The protective effects and mechanism of Ruyi Zhenbao Pill, a Tibetan medicinal compound, in a rat model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RZP) is a prescribed Tibetan formulation for the treatment of white-pulse-disease, yellow-water-disease as well as pain-related disease. RZP is composed of 30 medicinal materials including herbal medicine, animal medicine and mineral medicine. They are widely used in the Tibetan area to treat cerebrovascular disease, hemiplegia, rheumatism, and pain diseases for centuries. AIM OF THE STUDY: The aim of the present study was to evaluate the anti-osteoarthritis function of RZP and to clarify the underlying mechanisms. MATERIALS AND METHODS: The active components in RZP were identified using HPLC methods. Osteoarthritis (OA) animal model was established via intra-articular injection of papain in rat knees. After the administration of RZP (0.45, 0.9 g/kg) for 28 days, the clinical observation was conducted, and pathological changes as well as serum biochemical indexes were detected. Moreover, therapeutic targets and pathways of RZP were discussed. RESULTS: The results showed that RZP could suppress knee joint swelling and arthralgia, thus relieving joint pain and inflammation in OA rats. Microcomputed tomography (µCT)-based physiological imaging and staining pictures confirmed the therapeutic effects of RZP on OA symptoms including knee joint swelling and structural changes with progressive inflammation in OA rats. RZP could promote the synthesis or inhibit the degradation of COLⅡ, attenuate OA-induced OPN up-regulation and thus relieve the OA symptom. Furthermore, RZP (0.45-0.9 g/kg) could all ameliorate the imbalance of biomarkers related to OA such as MMP1, TNF-α, COX2, IL-1ß and iNOS in knee joints or serum. CONCLUSION: In conclusion, RZP could effectively relieve inflammatory reaction induced by OA injury and the formulation could be applied to the treatment of OA therapy.

Effects of different anesthesia methods on maternal and neonatal outcomes in pregnant patients with pulmonary arterial hypertension: a meta-analysis.

PURPOSE: To investigate the effects of different anesthesia methods on maternal and neonatal outcomes in pregnant patients with pulmonary arterial hypertension (PAH). METHODS: We searched PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang and QVIP for investigating the effects of general anesthesia (GA) and local anesthesia (LA) in pregnant patients with PAH. Results were expressed as weighted mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (CIs). Publication bias was assessed by the Begg's test. RESULTS: Totally, 18 articles containing 628 LA and 481 GA patients were involved in our study. The postoperative blood oxygen saturation (WMD = - 4.040, 95%CI: - 5.505 to - 2.576) and maternal mortality rate (RR = 0.507, 95%CI: 0.300-0.858) were lower in LA group than those in GA group. The postoperative systolic blood pressure (WMD = 15.647, 95%CI: 13.294-18.000) and postoperative diastolic blood pressure (WMD = 6.758, 95%CI: 5.715-7.802) were high in LA group compared with those in GA group. The mechanical ventilation time (WMD = - 4.112, 95%CI: - 4.655 to - 3.569), ICU admission time (WMD = - 4.176, 95%CI: - 4.523 to - 3.828), length of stay (WMD = -7.289, 95%CI: -7.799-6.779) were shorter in LA group than those in GA group. All P values were < 0.05. CONCLUSIONS: LA is superior to GA in regards to the postoperative blood oxygen saturation, the postoperative systolic blood pressure, postoperative diastolic blood pressure, the mechanical ventilation time, ICU admission time, length of stay and the maternal mortality rate. REGISTRATION NUMBER: osf.io/juybq ( https://osf.io/search/ ).

MARESIN 1 PREVENTS LIPOPOLYSACCHARIDE-INDUCED NEUTROPHIL SURVIVAL AND ACCELERATES RESOLUTION OF ACUTE LUNG INJURY.

Acute lung injury (ALI) is characterized by lung inflammation and diffuse infiltration of neutrophils. Neutrophil apoptosis is recognized as an important control point in the resolution of inflammation. Maresin 1 (MaR1) is a new docosahexaenoic acid-derived proresolving agent that promotes the resolution of inflammation. However, its function in neutrophil apoptosis is unknown. In this study, isolated human neutrophils were incubated with MaR1, the pan-caspase inhibitor z-VAD-fmk, and lipopolysaccharide (LPS) to determine the mechanism of neutrophil apoptosis. Acute lung injury was induced by intratracheal instillation of LPS. In addition, mice were treated with MaR1 intravenously at the peak of inflammation and administered z-VAD-fmk intraperitoneally. We found that culture of isolated human neutrophils with LPS dramatically delayed neutrophil apoptosis through the phosphorylation of AKT, ERK, and p38 to upregulate the expression of the antiapoptotic proteins Mcl-1 and Bcl-2, which was blocked by pretreatment with MaR1 in vitro. In mice, MaR1 accelerated the resolution of inflammation in LPS-induced ALI through attenuation of neutrophil accumulation, pathohistological changes, and pulmonary edema. Maresin 1 promoted resolution of inflammation by accelerating caspase-dependent neutrophil apoptosis. Moreover, MaR1 also reduced the LPS-induced production of proinflammatory cytokines and upregulated the production of the anti-inflammatory cytokine interleukin-10. In contrast, treatment with z-VAD-fmk inhibited the proapoptotic action of MaR1 and attenuated the protective effects of MaR1 in LPS-induced ALI. Taken together, MaR1 promotes the resolution of LPS-induced ALI by overcoming LPS-mediated suppression of neutrophil apoptosis.

Maresin 1 mitigates LPS-induced acute lung injury in mice.

BACKGROUND AND PURPOSE: Acute lung injury (ALI) is a severe illness with a high rate of mortality. Maresin 1 (MaR1) was recently reported to regulate inflammatory responses. We used a LPS-induced ALI model to determine whether MaR1 can mitigate lung injury. EXPERIMENTAL APPROACH: Male BALB/c mice were injected, intratracheally, with either LPS (3 mg·kg(-1) ) or normal saline (1.5 mL·kg(-1) ). After this, normal saline, a low dose of MaR1 (0.1 ng per mouse) or a high dose of MaR1 (1 ng per mouse) was given i.v. Lung injury was evaluated by detecting arterial blood gas, pathohistological examination, pulmonary oedema, inflammatory cell infiltration, inflammatory cytokines in the bronchoalveolar lavage fluid and neutrophil-platelet interactions. KEY RESULTS: The high dose of MaR1 significantly inhibited LPS-induced ALI by restoring oxygenation, attenuating pulmonary oedema and mitigating pathohistological changes. A combination of elisa and immunohistochemistry showed that high-dose MaR1 attenuated LPS-induced increases in pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), chemokines [keratinocyte chemokine, monocyte chemoattractant protein-5, macrophage inflammatory protein (MIP)-1α and MIP-1γ], pulmonary myeloperoxidase activity and neutrophil infiltration in the lung tissues. Consistent with these observations, flow cytometry and Western blotting indicated that MaR1 down-regulated LPS-induced neutrophil adhesions and suppressed the expression of intercellular adhesion molecule (ICAM)-1, P-selection and CD24. CONCLUSIONS AND IMPLICATIONS: High-dose MaR1 mitigated LPS-induced lung injury in mice by inhibiting neutrophil adhesions and decreasing the levels of pro-inflammatory cytokines.

BML-111, a lipoxin receptor agonist, attenuates ventilator-induced lung injury in rats.

Mechanical ventilation can cause structural and functional disturbances in the lung termed ventilator-induced lung injury (VILI). The aim of this study was to evaluate whether BML-111, a lipoxin receptor agonist, could attenuate VILI. Following induction of anesthesia and tracheostomy, Sprague-Dawley rats were ventilated with low tidal volume (6 mL/kg) or high tidal volume (20 mL/kg, HVT) for 4 h. Some rats subjected to HVT ventilation received BML-111 or vehicle (saline) by intraperitoneal injection. Some rats subjected to HVT and BML-111(1 mg/kg) received BOC-2 (a FPR2/ALX antagonist) intraperitoneally 30 min before BML-111. Sham rats were tracheotomized without ventilation. Treatment with BML-111 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury compared with HVT-induced lung injury. BML-111 decreased indices of inflammation such as interleukin 1ß, interleukin 6, tumor necrosis factor α, and bronchoalveolar lavage neutrophil infiltration. Administration with BML-111 suppressed the decrement of the nuclear factor κB (NF-κB) inhibitor IκB-α, diminished NF-κB activation, and reduced activation of mitogen-activated protein kinase in VILI. This study indicates that BML-111 attenuated VILI via a NF-κB and mitogen-activated protein kinase dependent mechanism. BML-111 may be a promising strategy for alleviation of VILI in patients subjected to mechanical ventilation.