Effects of heat-sensitive moxibustion combined with naprapathy and warming needle moxibustion combined with naprapathy in patients with periarthritis of shoulder.

OBJECTIVE: To evaluate the effects of heat-sensitive moxibustion (HSM) combined with naprapathy and warming needle moxibustion (WNM) combined with naprapathy on shoulder function and serum levels of calcitonin gene-related peptide (CGRP), substance P (SP), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) in patients with periarthritis of shoulder (POS). METHODS: From July 2017 to July 2020, sixty patients with POS admitted to our hospital were selected as the study subjects, and divided into HSM group (n=29) receiving HSM combined with naprapathy and WNM group receiving WNM combined with naprapathy (n=31). The changes in shoulder function, degrees of pain and serum levels of CGRP, SP, TNF-α and IL-2 were compared between the two groups. RESULTS: After treatment, the scores of myodynamia, pain, range of motion (ROM) of shoulder joint and activities of daily living (ADLs) were improved in both groups (P<0.05), and the scores in HSM group were remarkably higher than those in WNM group (P<0.05). Visual analogue scale (VAS) scores after 3 courses of treatment were lower than those after 1 and 2 courses of treatment respectively (P<0.05), and the VAS scores in HSM group were markedly lower than those in WNM group after 1, 2, and 3 courses of treatment (P<0.05). After treatment, the serum levels of CGRP, SP, TNF-α and IL-2 were decreased in both groups (P<0.05), and the levels in HSM group were noticeably lower than those in WNM group (P<0.05). CONCLUSION: HSM combined with naprapathy is superior to WNM combined with naprapathy in inhibition of inflammatory factors of pain and serum inflammatory factors, alleviating the pain and promoting the restoration of shoulder function in patients with POS.

Antifibrotic Effects of Kangxian Ruangan Capsule on Rats with Nonalcoholic Fatty Liver Fibrosis and Hepatic Stellate Cells through Regulation of TGF-ß and TLR4 Signaling Pathways.

Kangxian ruangan (KXRG) is a traditional Chinese medicine (TCM) formula consisting of 12 herbs. TCM syndrome differentiation proposes that KXRG exerts pharmacological effects against nonalcoholic fatty liver disease (NAFLD) fibrosis. This work investigates the effect of KXRG on NAFLD fibrosis in vivo and in vitro. In vivo, the NAFLD fibrosis model was constructed in Wistar rats using methionine- and choline-deficient (MCD) diet, followed by KXRG (0.92 g/kg/d) treatment for 8 weeks. In vitro, primary hepatic stellate cells (HSCs) were activated using platelet-derived growth factor (PDGF) and treated with KXRG. Molecular mechanisms underlying fibrosis were investigated. After 8 weeks, compared with the control groups, the histological lesions, degree of fibrosis, and inflammatory reaction increased with the MCD diet as demonstrated by histological changes and increased fibrosis-related (α-SMA, TGF-ß, COL1A1, and desmin, P < 0.01) and inflammation-related factors (TNF-α, MCP-1, and F4/80, P < 0.01), whereas they decreased with KXRG treatment (P < 0.01). KXRG not only inhibited the proliferation of activated HSCs and promoted their apoptosis but also resulted in G0-G1 arrest. Furthermore, KXRG suppressed HSC activation (P < 0.01), collagen synthesis (P < 0.01), and α-SMA expression (P < 0.01) with PDGF stimulation. In both the MCD diet-induced animal model and PDGF-induced cell model, KXRG inhibited TGF-ß and TLR4 signaling (P < 0.01), similar to corresponding small-molecule inhibitors. These results demonstrated that KXRG might exert suppressive effects against NAFLD fibrosis via regulating TGF-ß and TLR4 signaling. KXRG may act as a natural and potent therapeutic agent against NAFLD.

Reviewing Propolis with Multi-components in the Treatment of Oral Diseases through Multi-pathways and Multi-targets.

Propolis is a natural product made from the mixture of plant resin, saliva and wax collected by bees. It has been studied and concerned because of its high medicinal value and broad application prospects. Propolis has complex components, which can act on the body through multi-pathways and multi-targets to play the role of antibacterial, anti-inflammatory, anti-tumor and so on, and it can be used as an important resource for the prevention and treatment of oral diseases. In this review, we mainly reviewed components of propolis and its physiological activities against oral diseases, as well as the new dosage forms and applications of propolis in oral treatment. The purpose of this review is to explore the advantages of propolis in the treatment of oral diseases and the wide application of propolis in the field of oral health.

Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking.

BACKGROUND: At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. METHODS: First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein-protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. RESULTS: First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine-cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. CONCLUSIONS: DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

A Nasal Temperature and pH Dual-Responsive In Situ Gel Delivery System Based on Microemulsion of Huperzine A: Formulation, Evaluation, and In Vivo Pharmacokinetic Study.

Huperzine A (hup A), extracted from the Chinese medicinal plant Huperzia serrata, is a reversible and highly selective second-generation acetylcholine esterase (AchE) inhibitor for treating Alzheimer's disease (AD), but it suffers from low bioavailability in the brain. This study aimed to develop a nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of hup A (hup A-M-TPISG). The optimal formulation was obtained by central composite design and response surface methodology. The optimized mucoadhesive formulation, hup A-M-TPISG, was composed of pluronic F127 (20.80%), pluronic F68 (2.8%), and chitosan (0.88%) as the gel matrix, which could gelatinize under physiological conditions (29-34°C, pH 6.5) because of its temperature and pH responsiveness. The optimized hup A-M-TPISG formulation was further evaluated by in vitro release and in vivo pharmacokinetic studies via microdialysis. The in vitro release study showed continuous and steady drug release from hup A-M-TPISG, which was in accordance with the first-order model. Moreover, the pharmacokinetic results revealed that the optimized formulation for nasal administration, with convenient administration and improved patient compliance, could achieve similar brain-targeting properties as intravenous administration. In conclusion, the hup A-M-TPISG for intranasal administration, as an effective and safe vehicle, could enhance the absorption of hup A in vivo and would be a promising noninvasive alternative for partially improving brain-targeting therapy.

The Effect of Compound Sophora on Fluorouracil and Oxaliplatin Resistance in Colorectal Cancer Cells.

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P < 0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P < 0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

Protective effects of Kangxian ruangan capsule against nonalcoholic fatty liver disease fibrosis in rats induced by MCD diet.

Kangxian ruangan (KXRG) capsule is a classical formula containing various herbals that play a vital role of replenishing spleen and warming Yang. Traditional Chinese medicine believes that insufficiency of the spleen, damp-heat, and phlegm and stasis are the key factors to nonalcoholic fatty liver disease (NAFLD). The objective of this study was to investigate the effects of KXRG capsule on NAFLD fibrosis rats induced by MCD diet. The liver functions (ALT, AST and GGT) and levels of blood lipids (CHOL and TG) in each treatment group rats were significantly decreased, especially those in H-KXRG group. At the same time, the KXRG capsule alleviated the inflammatory response, histopathological changes and liver fibrosis of NAFLD fibrosis rats. In addition, the apoptosis of liver cells induced by diet was obvious via TUNEL staining. However, KXRG capsule reversed that negative change. Moreover, the levels of pro-apoptotic proteins (Caspase 3, 8, 9 and Bax) were reduced by exposure to KXRG capsule, except that the anti-apoptotic proteins (Bcl-2 and Bcl-XL) were elevated. In conclusion, KXRG relieved the progression of NAFLD fibrosis via maintaining the balance of TNF-α/IL-10 further relieving the inflammatory reaction, and regulating the balance of Bcl-2/Bax or Bcl-XL/Bax in a positive direction further activating damaged hepatocytes.