β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, β3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.     

Rosiridin Attenuates Scopolamine-Induced Cognitive Impairments in Rats via Inhibition of Oxidative and Nitrative Stress Leaded Caspase-3/9 and TNF-α Signaling Pathways

Aim: A monoterpene and bioactive component of the plant Rhodiola rosea (R. rosea), rosiridin has beneficial effects on the human central nervous system and enhances brain function. The goal of this scientific study was to determine if rosiridin might shield rats from neurocognitive problems induced by scopolamine. Methods: To track the potential toxicities in rats, the acute toxicity in rats was clarified. Rosiridin at a dose of 10 mg/kg was tested in rats for 14 days. At the conclusion of the investigation, behavioral parameters that were used to identify the rats’ cognitive and motor abilities were evaluated. Several biochemical parameters were estimated using the prepared homogenate, including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), radical scavengers produced by the body (Catalase-CAT, superoxide dismutase-SOD, and reduced glutathione-GSH), indicators of oxidative and nitrative burnout, pro-inflammatory (Interleukins- IL-1β, IL-6, interferon gamma IFN-ꝩ, and tumor necrosis factor-TNF-α), and cell apoptosis caspases 3 and 9. Results and Conclusion: A significant behavioral parameter restoration was seen in the rosiridin-treated group, including reduction in latency time during acquisition and retention trial in the Morris water maze test, and percentage of spontaneous alterations in the y-maze test, when compared to the disease control group that received scopolamine; rosiridin also altered the oxidative stress and neuroinflammatory markers, as well as restoring Ach and ChAT activities and normalizing GSH, SOD, MDA, TNF-α, nitrate, IL-1β, IL-6, IFN-ꝩ, caspases 3 and 9 levels. The results imply that rosiridin limits the effect of scopolamine on rat cognitive function.     

Anti-Inflammatory Effects of 6-Methylcoumarin in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and NF-κB Signaling Pathways

Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E₂ (PGE₂)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE₂ without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.     

Santamarine Shows Anti-Photoaging Properties via Inhibition of MAPK/AP-1 and Stimulation of TGF-β/Smad Signaling in UVA-Irradiated HDFs

Chronic UVA exposure results in elevated reactive oxygen species in skin which leads to photoaging characterized as upregulated matrix metalloproteinase (MMP)-1 and loss of collagen. Therefore, natural antioxidants are hailed as promising agents to be utilized against photoaging. In the current study, reynosin and santamarine, two known sesquiterpene lactones isolated from Artemisia scoparia, were analyzed for their anti-photoaging properties in UVA-irradiated human dermal fibroblasts (HDFs). Results showed that UVA irradiation (8 J/cm²) upregulated the MMP-1 secretion and expression, and suppressed collagen production, which were significantly reverted by santamarine treatment (10 µM). Although both reynosin and santamarine exhibited ROS scavenging abilities, reynosin failed to significantly diminish UVA-stimulated MMP-1 release. UVA-irradiated HDFs showed increased collagen production when treated with santamarine. As a mechanism to suppress MMP-1, santamarine significantly suppressed the UVA-induced phosphorylation of p38 and JNK and nuclear translocation of p-c-Fos and p-c-Jun. Santamarine promoted collagen I production via relieving the UVA-induced suppression on TGF-β and its downstream activator Smad2/3 complex. Antioxidant properties of santamarine were also shown to arise from stimulating Nrf2-dependent expression of antioxidant enzymes SOD-1 and HO-1 in UVA-irradiated HDFs. In conclusion, santamarine was found to be a promising natural antioxidant with anti-photoaging properties against UVA-induced damages in HDFs.     

Cryptotympana pustulata Extract and Its Main Active Component,Oleic Acid,Inhibit Ovalbumin-Induced Allergic Airway Inflammation through Inhibition of Th2/GATA-3 and Interleukin-17/RORγt Signaling Pathways in Asthmatic Mice

Cicadae Periostracum (CP), derived from the slough of Cryptotympana pustulata, has been used as traditional medicine in Korea and China because of its diaphoretic, antipyretic, anti-inflammatory, antioxidant, and antianaphylactic activities. The major bioactive compounds include oleic acid (OA), palmitic acid, and linoleic acid. However, the precise therapeutic mechanisms underlying its action in asthma remain unclear. The objective of this study was to determine the antiasthmatic effects of CP in an ovalbumin (OVA)-induced asthmatic mouse model. CP and OA inhibited the inflammatory cell infiltration, airway hyperresponsiveness (AHR), and production of interleukin (IL)7 and Th2 cytokines (IL-5) in the bronchoalveolar lavage fluid and OVA-specific imunoglobin E (IgE) in the serum. The gene expression of IL-5, IL-13, CCR3, MUC5AC, and COX-2 was attenuated in lung tissues. CP and OA might inhibit the nuclear translocation of GATA-binding protein 3 (GATA-3) and retinoic acid receptor-related orphan receptor γt (RORγt) via the upregulation of forkhead box p3 (Foxp3), thereby preventing the activation of GATA-3 and RORγt. In the in vitro experiment, a similar result was observed for Th2 and GATA-3. These results suggest that CP has the potential for the treatment of asthma via the inhibition of the GATA-3/Th2 and IL-17/RORγt signaling pathways.     

Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)CN bond construction

An efficient method for the construction of C(sp²)CN bonds directly from C(sp²-H) cyanation of 3-arylideneindolin-2-ones with benzoyl cyanide under transition metal-free condition is described. Various 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles were efficiently synthesized using air as an oxidant under mild conditions. This protocol has excellent functional group tolerance and can be easily scaled up with good efficiency. This reaction successfully offers an alternative to structurally diverse alkenyl nitriles.     

Rhodium-catalyzed NH-indole-directed ortho CH coupling of 2-arylindoles with diazo compounds via metal carbene migratory insertion

A high regioselective rhodium-catalyzed ortho CH coupling of 2-arylindoles with diazo compounds via NH-indole-directed CH bond activation has been developed. The catalytic reaction features mild reaction conditions, broad substrate scope and good functional group tolerability.     

Nanoparticles of Costus speciosus Ameliorate Diabetes-Induced Structural Changes in Rat Prostate through Mediating the Pro-Inflammatory Cytokines IL 6, IL1β and TNF-α

Diabetes mellitus is a common global health problem. Among the complications that are frequently associated with DM are the alternation of sexual function and fertility, especially in young men. This study aimed to assess the efficacy of nanoparticles of Costus speciosus (C. speciosus) in preserving the prostatic structure of diabetic rats and to explore the mechanism behind this effect. A model of DM was induced in male albino rats by a single intraperitoneally injection of streptozotocin (STZ, 60 mg/kg body weight). Five groups (n = 10 each) of rats were included in this study: the control, C. speciosus gold nanoparticles-treated (150 mg/kg body weight through gastric intubation for 30 days), untreated diabetic, metformin-treated diabetic (500 mg/kg/day gastric intubation for 30 days) and the C. speciosus-treated diabetic group. The blood glucose, insulin and testosterone levels as well as oxidants/antioxidants status were assessed in the serum. Gene expression of proinflammatory cytokines TNF-α, IL1β and IL-6 were assessed in the prostate homogenate. At the end of the experiment, the rats were sacrificed and the prostate was dissected out and prepared for histopathological and immunohistochemistry study using Ki67 and Bcl-2. C. Speciosus nanoparticles significantly decreased (p = 0.03) the blood glucose level while significantly increasing insulin (p = 0.01) and testosterone (p = 0.04) levels compared to the untreated diabetic rats. Oxidants/antioxidants status was markedly improved after administration of C. speciosus. Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1β and TNF-α was down-regulated in metformin- and C. speciosus-treated rats. The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67. In conclusion, the protective effect induced by C. speciosus nanoparticles on the prostate of diabetic rats might be directly mediated through the down-regulation of inflammatory cytokines and the up-regulation of antioxidant activity and indirectly mediated through the anti-hyperglycemic effect through enhancing insulin secretion.     

Structure elucidation of 11-amino-8-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam through selective acetylation and complete 1H and 13C NMR spectral assignment of the mono-, di- and triacetates

NMR techniques cannot unambiguously distinguish between 11-amino-8-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam and 8-amino-11-hydroxypentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam, both of which are possible products during the reaction of pentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-dione with Strecker reagents. Treatment of 11-amino-8-hydroxy-pentacyclo[5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane-8,11-lactam with acetic anhydride at room temperature produced a monoacetate. With acetic anhydride containing sodium acetate, a triacetate was obtained at reflux temperature. Treatment with acetyl chloride and N,N-dimethylaniline produced a diacetate. High-field 1H and 13C NMR techniques were used in the structure elucidation and assignment of the different NMR resonances of these three acetylated compounds.     

Palladium-catalyzed [5+2] oxidative annulation of N-Arylhydrazones with alkynes through CH activation to synthesize Benzo[d][1,2]diazepines

An efficient and novel method using palladium catalyst for the synthesis of benzo[d][1,2]diazepines by [5 + 2] annulation of N-arylhydrazones with alkynes has been developed. This methodology undergoes through eight membered palladacycle serving as a backbone for the formation of CC/CN bond to provide benzodiazepine derivatives in moderate to good yield.     

Synthesis of novel dithiocarbamates and xanthates using dialkyl azodicarboxylates: SN bond formation

A one?pot three?component route for the synthesis of a novel category of dithiocarbamates or xanthates is developed by a reaction of in-situ generated dithiocarbamic acids or xanthates with dialkyl azodicarboxylates under mild and catalyst-free conditions. The reaction is characterized by a wide scope, high efficiency and straightforward isolation protocol. The synthetic utility of the dithiocarbamates and xanthates was demonstrated on the preparation of symmetrical and unsymmetrical thioureas, isothiocyanates, and thiocarbamates.