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Natural Product Compounds from Plants in Neurodegenerative Diseases
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Priya Darshani, Md TanjimAlam, Prem P. Tripathi, V.S. Pragadheesh
Root ethanolic extract of Nardostachys jatamansi (D.Don) DC. delayed the neuronal injury induced in the 6-OHDA rat model of PD. Animals treated with this extract significantly attenuated the neurotoxin-induced lipid peroxidation led to the loss of catecholamine and increased the glutathione (GSH) content (Ahmad et al., 2006). Phytoconstituents like crocin and crocetin of Crocus sativus L. executed neuroprotective activity through antioxidant, anti-inflammatory and immunoregulatory pathways. Cannabinoids from the Cannabis sativa L. such as delta-9-tetrahydrocannabinol (THC) and cannabidiol showed neuroprotection through their antioxidant activity. Cannabinoid derivatives, namely AM404 and WIN-55212–2, showed therapeutic activity by recovering affected MAO dopaminergic neurons and constrain excitotoxicity, glial activation and oxidative injury that prevented the deterioration of nigrostriatal neurons. Additionally, cannabinoid compounds such as CE-178253, oleoylethanolamide, nabilone and HU210 have shown their consistent effects against bradykinesia and levodopa-induced dyskinesia in PD (Carrera and Cacabelos, 2019; Pertwee, 2015; Concannon et al., 2015).
Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Crocetin (Figure 12.40) is a naturally occurring apocarotenoid dicarboxylic acid found in the crocus flower and the fruits of Gardenia jasminoides. The chemical structure of crocetin forms the central core of crocin, the compound responsible for the color of saffron, and is claimed to contribute to the diverse health benefits reported for it including chemopreventive activity, although the mechanisms for this are unclear.
Carotenoids in Alzheimer’s Disease
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Crocus sativus (saffron) belongs to the Iridaceae family and has been extensively cultivated and used in India, Iran, Morocco, Greece, Turkey, Italy, Spain, Azarbaijan, Pakistan, Egypt, and China (Bhat and Broker, 1953; Leone et al., 2018). The active components of saffron include crocin and crocetin, which are atypical carotenoids with a 20-carbon atom chain (unlike the 35–40 carbon atom chains of other carotenoid pigments), with two carboxylic groups on either side (Leone et al., 2018). Crocins are carotenoids, which exhibit high water solubility due to the occurrence of a sugar moiety (Leone et al., 2018). Crocetin is an important antioxidant that has been extensively studied for its numerous health benefits (Frank 1961; Leone et al., 2018). Crocin has shown substantial protection against L-glutamate-induced damage in the HT22 mouse hippocampal neuron cell line by reducing the apoptotic rate, decreasing mitochondrial impairment, and attenuating intracellular reactive oxygen species (ROS) accumulation (Wang et al., 2019). Therefore, crocin is a potential compound for the treatment of AD by intervening with the oxidative stress-associated apoptosis signaling pathway (Wang et al., 2019).
Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer’s disease
Published in Expert Review of Neurotherapeutics, 2021
Marjan Talebi, Eleni Kakouri, Mohsen Talebi, Petros A. Tarantilis, Tahereh Farkhondeh, Selen İlgün, Ali Mohammad Pourbagher-Shahri, Saeed Samarghandian
Crocetin prevents the toxic effects of Aβ accumulation. In the study of Ahn et al. (2011), the authors used lyophilized Aβ protein and the formation of aggregates was tested in three independent steps including fresh Aβ protein, pre-formed fibrils, and pre-formed Aβ-oligomers. In all these cases, the addition of crocetin managed to hinder the formation of either of the de novo Aβ fibrils or the progression of Aβ oligomers. This was probably due to the capacity of crocetin to pass the BBB [153]. Crocetin was also tested on CD14+ monocytes derived from AD patients, against its capacity to degrade Aβ protein. Crocetin promoted Aβ degradation via activation of cathepsin B, a protease whose role in AD disease is to protect against Aβ intoxication [154,155]. In in vitro tests, using Hela cells, crocetin diminished Aβ production. The same effect was also observed following in vivo experiments in APP-SW transgenic mice, where administration of crocetin for 6 months lowered levels of Aβ insoluble fraction and contemporaneously improved learning and memory cognitive functions. The anti-inflammatory effect of crocetin was also examined and proved by its capacity to reduce levels of NF-kB-p65 and p53 tumor suppressor, indicating that apoptosis was attenuated. This was also supported by the inhibition of related inflammation cytokines entailing TNF-α, IL-1β, IL-8, and IL-6, whereas levels of IL-10, an anti-inflammatory interleukin, were increased [156].
Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects
Published in Nutritional Neuroscience, 2020
Leila Mohammadzadeh, Khalil Abnous, Bibi Marjan Razavi, Hossein Hosseinzadeh
Anti-inflammatory effects of crocin and crocetin have been reported in several studies suggesting that their anti-inflammatory effects may be related to antioxidant activity.70 The suppressive activities of crocin and crocetin on proinflammatory mediators including NO, IL-1β, TNF-α have been identified.71 In addition, in another study crocin reduced the mRNA expression of TNF-α, IL-1β, IL-6, interferon-γ (IFN-γ), NF-κB, COX-2 in chemically induced colitis in mice.72 Also, crocin and crocetin decreased lipopolysaccharide-stimulated microglial cell generation of TNF-α, IL-1β and NF-κB activation.71 Since, some anti-inflammatory drugs could reduce the risk of AD and in some cases enhance cognitive performance, thus anti-inflammatory effects of crocin may have a role in its ability to protect memory impairment induced by malathion.73,74
Crocus sativus L. Causes a Non Apoptotic Calpain Dependent Death in C6 Rat Glioma Cells, Exhibiting a Synergistic Effect with Temozolomide
Published in Nutrition and Cancer, 2019
Dimitrios Giakoumettis, Chryssa Pourzitaki, Theofanis Vavilis, Anastasia Tsingotjidou, Anastasia Kyriakoudi, Maria Tsimidou, Marina Boziki, Antonia Sioga, Nikolaos Foroglou, Aristeidis Kritis
The HPLC system consisted of a pump, model P4000 (Thermo Separation Products, San Jose, CA, USA), a Midas autosampler (Spark, Emmen, The Netherlands), and a UV 6000 LP DAD (Thermo Separation Products). Separation was carried out on a LiChroCART Superspher 100 C18 (125 × 4 mm i.d.; 4 µm) column (Merck, Darmstadt, Germany). The elution system used consisted of a mixture of water–acetic acid (1%, v/v) (A) and acetonitrile (B). The linear gradient was 20%–100% B in 20 min. The flow rate was 0.5 ml/min and the injection volume was 20 µl. The analytical sample was prepared from the crude saffron extract (0.001 g/10 ml) after dilution (1:2, v/v) and filtration through a 0.45 µm membrane filter. Chromatographic data were processed using the ChromQuest Version 3.0 software (Thermo Separation Products). Monitoring was in the range of 200–550 nm and quantification of crocetin esters was carried out by integration of the peak areas at 440 nm. Peak identification of trans-crocin 1 and trans-crocin 2 was achieved by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) as previously described by (51). Quantification of crocetin esters was accomplished with the aid of a calibration curve of crocin 1 within the range 27.5–475 ng/10 µl [y = 38683x – 710440; R2=0.99 (n = 7)].