Protective Effect of Natural Products against Huntington’s Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Lum, Pei Teng; Sekar, Mahendran; Gan, Siew Hua; Bonam, Srinivasa Reddy; Shaikh, Mohd Farooq

doi:10.1021/acschemneuro.0c00824

Cited by 35 publications

(40 citation statements)

References 157 publications

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“…Natural products, particularly plant-based medicines, have received a lot of attention in the last decade, due to their efficacy in disease prevention and treatment. [220][221][222][223] In this Figure 7 Effects of natural products on numerous skin conditions and possible drug delivery system. Nanocarriers are currently being used as a vehicle to deliver natural products to specific targeted regions in a regulated manner, as well as to overcome some of the drawbacks pertaining to the free compounds, such as poor bioavailability and rapid degradation.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Zaid¹,

Sekar²,

Bonam³

et al. 2022

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The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, welltolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Zaid¹,

Sekar²,

Bonam³

et al. 2022

DDDT

Self Cite

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“…Most common examples are catechin, curcumin, epigallocatechin gallate, and quercetin. 4 It is shown that polyphenol binds with protein/peptide through Schiff base formation. This involves reaction between primary amine groups of protein/peptide and ketone/aldehyde groups of oxidized polyphenol to produce imine bonds.…”

Section: Inhibiting Protein Aggregation By Antiamyloidogenic Small Mo...mentioning

confidence: 99%

“…Other molecules include thioflavin T derivatives that bind with the hydrophobic cavity of protein fibrils, different small molecule drugs that inhibit Aβ production or modulate enzyme activity. 4,[7][8][9]11 A wide variety of nanoscale materials such as nanoparticle, polymer micelle, and 2D materials (e.g., graphene) are identified for inhibiting protein aggregation. 6,7,27 They modulate fibril nucleation−growth kinetics via protein adsorption/binding on their surface.…”

Section: Inhibiting Protein Aggregation By Antiamyloidogenic Small Mo...mentioning

confidence: 99%

Inhibiting Protein Aggregation by Small Molecule-Based Colloidal Nanoparticles

et al. 2021

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Conspectus Protein aggregation is associated with different human diseases such as Alzheimer’s, Huntington’s, Parkinson’s, diabetes type II, and cataracts. Currently no effective treatment exists for many of these diseases, particularly for neurological disorders. Ongoing research focuses on understanding the origin of protein aggregation, nucleation–growth mechanism of protein aggregation, origin of cytotoxicity of protein aggregates, cellular response of toxic protein aggregates, progress of diseases at intra/extracellular space, and drug developments for respective diseases. Key issues are the identification of molecular drugs that can inhibit protein aggregation at early stage, lowering of toxicity due to protein aggregates, delivery of drugs to remote organ and intracellular space, clearing matured protein aggregates from cell/extracellular space/brain, and design of effective therapeutic strategy. Chemists and materials scientists have identified a wide variety of antiamyloidogenic small molecules, macromolecules, and nanomaterials. It is shown that antiamyloidogenic molecules prevent protein oligomerization via binding to protein, masking metal ions (via chelating with metal ions) that are responsible for protein aggregation via generating reactive oxygen species (ROS), and lowering protein–protein interaction via macromolecular crowding effect. Similarly, nanoscale materials with curved surface and multiple chemical functional groups act as adsorption/binding sites of proteins, modulate nucleation–growth kinetics of protein aggregation, and delay/inhibit protein aggregation in many cases. However, performance of all these antiamyloidogenic materials needs significant improvement, and proper therapeutic strategies are required for effective drug development. In this Account, we describe that the performance of antiamyloidogenic molecules can be greatly improved via appropriate design into colloidal and nanoparticle form. We first discuss different human diseases that are linked with protein aggregation, location and mechanism of protein aggregation, adverse effect of protein aggregates on cell functions, and progress of different diseases due to these effects. Next, we discuss different classes of antiamyloidogenic materials, their mechanism of inhibiting protein aggregation, and existing approaches for their utilization under in vitro/in vivo conditions. Further, we show that antiamyloidogenic performance of small molecules can be enhanced as high as 100 000-times if they are transformed into appropriately designed colloidal nanoparticles. In particular, we explain that such enhanced performance is due to increased bioavailability at intra/extracellular space, modular binding property with protein, and higher brain delivery option in nanoparticle form. Next, we discuss different strategies for the preparation of colloidal nanoparticle where antiamyloidogenic molecules are terminated or loaded with nanoparticle and polymer micelle and their mechanism of action. Finally, we discuss that a wide variet...

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“…In the present study, in addition to the behavioral assessments, we performed several biochemical estimations to explicate alterations that were linked with HD. Previously reported studies pointed out the influence of several biochemical parameters that contributed to the strengthening of the pathogenesis of HD [ 48 , 52 , 53 ]. The biochemical estimations mainly involved the assessment of oxidative stress parameters, estimation of proinflammatory mediators, quantification of several brain enzymatic activities (AchE and succinate dehydrogenase), and evaluation of the expression of several amines.…”

Section: Discussionmentioning

confidence: 99%

Anti-Huntington’s Effect of Rosiridin via Oxidative Stress/AchE Inhibition and Modulation of Succinate Dehydrogenase, Nitrite, and BDNF Levels against 3-Nitropropionic Acid in Rodents

et al. 2022

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Background: Rosiridin is a compound extracted from Rhodiola sachalinensis; water extracts of Rhodiola root elicit positive effects on the human central nervous system and improve brain function. They are also thought to be beneficial to one’s health, in addition to being antioxidants. The present study aims to evaluate the anti-Huntington’s effect of rosiridin against 3-nitropropionic acid (3-NPA)-induced Huntington’s disease (HD)-like effects in rats. Materials and Methods: The acute toxicity in rats was elucidated to track the conceivable toxicities in the rats. The effectiveness of rosiridin at a dosage of 10 mg/kg was evaluated against several dose administrations of 3-NPA-induced HD-like symptoms in the rats for 22 days. At the end of the study, behavioral parameters were assessed as a hallmark for the cognitive and motor functions in the rats. Similarly, after the behavioral assessment, the animals were sacrificed to obtain a brain tissue homogenate. The prepared homogenate was utilized for the estimation of several biochemical parameters, including oxidative stress (glutathione, catalase, and malondialdehyde), brain-derived neurotrophic factor and succinate dehydrogenase activity, and the glutamate and acetylcholinesterase levels in the brain. Furthermore, inflammatory mediators linked to the occurrence of neuroinflammation in rats were evaluated in the perfused brain tissues. Results: The rosiridin-treated group exhibited a significant restoration of behavioral parameters, including in the beam-walk test, latency in falling during the hanging wire test, and percentage of memory retention during the elevated plus-maze test. Further, rosiridin modulated several biochemical parameters, including oxidative stress, pro-inflammatory activity, brain-derived neurotrophic factor, nitrite, and acetylcholinesterase as compared to disease control group that was treated with 3-NPA. Conclusions: The current study exhibits the anti-Huntington’s effects of rosiridin in experimental animal models.

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Protective Effect of Natural Products against Huntington’s Disease: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Cited by 35 publications

References 157 publications

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Inhibiting Protein Aggregation by Small Molecule-Based Colloidal Nanoparticles

Anti-Huntington’s Effect of Rosiridin via Oxidative Stress/AchE Inhibition and Modulation of Succinate Dehydrogenase, Nitrite, and BDNF Levels against 3-Nitropropionic Acid in Rodents

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