Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach

Abstract

Background and Purpose: Sepsis is a life-threatening condition associated with secondary multiple organ injury. Acute lung injury (ALI) caused by sepsis has high morbidity and mortality in critical care units. Lianhua Qingwen (LHQW) is a traditional Chinese medicine composing of 11 herbs and 2 medicinal minerals. LHQW exhibits anti-inflammatory activity and is effective in treating pneumonia. Our study aimed to evaluate the effect of LHQW on sepsis-induced ALI and its underlying mechanism.Materials and Methods: A network pharmacology approach was used to predict the bioactive components and effective targets of LHQW in treating ALI. We established ALI model C57/BL6 mice via an intraperitoneal injection of LPS and inhibited p53 expression by pifithrin-α, in order to validate the mechanism by which LHQW exerted protective role in ALI. Hematoxylin-eosin staining was conducted to assess the severity of lung injury. The severity of inflammation was evaluated based on MPO (myeloperoxidase) activity. TUNEL assay was employed to detect apoptotic cells. The levels of p53 and caspase-3 were tested by immunohistochemical staining and Western blotting. The expression levels of Bcl-2, Bax, cytochrome C and caspase-9 were detected by Western blotting.Results: A total of 80 genes were associated with LHQW in the treatment of ALI. After PPI network construction, four active components (quercetin, luteolin, kaempferol and wogonin) and 10 target genes (AKT1, TP53, IL6, VEGFA, TNF, JUN, STAT3, MAPK8, MAPK1, and EGF) were found to be essential for ALI treatment. GO and KEGG analyses indicated that apoptosis pathway was mainly involved in the LHQW-ALI network. Animal experiments showed that LHQW was able to attenuate LPS-induced ALI, and medium-dose LHQW exhibited the most prominent effect. LHQW could inhibit the overexpression of p53 induced by LPS and suppress p53-mediated intrinsic apoptotic pathways by decreasing the levels of Bax, caspase-3 and caspase-9, increasing the expression of Bcl-2, and attenuating the release of cytochrome C in ALI mice.Conclusion: This study reveals that LHQW may alleviate LPS-induced ALI via inhibiting p53-mediated intrinsic apoptosis pathways.

Quercetin and Luteolin may be the New Effective Drugs for Radiation Pneumonitis: Based on a Systems Pharmacology

“…Inhibiting the TP53 -mediated endogenous apoptotic pathway can reduce the inflammatory response in acute lung injury. 15 Moreover, pulmonary fibrosis with lung cancer is not uncommon in the clinical real world. The relevant literature proves that some genes including the TP53 gene may be closely related to pulmonary fibrosis and lung cancer.…”

Antiviral Treatment Options for Severe Fever with Thrombocytopenia Syndrome Infections

“…According to the epidemic and clinical characteristics of SFTS, the disease belongs to the traditional Chinese medicine (TCM) category of “spring-warm syndrome,” “damp-warm syndrome,” or “summer-warm syndrome.” There are more than ten TCMs suggested to prevent and treat SFTS, according to an expert agreement on diagnosis and treatment of SFTS using TCM and Western medicine in China: Shengmai injection, Shenfu injection, Qingkailing injection, Xuebijing injection, Xiyanping injection, Reducing injection, Lanqin oral liquid, and Lianhua Qingwen capsule are among these TCMs. Lianhua Qingwen capsule contains 13 kinds of Chinese herbal medicine [ 61 ] and has the clinical indications of clearing heat, dispersing lungs, and detoxifying. Sterculia lychnophora , Phellodendri Chinensis cordex , Gardeniae fructus , Scutellariae radix , and Isatidis radix are all ingredients in oral liquid, a Chinese patent medicine.…”

Classic mechanisms and experimental models for the anti‐inflammatory effect of traditional Chinese medicine

“… 76 Lianhua Qingwen (LHQW), the world‐famous TCM used against COVID‐19, could effectively treat sepsis‐induced acute lung injury in an LPS‐induced systemic inflammation model. 81 Additionally, cecal ligation and puncture (CLP) also serves as a classical experimental model for systemic inflammation. CLP allows intestinal contents and bacteria to enter the abdominal cavity, causing abdominal infections and eventually systemic inflammation, and Shen‐Fu Decoction has been shown to ameliorate sepsis‐induced organic damage and mortality in a CLP model.…”

“…After intraperitoneally or intravenously injection, the compounds activate a systemic inflammation response, promote inflammatory cytokine secretion, regulate inflammation related signaling pathways, release ROS and eventually cause multiple organ damage 76 . Lianhua Qingwen (LHQW), the world‐famous TCM used against COVID‐19, could effectively treat sepsis‐induced acute lung injury in an LPS‐induced systemic inflammation model 81 . Additionally, cecal ligation and puncture (CLP) also serves as a classical experimental model for systemic inflammation.…”