Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson’s Disease

Abstract

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.

Inhibitory Effects of Myricetin on Lipopolysaccharide-Induced Neuroinflammation

“…Cells were maintained and cytotoxicity was performed as described previously [18,19]. Briefly, BV2 cells were treated with myricetin at concentrations of 0.1-50 µM for 1 h, subsequently stimulated with LPS for an additional 23 h, and incubated with 1 mg/mL MTT for 2 h.…”

“…Myricetin (dissolved in saline) was administered intraperitoneally once per day for 7 days. 2 h after the last drug administration, LPS (dissolved in saline) was injected intraperitoneally at a dose of 5 mg/kg [18,19].…”

Cicadidae Periostracum Attenuates Atopic Dermatitis Symptoms and Pathology via the Regulation of NLRP3 Inflammasome Activation

“…Moreover, in traditional Chinese medicine, CP is known as “Chantui” and has long been used to treat soreness of the throat, hoarseness, itching, and spasms, among other symptoms [ 15 , 16 ]. Recently, we reported the CP effectiveness in an MPTP-induced Parkinson's disease mouse model, via the regulation of the nurr1 gene [ 17 ]. Additionally, previous studies reported that the Periostracum cicada inhibits oxidative stress and inflammation caused by UVB irradiation in HaCaT keratinocytes [ 18 ].…”

Rapid and Simple Species Identification of Cicada Exuviae Using COI-Based SCAR Assay

“…CP has long been used as a traditional medicine to treat epilepsy, shock, smallpox, sedation, edema, and night-terror symptoms in Korea [12], and throat soreness, hoarseness, itching, and spasms in China [13]. Over the past few decades, many studies have demonstrated the pharmacological effects of CP, such as anticonvulsive, sedative, and hypothermic effects [14], as well as antianaphylactic [15], antiacne [16], antibacterial [17], anti-inflammatory [18,19], antiallergic [20], antitussive, expectorant, and antiasthmatic effects [21], and antiproliferative effects against cancer [22].…”

“…Over the past few decades, many studies have demonstrated the pharmacological effects of CP, such as anticonvulsive, sedative, and hypothermic effects [14], as well as antianaphylactic [15], antiacne [16], antibacterial [17], anti-inflammatory [18,19], antiallergic [20], antitussive, expectorant, and antiasthmatic effects [21], and antiproliferative effects against cancer [22]. Furthermore, a recent study revealed that CP benefits patients with Parkinson's disease by protecting dopaminergic neurons [12]. To ensure efficacy, the precise identification of the cicada species is necessary.…”