The attenuating effects of plumbagin on pro-inflammatory cytokine expression in LPS-activated BV-2 microglial cells

Abstract

Activated microglial cells produce the pro-inflammatory mediators such as nitric oxide (NO) and cytokines. The excessive release of these mediators can lead to neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Inhibition of the release of these pro-inflammatory molecules may prevent or halt the progression of these diseases. Plumbagin (PL), a naphthoquinone compound in the roots of the traditional medicinal plant Plumbago zeylanica L., showed anti-inflammatory effects on macrophages. However, PL effects on activated microglia remain unknown. In the present study, PL has been examined for its anti-inflammatory effect on LPS – activated microglial BV-2 cells. In this study, NO and iNOS expression were investigated in BV-2 microglial cells in the presence of PL or the selective iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). The results obtained indicate that PL was > 30-fold potent than L-NIL in inhibiting NO production with an IC50 of 0.39 μM. Our immunofluorescence study confirmed the ability of PL to significantly inhibit iNOS expression in the activated microglia. Furthermore, the extracellular microglial pro-inflammatory cytokine expression in the presence of 2 μM of PL was detected, quantified, and validated using cytokine antibody protein arrays and quantitative ELISA. The results obtained showed that PL significantly downregulated the expression of many cytokines including IL-1α, G-CSF, IL-12 p40/p70, MCP-5, MCP-1, and IL-6. In conclusion, PL potency in attenuating multiple pro-inflammatory agents indicates its potential to be used for neurodegenerative diseases.

Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells

“…Microglia cells can exert neuroprotective and neurotoxic functions in the brain. Activated by stimuli (e.g., LPS), they release pro-inflammatory factors such as NO, PGE 2 , chemokines, and cytokines [ 27 ], which cause neuronal death, and IL-6, which can up-regulate amyloid precursor protein synthesis and processing. These processes are considered hallmarks of neuro-inflammation involved in the pathological process of neurodegenerative diseases [ 28 ].…”

Quinones as preventive agents in Alzheimer’s diseases: focus on NLRP3 inflammasomes

“…Plumbagin is a naphthoquinone which is mostly present in Plumbago species, [ 65 ] which shows several pharmacological activities, including anti‐inflammatory, [ 66 ] neuroprotection, [ 67 ] antitumour activity [ 68 ] and antioxidant [ 69 ] effects. Plumbagin improves cognitive deficits and astrogliosis in STZ induced mouse model of AD via Nrf2/ARE mediated suppression of astrogliosis and inhibition of β‐secretase enzyme.…”

The inhibitory effects of plumbagin on the NF-қB pathway and CCL2 release in racially different triple-negative breast cancer cells

“…Recent reports indicate the use of PL in treating diseases that are associated with inflammation, such as rheumatoid arthritis [ 29 ]. Our previous study indicates that PL has a potent anti-inflammatory effect in BV-2 microglia cells [ 30 ]. The PL anticancer properties have been studied in many cancers including breast [ 31 ], prostate [ 32 , 33 ], and ovarian [ 34 ] cancers.…”