Prevention and treatment of inflammatory arthritis with traditional Chinese medicine: Underlying mechanisms based on cell and molecular targets

This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms. 

The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review

Stroke, as a neurological disorder with a poor overall prognosis, has long plagued the patients. Current stroke therapy lacks effective treatments. Ferroptosis has emerged as a prominent subject of discourse across various maladies in recent years. As an emerging therapeutic target, notwithstanding its initial identification in tumor cells associated with brain diseases, it has lately been recognized as a pivotal factor in the pathological progression of stroke. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a potential target and biomarker of catalytic unsaturated fatty acids mediating ferroptosis in stroke. Specifically, the upregulation of ACSL4 leads to heightened accumulation of lipid peroxidation products and reactive oxygen species (ROS), thereby exacerbating the progression of ferroptosis in neuronal cells. ACSL4 is present in various tissues and involved in multiple pathways of ferroptosis. At present, the pharmacological mechanisms of targeting ACSL4 to inhibit ferroptosis have been found in many drugs, but the molecular mechanisms of targeting ACSL4 are still in the exploratory stage. This paper introduces the physiopathological mechanism of ACSL4 and the current status of the research involved in ferroptosis crosstalk and epigenetics, and summarizes the application status of ACSL4 in modern pharmacology research, and discusses the potential application value of ACSL4 in the field of stroke. 

The role of ACSL4 in stroke: mechanisms and potential therapeutic target

Osteoarthritis (OA), the most common degenerative joint disease, can eventually lead to disability. However, no safe or effective intervention is currently available. Therefore, there is an urgent need to develop effective drugs that reduce cartilage damage and treat OA. 

Panaxatriol exerts anti-senescence effects and alleviates osteoarthritis and cartilage repair fibrosis by targeting UFL1

Abstract Astragalus glycyphyllos L. is widely used in Bulgarian folk medicine. Extracts from this plant have antiproliferative, antitumor and immune stimulating effects in vitro and in vivo. The aim of this study was to examine the potential antiviral activity of a standardized extract from the aerial parts of the plant and to formulate it in a suitable dosage form. A dry extract was obtained, and its phytochemical composition was determined by ultra-high-performance liquid chromatography–high resolution electrospray ionization mass spectrometry (UHPLC-HRESIMS). The extract contained flavonoids and predominantly saponins. 17(R),20(R)-3β,6α,16β-trihydroxycycloartanyl-23-carboxylic acid 16-lactone 3-O-β-D-glucopyranoside was used as a reference for quantitation. The extract had 3% saponins. The antiviral activity of the extract was tested against Simplexvirus humanalpha type 1 (acyclovir sensitive) and 2 (acyclovir resistant) in vitro. Between 60% and 70% of protection was reached against both virus strains when the extract (at the maximal non-toxic concentration of 0.6 mg/mL) was added simultaneously with and 1 h after Madine and Darby bovine kidney cell inoculation. The extract was also tested in combination with acyclovir only against Simplexvirus humanalpha type 1, in vitro. Further, the lyophilized extract was mixed with appropriate excipients aiming to prepare tablets via direct compaction. The optimized tablets fulfilled the requirements of the pharmacopoeia for disintegration and friability. Thus, the study demonstrated the possibility to formulate a standardized extract of A. glycyphyllos in tablets and their potential for adjuvant antiviral application in further trials.

Astragalus glycyphyllos L.: antiviral activity and tablet dosage formulation of a standardized dry extract

Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

/pdf/glycyrrhizin-inhibits-sars-cov-2-entry-into-cells-by-15x74ru6.pdf

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2

The activation of innate antiviral immunity is a promising approach for combatting viral infections. In this study, we screened Chinese herbs that activated human immunity and identified coptisine as a potent inhibitor of the influenza virus with an EC50 of 10.7 μM in MDCK cells. The time of an addition assay revealed that pre-treatment with coptisine was more effective at reducing viral replication than co-treatment or post-treatment. Our bulk RNA-sequencing data showed that coptisine upregulated the p21 signaling pathway in MDCK cells, which was responsible for its antiviral effects. Specifically, coptisine increased the expression of p21 and FOXO1 in a dose-dependent manner while leaving the MELK expression unchanged. Docking analysis revealed that coptisine likely inhibited MELK activity directly by forming hydrogen bonds with ASP-150 and GLU-87 in the catalytic pocket. These findings suggest that coptisine may be a promising antiviral agent that regulates the p21 signaling pathway to inhibit viral replication.

Coptisine Inhibits Influenza Virus Replication by Upregulating p21

Novel Benzamide Derivatives with Indole Moiety as Dual-Target Antiviral Agents: Rational Design, Efficient Synthesis, and Potent Anti-Influenza Activity Through Concurrent Binding to PAC Terminal Domain and Viral Nucleoprotein

Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds 3a-3g, carboxylic acid moiety compounds 4a-4g and piperazine amide moiety compounds 5a-5k at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The in vitro biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds 3g and 4g exhibited more excellent antibacterial activity, especially the activity against Staphylococcus aureus and Escherichia coli, showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds 4e-4g with carboxylic acid moiety can enhance the antibacterial activity. Compounds 5g-5k containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg2+ in the protein. 

Design, synthesis and antibacterial activity of novel 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives

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