Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.

Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.

Protective effects of curcumin against osteoporosis and its molecular mechanisms: a recent review in preclinical trials.

Osteoporosis (OP) is one of the most common metabolic skeletal disorders and is commonly seen in the elderly population and postmenopausal women. It is mainly associated with progressive loss of bone mineral density, persistent deterioration of bone microarchitecture, and increased fracture risk. To date, drug therapy is the primary method used to prevent and treat osteoporosis. However, long-term drug therapy inevitably leads to drug resistance and specific side effects. Therefore, researchers are constantly searching for new monomer compounds from natural plants. As a candidate for the treatment of osteoporosis, curcumin (CUR) is a natural phenolic compound with various pharmacological and biological activities, including antioxidant, anti-apoptotic, and anti-inflammatory. This compound has gained research attention for maintaining bone health in various osteoporosis models. We reviewed preclinical and clinical studies of curcumin in preventing and alleviating osteoporosis. These results suggest that if subjected to rigorous pharmacological and clinical trials, naturally-derived curcumin could be used as a complementary and alternative medicine for the treatment of osteoporosis by targeting osteoporosis-related mechanistic pathways. This review summarizes the mechanisms of action and potential therapeutic applications of curcumin in the prevention and mitigation of osteoporosis and provides reference for further research and development of curcumin.

[Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology].

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Protective Effect of Resveratrol on Knee Osteoarthritis and its Molecular Mechanisms: A Recent Review in Preclinical and Clinical Trials.

Osteoarthritis (OA) is one of the progressing chronic joint associated with by many complex factors such as age, obesity, and trauma. Knee osteoarthritis (KOA) is the most common type of OA. KOA is characterized by articular cartilage destruction and degeneration, synovial inflammation, and abnormal subchondral bone changes. To date, no practical clinical approach has been able to modify the pathological progression of KOA. Drug therapy is limited to pain control and may lead to serious side effects when taken for a long time. Therefore, searching for safer and more reliable treatments has become necessary. Interestingly, more and more research has focused on natural products, and monomeric compounds derived from natural products have received much attention as drug candidates for KOA treatment. Resveratrol (RES), a natural phenolic compound, has various pharmacological and biological activities, including anti-cancer, anti-apoptotic, and anti-decay. Recently, studies on the effects of RES on maintaining the normal homeostasis of chondrocytes in KOA have received increasing attention, which seems to be attributed to the multi-targeted effects of RES on chondrocyte function. This review summarizes preclinical trials, clinical trials, and emerging tissue engineering studies of RES for KOA and discusses the specific mechanisms by which RES alleviates KOA. A better understanding of the pharmacological role of RES in KOA could provide clinical implications for intervention in the development of KOA.