Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Atherosclerosis (AS) is one of the major catalysts of ischemic cerebrovascular disease, and the death and disease burden from AS and its cerebrovascular complications are increasing. Z-ligustilide (Z-LIG) is a key active ingredient in Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. In this paper, we first introduced LIG’s physicochemical properties and pharmacokinetics. Then, we reviewed Z-LIG’s intervention and therapeutic mechanisms on AS and its cerebrovascular complications. The mechanisms of Z-LIG intervention in AS include improving lipid metabolism, antioxidant and anti-inflammatory effects, protecting vascular endothelium, and inhibiting vascular endothelial fibrosis, pathological thickening, and plaque calcification. In ischemic cerebrovascular diseases complicated by AS, Z-LIG exerts practical neuroprotective effects in ischemic stroke (IS), transient ischemic attack (TIA), and vascular dementia (VaD) through anti-neuroinflammatory, anti-oxidation, anti-neuronal apoptosis, protection of the blood-brain barrier, promotion of mitochondrial division and angiogenesis, improvement of cholinergic activity, inhibition of astrocyte proliferation, and endoplasmic reticulum stress. This paper aims to provide a basis for subsequent studies of Z-LIG in the prevention and treatment of AS and its cerebrovascular complications and, thus, to promote the development of interventional drugs for AS.

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein–protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein–protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is emerging as one of the fastest-growing causes of liver-related deaths worldwide. It is necessary to find strategies to effectively prevent and treat NAFLD, as no definitive drug has been approved. Nobiletin (NOB) is the critical active ingredient of Chinese herbal medicines such as Citrus aurantium and Citri Reticulatae Pericarpium, which have anti-inflammatory, antioxidant, lipid regulating, and insulin resistance regulating effects. Numerous studies have demonstrated that NOB can prevent and treat the onset and progression of NAFLD. In this review, the mechanisms of NOB for treating NAFLD have been summarized, hoping to provide a basis for subsequent studies of NOB and to provide a research ground for the development of therapeutic drugs for NAFLD.

Carthamus tinctorius L. (Honghua, HH) is an herbal medicine and functional food widely used to treat chronic liver diseases, including liver fibrosis. By using network pharmacology and molecular docking experiments, the present study aims to determine the bioactive components, potential targets, and molecular mechanisms of HH for treating liver fibrosis. The components of HH were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and literature, and the SwissTargetPrediction database was used to predict the treatment targets of HH. Genecards and DisGeNET databases contained targets for liver fibrosis, and the STRING database provided networks of protein–protein interactions. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database of Annotation, Visualization and Integrated Discovery. The protein–protein interactive network and drug–component–major target–pathway interactive network were visualized and analyzed by Cytoscape software. Finally, Autodock Vina and Discovery Studio software were used for molecular docking Validation. A total of 23 candidate bioactive compounds with 187 treatment targets of HH were acquired from the databases and literature. A total of 121 overlapping targets between HH and liver fibrosis were found to provide the molecular basis for HH on liver fibrosis. Quercetin, beta carotene, and lignan were identified as key components with targeting to ESR1, PIK3CA, and MTOR. HH is engaged in the intervention of various signaling cascades associated with liver fibrosis, such as PI3K/AKT/mTOR pathway, MAPK pathway, and PPAR pathway. In conclusion, HH treats liver fibrosis through multi-component, multi-target, and multi-pathway mechanisms.