（一） 糖尿病肾病（Diabetic nephropathy，DN）是糖尿病最常见的微血管并发症之一，是导致糖尿病患者过早死亡和终末期肾病的主要原因。据报道，大约1/3的糖尿病患者会引发糖尿病肾病。临床上大多使用降糖药进行糖尿病肾病的防治，但单纯依赖控制血糖并不能完全阻止糖尿病肾病的病变进程。因此，寻找有效的干预手段仍是防治糖尿病肾病的重要研究课题。 基础研究和临床研究均证实晚期糖基化终末产物（AGEs）与其受体RAGE介导的信号通路在糖尿病肾病发病机制中发挥重要作用。目前针对AGEs为靶点的糖尿病肾病药物开发已处于临床试验中。针对RAGE为靶点，利用可溶性RAGE、RAGE抗体以及干预 RAGE 基因表达等手段在动物研究中已证实RAGE是防治糖尿病肾病的有效干预靶点。然而，目前尚无天然小分子RAGE拮抗剂用于糖尿病肾病防治的报道，临床上也未有以RAGE为靶点的糖尿病肾病防治药物开发。 栀子苷是中药栀子的有效成分，具有抗炎和降血糖作用。在本研究中，我们首次发现栀子苷对RAGE具有高度亲和性，与RAGE的V结构域形成氢键结合，竞争性阻断AGEs与RAGE结合，可作为新型天然的AGEs-RAGE阻断剂；我们首次证实栀子苷能够抑制AGEs-RAGE依赖性炎症反应，这个过程不依赖于降低RAGE的表达水平，与阻断AGEs与RAGE的结合密切有关，首次证实栀子苷可作为天然的RAGE拮抗剂；从AGEs-RAGE依赖性炎症信号通路，我们解释了栀子苷改善2型糖尿病肾病作用的新机制，提示栀子苷是防治糖尿病肾病的潜在药物。 本研究为栀子苷防治糖尿病肾病作用提供科学依据，也揭示了栀子苷抗炎作用的新机制，具有重要的科学价值。栀子苷作为天然RAGE拮抗剂，有望成为防治糖尿病并发症以及与RAGE相关疾病的潜在药物。 （二） 三七（Panax notoginseng (Burk.) F. H. Chen，NG）具有散瘀止血，消肿定痛之功效，经加热炮制后的熟三七（Steamed Panax notoginseng，SNG）具有滋补之功效，可能由于在加热过程中三七化学成分发生了改变。目前对熟三七的化学成分研究已有报道，但其整体药代动力学研究尚未见报道。对熟三七进行药代动力学研究将有助于我们更好地了解熟三七体内药代动力学特征及发挥作用的功效成分，更重要的是可以揭示熟三七特征性成分的体内吸收情况和生物利用度。目前用于定量熟三七成分的检测分析方法存在灵敏度低、背景噪声强、分析持续时间长等缺点，也无法同时对多成分进行快速定量分析。 因此，本研究中我们建立一种高效且高灵敏的LC-MS/MS方法，可同时定量检测大鼠血浆中来自熟三七的23种三萜类化合物（notoginsenosides Fa, Fc, R1, 20(S)-R2, 20(R)-R2, ginsenosides F4, Rb1, Rg1, Rd, Re, Rb2, 20(S)-Rh1, 20(R)-Rh1, Rh4, Rk1, Rk3, 20(S)-Rg2, 20(S)-Rg3, 20(R)-Rg3, Rg5, C-K, 20(S)-PPT, 20(S)-PPD）。并经方法学验证，该方法对所有分析物都具有良好的线性、精密度、准确度、回收率和稳定性。我们首次将该分析方法应用于熟三七的药代动力学研究，并根据体内暴露程度，首次提出Rb1、Fa、 Rd、Rk1、Rg5、Rk3、 Rh4、和20(S)-PPD可视为熟三七体内药动学标志物。该方法可广泛应用于含人参皂苷、三七皂苷成分的中药材及相关产品成分分析检测和体内药代动力学研究。

（I） Diabetic nephropathy (DN) is the most common microvascular complications of diabetes mellitus, leading to premature death and end-stage renal disease in patients worldwide. As reported, almost one-third of people with diabetes can cause DN. Current prevention strategies for DN mainly target on the management of hyperglycemia. However, these interventions could only partially attenuate some symptoms but failed to fully prevent the progression of DN. Therefore, the prevention and treatment of DN is still an important research topic. Both basic and clinical studies have confirmed the importance of advanced glycation end products (AGEs) binding its receptor RAGE mediated pathway in the pathogenesis of DN. The development of drugs for DN targeting AGEs are currently applied in clinical trials. Soluble RAGE, RAGE neutralizing antibodies, genetic deletion or a dominant-negative form of RAGE were used to support RAGE as a potentially effective therapeutic target for DN. However, no study to date reports whether natural small-molecule RAGE-specific antagonists could effectively prevent against the development and progression of DN. there is still no clinical research on the treatement of DN with RAGE as a target. Geniposide, as a natural acitive ingredient isolated from Chinese herb Gardenia jasminoides Ellis, exhibits anti-inflammatory and hypoglycemic effects. In this study, we for the first time identified geniposide as a novel natural RAGE antagonist that competitively blocks AGEs-RAGE interaction via forming hydrogen bonds at the V domain of RAGE. Geniposide functions as a novel natural AGEs-RAGE blocker that inhibited RAGE-dependent inflammatory signaling, an action that was independent of RAGE expression, and thereby protected against type 2 DN. We demonstrated that geniposide had beneficial effects against the development and progression of DN and deciphered a new underlying mechanism of its anti-inflammatory effect, which has scientific significance. Geniposide would be further developed in the future as a novel natural RAGE antagonist for treatment and prevention of diabetic complications and RAGE-related diseases. (II) Notoginseng, the root of Panax notoginseng (Burk.) F. H. Chen, has the effect of eliminating blood stasis, stoping bleeding, as well as mitigating swelling and pains. The steamed notoginseng (SNG) has been widely viewed as a tonic which likely due to the difference of chemical constituents obtained during steaming process, but its pharmacokinetic profile is entirely unknown. The study of PK properties of SNG would assist us to understand the efficacy of SNG better and enable the prediction of its role in the clinic. Moreover, the oral absorption and bioavailability data would be extremely critical regarding the usage of SNG unique saponins. Current quantification methods used for the determination of SNG saponins are difficult for simultaneous detection of multi-ginsenosides for low sensitivity, strong background noise, and long analytical duration time. To address this, we’ve developed an LC-MS/MS method with high efficiency and sensitivity for simultaneous quantification of 23 triterpenoids (notoginsenosides Fa, Fc, R1, 20(S)-R2, 20(R)-R2, ginsenosides F4, Rb1, Rg1, Rd, Re, Rb2, 20(S)-Rh1, 20(R)-Rh1, Rh4, Rk1, Rk3, 20(S)-Rg2, 20(S)-Rg3, 20(R)-Rg3, Rg5, C-K, 20(S)-PPT, 20(S)-PPD) from SNG in rat plasma. This validated approach exhibits great linearity, precisions, accuracy, recovery and stability for all analytes. Furthermore, we for the first time applied this method to the pharmacokinetic study of SNG, and proposed Rb1, Fa, Rd, Rk1, Rg5, Rk3, Rh4, and 20(S)-PPD to be suitable pharmacokinetic markers of SNG due to their high exposure levels of systemic plasma. Hence, this developed approach would be a powerful tool for future in vivo investigation of various sources of notoginseng-related samples.