评估药对对 BPH 的药理作用。随后，采用 UHPLC-Q-Exactive-Orbitrap-MS 进行前列腺组织样本的非靶向代谢组学分析，然后进行多变量统计分析。进一步采用 UHPLC-QQQ-MS 进行靶向代谢组学分析，以验证和补充非靶向代谢组学发现的脂质和氨基酸结果，阐明疾病、草药对和代谢途径之间的关系。
研究发现知母-黄柏可缓解 BPH 的进展并调节代谢失衡。前列腺组织中 13 种代谢物水平降低，11 种代谢物水平升高，包括甘油磷脂、花生四烯酸、柠檬酸等，这些改变的代谢物主要与 TCA 循环、花生四烯酸代谢、脂质代谢和氨基酸代谢有关。此外，还进行了靶向代谢组学分析以进一步研究脂质代谢紊乱，与模型组相比，知母-黄柏组血清中 5 种脂质和前列腺组织中 21 种脂质的水平发生变化，与甘油磷脂、鞘脂和甘油脂代谢密切相关。此外，氨基酸代谢可能通过激活精氨酸代谢途径进行调节。
本研究应用非靶向代谢组学和靶向代谢组学相结合的方法，探讨知母-黄柏治疗 BPH 的作用机制。综上所述，知母-黄柏可通过调节多种代谢途径改善内源性代谢物水平，在 BPH 治疗中发挥能量供应、抗炎和抗氧化应激作用。
