Ben Swann: As Governors and Mayors across the country are instituting “Stay at Home” Orders, there are big questions surrounding how parts of the government may be taking advantage of the coronavirus outbreak in violation of 1st, 2nd and 4th amendment rights of Americans.
PMID:
Neuroreport. 2020 Mar 12. Epub 2020 Mar 12. PMID: 32168101
Abstract Title:
Ginsenoside Rd attenuates blood-brain barrier damage by suppressing proteasome-mediated signaling after transient forebrain ischemia.
Abstract:
Ischemic stroke damages the blood-brain barrier (BBB), which leads to brain edema and increases the risk of intracranial hemorrhage. Proteasome inhibition has been found to protect the BBB against cerebral ischemia by suppressing neuroinflammation-mediated matrix metalloproteases-9 (MMP-9) activation. We recently showed that ginsenoside Rd (Rd), a major active ingredient of Panax ginseng, could suppress proteasome-mediated inflammation and be efficient for treating ischemic stroke but downstream mechanisms were still unidentified. For this purpose, Sprague-Dawley rats were subjected to focal cerebral ischemic injury. The activity of proteasome and its downstream effectors nuclear factor-kappa B (NF-κB) and MMP-9 were evaluated. Rd reduced the activity of 20S proteasome in a cell-free assay and inhibited proteasome activity in brain lysates after ischemic stroke. Rd administration suppressed ischemic injury-induced NF-κB activity and IκB degradation mediated by the proteasome. Moreover, Rd reduced the activity and level of MMP-9, a downstream effector of NF-κB, and protected against BBB damage as evidenced by reduced Evan's Blue leakage and brain edema after cerebral ischemic injury. Jointly, these data demonstrate that ginsenoside Rd attenuates the pathogenesis of cerebral ischemia-induced BBB damage, probably by inhibiting proteasome activity and sequentially suppressing NF-κB/MMP-9 pathway.
PMID:
Biol Trace Elem Res. 2020 Mar 16. Epub 2020 Mar 16. PMID: 32173789
Abstract Title:
Ginsenoside Rg3 Attenuates Aluminum-Induced Osteoporosis Through Regulation of Oxidative Stress and Bone Metabolism in Rats.
Abstract:
Aluminum (Al)-induced bone metabolism disorder is a primary cause of osteoporosis. Ginsenoside Rg3 (Rg3) has demonstrated therapeutic properties in the treatment of osteoporosis. The present study aimed to identify potential bone protection mechanisms of Rg3 against Al-induced osteoporosis in rats. In this study, forty healthy male Sprague-Dawley rats were randomly allocated into groups in which they were treated with AlCl(64 mg/kg/day) and/or Rg3 (20 mg/kg/day). AlClwas given orally to rats for 120 days, and from the 91st day, treated orally with Rg3 for 30 days. Rg3 attenuated AlCl-induced accumulation of Al by decreasing the bone mineral density in the lumbar spines, femoral metaphysis, and tibia, and inhibited AlCl-induced oxidative stress in rat bone by decreasing the levels of reactive oxygen species and malondialdehyde, while increasing glutathione peroxidase and superoxide dismutase activity. Rg3 facilitated bone formation by increasing the concentration of calcium, phosphorus, amino-terminal propeptide of type I procollagen, and carboxyl-terminal propeptide of type I procollagen, bone alkaline phosphatase activity in serum, and type I collagen, osteocalcin, and osteopontin protein expressions. Rg3 inhibited bone resorption by decreasing the content of N-terminal cross-linking telopeptide of type I collagen, C-terminal cross-linking telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5b activity in serum. Rg3 promoted the mRNA expression of growth regulation factors by increasing transforming growth factor-β1, bone morphogenetic protein-2, insulin-like growth factor I, and core-binding factor α1. The results demonstrate that Rg3 can significantly attenuate Al accumulation, facilitate bone formation, inhibit bone resorption, resist oxidative stress, and promote the expression of factors that regulategrowth. The results indicate that Rg3 is effective in alleviating AlCl-induced osteoporosis.
PMID:
Am J Transl Res. 2020 ;12(2):493-506. Epub 2020 Feb 15. PMID: 32194898
Abstract Title:
Ginsenoside Rg1 protects against cigarette smoke-induced airway remodeling by suppressing the TGF-β1/Smad3 signaling pathway.
Abstract:
Chronic obstructive pulmonary disease (COPD) is a devastating and common respiratory disease characterized by chronic inflammation and progressive airway remodeling. Ginsenoside Rg1 (GRg1), a major active component of, has been found to possess beneficial properties against acute lung injury and respiratory diseases. However, the effects of GRg1 on airway remodeling in COPD remain unclear. In this study, we aimed to investigate the potential protective effects of GRg1 on airway remodeling induced by cigarette smoke (CS) and the underlying mechanism. A rat model of COPD was established in which the animals were subjected to CS and GRg1 daily for 12 weeks. Subsequently, we evaluated lung function, inflammatory responses, along with airway remodeling and associated signaling factors. GRg1 treatment was found to improve pulmonary function, reduce airway collagen volume fraction, and markedly reduce the expression of IL-6, TNF-α, α-SMA, and collagen I. Moreover, GRg1 treatment decreased the expression of TGF-β1, TGF-βR1, and phosphorylated-Smad3., pretreatment of MRC5 human lung fibroblasts with GRg1 prior to exposure to cigarette smoke extract (CSE) reversed the cell ultrastructure disorder, decreased the expression of IL-6 and TNF-α, and significantly attenuated transdifferentiation of MRC5 cells by suppressing α-SMA and collagen I expression. Additionally, GRg1 suppressed the TGF-β1/Smad3 signaling pathway in CSE-stimulated MRC5 cells, whereas Smad3 over-expression abolished the anti-transdifferentiation effect of GRg1. In conclusion, the results of our study demonstrated that GRg1 improves lung function and protects against CS-induced airway remodeling, in part by down-regulating the TGF-β1/Smad3 signaling pathway.
PMID:
Nat Prod Res. 2019 Oct 22:1-7. Epub 2019 Oct 22. PMID: 31638430
Abstract Title:
Neuroprotective triterpene saponins from the leaves of.
Abstract:
Two new triterpene saponins, namely notoginsenoside Ng5 () and notoginsenoside Ng6 () were isolated from the leaves of, along with five known ones. Their structures were determined by chemical methods, NMR and X-ray experiments. The absolute configuration of compoundwith four sugar units was confirmed by single crystal X-ray analysis. Compoundsandinhibited PC12 cell damage induced by serum deprivation, and increased cell viability from 58.7 ± 6.7% to 66.7 ± 4.5%, 76.1 ± 6.1%, 64.7 ± 5.2% and 67.2 ± 5.0% at 10 μM, respectively.
PMID:
Int J Mol Med. 2020 Apr ;45(4):1225-1236. Epub 2020 Feb 6. PMID: 32124939
Abstract Title:
Panax notoginseng saponins prevent senescence and inhibit apoptosis by regulating the PI3K‑AKT‑mTOR pathway in osteoarthritic chondrocytes.
Abstract:
Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various anti‑inflammatory, anti‑oxidant and anti‑aging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)‑α‑induced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgery‑induced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)‑protein kinase B (AKT)‑mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagy‑related proteins and the anti‑apoptotic protein Bcl‑2 were significantly increased in PNS‑treated OA chondrocytes, but the expression levels ofBax and caspase‑3 were decreased; these effects were concentration‑dependent. TNF‑α significantly increased the expression of p‑PI3K/p‑AKT/p‑mTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3K‑AKT‑mTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)‑3 and MMP‑13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3K‑AKT pathway, thus delaying the degradation of articular cartilage.
PMID:
Drug Des Devel Ther. 2020 ;14:527-538. Epub 2020 Feb 5. PMID: 32103895
Abstract Title:
Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats.
Abstract:
Introduction: Epithelial-mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms.Methods: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p.o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin,α-SMA, and nephrin) as well as components of the Wnt/β-catenin pathway (wnt1, β-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively.Results: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1,β-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment.Conclusion: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/β-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.
PMID:
J Biol Chem. 2020 Mar 13 ;295(11):3576-3589. Epub 2020 Feb 6. PMID: 32029476
Abstract Title:
Parthenolide inhibits ubiquitin-specific peptidase 7 (USP7), Wnt signaling, and colorectal cancer cell growth.
Abstract:
It has been well-established that the deubiquitinating enzyme ubiquitin-specific peptidase 7 (USP7) supports cancer growth by up-regulating multiple cellular pathways, including Wnt/β-catenin signaling. Therefore, considerable efforts are directed at identifying and developing USP7 inhibitors. Here, we report that sesquiterpene lactone parthenolide (PTL) inhibits USP7 activity, assessed with deubiquitinating enzyme activity assays, including fluorogenic Ub-AMC/Ub-Rho110, Ub-VME/PA labeling, and Di-Ub hydrolysis assays. Further investigations using cellular thermal shift (CETSA), surface plasmon resonance (SPR), and mass spectrum (MS) assays revealed that PTL directly interacts with USP7. Consistent with the role of USP7 in stimulating Wnt signaling and carcinogenesis, PTL treatment inhibited the activity of Wnt signaling partly by destabilizing β-catenin. Moreover, using cell viability assays, we found that PTL suppresses the proliferation of colorectal cancer cells and induces apoptosis in these cells. Additionally, we examined the effects of two other sesquiterpene lactones (costunolide and α-santonin) on USP7 and Wnt signaling and found that α-methylene-γ-butyrolactone may provide a scaffold for future USP7 inhibitors. In summary, our findings reveal that PTL inhibits USP7 activity, identifying a potential mechanism by which PTL suppresses Wnt/β-catenin signaling. We further suggest that sesquiterpene lactones might represent a suitable scaffold for developing USP7 inhibitors and indicate that PTL holds promise as an anticancer agent targeting aberrant USP7/Wnt signaling.
PMID:
Mediators Inflamm. 2020 ;2020:6245798. Epub 2020 Mar 4. PMID: 32189995
Abstract Title:
Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model.
Abstract:
Rheumatoid arthritis is characterised by a chronic inflammatory response resulting in destruction of the joint and significant pain. Although a range of treatments are available to control disease activity in RA, bone destruction and joint pain exist despite suppression of inflammation. This study is aimed at assessing the effects of parthenolide (PAR) on paw inflammation, bone destruction, and pain-like behaviour in a mild collagen antibody-induced arthritis (CAIA) mouse model. CAIA was induced in BALB/c mice and treated daily with 1 mg/kg or 4 mg/kg PAR. Clinical paw inflammation was scored daily, and mechanical hypersensitivity was assessed on alternate days. At end point, bone volume and swelling in the paws were assessed using micro-CT. Paw tissue sections were assessed for inflammation and pre-/osteoclast-like cells. The lumbar spinal cord and the periaqueductal grey (PAG) and rostral ventromedulla (RVM) regions of the brain were stained for glial fibrillary acidic protein (GFAP) and ionised calcium-binding adaptor molecule 1 (IBA1) to assess for glial reactivity. Paw scores increased in CAIA mice from days 5-10and were reduced with 1 mg/kg and 4 mg/kg PAR on days 8-10. Osteoclast-like cells on the bone surface of the radiocarpal joint and within the soft tissue of the hind paw were significantly lower following PAR treatment (
PMID:
Gastroenterol Hepatol Bed Bench. 2020 ;13(1):14-22. PMID: 32190220
Abstract Title:
Royal jelly accelerates healing of acetate induced gastric ulcers in male rats.
Abstract:
Aim: This study examined the healing potential of royal jelly on the acetic acid induced wounds healing in male rat's gastric mucosa.Background: Scientific reports suggest that, bee products can help in the wounds healing.Methods: 96 adult male Wistar rats were divided into in 4 groups as follows: control, omeprazole 20 mg/kg, and royal jelly 50 and 200 mg/kg). Wound was induced in stomach mucosa of each rat with 100% acetic acid. Samples groups received omeprazole or royal jelly from 1st to 14th day after acetic ulcer induction. Gastric ulcer healing and histopathological parameters were evaluated on 4, 7, 10, 15th days after ulceration. Both descriptive and statistical analyses were used. P
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