Aspalathus linearis (Rooibos) Targets Adipocytes and Obesity-Associated Inflammation.

Excess weight and obesity are the fifth leading cause of death globally, and sustained efforts from health professionals and researchers are required to mitigate this pandemic-scale problem. Polyphenols and flavonoids found in Aspalathus linearis-a plant widely consumed as Rooibos tea-are increasingly being investigated for their positive effects on various health issues including inflammation. The aim of our study was to examine the effect of Rooibos extract on obesity and the associated low-grade chronic inflammatory state by testing antioxidant activity, cytokine secretions, macrophage polarization and the differentiation of human adipocytes through the development of adipospheroids. Rooibos extract significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFN-γ, IL-12, IL-2 and IL-17a) in human leukocytes. Additionally, Rooibos extract down-regulated LPS-induced macrophage M1 polarization, shown by a significant decrease in the expression of pro-inflammatory cytokines: TNFα, IL-8, IL-6, IL-1ß and CXCL10. In addition, Rooibos inhibited intracellular lipid accumulation and reduced adipogenesis by decreasing the expression of PPARγ, Ap2 and HSL in adipospheroids. A significant decrease in leptin expression was noted and this, more interestingly, was accompanied by a significant increase in adiponectin expression. Using a co-culture system between macrophages and adipocytes, Rooibos extract significantly decreased the expression of all studied pro-inflammatory cytokines and particularly leptin, and increased adiponectin expression. Thus, adding Rooibos tea to the daily diet is likely to prevent the development of obesity associated with chronic low-level inflammation.

Exploring the Therapeutic Potential of Ampelopsis grossedentata Leaf Extract as an Anti-Inflammatory and Antioxidant Agent in Human Immune Cells.

Inflammation is a vital protective response to threats, but it can turn harmful if chronic and uncontrolled. Key elements involve pro-inflammatory cells and signaling pathways, including the secretion of pro-inflammatory cytokines, NF-κB, reactive oxygen species (ROS) production, and the activation of the NLRP3 inflammasome. Ampelopsis grossedentata, or vine tea, contains dihydromyricetin (DHM) and myricetin, which are known for their various health benefits, including anti-inflammatory properties. Therefore, the aim of this study is to assess the impact of an extract of A. grossedentata leaves (50 µg/mL) on inflammation factors such as inflammasome, pro-inflammatory pathways, and macrophage polarization, as well as its antioxidant properties, with a view to combating the development of low-grade inflammation. Ampelopsis grossedentata extract (APG) significantly decreased ROS production and the secretion of pro-inflammatory cytokines (IFNγ, IL-12, IL-2, and IL-17a) in human leukocytes. In addition, APG reduced LPS/IFNγ -induced M1-like macrophage polarization, resulting in a significant decrease in the expression of the pro-inflammatory cytokines TNF-α and IL-6, along with a decrease in the percentage of M1 macrophages and an increase in M0 macrophages. Simultaneously, a significant decrease in NF-κB p65 phosphorylation and in the expression of inflammasome genes (NLRP3, IL-1ß and Caspase 1) was observed. The results suggest that Ampelopsis grossedentata could be a promising option for managing inflammation-related chronic diseases. Further research is needed to optimize dosage and administration methods.

Targeting Adiponectin in Breast Cancer.

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight and obesity increase the risk of postmenopausal breast cancer, and adipokines are the central players in this relationship. Produced and secreted predominantly by white adipose tissue, adiponectin is a bioactive molecule that exhibits numerous protective effects and is considered the guardian angel of adipokine. In the obesity-cancer relationship, more and more evidence shows that adiponectin may prevent and protect individuals from developing breast cancer. Recently, several updates have been published on the implication of adiponectin in regulating tumor development, progression, and metastases. In this review, we provide an updated overview of the metabolic signaling linking adiponectin and breast cancer in all its stages. On the other hand, we critically summarize all the available promising candidates that may reactivate these pathways mainly by targeting adiponectin receptors. These molecules could be synthetic small molecules or plant-based proteins. Interestingly, the advances in genomics have made it possible to create peptide sequences that could specifically replace human adiponectin, activate its receptor, and mimic its function. Thus, the obvious anti-cancer activity of adiponectin on breast cancer should be better exploited, and adiponectin must be regarded as a serious biomarker that should be targeted in order to confront this threatening disease.

Combination of Angiotensin (1-7) Agonists and Convalescent Plasma as a New Strategy to Overcome Angiotensin Converting Enzyme 2 (ACE2) Inhibition for the Treatment of COVID-19.

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2. Several reports proposed the use of ACE2 pharmacological inhibitors and ACE2 antibodies to block viral entry. However, ACE2 inhibition is associated with lung and cardiovascular pathology and would probably increase the pathogenesis of COVID-19. Therefore, utilizing ACE2 soluble analogs to block viral entry while rescuing ACE2 activity has been proposed. Despite their protective effects, such analogs can form a circulating reservoir of the virus, thus accelerating its spread in the body. Levels of ACE2 are reduced following viral infection, possibly due to increased viral entry and lysis of ACE2 positive cells. Downregulation of ACE2/Ang (1-7) axis is associated with Ang II upregulation. Of note, while Ang (1-7) exerts protective effects on the lung and cardiovasculature, Ang II elicits pro-inflammatory and pro-fibrotic detrimental effects by binding to the angiotensin type 1 receptor (AT1R). Indeed, AT1R blockers (ARBs) can alleviate the harmful effects associated with Ang II upregulation while increasing ACE2 expression and thus the risk of viral infection. Therefore, Ang (1-7) agonists seem to be a better treatment option. Another approach is the transfusion of convalescent plasma from recovered patients with deteriorated symptoms. Indeed, this appears to be promising due to the neutralizing capacity of anti-COVID-19 antibodies. In light of these considerations, we encourage the adoption of Ang (1-7) agonists and convalescent plasma conjugated therapy for the treatment of COVID-19 patients. This therapeutic regimen is expected to be a safer choice since it possesses the proven ability to neutralize the virus while ensuring lung and cardiovascular protection through modulation of the inflammatory response.

Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment.

Drug repurposing has lately received increasing interest in several diseases especially in cancers, due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins, including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways known for their role in cell proliferation and survival, such as the JAK/STAT pathway. CML therapy, based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However, 15% of patients are refractory to IM, where in some cases, 20-30% of patients become resistant. Thus, we suggest the repurposing of ACF in CML after IM failure or in combination with IM to improve the anti-tumor effects of IM. In this review, we present the different pharmacological properties of ACF along with its anti-leukemic effects in the hope of its repurposing in CML therapy.

Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells.

Acriflavine (ACF) is an antiseptic with anticancer properties, blocking the growth of solid and haematopoietic tumour cells. Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia-inducible factors (HIFs) activity, which are key effectors of hypoxia-mediated chemoresistance. In this study, we showed that ACF inhibits the growth and survival of chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cell lines in normoxic conditions. We further demonstrated that ACF down-regulates STAT5 expression in CML and AML cells but activates STAT3 in CML cells in a HIF-independent manner. In addition, we demonstrated that ACF suppresses the resistance of CML cells to tyrosine kinase inhibitors, such as imatinib. Our data suggest that the dual effect of ACF might be exploited to eradicate de novo or acquired resistance of myeloid leukaemia cells to chemotherapy.