Ethanol extract of Paridis rhizoma attenuates carrageenan-induced paw swelling in rats by inhibiting the production of inflammatory factors.

CONTEXT: Inflammation has been identified as a key factor contributing to the development of numerous diseases. Several anti-inflammatory drugs have been developed to treat inflammation-related diseases. However, some of such drugs are associated with varying degrees of side effects. Therefore, it is imperative to develop new anti-inflammatory drugs with reducing side effects for the treatment of inflammation-related diseases. Natural anti-inflammatory drugs have emerged as an important area of research in recent years. The study was to determine the anti-inflammatory mechanism of Paridis rhizoma extract (PRE) in rat models of acute inflammation induced by carrageenan and RAW264.7 cells models induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: PRE was investigated using the carrageenan-induced paw oedema model on rats in vivo. Histopathology examined the extent of inflammatory infiltration and tissue damage. The effect of PRE on the levels of specific cytokines was determined using enzyme-linked immunosorbent assay (ELISA). The Cell Counting Kit (CCK)-8 assay evaluated the cytotoxic effects of PRE on Raw264.7 cells. The mRNA expression levels of cytokines were quantified using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Western blot measured TNF-α, IL6, TLR4, p-P65, p-IKB, HO1, SOD1 and SOD2. Fluorescence measured the cellular levels of reactive oxygen species (ROS). RESULTS: PRE treatment reduced interstitial edema and structural damage in a dose-dependent manner in vivo. PRE inhibited inflammatory responses in vivo and in vitro, as evidenced by the decreased expression of inflammatory factors, production of ROS, and increased expression of SOD1, SOD2, and HO1. Moreover, PRE inhibited the activity of the nuclear factor kappa B (NF-kB) pathway. CONCLUSION: The anti-inflammatory activity and potential mechanism of PRE were demonstrated according to the results. PRE reduced LPS-induced inflammation in RAW264.7 cells by inhibiting the NF-KB signaling pathway and ROS production in vitro. PRE alleviated interstitial edema and structural damage in the carrageenan-induced paw edema model on rats in vivo. This study provided an idea for future development of PR-based anti-inflammatory drugs.

Traditional Chinese decoction Si Zhi Wan attenuates ovariectomy (OVX)-induced bone loss by inhibiting osteoclastogenesis and promoting apoptosis of mature osteoclasts.

Si Zhi Wan (SZW) is a traditional Chinese decoction used for osteoporosis treatment. Currently, the effect of SZW on ovariectomy (OVX)-induced bone loss and the underlying mechanisms remain unknown. Herein, we investigated the therapeutic effect of SZW on osteoporosis and explored the underlying mechanisms in vitro and in vivo. An OVX-induced bone loss model was established in vivo. After administration of SZW for 8 weeks, rats were sacrificed, and the uterus was weighted to calculate its index. The femur change was pathologically evaluated using hematoxylin and eosin (H&E) staining. The mineral density of the femur was observed by micro-CT. RAW264.7 cells were activated by receptor activator of nuclear factor-κB ligand (RANKL) in vitro. The effect of SZW on osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, Western blotting, and RT-PCR. The pro-apoptosis effect of SZW on mature osteoclasts was examined after induction of osteoclast maturation. Finally, the effect of SZW on the NF-κB pathway was evaluated. Our results demonstrated that SZW ameliorated OVX-induced bone loss in rats. In addition, SZW inhibited osteoclastogenesis and attenuated osteoclast-mediated bone resorption in vitro and in vivo. SZW also promoted apoptosis of mature osteoclasts. Mechanically, SZW exerts its effects by suppressing the NF-κB pathway. Overall, these findings demonstrated that SZW may be a potentially effective alternative treatment for osteoporosis.

Panaxatriol saponin ameliorates myocardial infarction-induced cardiac fibrosis by targeting Keap1/Nrf2 to regulate oxidative stress and inhibit cardiac-fibroblast activation and proliferation.

Cardiac fibrosis is a common precursor of ventricular dysfunction and heart failure. We investigated the role of oxidative stress in myocardial fibrosis and the protective effect of panaxatriol saponin (PTS) against myocardial infarction (MI)-induced cardiac fibrosis and explored the underlying mechanisms. In vitro, cell viability was tested using a cell counting kit. The reactive oxygen species (ROS) levels including hydrogen peroxide (H2O2) and superoxide anion (O2•-) were determined. Antioxidant enzyme levels were determined by immunofluorescence and Western blotting. Enzyme-linked immunosorbent assays, echocardiography, histological analysis, immunofluorescence staining, and molecular analysis were performed. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation was evaluated by molecular docking and immunoprecipitation. Finally, the mechanism by which PTS inhibits cardiac fibrosis was investigated using the Nrf2 activator ML334 and a small interfering RNA for Nrf2. Ang II-induced differentiation of cardiac fibroblasts was associated with oxidative stress, characterized by upregulation of α-smooth muscle actin, increased reactive oxygen species production, and inhibition of superoxide dismutase-1 and heme oxygenase expression. In addition, PTS improved cardiac function and ameliorated cardiac fibrosis in MI rats. It also reduced Ang II-induced fibroblast differentiation and proliferation, suppressed oxidative stress, and disrupted the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction by directly blocking the Nrf2 binding site in Keap1. Overexpression of Nrf2 by ML334 enhanced the antifibrotic effect of PTS. However, genetic ablation of Nrf2 abrogated the antifibrotic effect of PTS in cardiac fibrosis. Taken together, our findings suggest that Nrf2 has promise as a target and PTS as a therapeutic agent for cardiac fibrosis.

Pretreatment with Panaxatriol Saponin Attenuates Mitochondrial Apoptosis and Oxidative Stress to Facilitate Treatment of Myocardial Ischemia-Reperfusion Injury via the Regulation of Keap1/Nrf2 Activity.

Myocardial ischemia-reperfusion injury (MIRI) is a type of severe injury to the ischemic myocardium that can occur following recovery of blood flow, and for which, there is no effective treatment. Panaxatriol saponin (PTS), a major active component of P. notoginseng, has been used clinically to treat ischemia-related encephalopathy due to its antioxidant activity, but its effect on ischemic cardiomyopathy and underlying mechanism of action is still unclear. This study was performed to investigate the protective effect of PTS against MIRI and explore the potential underlying mechanisms. Hydrogen peroxide (H2O2) was used to stimulate cardiomyocytes, to mimic MIRI in vitro. Cell viability was tested using the CCK-8 method. The antioxidant activity of PTS in the H9c2 rat cardiomyocyte cell line was examined using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The levels of superoxide dismutase-1 (SOD1), SOD2, and heme oxygenase (HO-1) were determined by Western blotting and/or immunofluorescence. The antiapoptotic effect of PTS was determined. In addition, mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (ΔΨm) changes were assessed. Changes in Keap1/Nrf2 activation were evaluated by Western blotting analysis, molecular docking, and immunoprecipitation. An in vivo MIRI model was established in rats, and the myocardial infarct size was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Myocardial enzyme activities were determined by ELISA or biochemical analyses. Furthermore, changes in Nrf2 activation were evaluated, and the regulatory effect of PTS on cardiomyocyte apoptosis was examined using the Nrf2 blocker, ML385. The results showed that PTS ameliorated the cardiomyocyte injury induced by H2O2, characterized by increased cell viability, decreased reactive oxygen species (ROS) production, and promotion of SOD1, SOD2, and HO1 expression. PTS inhibited cardiomyocyte apoptosis in vivo and in vitro. PTS also reduced mPTP opening and stabilized ΔΨm in H9c2 cells. Molecular docking and immunoprecipitation study revealed that PTS can disrupt Keap1/Nrf2 interaction by directly blocking the binding site of Nrf2 in the Keap1 protein. In vivo, PTS decreased the area of myocardial infarction and attenuated pathological damage in ischemia-reperfusion (I/R) rats. In addition, the activities of myocardial injury markers were decreased by PTS. Finally, PTS regulated nuclear translocation of Nrf2, and ML385 blocked the therapeutic effect of PTS in vivo and in vitro. These results suggested that PTS has therapeutic potential for MIRI by targeting Keap1/Nrf2 activity.

Traditional Chinese medicine is a useful and promising alternative strategy for treatment of Sjogren's syndrome: A review.

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease involving exocrine glands. Current studies have found that the occurrence of the disease is closely related to genetic, environmental and neuroendocrine factors, as well as abnormal activation of T and B lymphocytes. The etiology and pathogenesis of pSS is complex, and there is a lack of specific targeted drugs. Traditional Chinese medicines (TCMs) have been comprehensively investigated for their treatment effects on pSS. Through a systematic review of the literature, we summarized the TCMs used to treat pSS, and find that there are four major ways that TCMs are used, including upregulation of aquaporin proteins, suppression of cell apoptosis, suppression of the abnormal activation of B lymphocytes and suppression of the abnormal activation of T lymphocytes (balancing T helper type [Th]1/Th2 & Th17/Treg and suppressing follicular helper T [Tfh] cells). However, there are not enough data about the active constituents, quality control, pharmacokinetics, toxicity and modern preparations of these TCMs; therefore, more investigations are needed. This paper highlights the importance of TCMs for treating pSS and provides guidance for future investigations.