Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
J Ethnopharmacol. 2019 Jun 28;238:111868. doi: 10.1016/j.jep.2019.111868. Epub 2019 Apr 11.
Rhei Radix et Rhizoma (rhubarb), as the preferred representative of cathartic drugs of traditional Chinese medicine (TCM), has a long history of medicinal use and multifarious functions that produce a wide range of dosage. In modern times, rhubarb and its prescriptions are not only used to treat common clinical diseases, but also achieve good results in the treatment of acute, dangerous, severe and difficult diseases. However, rhubarb also has an alias called "General", which means that its efficacy is relatively rapid.
The present study was conducted to simultaneously elucidate dosage-effect relationship of rhubarb of different efficacy, "Removing accumulation with purgation" (E1) and "Clearing heat and purging fire" (E2), providing reference for the safe and effective usage of rhubarb.
Three-week-old rats were randomly divided into the normal control group (Con.), model group (Mod.) and rhubarb groups with six doses (0.135, 0.27, 0.81, 1.35, 4.05, 8.1 g/kg). We established a constipation model with gastrointestinal accumulated heat induced by dyspepsia, taking defecation characteristics observed by metabolic cages, alvine pushing rate, gastrointestinal hormones in serum, etc., as indicators of E1, and taking TG, Na-K-ATPase, inflammatory factors and proteins, etc., as indicators of E2. The factor analytic approach was used to systematically evaluate the two effects and analyze the corresponding dosage-effect relationship.
The levels of Gas, AchE, TG, Na-K-ATPase, TNF-α, IL-1β, (p-)NF-κB p65, (p-)p38, (p-)ERK and p-JNK in model rats increased significantly while the levels of defecation, fecal water content, MTL, SS, ET, NTS, VIP, JNK and TLR4 decreased. Compared with the Mod., in rhubarb groups, the increase of faeces, alvine pushing rate, most gastrointestinal hormones, etc., reflected the therapeutic efficacy of E1, and the reduction of TG, Na-K-ATPase, expression levels of inflammatory indexes, etc., reflected the impact of E2. After the analysis, the effective threshold dose ranging from 0.67 to 5.37 g/kg (corresponding to 7.44-59.67 g in the clinic) was in the EC-EC range for E1 treatment and from 0.78 to 5.60 g/kg (equivalently clinical 8.67-62.22 g) was for E2 treatment. And the 1.6- and 1.2-fold rhubarb highest dose of Chinese Pharmacopoeia might be the optimal doses for E1 and E2 respectively. In general, however, the concentration of rhubarb liquid for overall efficacy is suggested to be between middle and highest dose of Chinese Pharmacopoeia.
A constipation model was used to elucidate two main effects of rhubarb, which was consistent with the characteristics of TCM syndrome. In the wide range of rhubarb dosage, low doses might have little or no effect and although high concentrations of rhubarb liquid enhanced curative efficacy, it would also have certain side effects on the body. Therefore, scientific-based experiments and rational analysis by mathematical models could contribute to the safe and effective application of rhubarb in the clinic.
大黄（大黄）作为中药（TCM）泻下药的首选代表，具有悠久的药用历史和多种功能，产生广泛的剂量。在现代，大黄及其方剂不仅用于治疗常见的临床疾病，而且在治疗急性、危险、严重和困难疾病方面也取得了良好的效果。然而，大黄也有一个别名叫做“将军”，这意味着它的疗效比较迅速。
本研究旨在同时阐明不同疗效（“通下除积”（E1）和“清热泻火”（E2））大黄的剂量-效应关系，为大黄的安全有效使用提供参考。
将 3 周龄大鼠随机分为正常对照组（Con.）、模型组（Mod.）和大黄组，共 6 个剂量（0.135、0.27、0.81、1.35、4.05、8.1 g/kg）。我们建立了一种由消化不良引起的胃肠道积热引起的便秘模型，以代谢笼观察的排便特征、排便率、血清胃肠激素等为指标，以 TG、Na-K-ATPase、炎症因子和蛋白质等为指标，以研究 E2。采用因子分析方法对两种效应进行系统评价，并分析相应的剂量-效应关系。
模型大鼠的 Gas、AchE、TG、Na-K-ATPase、TNF-α、IL-1β、（p-）NF-κB p65、（p-）p38、（p-）ERK 和 p-JNK 水平显著升高，而排便、粪便含水量、MTL、SS、ET、NTS、VIP、JNK 和 TLR4 水平降低。与模型组相比，大黄组粪便、排便率等增加，多数胃肠激素等反映 E1 的治疗作用，TG、Na-K-ATPase、炎症指标等表达水平降低，反映 E2 的影响。经过分析，0.67-5.37g/kg（相当于临床 7.44-59.67g）的有效阈值剂量范围为 E1 治疗的 EC-EC 范围，0.78-5.60g/kg（相当于临床 8.67-62.22g）为 E2 治疗。而中国药典大黄的 1.6 倍和 1.2 倍最高剂量可能分别是 E1 和 E2 的最佳剂量。总的来说，然而，建议大黄液的整体疗效浓度应在中高剂量的中国药典之间。
采用便秘模型阐明了大黄的两种主要作用，这与中医证候的特点是一致的。在大黄的广泛剂量范围内，低剂量可能几乎没有或没有作用，虽然高浓度的大黄液增强了疗效，但也会对身体产生一定的副作用。因此，基于科学的实验和数学模型的合理分析有助于大黄在临床上的安全有效应用。
