Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China.
Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China.
J Ethnopharmacol. 2018 Feb 15;212:95-105. doi: 10.1016/j.jep.2017.10.023. Epub 2017 Nov 5.
Radix Paeoniae Alba (Baishao, BS), one of the most commonly used traditional Chinese medicinal herbs, has many pharmacological effects including analgesic activity. Previous studies found that sulfur-fumigation, a post-harvest handling process developed to prevent mold contamination of medicinal herbs, altered the quality of BS. However, whether sulfur-fumigation affects the pharmacokinetics, safety and efficacy of BS warrants further investigation.
To evaluate the feasibility of sulfur-fumigation as a post-harvest handling process of BS from the viewpoints of pharmacokinetics, safety and efficacy.
The pharmacokinetic behaviors of four active components of BS and one characteristic component of sulfur-fumigated BS (S-BS) were evaluated by high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-TQ-MS/MS). The safety was investigated using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach after intragastric (i.g.) administration of non-fumigated BS (N-BS) and S-BS in rats. The analgesic efficacy was compared using hot-plate test in mice, after i.g. administration of N-BS and S-BS, at both high and low dosages.
Systemic exposures of paeoniflorin and oxypaeoniflorin, two analgesic components of BS, were significantly decreased in the S-BS treated group compared to the N-BS treated group, while paeoniflorin sulfonate, one of the sulfur-containing derivatives of S-BS, was detected in all time-points of S-BS treated group with the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (C) as high as 7077.06 ± 2232.97ng/mL*h and 1641.42 ± 634.79ng/mL respectively, which indicated that sulfur-fumigation altered the pharmacokinetic behaviors of BS. Besides, paeoniflorin sulfonate and its four metabolites with ambiguous toxicities, as well as one endogenous metabolite p-cresol glucuronide, the biomarker of disordered homeostasis of intestinal bacteria and bile acid, were identified as the characteristic metabolites in S-BS administered rats, suggesting that sulfur-fumigation reduced the safety of BS. Furthermore, the analgesic effects at both low and high dosages were decreased in different extent when compared to N-BS administered groups, indicating that sulfur-fumigation weakened the efficacy of BS.
Sulfur-fumigation altered the pharmacokinetics, as well as reduced the safety and efficacy of BS, suggesting that sulfur-fumigation is not recommended for post-harvest handling of BS.
白芍（白芍，BS）是最常用的中药之一，具有许多药理作用，包括镇痛活性。先前的研究发现，硫磺熏蒸是一种用于防止药用植物发霉污染的收获后处理方法，改变了 BS 的质量。然而，硫磺熏蒸是否会影响 BS 的药代动力学、安全性和疗效仍有待进一步研究。
从药代动力学、安全性和疗效的角度评估硫磺熏蒸作为 BS 收获后处理方法的可行性。
采用高效液相色谱三重四极杆质谱联用（HPLC-TQ-MS/MS）评价 BS 的四种活性成分和 BS 特征成分之一（硫磺熏制 BS，S-BS）的药代动力学行为。采用基于超高效液相色谱四极杆飞行时间质谱联用（UHPLC-QTOF-MS/MS）的代谢组学方法，在大鼠灌胃非熏制 BS（N-BS）和 S-BS 后，考察安全性。在高、低剂量下，采用热板试验比较灌胃 N-BS 和 S-BS 后小鼠的镇痛效果。
与 N-BS 组相比，S-BS 组 BS 的镇痛成分芍药苷和氧化芍药苷的全身暴露量显著降低，而 S-BS 中的一种含硫衍生物芍药苷磺酸盐在 S-BS 组的所有时间点均被检测到，其血浆浓度-时间曲线下面积（AUC）和最大血浆浓度（C）分别高达 7077.06±2232.97ng/mL*h 和 1641.42±634.79ng/mL，表明硫磺熏蒸改变了 BS 的药代动力学行为。此外，鉴定出芍药苷磺酸盐及其四种具有不确定毒性的代谢物，以及内源性代谢物对羟基苯乙酸葡萄糖醛酸，作为 S-BS 给药大鼠的特征代谢物，表明硫磺熏蒸降低了 BS 的安全性。此外，与 N-BS 给药组相比，低、高剂量下的镇痛效果均有不同程度的降低，表明硫磺熏蒸减弱了 BS 的疗效。
硫磺熏蒸改变了 BS 的药代动力学特性，降低了其安全性和疗效，表明硫磺熏蒸不建议用于 BS 的收获后处理。
