Identification of difluorinated curcumin molecular targets linked to traumatic brain injury pathophysiology

Sahebkar, Amirhossein; Sathyapalan, Thozhukat; Guest, Paul C.; Barreto, George E.

doi:10.1016/j.biopha.2022.112770

Cited by 6 publications

(3 citation statements)

References 66 publications

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“…Curcumin can be a promising antifatigue substitute for improving exercise performance [ 506 ]. Its derivatives have anti-inflammatory actions for drug repurposing in traumatic brain injury (TBI), but their molecular targets are not clear [ 507 ].…”

Section: The Health Benefits Of Curcuminoids (Curcumin Demethoxycurcu...mentioning

confidence: 99%

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

2023

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Phenolic compounds and flavonoids are potential substitutes for bioactive agents in pharmaceutical and medicinal sections to promote human health and prevent and cure different diseases. The most common flavonoids found in nature are anthocyanins, flavones, flavanones, flavonols, flavanonols, isoflavones, and other sub-classes. The impacts of plant flavonoids and other phenolics on human health promoting and diseases curing and preventing are antioxidant effects, antibacterial impacts, cardioprotective effects, anticancer impacts, immune system promoting, anti-inflammatory effects, and skin protective effects from UV radiation. This work aims to provide an overview of phenolic compounds and flavonoids as potential and important sources of pharmaceutical and medical application according to recently published studies, as well as some interesting directions for future research. The keyword searches for flavonoids, phenolics, isoflavones, tannins, coumarins, lignans, quinones, xanthones, curcuminoids, stilbenes, cucurmin, phenylethanoids, and secoiridoids medicinal plant were performed by using Web of Science, Scopus, Google scholar, and PubMed. Phenolic acids contain a carboxylic acid group in addition to the basic phenolic structure and are mainly divided into hydroxybenzoic and hydroxycinnamic acids. Hydroxybenzoic acids are based on a C6-C1 skeleton and are often found bound to small organic acids, glycosyl moieties, or cell structural components. Common hydroxybenzoic acids include gallic, syringic, protocatechuic, p-hydroxybenzoic, vanillic, gentistic, and salicylic acids. Hydroxycinnamic acids are based on a C6-C3 skeleton and are also often bound to other molecules such as quinic acid and glucose. The main hydroxycinnamic acids are caffeic, p-coumaric, ferulic, and sinapic acids.

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Section: The Health Benefits Of Curcuminoids (Curcumin Demethoxycurcu...mentioning

confidence: 99%

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

2023

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“…In recent years, many attempts to discover new and more specific pharmacological therapies to alleviate TBI damage have been explored [ 18 , 30 , 31 ]. Causes of secondary brain injury, such as inflammation and neuronal death, can also be treated with natural compounds [ 32 , 33 , 34 , 35 ] obtained from plants; they are used in treating many diseases due to their potent antioxidant effects [ 33 , 36 , 37 ] neutralizing reactive oxygen and nitrogen species (ROS/RNS), hence mitigating inflammation. In the case of TBI, they may be used for repurposing by reducing edema and exerting protection of the blood–brain barrier [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury

2023

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Neuroinflammation is a hallmark of traumatic brain injury (TBI)’s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin–Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson’s correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost.

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“…It is also reported that genetic polymorphisms might even increase the risk of sustaining TBI [13]. Furthermore, high-throughput transcriptome profiling and virtual screening studies demonstrated that the expression level of numerous genes changed in TBI disease [12,[16][17][18][19][20][21][22][23]. Despite many preclinical and clinical investigations, no practical pharmacotherapies are thought to enhance post-TBI treatment, and TBI therapy remains an unsolved problem [16,24,25].…”

Section: Introductionmentioning

confidence: 99%

Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study

Mahmoudi

Heydari

Markina

et al. 2022

Biomedicine & Pharmacotherapy

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Identification of difluorinated curcumin molecular targets linked to traumatic brain injury pathophysiology

Cited by 6 publications

References 66 publications

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

Therapeutic Potential of Phenolic Compounds in Medicinal Plants—Natural Health Products for Human Health

Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury

Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study

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