This study investigated the therapeutic efficacy of Higenamine (HG), an extract from Monkshood, in the context of rheumatoid arthritis (RA). As an autoimmune disorder, RA is characterized by significant bone destruction primarily driven by inflammatory processes. Analysis demonstrated marked infiltration of macrophages within RA immune cells. HG inhibited iNOS, TNF-α, and IL-1β expression in M1 macrophages while enhancing IL-10, Arg-1, and MCP-1 levels in M2 macrophages. Flow cytometry confirmed HG's capacity to promote the M1 to M2 macrophage transition. Transcriptomic analysis established connections between HG, RA, osteoclast differentiation, and the THBS-1/TGF-β signaling pathway, indicating its potential to mitigate bone destruction. In vitro studies showed that HG diminished osteoclast differentiation and downregulated V-ATPase, Ctsk, TRAP, THBS-1, and TGF-β expression. In vivo, HG alleviated arthritis symptoms in collagen-induced arthritis (CIA) mice, reduced M1 macrophage accumulation, modulated THBS-1/TGF-β signaling, and lessened joint damage. Micro-CT imaging and staining corroborated the reduction in osteoclast numbers and improvement in bone homeostasis. In summary, HG presents a promising therapeutic avenue for RA and associated bone destruction through modulation of the THBS-1/TGF-β signaling pathway.

This study aims to identify potential targets and regulatory mechanisms of Astragaloside Ⅳ (AS-Ⅳ) in treating intervertebral disc degeneration (IDD) through network pharmacology analysis with experimental validation. Lumbar spine instability (LSI) mouse models were first established and treated with AS-Ⅳ. Micro-CT, safranin O-fast green staining, IDD score, RT-PCR and immunohistochemistry staining were employed to demonstrate the effect of AS-Ⅳ. Network pharmacology was used to predict the signaling pathways and potential targets of AS-Ⅳ in treating IDD. RT-PCR and immunohistochemistry staining were used to elucidate and validate the mechanism of AS-Ⅳ in vivo. Animal experiments showed that AS-Ⅳ maintained disc height and volume, improved matrix metabolism in LSI mice, and restored Col2α1, ADAMTS-5, Aggrecan, and MMP-13 expression in degenerated discs. Network pharmacology analysis identified 32 cross-targets between AS-Ⅳ and IDD, and PPI network analysis filtered out 11 core genes, including ALB, MAPK1, MAPK14 (p38 MAPK), EGFR, TGFBR1, MAPK8, MMP3, ANXA5, ESR1, CASP3, and IGF1. Enrichment analysis revealed that 7 of the 11 core target genes enriched in the MAPK signaling pathway, and AS-Ⅳ exhibited stable binding to them according to molecular docking results. Experimental validation indicated that AS-Ⅳ reversed mRNA levels of 7 core targets in degenerated disc tissues in LSI mice. Immunohistochemistry staining further revealed that AS-Ⅳ treatment mainly depressed IDD-elevated protein levels of EGFR, p38 MAPK and CASP3 in the annulus fibrosus. This study elucidates that AS-Ⅳ alleviates lumbar spine instability-induced IDD in mice, suggesting the mechanism may involve inhibition of the EGFR/MAPK signaling pathway.

OBJECTIVE:The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform.METHODS:The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking.RESULTS:28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP.CONCLUSION:Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.

Higenamine (HG) is a chemical compound found in various plants, such as aconite. Recent pharmacological studies have demonstrated its effectiveness in the management of many diseases. Several mechanisms of action of HG have been proposed; however, they have not yet been classified. This review summarises the signalling pathways and pharmacological targets of HG, focusing on its potential as a naturally extracted drug. Articles related to the pharmacological effects, signalling pathways and pharmacological targets of HG were selected by searching the keyword "Higenamine" in the PubMed, Web of Science and Google Scholar databases without limiting the search by publication years. HG possesses anti-oxidant, anti-apoptotic, anti-inflammatory, electrophysiology regulatory, anti-fibrotic and lipid-lowering activities. It is a structural analogue of catecholamines and possesses characteristics similar to those of adrenergic receptor ligands. It can modulate multiple targets, including anti-inflammation- and anti-apoptosis-related targets and some transcription factors, which directly or indirectly influence the disease course. Other naturally occurring compounds, such as cucurbitacin B (Cu B) and 6-gingerol (6-GR), can be combined with HG to enhance its anti-apoptotic activity. Although significant research progress has been made, follow-up pharmacological studies are required to determine the exact mechanism of action, new signalling pathways and targets of HG and the effects of using it in combination with other drugs.

During the last decade, osteoarthritis (OA) has become one of the most prevalent musculoskeletal diseases worldwide. OA is characterized by progressive loss of articular cartilage, abnormal remodeling of subchondral bone, hyperplasia of synovial cells, and growth of osteophytes, which lead to chronic pain and disability. The pathological mechanisms underlying OA initiation and progression are still poorly understood. Non-coding RNAs (ncRNAs) constitute a large portion of the transcriptome that do not encode proteins but function in numerous biological processes. Cumulating evidence has revealed a strong association between the changes in expression levels of ncRNA and the disease progression of OA. Moreover, loss- and gain-of-function studies utilizing transgenic animal models have demonstrated that ncRNAs exert vital functions in regulating cartilage homeostasis, degeneration, and regeneration, and changes in ncRNA expression can promote or decelerate the progression of OA through distinct molecular mechanisms. Recent studies highlighted the potential of ncRNAs to serve as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA. MiRNAs and lncRNAs are two major classes of ncRNAs that have been the most widely studied in cartilage tissues. In this review, we focused on miRNAs and lncRNAs and provided a comprehensive understanding of their functional roles as well as molecular mechanisms in cartilage homeostasis and OA pathogenesis.

Endothelial progenitor cells (EPCs) are important in tumor angiogenesis. Stromal cell-derived factor-1 alpha (SDF-1 alpha) and its receptor C-X-C chemokine receptor type 4 (CXCR4) are key in stem cell homing. Melittin, a component of bee venom, exerts antitumor activity, however, the underlying mechanisms remain to be elucidated. The present study aimed to assess the effects of melittin on EPCs and angiogenesis in a mouse model of osteosarcoma. UMR-106 cells and EPCs were treated with various concentrations of melittin and cell viability was determined using the MTT assay. EPC adherence, migration and tube forming ability were assessed. Furthermore, SDF-1 alpha, AKT and extracellular signal-regulated kinase (ERK) 1/2 expression levels were detected by western blotting. Nude mice were inoculated with UMR-106 cells to establish an osteosarcoma mouse model. The tumors were injected with melittin, and its effects were assessed by immunohistochemistry and immunofluorescence. Melittin decreased the viability of UMR-106 cells and EPCs. In addition, it decreased EPC adhesion, migration and tube formation when compared with control and SDF-1 alpha-treated cells. Melittin decreased the expression of phosphorylated (p)-AKT, p-ERK1/2, SDF-1 alpha and CXCR4 in UMR-106 cells and EPCs when compared with the control. The proportions of cluster of differentiation (CD) 34/CD133 double-positive cells were 16.4 +/- 10.4% in the control, and 7.0 +/- 4.4, 2.9 +/- 1.2 and 1.3 +/- 0.3% day, respectively (P<0.05). At 11 days, melittin reduced the tumor size when compared with that of the control (control, 4.8 +/- 1.3 cm(3); melittin, 3.2 +/- 0.6, 2.6 +/- 0.5, and 2.0 +/- 0.2 cm(3) for 160, 320 and 640 mu g/kg, respectively; all P<0.05). Melittin decreased the microvessel density, and SDF-1 alpha and CXCR4 protein expression levels in the tumors. Melittin may decrease the effect of osteosarcoma on EPC-mediated angiogenesis, possibly via inhibition of the SDF-1 alpha/CXCR4 signaling pathway.

Objective: To investigate the effects of melittin on expression of HIF-1α and vascular endothelial growth factors( VEGF) of Saos-2 cell line,and to explore its mechanism. Methods: We set up blank control group,hypoxia group and melittin groups of different concentrations( 2 μg / ml,4 μg / ml,8 μg / ml). The HIF-1α expression was detected by WesternBlot and changes of transcriptional levels of HIF-1α and VEGF mRNA were detected by RT-PCR. Results: Compared with blank control group,the expressions of HIF-1α and VEGF mRNA were increased in hypoxia group markedly( P 0. 05); the HIF-1α expressions in Melittin groups were lower than that of the hypoxia group( P 0. 05),with dose-dependent manner; the VEGF mRNA levels in melittin groups were lower than that of the hypoxia group( P 0. 05),with dose-dependent manner. Conclusion: Simulated hypoxia condition can induce the activity of Saos-2 pathway in Saos-2 cell line. Melittin can inhibit the the activity of Saos-2 pathway in Saos-2 cell line by inhibiting the HIF-1α expression and influencing VEGF mRNA expression. So we think that melittin may inhibit osteosarcoma angiogenesis by this way to achieve anti-tumor effect.

沈丕安教授从医50余年,从事类风湿关节炎临床治疗超过30年,对类风湿关节炎的治疗有其独到的见解和方法,并研制出组方羌活地黄汤。在临床运用此方治疗大量患者有效的前提下,沈丕安教授带领其助手也做了相关的实验研究,以期阐明羌活地黄汤治疗类风湿关节炎的免疫机制和作用原理,并且已经取得了一定的成果。

沈丕安教授在治疗一例反复诊断不明的毒性弥漫性甲状腺肿(GD)的患者时，分别早期采用清热泻火，凉血化瘀方法解决患者发热问题，明确该患者为GD后，采取免疫调节的治法：清热化瘀，消痰散结，改善了该患者相应甲亢症状，取得了良好的效果。

OBJECTIVE:To investigate the effects of Sangen Decoction, a compound Chinese herbal medicine, on osteoclastogenesis and bone resorption function of osteoclasts induced by polymethylmethacrylate particles in vitro. METHODS:Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) were used to induce differentiation of bone marrow-derived macrophages (BMMs) towards osteoclasts. BMMs and polymethylmethacrylate particles with ratio of 1:3 were added to the 24-well plate and 96-well plate with bone slices respectively. A total of 50 male SD rats were divided into 5 groups randomly with each group containing 10 rats. After being treated with different drugs, serum samples of rats in each group were extracted, i.e., the blank serum, Western medicine (ibandronate) serum and high-, medium-, and low-dose Sangen Decoction serum and were added to the medium respectively. The tartrate-resistant acid phosphatase (TRAP) staining was used to identify the differentiation of BMMs and for counting of osteoclasts. Area of lacuna induced by osteoclast bone resorption on the bone slices was measured by computer image processing. RESULTS:Numbers of osteoclasts of treatment groups were less than that of blank group by TRAP staining (P<0.05); numbers of osteoclasts of positive control group and high-dose Sangen Decoction group were much lower than those of medium- and low-dose Sangen Decoction groups (P<0.05), and no difference was found between Western medicine group and high-dose Sangen Decoction group (P>0.05). In bone resorption assay, area of lacuna of blank group was larger than those of treatment groups (P<0.05); areas of lacuna of Western medicine group and high-dose Sangen Decoction group were much smaller than those of medium- and low-dose Sangen Decoction groups (P<0.05), and no difference was found between Western medicine group and high-dose Sangen Decoction group (P>0.05). CONCLUSION:Sangen Decoction can inhibit osteoclastogenesis induced by polymethylmethacrylate particles as well as bone resorption function of osteoclasts.