ABSTRACT
Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of its action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF; then, their targets were obtained from TCMSP, ETCM, ITCM, and SwissTargetPrediction databases. RA disease-related targets were obtained from DisGeNET, OMIM, and GeneCards databases, and 99 overlapped targets were obtained using a Venn diagram. The protein-protein interaction network (PPI), the compound-target network (CT), and the compound-potential target genes-signaling pathways network (CPS) were constructed and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. The core therapeutic targets were predicted via network pharmacology analysis as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, and RELA, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in a mouse model of xylene-induced ear edema and had strong analgesic effect on acetic acid-induced writhing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF was able to alleviate toe swelling and ameliorate joint damage. The elevated serum content levels of IL-6, COX-2, TNF-α, IL-1ß, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may regulate the ERK and NF-κB pathway. The results provide a new perspective for the topical application of CF for treatment of RA.
ABSTRACT
Background: The classical prescription Gualou Guizhi decoction (GL), a mixture of Radix Trichosanthis, Ramulus Cinnamomi, Radix Paeoniae Alba, Radix Glycyrrhizae, Zingiberis Rhizoma Recens, and Fructus Ziziphus Jujuba, was clinically used in the treatment of limb spasms after stroke and has achieved remarkable therapeutic effects. However, the underlying mechanism still needs to be further explored. Methods: Cerebral ischemia/reperfusion (CI/R) in Sprague-Dawley rats was induced by middle cerebral artery occlusion followed by filament removal. GL was intragastrically administered once daily for 7 or 14 consecutive days. The effect of GL on neurobehavioral impairment was evaluated. 18F-FDG micro-PET imaging was used to detect the effects of GL on glucose utilization in neural cells after CI/R. Immunohistochemical staining of glucose transporter 1 (Glut-1), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule-1 (Iba-1) was further performed to show the effects of GL on cerebral glucose transport and the activation of inflammatory-related glial cells. Markers related to the microglial subtype were also assessed to investigate the effects of GL on microglia polarization. Results: Neurological deficits induced by CI/R were significantly improved by GL administration. GL restored the glucose uptake in the ischemic hemisphere. Glut-1, the major glucose transporter in the brain, was significantly increased after GL treatment. Moreover, GL mitigated the activation of astrocytes and microglia after CI/R. Furthermore, GL significantly decreased proinflammatory M1-type microglial markers TNF-α and iNOS, while increasing anti-inflammatory M2 microglial markers CD206 and Arg-1. Conclusion: GL enhanced the uptake and utilization of glucose in neural cells after CI/R. It exerted significant anti-inflammatory effects by regulating the polarization of microglia. These results provided further evidence supporting the clinical application of GL in the treatment of cerebral ischemic stroke.
ABSTRACT
OBJECTIVE: To investigate the ability of the pericardium meridian (PM) to mitigate or enhance the cardiotoxic effects of aconitine injected at specific acupoint and non-acupoint sites in rabbits. METHODS: This study consisted of 3 experiments that were designed to test the effects of injection of 30 µg/kg of aconitine at acupoints on the PM (Test 1), at non-acupoint sites on the PM (Test 2), and at acupoints on other meridians and non-meridian sites (Test 3). In Test 1, 24 rabbits were randomly assigned to receive injections at Quze (PC3), Tianquan (PC2), or intramuscularly. In Test 2, 24 rabbits were randomly assigned to receive injections of aconitine at non-acupoint I, non-acupoint II, or intramuscularly. In Test 3, 48 rabbits were randomly assigned to receive injections at Neiguan (PC6), Sanyinjiao (SP6), Yangjiao (GB35), a non-meridian and non-acupoint site (NMNA), intravenously, and intramuscularly. Electrocardiographs of the rabbits were performed before, during and after injection to determine the incidence of arrhythmia, latency of ventricular rhythm, and recovery rate after aconitine injection. The recovery time index and extent of arrhythmia scores were calculated. RESULTS: In all groups the incidence of arrhythmia was 100%, and the latency of ventricular rhythm was less than 30 min. In Tests 1 and 2, the recovery rates of the Quze and non-acupoint II groups were significantly higher than those of the muscular group (P < 0.05). In Test 3, the recovery time index and extent of arrhythmia scores of the Neiguan group were low. There were no significant differences between the other acupoint groups, or the NMNA group, when compared with the group receiving aconitine intramuscularly. CONCLUSIONS: Acupoints or non-acupoints along the PM could reduce the severity of the arrhythmia induced by aconitine in healthy rabbits. Meridians play an important role in protecting body functions.
