OBJECTIVES: To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
Animals ; Toll-Like Receptor 4/metabolism* ; Neuralgia/metabolism* ; Mice ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sciatic Nerve/injuries* ; Male ; Molecular Docking Simulation ; Disease Models, Animal ; Interleukin-6

OBJECTIVETo observe the effect of Huogu II formula compatible with different channel ushering drugs on the homing of bone marrow stem cells of osteonecrosis of the femoral head (ONFH) induced by liquid nitrogen freezing in rabbits and discuss the mechanism for preventing and treating ONFH.

METHODThe ONFH model was established by liquid nitrogen freezing of 84 rabbits. They were randomly assigned to the model group and the Huogu II formula group and groups of Huogu II formula combining with Achyranthis Bidentatae Radix, Asari Radix et Rhizoma, Angelicae Pubescentis Radix, Platycodonis Radix. The remaining 14 rabbits were sham-operated. During the course of ONFH modeling, all of the rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor (rhG-CSF)(30 microg x kg(-1) x d(-1), for consecutively 7 days). Meanwhile, normal saline and decoction of the formulae were orally administrated respectively. WBC was counted in peripheral blood before and after the injection of rhG-CSF. HE stainings at the 2nd and the 4th weeks after the modeling were adopted to observe histopathological changes, vascular morphology was observed by ink perfusion, BrdU and SDF-1 were determined by immunohistochemical assay in femoral heads of the left hind leg.

RESULTCompared with the sham-operated group, the Huogu II formula group showed decrease in the ratio of empty lacuna and increase in vessel area, number of BrdU positive cells and SDF-1 level. In comparison with the model group, the Achyranthis Bidentatae Radix group displayed decreasing empty lacuna ratio and increasing vessel area at the 4th week and increasing SDF-1 at the 2nd week; the Platycodonis Radix group revealed a notably increasing empty lacuna ratio and a sharp decrease in the number of BrdU positive cells at 4th week; Asari Radix et Rhizoma and Angelicae Dubescentis Radix groups showed no remarkable change.

CONCLUSIONHuogu II formula can promote the directional homing of bone marrow stem cell to the necrosis area. Channel ushering drug achyranthes can further boost above effects of Huogu II formula.

Animals ; Bone Marrow Cells ; cytology ; Bromodeoxyuridine ; metabolism ; Chemokine CXCL12 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Femur Head Necrosis ; blood ; drug therapy ; metabolism ; pathology ; Gene Expression Regulation ; drug effects ; Humans ; Leukocyte Count ; Male ; Rabbits ; Stem Cells ; cytology ; drug effects

OBJECTIVETo learn the effects of coptis in treating neonatal jaundice and to find the index that guides the clinical administration of the medicine.

METHODClinical data of 412 cases of neonatal jaundice were studied retrospectively, and univariate and multivariate analysis were made to the factors affecting the incidence according to the Cox model which led to the establishment of the predictive equation. According to the regression coefficients, the relative risk, wald value, the coptis effects were evaluated on the incidence of neonatal jaundice.

RESULTSingle-factor Cox model analysis shows that there are five main factors affecting the incidence of neonatal jaundice, Multivariate Cox model analysis indicates that the five main factors are also independent factors that affect the incidence, the roles of which, ranking from minor to major are, in turn, age, applied coptis, ethnic, G6PD deficiency and cesarean section. Among them, the regression coefficient is -0.259, relative risk 0.772, wald value 6.832. It sugguests that coptis may reduce the incidence of neonatal jaundice, and that it is a protective factor. The prediction equation, by regression coefficients, which has been used to establish the incidence of neonatal jaundice, is as following: h(t, x) = h0 (t) exp (- 0.022 x2 - 0.494x3 + 0.344x8 + 0.226x9 - 0.259x10).

CONCLUSIONCoptis is one of the important factors that affect the occurrence of neonatal jaundice, and it has a protective effect in preventing neonatal jaundice from occurrence.

Coptis ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; drug therapy ; Male ; Proportional Hazards Models ; Retrospective Studies