A network pharmacology, molecular docking and <i>in vitro</i> investigation of <i>Picrorhiza kurroa</i> extract for the treatment of diabetic nephropathy
Creators: name: Pal, Shiv
name: Yellurkar, Manoj Limbraj
name: Das, Pamelika
name: Prasanna, Vani Sai
name: Sarkar, Sulogna
name: Gajbhiye, Rahul L.
name: Taraphdar, Amit Kumar
name: Velayutham, Ravichandiran
name: Arumugam, Somasundaram
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer

description: <i>Picrorhiza kurroa</i> Royle ex Benth. (<i>P. kurroa</i>/PK/Kutki), a Himalayan herb belonging to the family <i>Scrophulariaceae,</i> 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 <i>P. kurroa</i> for the treatment of diabetic nephropathy (DN) was investigated by network pharmacology, molecular docking and <i>in vitro</i> assays. Numerous databases have been screened and 33 <i>P. kurroa</i> 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. <i>kurroa</i> interacted with 14 significant proteins/genes associated with DN. <i>P. kurroa</i> extract was proven to enhance the survival rate of HEK cells significantly. Protein expression analysis using Western blot demonstrated that <i>P. kurroa</i> 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 <i>P. kurroa</i> extract on DN disease was evident in the <i>in-vitro</i> studies aided by network pharmacology and molecular docking.