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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
Resveratrol, a polyphenol antioxidant found in cranberries, peanuts, grapes and red wine, has shown its beneficial role in treating PD. Resveratrol protects the SH-SY5Y cells by progressively inducing the collapse of α-synuclein. A recent in vivo study reported that resveratrol possesses the therapeutic capability for rotenone, 6-OHDA and MPTP-induced PD by preventing ER stress-mediated apoptosis, over-expressing antioxidant enzymes and suppressing α-synuclein expression, respectively. Nanoencapsulation of resveratrol increased its bioavailability, thus prolonging neuronal survival against oxidative stress. An emulsion of resveratrol and Vitamin E increased the availability of resveratrol in the brain and thus reduced the oxidative stress of PD, improved coordination movements and memory performance in the mouse model. Atremorine, a phytobioactive agent obtained from Vicia faba L., has demonstrated protection against MPTP-induced dopaminergic neurodegeneration, inhibition of MPTP-induced microglial activation and neurotoxicity in substantia nigra along with improvement of motor function in MPTP-induced mice. According to preclinical and clinical studies, atremorine is an effective nutraceutical and manifests anti-inflammatory, neuroprotective and antioxidant effects, presenting the ability to regulate neuroendocrine function in PD (Carrera and Cacabelos, 2019).
Micronutrients for the Prevention and Improvement of the Standard Therapy for Parkinson’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Decreased expression of miR-205 and elevated levels of its target protein LRRK2 were found in the autopsied frontal cortex tissues of patients with sporadic PD.97 Reduced expression of miR-34b and increased levels of its target protein adenosine A2A receptor (A2AR) were found in the autopsied brain tissue of PD patients as well as in the putamen of incidental PD cases (Braak stages 1-2).87 In early-stage PD, decreased expression levels of miR-34b and elevated levels of pathogenic protein A2AR were found in the brain.98 Deletion of these microRNAs reduced the viability of differentiated dopaminergic neurons (SH-SY5Y cell line). Downregulation of the expression of miR-34b and miR-34c increased the levels of alpha-synuclein causing neurodegeneration.99 These findings suggest that miR-34b and miR-34c may target more than one protein. Alterations in the levels of microRNAs in PD could be due to changes in their transcription, processing by Dorsa and Dicer in the nucleus and cytoplasm, respectively or their stability.
Novel Drug Delivery Systems for Nutraceuticals with Anticancer Properties
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Priyanka Bhatt, Imran Vhora, Rohan Lalani
Newer approaches include co-delivery of anticancer nutraceuticals with other nutraceuticals or pharmaceuticals for enhanced effectiveness against cancer cells. A lot of research has been directed at chemosensitization and chemoenhancement of nutraceuticals to anticancer pharmaceuticals. Wang et al. developed mPEG-PCL micelles co-loaded with curcumin and doxorubicin for systemic therapy [90]. In vivo studies on the LL/2 lung carcinoma xenograft model in mice demonstrated that the co-loaded micelle formulation enhanced the efficacy compared to micelles of individual drugs or free drugs, demonstrating the synergistic effects between curcumin and doxorubicin as well as effectiveness of delivery system, which provided sustained levels of drugs in blood. Moreover, co-delivery can improve the bioavailability of the anticancer nutraceuticals. Recently, electron spray method has been developed for preparation of curcumin-loaded zein nanoparticles coated with piperine-embedded chitosan layer in order to get advantages of piperine’s pGP inhibitory activity and chitosan’s absorption enhancement activity [91]. The nanoparticles have shown increased in vitro cytotoxicity against SH-SY5Y neuroblastoma cells. In another study, PLGA nanoparticles were co-loaded with rapamycin (pGP substrate) and piperine to enhance the oral absorption and enhance its effectiveness [92]. In another study, triptolide-loaded and celastrol-loaded silk fibroin nanoparticles were prepared [93]. Both nanoparticles showed—two- to threefold more potent cytotoxicity against MIA PaCa-2 and PANC-1 pancreatic cancer cell lines. Moreover, combination of both nanoparticles showed synergistic activity. Figure 10.4 is a graphical representation of various nanocarrier systems explored for the delivery of anticancer nutraceutical drugs for cancer therapy.
Network pharmacology and in vitro experimental verification to explore the mechanism of Sanhua decoction in the treatment of ischaemic stroke
Published in Pharmaceutical Biology, 2022
Wei Zhang, Li Zhang, Wen jun Wang, Shanbo Ma, Mingming Wang, Minna Yao, Ruili Li, Wei wei Li, Xian Zhao, Dongmei Hu, Yi Ding, Jingwen Wang
SHD reduced ischaemia–reperfusion injury, as verified by experiments. As shown in Figure 7(A), SHD alone (12.5–100 μg/mL) showed slight effects on cell viability compared with the sham group. As shown in Figure 7(B), SH-SY5Y cell viability was significantly decreased in the OGD group (p < 0.05). However, pre-treatment with SHD (12.5, 25, 50 and 100 μg/mL) exhibited a protective effect and significantly improved the cell survival rate (p < 0.05). The protective effect of SHD was dose-dependent, and the median effective dose (ED50) value was 47.1 μg/mL. To further investigate the protective effect of SHD, LDH levels were measured. As shown in Figure 7(C), the OGD groups had distinctly increased LDH levels (p < 0.05). Conversely, SHD at different concentrations lowered LDH release (p < 0.05). As shown in Figure 7(D,E), the proportion of apoptotic cells in the OGD group was apparently increased compared with that in the sham group (p < 0.01). SHD treatment prevented the apoptosis induced by OGD (p < 0.01). Moreover, treatment with 100 μg/mL SHD elicited a greater protective effect against apoptosis than treatment with 12.5, 25 and 50 μg/mL SHD (p < 0.01). These findings confirmed the protective effect of SHD against neuronal cell damage.
Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Zofia Chrienova, Eugenie Nepovimova, Rudolf Andrys, Rafael Dolezal, Jana Janockova, Lubica Muckova, Lenka Fabova, Ondrej Soukup, Patrik Oleksak, Martin Valis, Jan Korabecny, José Marco-Contelles, Kamil Kuca
Since the target organ of proposed hybrids is supposed to be CNS, the neuronal toxicity profile of selected compounds 7, 15, 20, 21, 23, and 25 on human neuroblastoma cell line (SH-SY5Y) using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetraziolium bromide (MTT) assay, was determined. The results are presented in Table 4, in terms of mean concentration to cause 50% growth inhibition (IC50). THA, 6-chlorotacrine, 7-MEOTA, and 7-PhOTHA were tested as well as reference compounds. Reduction in cell viability of SH-SY5Y was observed for all selected hybrids. Looking at the IC50 values of 7-PhOTHA analogues 7, 15, and 25 and 6-chlorotacrine derivative 23, it is evident that they exerted more pronounced ability to decrease the viability of neuronal cells compared to THA. Their toxicity ranged in the same order of magnitude as their parent compounds 7-PhOTHA and 6-chlorotacrine. Although the insertion of the propylene linker in compounds 20 and 21 led to increase in the inhibitory potential towards ChEs comparing THA, in term of in vitro neurotoxicity, the effect was quite opposite, i.e. insertion of the side chain caused an increase in cytotoxicity of mentioned compounds. Such phenomenon could be attributed to the higher lipophilicity of the hybrids. Quite interestingly, compound 23, active towards AChE and ligand 15, active towards MAO-B at approx. 1 μM concentration, could be considered relatively safe.
Differential expression and significance of miRNAs in plasma extracellular vesicles of patients with Parkinson’s disease
Published in International Journal of Neuroscience, 2022
Shishuai Xie, Wanxiang Niu, Feng Xu, Yuping Wang, Shanshan Hu, Chaoshi Niu
The viability of SH-SY5Y cells was measured by using CCK-8 (Beyotime Biotechnology, Shanghai, China) assay. SH-SY5Y cells were seeded into 96-well plates with 1 × 104 cells/well for 12 h. Then SH-SY5Y cells were induced by different concentrations of MPP+ (0, 0.25, 0.5, 1 and 2 mM, 1 mM = 1 mol/mL; Sigma, St. Louis, MO) for 12, 24, 36 and 48 h in 96-well plates. Next, CCK8 solution and medium were mixed in a ratio of 1:10. After removal of the culture medium, a 100 μL mixture as discussed above was added to each well and the plates were incubated at 37 °C for 2 h at the indicated time points. The absorbance of each sample was measured at 450 nm using a microplate reader (TECAN, Männedorf, Switzerland). All experiments were performed independently in triplicate. The absorbance of control group was considered as 100% of cell viability.