Development and evaluation of a novel chromium III-based compound for potential inhibition of emerging SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused 403 million cases of coronavirus disease (COVID-19) and resulted in more than 5.7 million deaths worldwide. Extensive research has identified several potential drug treatments for COVID-19. However, the development of new compounds or therapies is necessary to prevent the emergence of drug resistance in SARS-CoV-2. In this study, a novel compound based on hexaacetotetraaquadihydroxochromium(III)diiron(III) nitrate, which contains small amounts of chromium (III), was synthesised and evaluated for its effectiveness against multiple variants of COVID-19 using both in vitro and in vivo models. This innovative compound demonstrated interference with the interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2). Furthermore, in vitro experiments showed that this compound downregulated the expression of ACE2 and transmembrane serine protease 2 (TMPRSS2). It also exhibited a reduction in the activity of 3-chymotrypsin-like protease (3CL) and RNA-dependent RNA polymerase (RdRp). Pretreatment with this small chromium (III)-based compound resulted in reduced ACE2-rich cell infection by various variants of SARS-CoV-2 spike protein-pseudotyped lentivirus. Finally, the compound effectively inhibited viral infection by multiple variants of SARS-CoV-2 spike protein-pseudotyped lentivirus in both the abdominal and thoracic regions of mice. In conclusion, this compound lowers the likelihood of SARS-CoV-2 entry into cells, inhibits viral maturation and replication in vitro, and reduces infection levels of multiple variants of SARS-CoV-2 spike protein-pseudotyped lentivirus in the abdomen and thorax following pretreatment. Small chromium (III)-based compounds have the potential to restrict the progression of SARS-CoV-2 infections.

Tetrahydrobiopterin from cyanide-degrading bacterium Bacillus pumilus strain SVD06 induces apoptosis in human lung adenocarcinoma cell (A549).

Tetrahydrobiopterin (BH4) is an essential biological cofactor and a derivative of pterin which is considered potent anticancer agents. In continuation of our previous study on the identification of BH4 from cyanide-degrading Bacillus pumilus, the present study focuses on evaluating the anticancer properties of BH4 on A549, a human lung adenocarcinoma. Anticancer activity analysis shows that BH4 inhibited A549 cell growth after 24 h of incubation with 0.02 mg/mL. In acridine orange/ethidium bromide staining, BH4-treated A549 cells showed apoptotic morphology. BH4 treatment caused cell cycle arrest at G0/G1 phase compared to control cells. BH4 augmented p53 expression in alveolar cancer cells by downregulating MDM2 levels. There was downregulation of casp-3 and upregulation of iNOS gene in BH4-treated A549 cells. Further, docking studies indicated that BH4 had significant interactions with the above proteins affirming the apoptosis mechanism. Thus, BH4 could be considered a potential anticancer drug.

Artemisia argyi extract induces apoptosis in human gemcitabine-resistant lung cancer cells via the PI3K/MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi H. Lév. & Vaniot (Asteraceae), also called "Chinese mugwort", is frequently used as a herbal medicine in China, Japan, Korea, and eastern parts of Russia. It is known as "ai ye" in China and "Gaiyou" in Japan. In ancient China, the buds and leaves of A. argyi were commonly consumed before and after Tomb-sweeping Day. It is used to treat malaria, hepatitis, cancer, inflammatory diseases, asthma, irregular menstrual cycle, sinusitis, and pathologic conditions of the kidney and liver. Although A. argyi extract (AAE) has shown anti-tumor activity against various cancers, the therapeutic effect and molecular mechanism of AAE remains to be further studied in lung cancer. AIM OF THE STUDY: This study aimed to demonstrate the anti-tumor effect of AAE and its associated biological mechanisms in CL1-0 parent and gemcitabine-resistant (CL1-0-GR) lung cancer cells. EXPERIMENTAL PROCEDURE: Human lung cancer cells CL1-0 and CL1-0-GR cells were treated with AAE. Cell viability was assessed using the MTT, colony, and spheroid formation assays. Migration, invasion, and immunofluorescence staining were used to determine the extent of epithelial- mesenchymal transition (EMT). JC-1 and MitoSOX fluorescent assays were performed to investigate the effect of AAE on mitochondria. Apoptosis was detected using the TUNEL assay and flow cytometry with Annexin V staining. RESULT: We found that A. argyi significantly decreased cell viability and induced apoptosis, accompanied by mitochondrial membrane depolarization and increased ROS levels in both parent cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0-GR). AAE-induced apoptosis is regulated via the PI3K/AKT and MAPK signaling pathways. It also prevents CL1-0 and CL1-0-GR cancer cell invasion, migration, EMT, colony formation, and spheroid formation. In addition, AAE acts cooperative with commercial chemotherapy drugs to enhance tumor spheroid shrinkage. CONCLUSION: Our study provides the first evidence that A. argyi treatment suppresses both parent and gemcitabine-resistant lung cancer cells by inducing ROS, mitochondrial membrane depolarization, and apoptosis, and reducing EMT. Our finding provides insights into the anti-cancer activity of A. argyi and suggests that A. argyi may serve as a chemotherapy adjuvant that potentiates the efficacy of chemotherapeutic agents.

Novel anti-aging herbal formulation Jing Si displays pleiotropic effects against aging associated disorders.

Common characteristics of aging include reduced somatic stem cell number, susceptibility to cardiac injuries, metabolic imbalances and increased risk for oncogenesis. In this study, Pleiotropic anti-aging effects of a decoction Jing Si herbal drink (JS) containing eight Traditional Chinese Medicine based herbs, with known effects against aging related disorders was evaluated. Adipose derived mesenchymal stem cells (ADMSCs) from 16 week old adult and 24 month old aging WKY rats were evaluated for the age-related changes in stem cell homeostasis. Effects of JS on self-renewal, klotho and Telomerase Reverse Transcriptase expression DNA damage response were determined by immunofluorescence staining. The effects were confirmed in senescence induced human ADMSCs and in addition, the potential of JS to maintain telomere length was evaluated by qPCR analysis in ADMSCs challenged for long term with doxorubicin. Further, the effects of JS on doxorubicin-induced hypertrophic effect and DNA damage in H9c2 cardiac cells; MPP+-induced damages in SH-SY5Y neuron cells were investigated. In addition, effects of JS in maintaining metabolic regulation, in terms of blood glucose regulation in type-II diabetes mice model, and their potential to suppress malignancy in different cancer cells were ascertained. The results show that JS maintains stem cell homeostasis and provides cytoprotection. In addition JS regulates blood glucose metabolism, enhances autophagic clearances in neurons and suppresses cancer growth and migration. The results show that JS acts on multiple targets and provides a cumulative protective effect against various age-associated disorders and therefore it is a candidate pleiotropic agent for healthy aging.