Ammopiptanthus nanus (M. Pop.) Cheng f. stem ethanolic extract ameliorates rheumatoid arthritis by inhibiting PI3K/AKT/NF-κB pathway-mediated macrophage infiltration.

Ammopiptanthus nanus (M. Pop.) Cheng f. (A. nanus), a traditional Kirgiz medicinal plant, its stem has shown potential in treating rheumatoid arthritis (RA) in China, either through oral medication or by topical application directly to the affected joints, but its underlying mechanism of action remains unexplored. The purpose of this study is to elucidate pharmacological mechanism of A. nanus in ameliorating RA using a comprehensive approach that combines network pharmacology, molecular docking and experimental evaluations. Firstly, the major constituents of A. nanus stem ethanolic extract were identified and quantified by High-Performance Liquid Chromatography (HPLC). Disease target data from Gene Cards database was then used to define RA-associated targets. A protein-protein interaction (PPI) network was created via STRING database. The DAVID database powered gene ontology (GO) function and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to gain functional insights. In vitro, RAW264.7 cells were treated with A. nanus to investigate the roles of target proteins and pathways during lipopolysaccharide (LPS) - induced inflammation. Immunofluorescence assays were performed to assess the effects of A. nanus on macrophage infiltration. The key targets and signalling pathways were validated using enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), molecular docking, immunohistochemical analysis, western blotting and immunofluorescence. Finally, the therapeutic potential of A. nanus in RA was evaluated in a carrageenan-induced rat model. Network analysis identified 31 potential targets of A. nanus associated with RA, including 10 hub targets. KEGG analysis highlighted the involvement of PI3K/AKT signaling pathway. In vivo experiments demonstrated that A. nanus treatment significantly protected against carrageenan-induced inflammatory paw tissue and attenuated macrophage infiltration. Both in vivo and in vitro experiments confirmed that A. nanus significantly downregulated the protein expression of COX-2, iNOS and IL-1β, and inhibited PI3K/AKT/NFκB pathway, which are closely linked to RA. Furthermore, molecular docking and cellular thermal shift assay revealed that licoflavanone showed a strong binding affinity with key targets. In summary, this study provides the first evidence of the potent anti-inflammatory activity of A. nanus in experimental RA. The mechanism of action appears to involve inactivation of the PI3K/AKT/NF-κB pathway-mediated macrophage infiltration. These findings indicate that A. nanus has significant potential as a therapeutic potential agent for RA treatment and offer novel insights for future research and drug development in this field.

Yao Y ，Wang J ，Zhang H ，Peng T ，Sun Y ，Zhang R ，Meng X ，Lu X ，Gao Y ，Jin Y ，Zhang Y ，Chen L ... -  《-》

Sappanone A attenuates rheumatoid arthritis via inhibiting PI3K/AKT/NF-κB and JAK2/STAT3 signaling pathways in vivo and in vitro.

Sappanone A (SA), a bioactive compound in Caesalpinia sappan L., has anti-inflammation, antioxidant, and bone protection activities. But its effect on rheumatoid arthritis (RA) and the underlying mechanism are incompletely understood. Candidate targets of SA against RA were screened by network pharmacology and further validated by molecular docking. CIA rats and HFLS-RA were used to explore the effect and mechanism of SA on RA in vivo and in vitro, respectively. Macroscopic inspection (body weight, paw swelling, arthritis index), histological examination and micro-CT were used to evaluate the anti-RA effect of SA in vivo. ELISA and western blotting were used to explore the effects of SA on the levels of inflammatory cytokines in serum and the phosphorylation level of key proteins in tissue, respectively. Moreover, agonists and inhibitors of key proteins were used on HFLS-RA to explore the underlying mechanism of SA. Finally, immunofluorescence was utilized to explore the effects of SA on apoptosis in HFLS-RA. SA significantly reduced arthritis index, alleviated paw swelling, and improved inflammatory cell infiltration and cartilage degradation in CIA rats. The levels of the pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-17 were decreased while the level of the anti-inflammatory cytokine IL-10 was promoted by SA. The SA also down-regulated the protein phosphorylation levels of JAK2, STAT3, PI3K, AKT and p65 in vivo and in vitro. Furthermore, SA reversed the agonist-induced increase in phosphorylation levels of PI3K/AKT/NF-κB and JAK2/STAT3 pathway-related proteins. In addition, SA acted on the phosphorylation levels of these proteins in the same trend as the pathway inhibitors and dose-dependently reduced the phosphorylation levels of PI3K/AKT/NF-κB pathway proteins. The immunofluorescence results suggested that SA could promote apoptosis in HFLS-RA. SA could inhibit inflammatory symptoms and bone destruction in CIA, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB and JAK2/STAT3 pathways. Hence, SA could be developed as a potential anti-RA therapeutic drug.

Deng C ，Sun S ，Zhang H ，Liu S ，Xu X ，Hu Y ，Ma H ，Xin P ... -  《-》

Based on network pharmacology, molecular docking and experimental verification to reveal the mechanism of Andrographis paniculata against solar dermatitis.

Solar dermatitis (SD) is an acute, damaging inflammation of the skin caused by UV exposure, especially UVB. Therefore, the discovery of novel anti-SD therapeutic agents is crucial. Andrographis paniculata (AP) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that AP has potential therapeutic effects on SD. However, the therapeutic mechanisms of AP against SD have not yet been completely elucidated, which is an unexplored field. This study employed network pharmacology, molecular docking and experimental verification to ascertain the active constituents, possible targets, and biological pathways associated with AP in the treatment of SD. AP-related active ingredients and their potential targets were screened from TCMSP and Swiss Target Prediction database, respectively. Potential therapeutic targets of SD were collected using the GeneCards, DrugBank and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (D-C-T-D) through Cytoscape to identify the major components, core targets of AP against SD. Next, the GO and KEGG pathway was identified by the David database of AP in the treatment of SD. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. In this paper, we used UVB-irradiated HaCaT keratinocytes as an in vitro model and established the dorsal skin of UVB-irradiated ICR mice as an in vivo model to explore the mechanism for further verification. There were 24 active components and 63 related target genes in AP against SD. PPI analysis showed that AKT-1, TNF-α, IL6, MMP9, EGFR, and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis revealed that the PI3K-Akt signaling pathway may be central in the anti-SD system. The molecular docking results showed that the main active components of AP have strong binding affinity with hub genes. In vitro results showed that WG had a protective effect on UVB-intervened HaCat cells. Western blot analysis showed that WG intervention achieved anti-inflammation by reducing the phosphorylated expression of AKT, PI3K proteins in the PI3K-AKT signaling pathway and downregulating the expression of TNF-α, IL-6, EGFR. Furthermore, Histological analysis confirmed that administration of WG to ICR mice significantly ameliorated UVB-induced skin roughness, epidermal thickening, disturbed collagen fiber alignment and wrinkles. Meanwhile, immunohistochemistry showed that administration of WG to ICR mice significantly reduced UVB-induced expression of MMP9, MPO, F4/80 in the skin. These results provide new insights into the contribution of WG to the development of clinical treatment modalities for UVB-induced SD. The crucial element in the fight against SD is WG, with the primary route being PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro and vivo experiments showed that WG could inhibit the expression level of the hub genes by inhibiting the PI3K/Akt pathway. In summary, the information presented in this study indicates that WG might be utilised as a treatment for UVB-induced SD.

Deng Q ，Chen W ，Deng B ，Chen W ，Chen L ，Fan G ，Wu J ，Gao Y ，Chen X ... -  《-》

Ferulic acid from Angelica sinensis (Oliv.) Diels ameliorates lipid metabolism in alcoholic liver disease via AMPK/ACC and PI3K/AKT pathways.

Lu J ，Wang C 《-》

Network pharmacology and experimental validation for deciphering the action mechanism of Fritillaria cirrhosa D. Don constituents in suppressing breast carcinoma.

Bhat BA ，Rashid Mir W ，Alkhanani M ，Almilaibary A ，Mir MA ... -  《-》