Pal Shiv, Yellurkar Manoj Limbraj, Das Pamelika, Sai Prasanna Vani, Sarkar Sulogna, Gajbhiye Rahul L, Taraphdar Amit Kumar, Velayutham Ravichandiran, Arumugam Somasundaram
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) Hajipur, Export Promotion Industrial Park (EPIP), Industrial area Hajipur, Bihar, India.
National Institute of Pharmaceutical Education and Research (NIPER), Chunilal Bhawan, Kolkata, India.
J Biomol Struct Dyn. 2024 Feb 14:1-12. doi: 10.1080/07391102.2024.2314259.
Royle ex Benth. (/PK/Kutki), a Himalayan herb belonging to the family is widely known for its hepatoprotective activity. Traditionally, it is found to be effective for upper respiratory tract disorders, kidney and liver problems, dyspepsia and chronic diarrhoea but the mechanism of action is unclear. In this study, the mode of action of for the treatment of diabetic nephropathy (DN) was investigated by network pharmacology, molecular docking and assays. Numerous databases have been screened and 33 bioactive compounds and 56 targets were identified. The compounds-targets network, targets-pathways network and compounds-targets-pathways network were constructed. The major bioactive compounds include picrorhizaoside D, scrophuloside A, vanillic acid, arvenin I, cinnamic acid, picein, 6-feruloyl catalpol, picroside V, pikuroside, apocynin, picroside I, picroside IV, androsin, cucurbitacin P, boschnaloside, kutkoside, cucurbitacin O, cucurbitacin K, picracin, etc. The potential protein targets identified in this study were MMP1, PRKCA, MMP7, IL18, IL1, TNF, ACE, ASC, CASP1, NLRP3, MAP, KURROA1, mitogen-activated protein kinase (MAPK)14 and MAPK8. In the Database for annotation visualization and integrated discovery (DAVID) pathways and Gene Ontology enrichment analysis, 14 major DN signalling pathways were identified, including MAPK, renin-angiotensin system (RAS), TNF, signal transducer and activator of transcription (JAK-STAT), TLR, vascular endothelial growth factor (VEGF), mTOR, Wnt, Ras, PPARs, NFB, NOD and phosphatidylinositol signalling pathways. A molecular docking study revealed that 32 bioactive compounds of P. interacted with 14 significant proteins/genes associated with DN. extract was proven to enhance the survival rate of HEK cells significantly. Protein expression analysis using Western blot demonstrated that extract significantly altered the expression of p47phox, p67phox, gp91phox, IL-1 and TGFβ-1. As a result of network pharmacology and docking work, new concepts for discovering bioactive compounds and effective modes of action could be developed. The potential effect of extract on DN disease was evident in the studies aided by network pharmacology and molecular docking.
罗伊尔弯花黄堇（/PK/库奇），一种属于该科的喜马拉雅草药，因其肝脏保护活性而广为人知。传统上，它被发现对上呼吸道疾病、肾脏和肝脏问题、消化不良和慢性腹泻有效，但其作用机制尚不清楚。在本研究中，通过网络药理学、分子对接和实验研究了其治疗糖尿病肾病（DN）的作用方式。筛选了众多数据库，鉴定出33种生物活性化合物和56个靶点。构建了化合物-靶点网络、靶点-通路网络和化合物-靶点-通路网络。主要生物活性化合物包括胡黄连苷D、玄参苷A、香草酸、田野燕麦苷I、肉桂酸、松柏苷、6-阿魏酰梓醇、胡黄连苷V、胡黄连苷、鱼藤素、胡黄连苷I、胡黄连苷IV、安德洛辛、葫芦素P、波希鼠李苷、库奇苷、葫芦素O、葫芦素K、苦味质等。本研究中鉴定出的潜在蛋白质靶点为基质金属蛋白酶1（MMP1）、蛋白激酶Cα（PRKCA）、基质金属蛋白酶7（MMP7）、白细胞介素18（IL18）、白细胞介素1（IL1）、肿瘤坏死因子（TNF）、血管紧张素转换酶（ACE）、凋亡相关斑点样蛋白（ASC）、半胱天冬酶1（CASP1）、NLR家族含pyrin结构域蛋白3（NLRP3）、丝裂原活化蛋白（MAP）、库罗阿1（KURROA1）、丝裂原活化蛋白激酶（MAPK）14和MAPK8。在注释可视化与整合发现数据库（DAVID）通路和基因本体富集分析中，鉴定出14条主要的DN信号通路，包括MAPK、肾素-血管紧张素系统（RAS）、TNF、信号转导子和转录激活子（JAK-STAT）、Toll样受体（TLR）、血管内皮生长因子（VEGF）、哺乳动物雷帕霉素靶蛋白（mTOR）、Wnt、Ras、过氧化物酶体增殖物激活受体（PPARs）、核因子κB（NFB）、核苷酸结合寡聚化结构域（NOD）和磷脂酰肌醇信号通路。分子对接研究表明，紫堇提取物的32种生物活性化合物与14种与DN相关的重要蛋白质/基因相互作用。紫堇提取物被证明能显著提高人胚肾（HEK）细胞的存活率。使用蛋白质印迹法进行的蛋白质表达分析表明，紫堇提取物显著改变了p47吞噬细胞氧化酶（p47phox）、p67吞噬细胞氧化酶（p67phox）、gp91吞噬细胞氧化酶（gp91phox）、白细胞介素1（IL-1）和转化生长因子β-1（TGFβ-1）的表达。由于网络药理学和对接工作，可以开发发现生物活性化合物和有效作用方式的新概念。在网络药理学和分子对接辅助的实验研究中，紫堇提取物对DN疾病的潜在作用是明显的。
