| In vitro: |
| Pharmacol Res. 2018 Mar;129:262-273. | | Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer's disease.[Pubmed: 29179999 ] | Alzheimer's disease (AD) is the most prevalent form of dementia. The exact pathophysiology of this disease remains incompletely understood and safe and effective therapies are required.
METHODS AND RESULTS:
AD is highly correlated with neuroinflammation and oxidative stress in brain causing neuronal loss.
Nuclear factor of activated B-cells (NF-κB) is involved in physiological inflammatory processes and thus representing a promising target for inflammation-based AD therapy. Phytochemicals are able to interfere with the NF-κB pathway. They inhibit the phosphorylation or the ubiquitination of signaling molecules, and thus, inhibit the degradation of IκB. The translocation of NF-κB to the nucleus and subsequent transcription of pro-inflammatory cytokines are inhibited by the actions of phytochemicals. Additionally, natural compounds preventing the interaction of NF-κB can block NF-κB's transcriptional activity by inhibiting its binding to target DNA. Many polyphenols including curcumin, resveratrol, pterostilbene, punicalagin, macranthoin G, salidroside, 4-O-methylhonokiol, lycopene, genistein, Obovatol and gallic acid were reported as potent NF-κB inhibitors for AD treatment. Several alkaloids such as galantamine, glaucocalyxin B, tetrandrine, berberine, oridonin, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in vivo. Besides, vitamins, tanshinone IIA, artemisinin, dihydroasparagusic acid, geniposide, xanthoceraside, l-theranine, 1,8-cineole and paeoniflorin were described as promising NF-κB inhibitors.
CONCLUSIONS:
In conclusion, natural products from plants represent interesting candidates for AD treatment. They may qualify as promising compounds for the development of derivatives providing enhanced pharmacological features. | | J Antibiot (Tokyo). 2017 Nov;70(11):1065-1069. | | Inhibitory effect of obovatol from Magnolia obovata on the Salmonella type III secretion system.[Pubmed: 28874849 ] | In many pathogenic Gram-negative bacteria, such as Salmonella, Escherichia coli, Yersinia and Chlamydia spp., which cause diseases in humans, the type III secretion system (TTSS) is an important virulence factor that translocates effector proteins into the cytosol of host cells. Thus, the TTSS is a good target for antibacterial agents.
METHODS AND RESULTS:
Here we used a hemolysis assay to search for TTSS inhibitors and found that a compound from Magnolia obovata called obovatol blocks the TTSS of Salmonella. Obovatol showed potent inhibitory activity (IC50=19.8 μM) against the TTSS-related hemolysis of Salmonella, which was not due to a reduction of bacterial growth. Instead, the compound inhibited bacterial motility, TTSS-related mRNA expression and effector protein secretion.
CONCLUSIONS:
These data demonstrate the inhibitory effect of obovatol on the Salmonella TTSS and suggest that it could be useful for the prevention and supplementary treatment of bacterial infections. | | Eur J Pharmacol. 2014 Jan 15;723:473-80. | | Inhibitory effects of obovatol on osteoclast differentiation and bone resorption.[Pubmed: 24334279 ] | Osteoclasts are polykaryons that have the unique capacity to degrade bone. Modulation of osteoclast formation and function is a promising strategy for the treatment of bone-destructive diseases.
METHODS AND RESULTS:
Here, we report that obovatol, a natural compound isolated from Magnolia obovata, inhibits receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation in vitro and inflammatory bone loss in vivo. We found that obovatol strongly inhibited osteoclast formation from bone marrow-derived macrophages in a dose-dependent manner without cytotoxicity. Obovatol significantly suppressed RANKL-induced activation of NF-κB, c-Jun-N-terminal kinase, and extracellular signal-regulated kinase signaling pathways. Obovatol also inhibited RANKL-induced expression of the genes c-Fos and nuclear factor of activated T cells c1, which are transcription factors important for osteoclastogenesis. In addition to osteoclast differentiation, obovatol blocked cytoskeletal organization and abrogated the bone resorbing activity of mature osteoclast. Obovatol also accelerated osteoclast apoptosis through the induction of caspase-3 activation. Consistent with its in vitro anti-resorptive effect, obovatol prevented bone loss induced by lipopolysaccharide in vivo.
CONCLUSIONS:
Together, our data suggest that obovatol may be a useful therapeutic agent for the treatment of pathological bone disorders characterized by excessive osteoclastic bone resorption. | | Arch Pharm Res. 2012 Dec;35(12):2191-8. | | Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activities.[Pubmed: 23263814] | Obovatol has been reported biological activities such as muscle relaxative, anti-gastric ulcer, anti-allergic and anti-bacterial activities.
METHODS AND RESULTS:
The present study was undertaken to investigate the effect of diacetylated obovatol, an obovatol derivative, on rabbit platelet aggregation, and their possible molecular mechanisms. Effects of diacetylated obovatol on platelet activation including aggregation and serotonin secretion were examined. In addition, we investigated the effect of diacetylated obovatol on archidonic acid and metabolites liberation and intracellular calcium mobilization. Diacetylated obovatol concentration-dependently inhibited the washed rabbit platelet aggregation induced by collagen and arachidonic acid, suggesting that diacetylated obovatol may selectively inhibits collagen- and arachidonic acid-mediated signal transduction. In accordance with these results, diacetylated obovatol showed a concentration-dependent decrease in cytosolic Ca(2+) mobilization and serotonin secretion. However, diacetylated obovatol did not inhibit arachidonic acid liberation; on the other hand, diacetylated obovatol inhibited the formation of arachidonic acid metabolites such as thromboxane A(2), prostaglandin D(2) and 12-HETE through interfering with cyclooxygenase (COX)-1 and lipoxygenase (LOX) activities.
CONCLUSIONS:
The results demonstrated that diacetylated obovatol has antiplatelet activities through inhibition of COX-1 and LOX activities. |
|
| In vivo: |
| J Atheroscler Thromb. 2011;18(8):659-69. | | Antiplatelet activity of obovatol, a biphenolic component of Magnolia Obovata, in rat arterial thrombosis and rabbit platelet aggregation.[Pubmed: 21512279] | Thrombosis occurs in the coronary arteries via the activation of platelets, and leads to acute myocardial infarction and sudden death. Obovatol, a major biphenolic component of Magnolia Obovata leaves, displays anti-inflammatory and acyl Co-A cholesterol acyltrasferase inhibitory effects. The purpose of this study was to determine the effects of Obovatol on thrombus formation in vivo and platelet activation in vitro and ex vivo.
METHODS AND RESULTS:
We investigated the antiplatelet and antithrombotic activities of Obovatol in rat carotid arterial thrombosis in vivo along with platelet aggregation in vitro and ex vivo. Its possible cellular mechanism of antiplatelet activity was investigated by testing PLC-γ2 activation, arachidonic acid cascade, calcium mobilization and granule secretion. Oral administration of Obovatol prevented carotid thrombosis, but also significantly inhibited collagen-induced platelet aggregation. Obovatol did not change coagulation times, such as activated partial thromboplastin time and prothrombin time, indicating that the antithrombotic effect of Obovatol might be due to antiplatelet activity rather than anticoagulation activity. Obovatol inhibited in vitro collagen- and arachidonic acid-induced rabbit platelet aggregation in a concentration-dependent manner (1-10 μM), with IC(50) values of 2.4 ± 0.8 and 4.8 ± 0.9 μM, respectively. Obovatol blocked collagen-mediated phospholipase C-γ2 phosphorylation, cytoplasmic calcium mobilization, arachidonic acid liberation and serotonin secretion.
CONCLUSIONS:
Obovatol has a potent antithrombotic effect, which may be due to antiplatelet activity. The antiplatelet activity of Obovatol is mediated by inhibition of PLC-γ2 phosphorylation. Thus, Obovatol may be a potential candidate to treat cardiovascular disease. |
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