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COVID-19 continues to spread around the world. This is mainly because new variants of the SARS-CoV-2 virus emerge due to genomic mutations, evade the immune system and result in the effectiveness of current therapeutics being reduced. We previously established a series of detection platforms, comprising computational docking analysis, S-protein-based ELISA, pseudovirus entry, and 3CL protease activity assays, which allow us to screen a large library of phytochemicals from natural products and to determine their potential in blocking the entry of SARS-CoV-2. In this new screen, rutaecarpine (an alkaloid from Evodia rutaecarpa) was identified as exhibiting anti-SARS-CoV-2 activity. Therefore, we conducted multiple rounds of structure-activity-relationship (SAR) studies around this phytochemical and generated several rutaecarpine analogs that were subjected to in vitro evaluations. Among these derivatives, RU-75 and RU-184 displayed remarkable inhibitory activity when tested in the 3CL protease assay, S-protein-based ELISA, and pseudovirus entry assay (for both wild-type and omicron variants), and they attenuated the inflammatory response induced by SARS-CoV-2. Interestingly, RU-75 and RU-184 both appeared to be more potent than rutaecarpine itself, and this suggests that they might be considered as lead candidates for future pharmacological elaboration.

Laminaria japonica (LJ) is a common seaweed, which has been widely used as functional food and medicine, but its pharmaceutical activities in angiogenic regulation are unclear. Here, different lines of studies provide evidence to the suppressive effects of LJ extract in VEGF-medicated angiogenic function. In cellular level, LJ extract significantly inhibited VEGF-mediated endothelial cell proliferation, migration, invasion and tube formation. For in vivo verification, LJ extract suppressed the VEGF-induced formation of sub-intestinal vessels in zebrafish embryo model. In signalling cascades, LJ extract decreased the amount of phosphorylated VEGF receptor-2, as triggered by VEGF, and subsequently some key related downstream elements were obviously inactivated. In parallel, NO production and ROS formation, as induced by VEGF, were significantly attenuated. Thus, these preclinical findings promoted the possible development of LJ extract as a potential therapeutic agent for prevention and clinical treatment of angiogenesis-related diseases. © 2024 The Authors

Introduction: COVID-19, caused by the novel coronavirus SARS-CoV-2, has been a constant threat to public health since its outbreak in early 2019. Despite the development of vaccines and therapeutic drugs, the effectiveness of preventing both the infection and recurrence of this respiratory disease is limited due to emerging variants and their side effects. Hence, the development of potent and safe anti-SARS-CoV-2 therapeutic agents is still in urgent demand. Methods: We previously developed a screening platform comprising various pseudovirus entry tests in conjunction with a computational docking modulation protocol. With this platform, we demonstrated that the extract of Evodia Fructus and its main chemical component, rutaecarpine, inhibited SARS-CoV-2 entry by suppressing the S-protein-ACE2 complex. Results: Here, we reveal that when the extract of Stephaniae Tetrandrae Radix or its chemical component, tetrandrine (a well-known TPC2 inhibitor), is combined with Evodiae Fructus extract or rutaecarpine, respectively, then these act in a synergistic manner to block the entry of SARS-CoV-2. Conclusion: Given the fact that herbal extracts have been effectively used in clinical applications and have well-established safety records, our current findings suggest that these drug combinations might be considered as potential anti-COVID-19 treatments.

Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism in relieving the clinical symptoms is unclear. Several lines of evidence point to a strong link between constipation and gut microbiota. Short-chain fatty acids (SCFAs) and microbial metabolites have been shown to affect 5-HT synthesis by activating the GPR43 receptor localized on intestinal enterochromaffin cells, since 5-HT receptors are known to influence colonic peristalsis. The objective of this study was to evaluate the efficacy of XCQ in alleviating clinical symptoms in a mouse model of STC induced by loperamide. The application of loperamide leads to a decrease in intestinal transport and fecal water, which is used to establish the animal model of STC. In addition, the relationship between constipation and gut microbiota was determined. The herbal materials, composed of Rhei Radix et Rhizoma (Rhizomes of Rheum palmatum L., Polygonaceae) 55.2 g, Magnoliae Officinalis Cortex (Barks of Magnolia officinalis Rehd. et Wils, Magnoliaceae) 27.6 g, and Aurantii Fructus Immaturus (Fruitlet of Citrus aurantium L., Rutaceae) 36.0 g, were extracted with water to prepare the XCQ decoction. The constipated mice were induced with loperamide (10 mg/kg/day), and then treated with an oral dose of XCQ herbal extract (2.0, 4.0, and 8.0 g/kg/day) two times a day. Mosapride was administered as a positive drug. In loperamide-induced STC mice, the therapeutic parameters of XCQ-treated mice were determined, i.e., (i) symptoms of constipation, composition of gut microbiota, and amount of short-chain fatty acids in feces; (ii) plasma level of 5-HT; and (iii) expressions of the GPR43 and 5-HT4 receptor in colon. XCQ ameliorated the constipation symptoms of loperamide-induced STC mice. In gut microbiota, the treatment of XCQ in STC mice increased the relative abundances of Lactobacillus, Prevotellaceae_UCG_001, Prevotellace

Background: Various brain disorders, including neurodegenerative diseases and major depressive disorders, threaten an increasing number of patients. Seabuckthorn, a fruit from Hippophae rhamnoides L., is an example of

Understanding the adaptive ecological divergence provides important information for revealing biodiversity generation and maintenance. Adaptive ecology divergence in populations occurs in various environments and locations, but its genetic underpinnings remain elusive. We generated a chromosome-level genome of Eleutheronema tetradactylum (~582 Mb) and re-sequenced 50 allopatric E. tetradactylum in two independent environmental axes in China and Thailand Coastal waters as well as 11 cultured relatives. A low level of whole genome-wide diversity explained their decreased adaptive potential in the wild environment. Demographic analysis showed evidence of historically high abundance followed by a continuous distinct decline, plus signs of recent inbreeding and accumulation of deleterious mutations. Extensive signals of selective sweeps with signs of local adaptation to environmental differentiation between China and Thailand at genes related to thermal and salinity adaptation were discovered, which might be the driving factors of the geographical divergence of E. tetradactylum. Many genes and pathways subjected to strong selection under artificial breeding were associated with fatty acids and immunity (ELOVL6L, MAPK, p53/NF-kB), likely contributing to the eventual adaptation of artificial selective breeding. Our comprehensive study provided crucial genetic information for E. tetradactylum, with implications for the further conservation efforts of this threatened and ecologically valuable fish.