Impact of protocatechuic acid on alleviation of pulmonary damage induced by cyclophosphamide targeting peroxisome proliferator activator receptor, silent information regulator type-1, and fork head box protein in rats

Abstract

Cyclophosphamide (CP) is a chemotherapeutic agent that causes pulmonary damage by generating free radicals and pro-inflammatory cytokines. Pulmonary damage has a high mortality rate due to the severe inflammation and edema occurred in lung. PPARγ/Sirt 1 signaling has been shown to be cytoprotective effect against cellular inflammatory stress and oxidative injury. Protocatechuic acid (PCA) is a potent Sirt1 activator and exhibits antioxidant as well as anti-inflammatory properties. The current study aims to investigate the therapeutic impacts of PCA against CP-induced pulmonary damage in rats. Rats were assigned randomly into 4 experimental groups. The control group was injected with a single i.p injection of saline. CP group was injected with a single i.p injection of CP (200 mg/kg). PCA groups were administered orally with PCA (50 and 100 mg/kg; p.o.) once daily for 10 consecutive days after CP injection. PCA treatment resulted in a significant decrease in the protein levels of MDA, a marker of lipid peroxidation, NO and MPO along with a significant increase in GSH and catalase protein levels. Moreover, PCA downregulated anti-inflammatory markers as IL-17, NF-κB, IKBKB, COX-2, TNF-α, and PKC and upregulated cytoprotective defenses as PPARγ, and SIRT1. In addition, PCA administration ameliorated FoxO-1 elevation, increased Nrf2 gene expression, and reduced air alveoli emphysema, bronchiolar epithelium hyperplasia and inflammatory cell infiltration induced by CP. PCA might represent a promising adjuvant to prevent pulmonary damage in patients receiving CP due to its antioxidant and anti-inflammatory effects with cytoprotective defenses.

Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC‐MS/MS methods for simultaneous determination of 19 main active components

“…The benefits of G. biloba and its preparations in the prevention and treatment of cardiovascular diseases mainly derive from the effective chemical components such as flavonoids and terpenoid lactones. In this study, through data mining and network pharmacology analysis of relevant literature, we found that the organic acid components (protocatechuic acid, caffeic acid, chlorogenic acid, and gallic acid), flavonoid components (quercetin‐3‐O‐glucoside, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, isorhamnetin‐3‐O‐rutinoside, isorhamnetin‐3‐O‐glucoside, apigenin‐7‐O‐glucoside, and apigenin), and terpenoid lactones (bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J) had different effects such as anti‐inflammatory and anti‐oxidative activities, protecting the nervous system, changing blood rheology, and so on 22–50 . These components may be the potential active substance basis of its anti‐IS effect, so they were included in the scope of analysis and investigation of the active components of GBE against IS.…”

“…Quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, and isorhamnetin‐3‐O‐rutinoside can inhibit the PI3K‐Akt, NF‐κB, and other signalling pathways and reduce cardiovascular and cerebrovascular injuries 37–44 . The ingredients such as caffeic acid, protocatechuic acid, gallic acid, bilobalide, ginkgolide A, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐glucoside, and isorhamnetin‐3‐O‐rutinoside also have anti‐oxidative, free radical‐scavenging, and anti‐apoptotic effects 22–50 . Consequently, it was deduced that anti‐inflammatory, anti‐oxidative, anti‐apoptotic, and other activities are the main anti‐IS effects of GBE.…”

“…Based on literature data mining, flavonoid‐glycosides and terpenes in G. biloba are the main components of its pharmacological activities such as anti‐inflammatory, antioxidant, blood circulation‐improving, and platelet anti‐aggregatory activities 22–51 . Therefore, the above ingredients were selected for the study of the active ingredients of GBE against IS, as shown in Table 1.…”

Anti-Inflammatory and Protective Effects of Water Extract and Bioferment from Sambucus nigra Fruit in LPS-Induced Human Skin Fibroblasts

“…It also showed strong anti-inflammatory potential in different in vitro models and suppressed LPS-induced inflammation by affecting different metabolic pathways, including the SIRT1/ NF-kappaB and MAPK signaling pathways [ 46 , 47 ]. An in vivo study also confirmed its ability to alleviate inflammation, e.g., PA downregulated inflammatory markers such as IL-17, NF-κB, IKBKB, COX-2, and TNF-α in rats with induced pulmonary damage [ 48 ] and lowered the level of proinflammatory cyclooxygenase-2 in the brain and liver of rats with carbon tetrachloride-induced cytotoxicity [ 49 ]. PA is also a potent antioxidant, and it has been shown that it significantly decreases the level of malondialdehyde (MDA), a marker of lipid peroxidation, and increases the level of GSH and catalase, enzymes belonging to internal antioxidant system [ 48 ].…”

Gastrodin ameliorates neuroinflammation in Alzheimer’s disease mice by inhibiting NF-κB signaling activation via PPARγ stimulation

“…In terms of antiinflammation, PPARγ is expressed in both monocytes macrophages, which, after activation, inhibits monocytes or macrophages from producing inflammatory mediators IL-1β, IL-6, TNF-α, as well as inducible nitric oxide synthase [16]. PPARγ inhibits the proinflammatory gene expressions at the transcriptional level by antagonizing the activities of transcription factors like NF-κB, AP-1 and STAT1 [17], and its agonists can effectively inhibit the inflammatory molecule production mediated by microglia and astrocytes in the central nervous system [18,19]. GAS, as a small-molecule liposoluble monomer compound extracted from Rhizoma Gastrodiae with good druggability, has recently been approved as a therapeutic drug.…”