Exploration of Hanshi Zufei prescription for treatment of COVID-19 based on network pharmacology.

Objective: Network pharmacology combines drug and disease targets with biological information networks based on the integrity and systematicness of the interactions between drugs and disease targets. This study aims to explore the molecular basis of Hanshi Zufei formula for treatment of COVID-19 based on network pharmacology and molecular docking techniques. Methods: Using TCMSP, the chemical constituents and molecular targets of Atractylodis Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Pogostemonis Herba, Tsaoko Fructus, Ephedrae Herba, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, and Arecae Semen were investigated. The predicted targets of novel coronavirus were screened using the NCBI and GeneCards databases. To further screen the drug-disease core targets network, the corresponding target proteins were queried using multiple databases (Biogrid, DIP, and HPRD), a protein interaction network graph was constructed, and the network topology was analyzed. The molecular docking studies were also performed between the network's top 15 compounds and the coronavirus (SARS-CoV-2) 3CL hydrolytic enzyme and angiotensin conversion enzyme II (ACE2). Results: The herb-active ingredient-target network contained nine drugs, 86 compounds, and 49 drug-disease targets. Gene ontology (GO) enrichment analysis resulted in 1566 GO items (P < 0.05), among which 1438 were biological process items, 35 were cell composition items, and 93 were molecular function items. Fourteen signal pathways were obtained by enrichment screening of the KEGG pathway database (P < 0.05). The molecular docking results showed that the affinity of the core active compounds with the SARS-CoV-2 3CL hydrolase was better than for the other compounds. Conclusion: Several core compounds can regulate multiple signaling pathways by binding with 3CL hydrolase and ACE2, which might contribute to the treatment of COVID-19.

Hesperidin protects against cisplatin-induced cardiotoxicity in mice by regulating the p62-Keap1-Nrf2 pathway.

Hesperidin (HES) is an abundant and economical dietary bioflavonoid, and it has several pharmacological properties such as antioxidant activity and powerful cardiac protection. However, HES protection against cisplatin (CP)-induced cardiotoxicity and its mechanism have not been fully clarified. The current study was performed to further elucidate the mechanism of HES against CP-induced cardiotoxicity. Mice were orally administered HES (100 or 300 mg kg-1 day-1) for 7 consecutive days and then injected intraperitoneally (i.p.) with CP (5 mg kg-1) on days 3 and 6. On day 8, mice were anaesthetised with sodium pentobarbital (50 mg kg-1, i.p.), and blood and heart samples were collected for analysis. HES treatment reduced CP-induced cardiac pathologic damage and leakage of the myocardial markers cardiac troponin I (cTnI), creatine kinase (CK), and lactate dehydrogenase (LDH). HES treatment reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which is an oxidative product, and increased antioxidant marker levels including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). HES also reduced the CP-induced release of the inflammatory factors tumour necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, HES treatment up-regulated the expression of anti-apoptotic protein Bcl-2 and down-regulated the expression of pro-apoptotic proteins Bax and Caspase-3. HES treatment also improved the expression of pathway proteins p62 and Nrf2 and inhibited the increase in CP-induced Keap1 expression. Thus, HES may provide protection against CP cardiotoxicity through inhibiting oxidative stress, inflammation, and apoptosis, which may contribute to activation of the p62-Keap1-Nrf2 signalling pathway. These findings suggest that HES may be a promising protective agent against CP cardiotoxicity in future anticancer clinical practice.

Based on Activation of p62-Keap1-Nrf2 Pathway, Hesperidin Protects Arsenic-Trioxide-Induced Cardiotoxicity in Mice.

Background: Hesperidin (HES) is a flavonoid glycoside found in the tangerine peel and has antioxidant properties. Arsenic trioxide (ATO) is an anti-tumour drug; however, its serious cardiotoxicity limits its clinical application. In addition, the protection of HES against ATO-induced cardiotoxicity has not been explored. Objective: The study aims to investigate and identify the underlying effect and mechanism of HES on ATO-induced cardiotoxicity. Methods: Fifty mice were randomly assigned to five groups. Mice were orally given HES:100 or 300 mg/kg/day concurrently and given ATO intraperitoneal injections: 7.5 mg/kg/day for 1 week. Blood and heart tissues were collected for examination. Evaluated in serum was the levels of creatine kinase (CK), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI). In addition, evaluated in heart tissues were the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, cleaved-Caspase-3, p62, Kelch-like ECH-associated protein 1 (Keap1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The heart tissues were also examined for histopathology and mitochondrial ultrastructure. Results: Compared with the ATO group, the HES treatment groups reduced the levels of CK, LDH, cTnI, ROS, MDA, TNF-α, IL-6, Bax, Caspase-3, cleaved-Caspase-3 and Keap1 and enhanced the levels of SOD, GSH, CAT, Bcl-2, p62 and Nrf2. Conclusions: The results demonstrate that HES protects against ATO-induced cardiotoxicity, through inhibiting oxidative stress, and subsequent inflammation and apoptosis. The underlying results are closely related to the regulation of the p62-Keap1-Nrf2 signalling pathway.

Gentianella acuta mitigates cardiovascular damage and inflammation in diet-induced hypercholesterolaemic rats.

Gentianella acuta (G. acuta) has been widely used as a traditional medicine by Chinese Mongolian populations for the treatment of heart diseases and has also been tested in modern pharmacological experiments. However, the effects of G. acuta on cardiovascular damage and inflammation under conditions of hypercholesterolaemia remain unclear. The present study investigated the effects and mechanisms of the water extract of G. acuta on cardiovascular damage and inflammation caused by a high-cholesterol diet. Male Sprague-Dawley rats were fed a high-cholesterol diet for 4 weeks to establish the hypercholesterolaemia rat model, and they were administered physiological saline or 1.2 g/kg of G. acuta by gavage starting from the 15th day. After the last administration, the blood, heart and thoracic aorta samples were collected and examined. It was revealed that G. acuta treatment could ameliorate cardiomyocyte disorder and thoracic aortic vessel wall damage, reduce serum lipid levels and inflammatory factors and improve heart function. Compared with the Model group, the serum levels of triglycerides, total cholesterol, low-density lipoprotein and tumour necrosis factor-α were decreased, and the high-density lipoprotein and interleukin-10 levels were increased in the Model-G group. Moreover, in both the heart and thoracic aorta, G. acuta reduced the expression and phosphorylation of inhibitor of nuclear factor kappa-B kinase ß (IKKß), inhibitor of NF-κB-α (IκBα) and p-nuclear factor kappa-B (NF-κB). Therefore, G. acuta may exert an inhibitory effect on the IKK/IκB/NF-κB signalling pathway to protect the heart and thoracic aorta in hypercholesterolaemic rats.