Ginsenoside Rb1 improves brain, lung, and intestinal barrier damage in middle cerebral artery occlusion/reperfusion (MCAO/R) micevia the PPARγ signaling pathway.

Ischemic stroke causes brain inflammation and multi-organ injury, which is closely associated with the peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathway. Recent studies have indicated that ginsenoside Rb1 (GRb1) can protect the integrity of the blood-brain barrier after stroke. In the current study, a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγ signaling pathway. Staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and Doppler ultrasonography were employed to detect pathological changes. Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs (tight junctions) and AJs (adherent junctions). Western blot and immunofluorescence were used to determine the levels of cell junction proteins, PPARγ and NF-κB. Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular, pulmonary vascular, and intestinal epithelial connexins. In brain, lung, and intestinal tissues, GRb1 activated PPARγ, decreased the levels of phospho-NF-κB p65, and inhibited the production of proinflammatory cytokines, thereby maintaining barrier permeability. However, co-treatment with GRb1 and the PPARγ antagonist GW9662 reversed the barrier-protective effect of GRb1. These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγ pathway.

Metabolomic Profiling of Brain Protective Effect of Edaravone on Cerebral Ischemia-Reperfusion Injury in Mice.

Edaravone (EDA) injection has been extensively applied in clinics for treating stroke. Nevertheless, the metabolite signatures and underlying mechanisms associated with EDA remain unclear, which deserve further elucidation for improving the accurate usage of EDA. Ischemia stroke was simulated by intraluminal occlusion of the right middle cerebral artery for 1 h, followed by reperfusion for 24 h in mice. Brain infarct size, neurological deficits, and lactate dehydrogenase (LDH) levels were improved by EDA. Significantly differential metabolites were screened with untargeted metabolomics by cross-comparisons with pre- and posttreatment of EDA under cerebral ischemia/reperfusion (I/R) injury. The possibly involved pathways, such as valine, leucine, and isoleucine biosynthesis, and phenylalanine, taurine, and hypotaurine metabolisms, were enriched with differential metabolites and relevant regulatory enzymes, respectively. The network of differential metabolites was constructed for the integral exhibition of metabolic characteristics. Targeted analysis of taurine, an important metabolic marker, was performed for further validation. The level of taurine decreased in the MCAO/R group and increased in the EDA group. The inhibition of EDA on cerebral endothelial cell apoptosis was confirmed by TdT-mediated dUTP nick-end labeling (TUNEL) stain. Cysteine sulfinic acid decarboxylase (CSAD), the rate-limiting enzyme of taurine generation, significantly increased along with inhibiting endothelial cell apoptosis after treatment of EDA. Thus, CSAD, as the possible new therapeutic target of EDA, was selected and validated by Western blot and immunofluorescence. Together, this study provided the metabolite signatures and identified CSAD as an unrecognized therapeutic intervention for EDA in the treatment of ischemic stroke via inhibiting brain endothelial cell apoptosis.

Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19.

Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.

YiQiFuMai Lyophilized Injection ameliorates tPA-induced hemorrhagic transformation by inhibiting cytoskeletal rearrangement associated with ROCK1 and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombolytic therapy with tissue plasminogen activator (tPA) after ischemic stroke exacerbates blood-brain barrier (BBB) breakdown and leads to hemorrhagic transformation (HT). YiQiFuMai Lyophilized Injection (YQFM) is a modern preparation derived from Sheng-mai San (a traditional Chinese medicine). YQFM attenuates the BBB dysfunction induced by cerebral ischemia-reperfusion injury. However, whether YQFM can suppress tPA-induced HT remains unknown. AIM OF THE STUDY: We investigated the therapeutic effect of YQFM on tPA-induced HT and explored the underlying mechanisms in vivo and in vitro to improve the safety of tPA use against stroke. METHODS: Male C57BL/6J mice were subjected to 45 min of ischemia and 24 h of reperfusion. tPA (10 mg/kg) were infused 2 h after occlusion and YQFM (0.671 g/kg) was injected 2.5 h after occlusion. The in vitro effect of YQFM (100, 200, 400 µg/mL) on tPA (60 µg/mL)-induced dysfunction of the microvascular endothelial barrier in the brain following oxygen-glucose deprivation/reoxygenation (OGD/R) was observed in bEnd.3 cells. RESULTS: YQFM suppressed tPA-induced high hemoglobin level in the brain, mortality, neurologic severity score, BBB permeability, expression and activation of matrix metalloproteinase (MMP)-9 and MMP-2, and degradation of tight-junction proteins. Furthermore, YQFM significantly blocked tPA-induced brain microvascular endothelial permeability and phosphorylation of Rho-associated kinase (ROCK)1, myosin light chain (MLC), cofilin and p65 in vivo and in vitro. CONCLUSION: YQFM suppressed tPA-induced HT by inhibiting cytoskeletal rearrangement linked with ROCK-cofilin/MLC pathways and inhibiting the nuclear factor-kappa B pathway to ameliorate BBB damage caused by tPA.

Neuroprotective effect of liquiritin against neuropathic pain induced by chronic constriction injury of the sciatic nerve in mice.

Managing of neuropathic pain remains clinically challenging because the existing pharmacotherapies are either ineffective or non-specific. Therefore, developing novel alternatives is essential for better treatment. Liquiritin is an active component extracted from Glycyrrhizae radix and has potential neuroprotective action. This study aimed to investigate the protective efficacy of liquiritin on chronic constriction injury (CCI)-induced neuropathic pain in mice. Liquiritin (30, 60, and 120mg/kg) and pregabalin (40mg/kg) were administered intragastrically for 7 consecutive days starting on the 8th day post-surgery. Behavioral parameters and sciatic functional index were assessed on days 0, 7, 8, 10, 12, and 14. Electrophysiological and histopathological changes were analyzed on the 14th day. Immunofluorescence and Western blot were used to evaluate the expression of glial cells and the protein levels of inflammatory cytokines in the spinal cord, respectively. Results showed that liquiritin dose-dependently reduced hyperalgesia and allodynia and increased the sciatic functional index and motor nerve conduction velocities. Moreover, liquiritin restored the injured axon and myelin sheath, inhibited the activation of astrocyte and microglia, down-regulated the pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1ß), and simultaneously up-regulated the anti-inflammatory cytokine IL-10. Our study revealed that liquiritin exerted a neuroprotective effect on CCI-induced neuropathic pain, which might be attributed to its direct protective effect on damaged nerves and its anti-inflammatory activity at the level of the spinal cord. Therefore, liquiritin shows promise as a compound for the development of novel analgesic agents that can be used to effectively treat intractable neuropathic pain.

Neuroprotective Effect of Matrine in Mouse Model of Vincristine-Induced Neuropathic Pain.

Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 µg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T-AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-α, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti-inflammatory actions.

Antinociceptive effects of gentiopicroside on neuropathic pain induced by chronic constriction injury in mice: a behavioral and electrophysiological study.

Gentiopicroside (Gent) is promising as an important protective secoiridoid compound against pain. The present study was designed to investigate whether administration of Gent would alleviate the expression of nociceptive behaviors and whether it would cause the relevant electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in mice. Gent was administered from the seventh day after surgery for 8 consecutive days. Behavioral parameters and sciatic functional index were assessed immediately before surgery and on days 7, 8, 10, 12, and 14 post-CCI, and electrophysiological activities of sciatic nerve were recorded immediately after the behavioral test on the last day. The present study has shown that administration of Gent (at a dose of 50 and 100 mg/kg) increased behavioral parameters from day 8 compared with the CCI-NS group. Electrophysiological data indicated that CCI caused a significant reduction in nerve conduction velocities in the sciatic nerves and the amplitudes of compound action potential, while Gent at a dose of 50 or 100 mg/kg caused a significant recovery of electrophysiological changes induced by CCI. Our data indicated that Gent has antinociceptive effects on neuropathic pain induced by CCI.

[Subcellular distribution of phenanthrene in plant root tissues].

Subcellular distribution of phenanthrene as a representative of polycyclic aromatic hydrocarbons (PAHs) in roots of five plants was investigated using a greenhouse hydroponic experiment. Results showed that, with the increase of the equilibrium concentrations of phenanthrene in solution from 0.056 to 0.39 mg x L(-1), the respective concentrations of phenanthrene in root, root cell organelle and cell wall increased from 26.85, 20.01 and 36.19 mg x kg(-1) to 56.91, 49.54 and 59.77 mg x kg(-1), and their concentration factors decreased from 357.14, 479.49, and 649.25 L x kg(-1) to 145.92, 127.04, and 153.26 L x kg(-1), respectively. The concentrations of phenanthrene in ryegrass root tissues followed the order of cell organelle > root > cell wall. In addition, concentrations of phenanthrene in cell organelle were generally 21%-163% higher than those in cell wall. As to the roots of five different tested plants growing in solution with initial phennathrene concentration of 1 mg x L(-1) after 144 h cultivation, the concentrations of phenanthrene were 48.64-145.2 mg x kg(-1) in root cell organelle, which were observed to be higher than those (15.86-74.49 mg x kg(-1)) in root cell wall. The subcellular distribution (%) of phenanthrene was in the following order: cell organelle > cell wall > cell soluble fraction. Based on the detected amounts of phenanthrene in subcellular fractions of plant root tissues, about 46%-53% and 31%-40% of phenanthrene were observed in root cell organelle and cell wall.