Protective effect of puerarin against burn‑induced heart injury in rats

Abstract

The present study evaluated the potential protective effects of puerarin and its associated mechanism on burn-induced myocardial damage. A total of 40 healthy adult Wistar rats were randomly divided into four groups: i) Sham; ii) burn; iii) burn + puerarin; and iv) puerarin. Serum levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 were measured using ELISA. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were determined in myocardial homogenates using a commercial assay kit. TUNEL staining and western blot analysis of cleaved and pro-caspase-3 were also performed to assess apoptosis. Activation of p38-MAPK, ERK, JNK and AKT were measured using western blot analysis. Left ventricular systolic pressure, maximum rates of increase/decrease in left ventricular pressure, creatine kinase MB activity and cardiac troponin T levels were found to be altered in the burn group 12 h after burn, which were reversed by puerarin treatment. Injection of puerarin following burn injury also reduced heart water content. Serum levels of IL-1β, TNF-α and IL-6 were significantly higher in the burn group compared with those in the sham group. Puerarin treatment reduced serum levels of IL-1β, TNF-α and IL-6, in addition to reducing MPO activity and MDA levels in myocardial tissues. Puerarin inhibited the activation of caspase-3, p38, ERK and JNK following severe burn, but elevated Akt activation following severe burn. In conclusion, puerarin improved cardiac function in rats following severe burn injury, which may be due to reduced myocardial injury, inhibition of cardiomyocyte apoptosis and reduced oxidative inflammatory stress; the MAPK and AKT signaling pathways are proposed to the underlying mechanism of these findings.

Puerarin protects against sepsis-induced myocardial injury through AMPK-mediated ferroptosis signaling

“…Numerous studies have indicated that many traditional Chinese herbs have potent anti-inflammatory and antioxidant properties [ 12 – 15 ]. Due to various diseases, Puerarin can effectively reduce oxidative stress and inflammation in the myocardium [ 37 , 38 ]. In addition, through our research, we demonstrate that Puerarin significantly reduced oxidative stress indicators (MDA, GSH, and SOD) and inflammatory cytokines (TNF-α, IL-6, and IL-10) in the serum of LPS model rats.…”

Chinese Herbs and Repurposing Old Drugs as Therapeutic Agents in the Regulation of Oxidative Stress and Inflammation in Pulmonary Diseases

“…A growing number of studies have indicated that both exogenous and endogenous ROS participate in the pathogenesis of pulmonary disorders, such as ARDS, COPD, ↑Nrf2 translocation, ↑HO-1, ↓pulmonary vascular remodeling via inhibiting EndMT [87,237,238] ↓pulmonary fibrosis, ↓cyclin D1, ↓cyclin E1, ↓cyclin B1, ↓Bcl-2 protein, ↑p53, ↑p21, ↑cleaved caspase-3 protein [234] repress the adhesion of bacteria [235] ↑SOD, ↑catalase, ↑glutathione peroxidase ↓ type I collagen I, ↓endogenous TGF-β1, ↓α-SMA [236,238] ↓MAPK and NF-κB signaling pathways [40,237] ↓TNF-α, ↓IL-6, ↓IL-1β, ↓MCP-1 [237] Asiatic acid ↓pulmonary fibrosis [241,242] ↓TGF-β1, ↓Collagen I, ↓Collagen III, ↓α-SMA, ↓TIMP-1, ↓NLRP3 inflammasome, ↓Smads and ERK1/2 [242][243][244] ↓ROS, ↓neutrophil elastase (NE) activity, ↓MCP-1, ↓recruitment of inflammatory cells, ↓MAPKs, ↓NF-kB, ↑Nrf2, ↑HO-1, ↑SOD3, ↑catalase [41,243,244] Celastrol ↓NF-κB signaling pathway, ↓NLRP3 activity [245][246] ↓IL-8, ↓TNFα, ↓MCP -1, ↑SOD, ↑catalase, ↓Ednrb/Kng1 signaling pathway [248] ↓MMP 2/9, ↑Nrf2, ↑HO-1, ↑GSTs, ↑NQO1 [88] ↓Bax, ↓caspase-3 [249] Fisetin ↓TNFα, ↓PARP-1 [253] ↓neutrophils and macrophage infiltration, ↓MPO activity, ↓TLR4 expression, ↓NF-κB [254,255] ↑Nrf2, ↑HO-1, ↑glutathione peroxidase-2, ↑reduced glutathione, ↑SOD [89] Galangin ↓TGF-β1-ROS-MAPK pathway, ↓goblet cell hyperplasia, ↓collagen deposition, ↓α-SMA expression, ↓VEGF, ↓MMP-9 [257] ↓IL-4, 5, 13, 17, ↓TNF-α, ↓NO, ↓ROS, ↓EPO, ↓IgE, ↑IFN-γ, ↑PPARγ activity [258] Kaempferol ↓TAK1, ↓NF-κB, ↓MAPK, ↓cytokine production [45,262,264,265] ↓ROS …”

“… 88 Celastrol also reduced the protein levels of Bax and caspase-3 activity to induce anti-inflammatory and anti-apoptotic effects in burn-induced lung injury. 249 …”

Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation

“…Our findings demonstrated that celastrol was able to reduce both SARS-CoV-2 viral load and IL-6 production in two human cell lines, suggesting that this compound exerts anti-SARS-CoV-2 effects of clinical relevance to face the current pandemic. Several pharmacological applications of celastrol are associated with Covid-19 severity, including comorbidities such as obesity, diabetes, hypertension, and metabolic syndrome [95][96][97][98] , and pathological events such as non-homeostatic production of pro-inflammatory cytokines, thrombus generation, and formation of neutrophil extracellular traps [99][100][101] . Celastrol is currently under clinical trials to treat a variety of diseases, including different types of cancer, neurodegenerative disorders, and inflammatory conditions such as rheumatoid arthritis, psoriasis, and Crohn's disease [102][103][104][105][106] .…”