Vol 27, No 14 (2024)

Viruses are the cause of many human pathogenesis-related conditions. A serious hazard to public health has been created because of the increase in worldwide travel, fast urbanization, and infectious epidemics. At the same time, no preventative vaccines or antiviral treatments are currently available. Resources for developing new antiviral medications can be found in enhanced natural products and herbal medicines. These natural substances have aided the research on developing preventive vaccines and antiviral treatments. Based primarily on in vitro and in vivo searches, this review aims to explore the antiviral properties of plant extracts and some isolated plant natural products. Only a few antiviral medications have been given clinical approval, while numerous viruses continue to elude adequate immunization. Therefore, developing novel antiviral medicines is crucial, and natural substances make excellent sources for these new drugs. This review highlights various natural herbal drugs possessing antiviral properties.

Parkinson's disease (PD), the most common brain-related neurodegenerative disorder, is comprised of several pathophysiological mechanisms, such as mitochondrial dysfunction, neuroinflammation, aggregation of misfolded alpha-synuclein, and synaptic loss in the substantia nigra pars compacta region of the midbrain. Misfolded alpha-synuclein, originating from damaged neurons, triggers a series of signaling pathways in both glial and neuronal cells. Activation of such events results in the production and expression of several proinflammatory cytokines via the activation of the nuclear factor κB (NF-κB) signaling pathway. Consequently, this cascade of events worsens the neurodegenerative processes, particularly in conditions, such as PD and synucleinopathies. Microglia, astrocytes, and neurons are just a few of the many cells and tissues that express the NF-κB family of inducible types of transcription factors. The dual role of NF-κB activation can be crucial for neuronal survival, although the classical NF-κB pathway is important for controlling the generation of inflammatory mediators during neuroinflammation. Modulating NF-κB-associated pathways through the selective action of several agents holds promise for mitigating dopaminergic neuronal degeneration and PD. Several naturally occurring compounds in medicinal plants can be an effective treatment option in attenuating PD-associated dopaminergic neuronal loss via selectively modifying the NF-κB-mediated signaling pathways. Recently, flavonoids have gained notable attention from researchers because of their remarkable anti-neuroinflammatory activity and significant antioxidant properties in numerous neurodegenerative disorders, including PD. Several subclasses of flavonoids, including flavones, flavonols, isoflavones, and anthocyanins, have been evaluated for neuroprotective effects against in vitro and in vivo models of PD. In this aspect, the present review highlights the pathological role of NF-κB in the progression of PD and investigates the therapeutic potential of natural flavonoids targeting the NF-κB signaling pathway for the prevention and management of PD-like manifestations with a comprehensive list for further reference. Available facts strongly support that bioactive flavonoids could be considered in food and/or as lead pharmacophores for the treatment of neuroinflammation-mediated PD. Furthermore, natural flavonoids having potent pharmacological properties could be helpful in enhancing the economy of countries that cultivate medicinal plants yielding bioactive flavonoids on a large scale.

Background:Collateral arteries provide an alternative source to the myocardium resulting from ischemia due to occlusive coronary artery disease and may help preserve myocardial function in the case of coronary artery disease (CAD). Although collateral development is so important, its pathophysiology has not been fully elucidated. Till now, no study has investigated the relationship between Fibroblast growth factor-21(FGF-21) and coronary collateral.

Objective:This study aims to investigate the pathophysiology of coronary collateral development.

Methods:In our study, which we planned as a case-control, 60 consecutive patients with ≥90 stenosis in at least one large coronary artery as a result of coronary angiography (CAG) and 30 patients with normal coronary angiography were included in the study cross-sectional. Demographic, echocardiographic and laboratory data were recorded. Coronary collateral circulation was evaluated using the Rentrop-Cohen method. FGF-21 levels were measured in all individuals.

Results:In the analysis, no significant difference was observed between the two groups in basic biochemical parameters other than HDL (p>0.05 for all). FGF-21 level was statistically significantly higher in the patient group compared to the control group (p: 0.003). Also, the FGF-21 level was found to be statistically significantly higher in the good collateral circulation group than the poor (p:0.006). Univariate and multivariate logistic regression analysis was performed to predict the presence of collateral. We found that FGF-21(p=0.006), and C-reactive protein (p=0.020) predicted the presence of collateral independently.

Conclusion:Collateral formation and cardiac prognosis are closely related. Our study is the first to investigate the relationship between collateral formation and FGF-21. Our study showed that the FGF-21 level is an independent predictor of collateral formation. In addition, there was a significant difference between bad and good collateral formation regarding FGF-21 levels.

Objective::Endothelial cells (ECs) can provide cell protection for cardiomyocytes (CMs) under hypoxia-reoxygenation (HR) conditions by secreting derived factors. This study aimed to explore the role of curcumin (CUR) in ECs for protecting CMs from HR injury.

Methods::A co-culture system for ECs and CMs was set up, and subjected to HR. The transcription, expression, and secretion of FGF2 were detected by RT-qPCR, western blot, and ELISA, respectively. siRNAs specifically targeting FGF2 were transfected into ECs. FGF2 receptor- specific inhibitors (AZD4547) were used to treat CMs.

Results::The co-culture with ECs did not affect the proliferation of CMs, while CUR and ECs co-culture had a synergistic effect on promoting the proliferation of CMs in HR. Furthermore, the co-culture with ECs did not affect the apoptosis and autophagy of CMs in HR. However, the co-culture of ECs after CUR treatment inhibited the apoptosis and autophagy of CMs in HR. CUR treatment significantly enhanced FGF2 mRNA, protein, and secretion levels of ECs in HR. In addition, CUR treatment increased FGF2 levels in the CMs medium in the ECs and CMs co-culture system. The reduction of FGF2 levels in the medium and the inhibition of FGF2 receptors significantly inhibited the proliferation of CMs and significantly promoted the apoptosis and autophagy of CMs in HR.

Conclusion::Focusing on the protective effects of CUR and ECs on cardiomyocytes is of great significance for the treatment of clinical myocardial HR injury.

Aim:An analysis of bioinformatics and cell experiments was performed to verify the relationship between gasdermin D (GSDMD), an executive protein of pyroptosis, and Alzheimer's disease (AD).

Methods:The training set GSE33000 was utilized to identify differentially expressed genes (DEGs) in both the AD group and control group, as well as in the GSDMD protein high/low expression group. Subsequently, the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) regression analysis were conducted, followed by the selection of the key genes for the subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The association between GSDMD and AD was assessed and confirmed in the training set GSE33000, as well as in the validation sets GSE5281 and GSE48350. Immunofluorescence (IF) was employed to detect the myelin basic protein (MBP), a distinctive protein found in the rat oligodendrocytes (OLN-93 cells). A range of concentrations (1-15 µmol/L) of β-amyloid 1-42 (Aβ1-42) were exposed to the cells, and the subsequent observations were made regarding cell morphology. Additionally, the assessments were conducted to evaluate the cell viability, the lactate dehydrogenase (LDH) release, the cell membrane permeability, and the GSDMD protein expression.

Results:A total of 7,492 DEGs were screened using GSE33000. Subsequently, WGCNA analysis identified 19 genes that exhibited the strongest correlation with clinical traits in AD. Additionally, LASSO regression analysis identified 13 key genes, including GSDMD, AFF1, and ATOH8. Furthermore, the investigation revealed that the key genes were associated with cellular inflammation based on GO and KEGG analyses. Moreover, the area under the curve (AUC) values for the key genes in the training and validation sets were determined to be 0.95 and 0.70, respectively. Significantly, GSDMD demonstrated elevated levels of expression in AD across both datasets. The positivity of MBP expression in cells exceeded 95%. As the concentration of Aβ1-42 action gradually escalated, the detrimental effects on cells progressively intensified, resulting in a gradual decline in cell survival rate, accompanied by an increase in lactate dehydrogenase release, cell membrane permeability, and GSDMD protein expression.

Conclusion:The association between GSDMD and AD has been observed, and it has been found that Aβ1-42 can induce a significant upregulation of GSDMD in OLN-93 cells. This suggests that Aβ1-42 has the potential to induce cellular pyroptosis and can serve as a valuable cellular pyroptosis model for the study of AD.

Background:Thyroid Cancer (TC) is an endocrine organ malignancy that has become more common in recent decades. Vernodalin (VN), a cytotoxic sesquiterpene, has been reported to exhibit anticancer properties against human breast and liver cancer cells. However, no study has explored the efficacy of VN with respect to its antiproliferative and apoptotic action on human Papillary Thyroid Cancer cells (PTC).

Objective:The study intended to examine the antitumor and antiproliferative effects of VN and the apoptosis mechanisms underlying its action on TPC-1 human PTC cells.

Methods:In this study, we examined the VN cell viability by MTT assay; performed ROS measurement by DCFH staining method, MMP identification by Rh-123 staining method, and apoptotic morphological assay by employing AO/EB and DAPI stain method, and further, p38 MAPK/ERK/JNK cell proliferation markers were determined by western blotting technique.

Results:The findings showed that VN could inhibit the growth of PTC cells by increasing intracellular ROS, damaging MMP, and stimulating apoptosis in a concentration-dependent manner. The study demonstrated how VN inhibited TPC-1 cell viability by causing ROS-induced cell death via the MAPK signaling pathway.

Conclusion:VN may serve as an agonist to impact apoptosis in PTC cells. In human PTC, VN could play an effective role in chemotherapy. More studies pertaining to animal tumor models are needed to prove its anti-cancer effectiveness in vivo.