Background and Purpose: Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP‐activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms.Experimental Approach: The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg⁻¹·day⁻¹) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro.Key Results: Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose‐dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside‐stimulated AMPK activation was found to suppress the expression of PEPCK and glucose‐6‐phosphatase. Salidroside‐induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio.Conclusions and Implications: Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria‐related AMPK/PI3K/Akt/GSK3β pathway

COVID-19 broke out in the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found that the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2's stronger infectious nature than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products was screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, diminazene, showed the highest inhibition effects on furin with an IC50 of 5.42 ± 0.11 μM, which might be used for the treatment of COVID-19.

Asperterpenes A (1) and B (2), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from Aspergillus terreus in very limited amounts of 3.6 mg and 1.8 mg, respectively. The absolute structure of 1 was determined using X-ray diffraction. Because of the low yield of 1, a comprehensive characterization of the BACE1 inhibitory activities of 1 was completed via molecular biological, cell and animal studies guided by in silico target confirmation (ISTC). ISTC assays suggested that compounds 1 and 2 might be BACE1 inhibitors. In cell-based tests, asperterpenes A and B, as natural products, exhibited promising inhibitory activities against BACE1, with IC₅₀ values of 78 and 59 nM, respectively. LY2811376 (the positive control), one of the most potent clinical BACE1 inhibitors, has shown an IC₅₀ value of 260 nM. In vivo, compound 1 exhibited activity similar to that of LY2811376 against Alzheimer's disease (AD) in 3xTg AD mice. Taken together, these findings demonstrate that asperterpene A, which contains a novel carbon skeleton, is the first terpenoid to exhibit effective BACE1 inhibitory activity. Moreover, 1 represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of AD.