The draft genome and multi-omics analyses reveal new insights into geo-herbalism properties of Citrus grandis 'Tomentosa'.

Citrus grandis 'Tomentosa' (CGT) (Huajuhong, HJH) is a widely used medicinal plant, which is mainly produced in Guangdong and Guangxi provinces of South China. Particularly, HJH from Huazhou (HZ) county of Guangdong province has been well-regarded as the best national product for geo-herbalism. But the reasons for geo-herbalism property in HJH from HZ county remains a mystery. Therefore, a multi-omics approach was applied to identify the nature of the geo-herbalism in CGT from three different regions. The comprehensive screening of differential metabolites revealed that the Nobiletin content was significantly different in HZ region compared to other regions, and could be employed as a key indicator to determine the geo-herbalism. Furthermore, the high-quality genome (N50 of 9.12 Mb), coupled with genomics and transcriptomics analyses indicated that CGT and Citrus grandis are closely related, with a predicted divergence time of 19.1 million years ago (MYA), and no recent WGD occurred in the CGT, and the bioactive ingredients of CGT were more abundant than that of Citrus grandis. Interestingly, Nobiletin (Polymethoxyflavones) content was identified as a potential indicator of geo-herbalism, and O-methyltransferase (OMT) genes are involved in the synthesis of Polymethoxyflavones. Further multi-omics analysis led to the identification of a novel OMT gene (CtgOMT1) whose transient overexpression displayed significantly higher Nobiletin content, suggesting that CtgOMT1 was involved in the synthesis of Nobiletin. Overall, our findings provide new data resources for geo-herbalism evaluation, germplasm conservation and insights into Nobiletin biosynthesis pathways for the medicinal plant C. grandis 'Tomentosa'.

Network Pharmacology Analysis of Damnacanthus indicus C.F.Gaertn in Gene-Phenotype.

Damnacanthus indicus C.F.Gaertn is known as Huci in traditional Chinese medicine. It contains a component having anthraquinone-like structure which is a part of the many used anticancer drugs. This study was to collect the evidence of disease-modulatory activities of Huci by analyzing the published literature on the chemicals and drugs. A list of its compounds and direct protein targets is predicted by using Bioinformatics Analysis Tool for Molecular Mechanism of TCM. A protein-protein interaction network using links between its directed targets and the other known targets was constructed. The DPT-associated genes in net were scrutinized by WebGestalt. Exploring the cancer genomics data related to Huci through cBio Portal. Survival analysis for the overlap genes is done by using UALCAN. We got 16 compounds and it predicts 62 direct protein targets and 100 DPTs and they were identified for these compounds. DPT-associated genes were analyzed by WebGestalt. Through the enrichment analysis, we got top 10 identified KEGG pathways. Refined analysis of KEGG pathways showed that one of these ten pathways is linked to Rap1 signaling pathway and another one is related to breast cancer. The survival analysis for the overlap genes shows the significant negative effect of these genes on the breast cancer patients. Through the research results of Damnacanthus indicus C.F.Gaertn, it is shown that medicine network pharmacology may be regarded as a new paradigm for guiding the future studies of the traditional Chinese medicine in different fields.