Bisdemethoxycurcumin exerts a cell-protective effect via JAK2/STAT3 signaling in a rotenone-induced Parkinson’s disease model in vitro

He, Duanqun; Chen, Shuangxi; Xiao, Zijian; Wu, Honglu; Zhou, Guijuan; Xu, Chenlin; Chang, Yunqian; Li, Yihui; Wang, Gang; Xie, Ming

doi:10.5603/fhc.a2020.0011

Cited by 18 publications

(9 citation statements)

References 35 publications

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“…Western blot analysis was conducted as described in previous studies. − After the sample loading buffer was added, the tissue lysates were heated at 95 °C for 15 min and subjected to 10% SDS–PAGE, following an electroblot onto PVDF membranes. Then, membranes were blocked with 5% BSA diluted in Tris–HCl saline buffer for 1 h, following an incubation with the following primary antibodies: rabbit anti- nNOS (1:1000, ab76067, Abcam) or mouse anti-β-actin (1:1000; ab8226, Abcam) overnight at 4 °C.…”

Section: Materials and Methodsmentioning

confidence: 99%

Artemisinin Facilitates Motor Function Recovery by Enhancing Motoneuronal Survival and Axonal Remyelination in Rats Following Brachial Plexus Root Avulsion

Chen

et al. 2021

ACS Chem. Neurosci.

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Artemisinin (ART), a well-known antimalarial medicine originally isolated from the plant Artemisia annua, exerts neuroprotective effects in the nervous system owing to an antioxidant effect. Here, we determined whether ART is capable of inhibiting the oxidative stress to enhance motoneuronal (MN) survival to promote motor function recovery of rats following brachial plexus root avulsion (BPRA) with reimplantation surgery. Rats following BPRA and reimplantation were subcutaneously injected with 500 μL of PBS or 16 mg/mL ART once daily for 7 days after surgery. Terzis grooming test (TGT), histochemical staining, real-time polymerase chain reaction, and Western blot were conducted to determine the recovery of motor function of the upper limb, the survival rate of MNs, the oxidative stress levels in the ventral horn of the spinal cord, the morphology of abnormal musculocutaneous nerve fibers, the remyelination of axons in musculocutaneous nerves, and the degree of bicep atrophy. ART significantly increased TGT score, improved the survival of MNs, inhibited the oxidative stress, ameliorated the abnormal morphology of fibers in the musculocutaneous nerve, promoted the remyelination of axons, and alleviated muscle atrophy. Take together, ART can improve the survival of MNs and axonal remyelination to promote the motor function recovery via inhibiting oxidative stress, suggesting that ART may represent a new approach to the therapy of spinal root avulsion.

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Section: Materials and Methodsmentioning

confidence: 99%

Artemisinin Facilitates Motor Function Recovery by Enhancing Motoneuronal Survival and Axonal Remyelination in Rats Following Brachial Plexus Root Avulsion

Chen

et al. 2021

ACS Chem. Neurosci.

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“…Interestingly, another anti-diabetic drug MCC-555 reported to sensitize insulin signalling, can aid in the proper management of blood glucose levels, and amend inflammatory responses during SARS-CoV-2 infections 60,61 . Bisdemethoxycurcumin, a naturally occurring curcumin analogue, and Icilin, an activator of Transient Receptor Potential Melastatin–8 (TRPM8), are reported to possess anti-inflammatory properties and may also attenuate systemic inflammation or lung injury 62,63 . The inhibitory potential of the identified compounds and their reported clinical and pharmacological profile indicates that repurposing these drugs as monotherapy or combination therapy, should substantially speedup the drug development process against COVID-19 (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid

Dhaka

Singh

Choudhary

et al. 2022

Preprint

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SARS-CoV-2 nucleocapsid protein (N-protein) is a virus specific multitasking protein, responsible for recognition and encapsidation of the viral genome. The N-terminal domain (NTD) of N-protein has a major role of packaging viral RNA genome into a long helical nucleocapsid structure. In this study, using structure-based drug repurposing strategy, small molecules from a FDA approved, natural product, and LOPAC1280 libraries have been virtually screened against the RNA binding pocket of SARS-CoV-2 NTD and twelve candidate molecules with high binding affinity were identified. Highly sensitive isothermal titration calorimetry (ITC) method was utilized to confirm binding of these molecules to purified NTD protein. In vitro cell-based SARS-CoV-2 antiviral assays demonstrate that nine of these identified molecules are highly efficacious in inhibiting virus replication with half maximal effective concentration (EC50) ranging from 0.98 μM-10 μM. FDA approved drugs: Telmisartan, an angiotensin II type 1 (AT1) receptor antagonist used in the management of hypertension and Bictegravir, an HIV-1 integrase inhibitor showed significant inhibitory activity against SARS-CoV-2 with a EC50 values of 1.02 μM and 8.11 μM respectively. Additionally, Bisdemethoxycurcumin, a natural analogue of curcumin and MCC-555, an anti-diabetic drug exerted antiviral activity with EC50 values of 1.64 μM and 4.26 μM, respectively. Taken together, this is the first report of drug molecules targeting the NTD of SARS-CoV-2 N-protein and the data presented in this study exhibit high potential for development of COVID-19 therapy based on drug repurposing

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“…In addition, we employed the JAK2/STAT3 pathway inhibitor SC99 for the joint experiments. He et al have discovered a protective influence in a rotenone-induced PD model via enhancing the JAK2/STAT3 pathway (He et al, 2020). Wang et al have also shown that AS-IV can activate the JAK2/STAT3 pathway to stimulate angiogenesis, thereby playing a role in the clinical treatment of ischemic diseases (Wang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…JAK2/STAT3 pathway is implicated in the neuroprotective effect of linagliptin on behavior disorders in mice (Elbaz et al, 2018). Bisdemethoxycurcumin is reported to play a protective role in a rotenone-induced PD model via the JAK2/STAT3 signaling pathway (He et al, 2020). However, whether AS-IV can prevent the injury of 6-OHDA-treated SH-SY5Y cells via regulating the JAK2/STAT3 pathway remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Xu¹,

Yang²,

Huang³

et al. 2021

Front. Neurosci.

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ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and MethodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

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Bisdemethoxycurcumin exerts a cell-protective effect via JAK2/STAT3 signaling in a rotenone-induced Parkinson’s disease model in vitro

Cited by 18 publications

References 35 publications

Artemisinin Facilitates Motor Function Recovery by Enhancing Motoneuronal Survival and Axonal Remyelination in Rats Following Brachial Plexus Root Avulsion

Artemisinin Facilitates Motor Function Recovery by Enhancing Motoneuronal Survival and Axonal Remyelination in Rats Following Brachial Plexus Root Avulsion

Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

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