Network analysis, in vivo, and in vitro experiments identified the mechanisms by which Piper longum L. [Piperaceae] alleviates cartilage destruction, joint inflammation, and arthritic pain

Abstract

Osteoarthritis (OA) is characterized by irreversible joint destruction, pain, and dysfunction. Piper longum L. [Piperaceae] (PL) is an East Asian herbal medicine with reported anti-inflammatory, analgesic, antioxidant, anti-stress, and anti-osteoporotic effects. This study aimed to evaluate the efficacy of PL in inhibiting pain and progressive joint destruction in OA based on its anti-inflammatory activity, and to explore its potential mechanisms using in vivo and in vitro models of OA. We predicted the potential hub targets and signaling pathways of PL through network analysis and molecular docking. Network analysis results showed that the possible hub targets of PL against OA were F2R, F3, MMP1, MMP2, MMP9, and PTGS2. The molecular docking results predicted strong binding affinities for the core compounds in PL: piperlongumine, piperlonguminine, and piperine. In vitro experiments showed that PL inhibited the expression of LPS-induced pro-inflammatory factors, such as F2R, F3, IL-1β, IL-6, IL-17A, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NOS2, PTGS2, PGE2, and TNF-β. These mechanisms and effects were dose-dependent in vivo models. Furthermore, PL inhibited cartilage degradation in an OA-induced rat model. Thus, this study demonstrated that multiple components of PL may inhibit the multilayered pathology of OA by acting on multiple targets and pathways. These findings highlight the potential of PL as a disease-modifying OA drug candidate, which warrants further investigation.

Network Pharmacology and Experimental Verifications to Discover Scutellaria baicalensis Georgi’s Effects on Joint Inflammation, Destruction, and Pain in Osteoarthritis

“…Therefore, this study investigated whether SB is a promising multicomponent material that can ameliorate the multi-pathology of OA through computational prediction and experimental validation. For pharmacological prediction, we used network pharmacology analysis, a technique that predicts the complex relationships between multiple components and multiple targets in natural products from a network science perspective [29][30][31][32][33][34][35]. This method allows more precise predictive information to be derived about the drug-targetdisease relationship, which provides the basis for designing optimized experiments to explore the mechanisms of action of multicomponent herbal medicines, including SB.…”

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study

“…In the context of this research topic, the anti-inflammatory activity of natural products is particularly worthy of attention due to their low toxicity, ease of management of long-standing diseases, and multifaceted targeted modulation of inflammation by multiple active components [9][10][11]. In particular, east Asian herbal medicine (EAHM) has accumulated extensive human dosage information with historical context for hundreds of millions of people throughout East Asia and has recently been studied from a modern perspective [12][13][14][15][16][17][18]. Consequently, this group of materials has potential comparative advantages over other DMOAD natural product candidates in terms of safety and efficacy.…”