Protective Effects of Aqueous Extracts of the Herb of Paederia scandens (Lour.) Merr. against HCl/EtOH-Induced Gastric Ulcer in Rats: Involvement and Inhibitors’ Identification of NF-κB Signaling

Abstract

Paederia scandens (Lour.) Merr. (P. scandens), as an edible and medicinal herb, is commonly used for treating gastric ulcer in China; however, its mechanistic and effective substances’ studies remain limited. This study aimed to investigate the antigastric ulcer effects of aqueous extracts of P. scandens (PS-AE) and explore the involvement of NF-κB signaling in this effect. In addition, the study aimed to identify the effective substances by exploring NF-κB inhibitors. The main components of PS-AE were identified using an UPLC-MS method. HCl/EtOH-induced acute gastric ulcer in rats, and LPS-stimulated RAW264.7 cells were used to determine the antigastric ulcer effects of PS-AE in vivo and in vitro, respectively. Histopathological changes of the ulcer tissues were observed using staining methods of HE and PAS; secretions of inflammatory cytokines and oxidative stress indexes were measured using biochemical test kits; protein levels of NF-κB signaling pathway-related molecules were measured using Western Blot. NF-κB inhibitors’ identification in P. scandens was performed by developing HipHop pharmacophore model, and the results were further validated by molecular docking. In vivo, PS-AE significantly attenuated gastric ulcer in rats; reduced inflammation by adjusting the inflammatory cytokines TNF-α, IL-1β, and IL-6 levels; and induced oxidative stress can be alleviated via adjusting the levels of SOD, MDA, and GSH-Px. In addition, PS-AE may play an anti-inflammatory role mainly through NF-κB signaling pathway. Following pharmacophore modeling and molecular docking, 13 potential inhibitors targeting NF-κB were identified. In addition, in vitro, PS-AE and paederoside could significantly inhibit the activation of NF-κB p65 and the productions of downstream cytokines including NO, TNF-α, and IL-6. PS-AE protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway. 13 potential NF-κB-targeting inhibitors are probably effective substances contributing to the herb’s pharmacological effect. In practical application, Paederia scandens, a traditional food and medicinal plant, possessed diversified chemical components and multiple pharmacological activities (anti-inflammatory, bacteriostasis, and antioxidative.). In China, P. scandens has been used as a traditional medicine to treat gastritis for hundreds of years, and it may be a potentially effective dietary product to improve gastric ulcer. This study shows that P. scandens exerts protective effects on gastric ulcer damage induced by HCl/EtOH in rats, which is probably associated with its antioxidant effect and the inhibitory effects on levels of inflammatory mediators regulated by NF-κB signaling pathway, which provides pharmacological justifications for the functional food use of P. scandens for treating gastric disease.

Advances in the Chemical Components and Pharmacological Effects of Paederia Scandens

“…Comparative studies have highlighted the advantages of Paederia scandens over conventional synthetic analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) [22] . Unlike NSAIDs, which can cause adverse effects like gastrointestinal bleeding and renal toxicity with long-term use, The plant has shown a remarkably lower incidence of such side effects in both acute and chronic administration studies [1]. This suggests that Paederia scandens can be a safer alternative for managing pain, particularly for patients requiring long-term pain management.…”

“…These compounds also inhibit the activity of H+/K+-ATPase, the enzyme responsible for gastric acid secretion. By lowering acid secretion and bolstering the mucosal defenses, Paederia scandens effectively prevents the development of gastric ulcers [1,24] .…”

“…Historically, it has been employed to treat a wide range of ailments, making it a staple in herbal medicine preparations. In traditional Chinese medicine, the plant is primarily used for its reputed effects in alleviating symptoms associated with gastrointestinal disorders, reducing inflammation, and managing pain [1] . These traditional uses have garnered global attention, both locally and within the scientific community.…”

“…For gastrointestinal disorders, it is used to improve digestion, treat dysentery, and relieve abdominal pain. Its anti-inflammatory properties make it a common remedy for arthritis and rheumatism, highlighting its role in both pain and inflammation management [1,2] . Moreover, it is also utilized in formulations aimed at treating simple headaches, edema, and fever [1] .…”

“…Its anti-inflammatory properties make it a common remedy for arthritis and rheumatism, highlighting its role in both pain and inflammation management [1,2] . Moreover, it is also utilized in formulations aimed at treating simple headaches, edema, and fever [1] . The growing interest in Paederia scandens can be attributed to its diverse range of bioactive compounds, including iridoids, flavonoids, and triterpenoids, which are believed to confer its medicinal properties [3] .…”