Pretreatment with rosavin attenuates PM2.5‐induced lung injury in rats through antiferroptosis via PI3K/Akt/Nrf2 signaling pathway

Abstract

Inflammation and oxidative stress caused by fine particulate matter (PM2.5) increase the incidence and mortality rates of respiratory disorders. Rosavin is the main chemical component of Rhodiola plants, which exerts anti‐oxidative and antiinflammatory effects. In this research, the potential therapeutic effect of rosavin was investigated by the PM2.5‐induced lung injury rat model. Rats were instilled with PM2.5 (7.5 mg/kg) suspension intratracheally, while rosavin (50 mg/kg, 100 mg/kg) was delivered by intraperitoneal injection before the PM2.5 injection. It was observed that rosavin could prevent lung injury caused by PM2.5. PM2.5 showed obvious ferroptosis‐related ultrastructural alterations, which were significantly corrected by rosavin. The pretreatment with rosavin downregulated the levels of tissue iron, malondialdehyde, and 4‐hydroxynonenal, and increased the levels of glutathione. The expression of nuclear factor E2‐related factor 2 (Nrf2) was upregulated by rosavin, together with other ferroptosis‐related proteins. RSL3, a specific ferroptosis agonist, reversed the beneficial impact of rosavin. The network pharmacology approach predicted the activation of rosavin on the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway. LY294002, a potent PI3K inhibitor, decreased the upregulation of Nrf2 induced by rosavin. In conclusion, rosavin prevented lung injury induced by PM2.5 stimulation and suppressed ferroptosis via upregulating PI3K/Akt/Nrf2 signaling pathway.

Astaxanthin alleviates fine particulate matter (PM2.5)-induced lung injury in rats by suppressing ferroptosis and apoptosis

“…Several previous studies have revealed that PM 2.5 can increase the uptake and storage of iron in cells, manifested by increased TFRC and FTH1 expression levels, ultimately accumulating iron in cells. 15,46 The same results were obtained in our study, where TFRC and FTH1 expression levels rose significantly in lung tissue after PM 2.5 exposure, and this situation was significantly alleviated after ASX intervention. SLC7A11, a cystine/glutamate xCT transport protein, is involved in forming and releasing GSH, which is crucial for the occurrence and development of ferroptosis.…”

“…43,44 This indicated that there may be a link between ferroptosis and lung damage caused by PM 2.5 , which has also been confirmed in previous studies. [45][46][47] Therefore, we examined the iron accumulation level in lung tissue and the iron deathrelated protein expression to explore whether ASX can protect against PM 2.5 -induced lung injury by inhibiting ferroptosis. Our study found that the iron content significantly increased in the rat lung tissue after PM 2.5 exposure, and ASX intervention could reduce this increase.…”

Rosavin: Research Advances in Extraction and Synthesis, Pharmacological Activities and Therapeutic Effects on Diseases of the Characteristic Active Ingredients of Rhodiola rosea L.

“…Pretreatment with Rosavin reduced the levels of tissue iron and MDA and increased glutathione levels in the lung tissue. Mechanistic studies showed that Rosavin upregulated the expression of Nrf2 and other ferroptosis-related proteins, whereas a specific ferroptosis agonist RSL3 was able to reverse the protective effect of Rosavin and the intracellular phosphatidylinositol kinase (PI3K) inhibitor LY294002 decreased the upregulation of Nrf2 induced by Rosavin [62]. The study suggests that Rosavin can prevent PM2.5-induced lung injury through antiferroptosis via the PI3K/Akt/Nrf2 signaling pathway.…”

“…In the current studies, the gavage dosage of Rosavin is approximately 50-200 mg/kg [45,62], with a maximum dosage of 360 mg/kg [38]; most intraperitoneal doses are within 10 mg/kg [56,68], with a maximum dosage of 30 mg/kg [36]. However, there are no studies to identify Rosavin's toxicity, and the systemic toxicological analysis in the liver and kidney after using Rosavin is still unclear.…”

Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis

“…Tectoridin, a flavonoid from the rhizome of Belamcanda chinensis, activates the Nrf2 signaling pathway to prevent ferroptosis in lung damage [141]. Similarly, rosavin, a key glycoside from Rhodiola plants, protects against PM2.5-induced lung injury by activating the PI3K/Akt/Nrf2 pathway to inhibit ferroptosis [142]. Astragaloside IV (Ast-IV), a principal glycosidic molecule found in astragalus, effectively modulates ferroptosis and curbs iron-dependent ROS buildup in ALI triggered by PM2.5.…”