Natural compound library screening to identify berberine as a treatment for rheumatoid arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) play a critical role on the exacerbation and deterioration of rheumatoid arthritis (RA). Aberrant activation of FLS pyroptosis signaling is responsible for the hyperplasia of synovium and destruction of cartilage of RA. This study investigated the screened traditional Chinese medicine berberine (BBR), an active alkaloid extracted from the Coptis chinensis plant, that regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis. METHODS: First, BBR was screened using a high-throughput drug screening strategy, and its inhibitory effect on RA-FLS was verified by in vivo and in vitro experiments. Second, BBR was intraperitoneally administrated into the collagen-induced arthritis rat model, and the clinical scores, arthritis index, and joint HE staining were evaluated. Third, synovial tissues of CIA mice were collected, and the expression of NLRP3, cleaved-caspase-1, GSDMD-N, Mst1, and YAP was detected by Western blot. RESULTS: The administration of BBR dramatically alleviated the severity of collagen-induced arthritis rat model with a decreased clinical score and inflammation reduction. In addition, BBR intervention significantly attenuates several pro-inflammatory cytokines (interleukin-1ß, interleukin-6, interleukin-17, and interleukin-18). Moreover, BBR can reduce the pyroptosis response (caspase-1, NLR family pyrin domain containing 3, and gasdermin D) of the RA-FLS in vitro, activating the Hippo signaling pathway (Mammalian sterile 20-like kinase 1, yes-associated protein, and transcriptional enhanced associate domains) so as to inhibit the pro-inflammatory effect of RA-FLS. CONCLUSION: These results support the role of BBR in RA and may have therapeutic implications by directly repressing the activation, migration of RA-FLS, which contributing to the attenuation of the progress of CIA. Therefore, targeting PU.1 might be a potential therapeutic approach for RA. Besides, BBR inhibited RA-FLS pyroptosis by downregulating of NLRP3 inflammasomes (NLRP3, caspase-1) and eased the pro-inflammatory activities via activating the Hippo signaling pathway, thereby improving the symptom of CIA.

Unusual ent-Kaurane Diterpenes from the Coffea Cultivar S288 Coffee Beans and Molecular Docking to α-Glucosidase.

A total of 11 new (1-11) and 2 known (12 and 13) ent-kaurane diterpene derivatives were identified from the roasted beans of Coffea cultivar S288. Their structures were established by extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance (heteronuclear single-quantum correlation, heteronuclear multiple-bond correlation, correlation spectroscopy, and rotating-frame Overhauser enhancement spectroscopy), high-resolution electrospray ionization mass spectrometry, and X-ray analyses. Cafespirone acid A (1) represents the first example of diterpene featuring a spirocyclic skeleton constructed from a 6/6/5 tricyclic system. Cafeane acid A (2) possesses a 6/6/6/5 tetracyclic system as a result of the C/D ring rearrangement. Furthermore, compounds 1-12 were evaluated for their α-glucosidase inhibitory activity. The results showed that compounds 2, 4, 5, 6, 7, 10, and 11 had a moderate inhibitory effect on α-glucosidase, and half-maximal inhibitory concentration values of compounds 4, 6, 7, and 10 were 18.76 ± 1.46, 4.88 ± 0.03, 12.35 ± 0.91, and 12.64 ± 0.59 µM, respectively, compared to the positive control acarbose (60.71 ± 16.45 µM). Additionally, the molecular docking experiments showed that the carbonyl group at C-19 of compounds 4, 6, and 7 formed strong hydrogen bonds with ARG315, which may make them have moderate inhibitory activity.

[Progress on rheumatoid arthritis in elderly].

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment.

[Treatment of diabetic foot by clearing heat, detoxification, activating blood, and dredging collaterals method].

OBJECTIVE: To study the mechanism of treating diabetic foot by clearing heat, detoxification, activating blood, and dredging collaterals method. METHODS: Sixty diabetic foot patients were randomly assigned to the treatment group and the control group, 30 cases in each group. On the basis of the same routine treatment, patients in the treatment group were treated by Qingjie Tongluo Recipe (QTR) plus external washing of Chinese herbs plus external dressing by herbs with removing necrosis and promoting granulation actions, while those in the control group were treated with routine aseptic external dressing. Three months was taken as one therapeutic course. The wound area and basic fibroblast growth factor (bFGF) were detected before and after treatment. The content of vascular endothelial growth factor (VEGF), the peripheral vascular and nerve functions were also measured. The therapeutic effects were also observed. RESULTS: After treatment, in the treatment group,15 patients were cured, 12 markedly effective, 2 effective, 1 ineffective, the cure rate was 50.0% and the total effective rate was 96.7%, while in the control group, 9 cases were cured, 6 markedly effective, 8 effective, 7 ineffective, the cure rate was 30.0% and the total effective rate was 76.7%. The total effective rate was better in the treatment group than in the control group (P <0. 01). The contents of bFGF and VEGF were significantly higher in the two groups after treatment (P <0.01). Besides, better results were obtained in the treatment group (P < 0.01). The blood flow speed of the dorsalis pedis artery, the inner diameter of the dorsalis pedis artery, and the common peroneal nerve conduction velocity were somewhat improved (P <0.05, P <0.01). Besides, better results were obtained in the treatment group (P <0.01). CONCLUSIONS: QTR combined external washing plus external dressing by herbs with removing necrosis and promoting granulation actions could promote the healing of diabetic foot induced ulcers, improve the vascular and nerve functions. Its efficacy was superior to that of the control group.

[Design of a lithium-ion battery recharging circuit used in wireless electrical stimulation apparatus for urinary incontinence].

We introduce in this paper a novel design of the lithium-ion battery automatically-charging circuit used in portable wireless electronic stimulation therapeutic apparatus for urinary incontinence, including its working principles, structure and characteristic.

Effect of NO donor sodium nitroprusside on lipopolysaccharide induced acute lung injury in rats.

Nitric oxide (NO) donor-sodium nitroprusside (SNP) mitigates acute lung injury (ALI), but the mechanism of this protection is incompletely known. We investigated the effect of SNP on lipopolysaccharide (LPS)-induced ALI in rats. Forty-eight male Wistar rats were randomly assigned into six groups: the sham-operation group (S group), the LPS instillation group (LPS group), the haemin, a haeme oxygenase-1 (HO-1) inducer, pretreatment group (HM group), the haemin pretreatment plus LPS instillation group (HM+LPS group), the SNP alone and SNP plus LPS treatment groups. Macroscopic and histopathological examinations and immunohistochemistry analysis were performed for the lung specimens 8h after LPS instillation. Intratracheal administration of LPS induced significant expressions of the inducible isoform of NO synthase (iNOS) and HO-1, while both haemin pretreatment and SNP treatment increased the expression of HO-1 and prevented the expression of iNOS. In the LPS group, the wet-dry weight ratio (W/D), bronchoalveolar lavage fluid (BALF) protein, and lung malondialdehyde (MDA) content were significantly higher than those in the sham-operation group, which were reversed by the pretreatment with haemin or administration of SNP. These results suggest that HO-1 plays a protective role against LPS-induced acute lung injury, which may be achieved at least in part, via inactivating the iNOS/NO system that is involved in the pathophysiological process of LPS-induced acute lung injury. The nitric oxide (NO) donor-SNP ameliorates LPS-induced ALI, which may be related to the induction of HO-1 and the subsequent inhibition of iNOS.

Effect of Radix Paeoniae Rubra on the expression of HO-1 and iNOS in rats with endotoxin-induced acute lung injury.

OBJECTIVE: To investigate the effect of Radix Paeoniae Rubra (RPR) on the expression of heme oxygenase (HO-1) and induced nitric oxide synthase (iNOS) in endotoxin-induced acute lung injury in rats and its protective mechanism. METHODS: Forty Wistar rats were divided randomly into 5 groups with 8 rats in each group: saline control group (NS group), lipopolysaccharide group (LPS group), RPR-treatment group, RPR-prevention group and Hemin group. The effect of RPR on protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, malondialdehyde (MDA) content in the lung and the activity of serum NO were observed. Arterial blood was drawn for blood-gas analysis. The expression of HO-1 and iNOS in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. The histological changes of the lung were observed under light microscope. RESULTS: Compared with that in NS group, the expression of HO-1 and iNOS was markedly increased in LPS group (P<0.01). In RPR-treatment, RPR-prevention, and Hemin groups, the expression of iNOS was significantly lower, while the expression of HO-1 was higher than that in LPS group (P<0.05). The protein content, the ratio of neutrophiles in bronchoalveolar lavage fluid, the content of MDA and the activity of serum NO in LPS group were significantly higher than those in NS group (P<0.01). There was a significant decrease in the level of arterial bicarbonate and partial pressure of oxygen in the LPS group (P<0.01); these parameters of lung injury however, were significantly lower in RPR-treatment, RPR-prevention, and Hemin groups than LPS group (P<0.05 or P<0.01). The pathologic changes of lung tissues were substantially attenuated in RPR-treatment, RPR-prevention, and Hemin groups than LPS group. CONCLUSIONS: The high expression of HO-1 reflects an important protective function of the body during lipopolysaccharide-induced acute lung injury. The protective effect of RPR on lipopolysaccharide-induced acute lung injury is related to the inhibition of iNOS expression and the induction of HO-1 expression.