Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models

Jacquet, Aurélie de Rus; Ambaw, Abeje; Tambe, Mitali A.; Ying, Sin; Timmers, Michael; Grace, Mary H.; Wu, Qingli; Simon, James E.; McCabe, George P.; Lila, Mary Ann; Shi, Riyi; Rochet, Jean-Christophe

doi:10.1039/d1fo00007a

Cited by 18 publications

(23 citation statements)

References 148 publications

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“…Rats lesioned with the PD-related neurotoxin 6-OHDA (6-hydroxydopamine) showed less motor impairment after receiving isoflavone-rich soy extract. These results imply that plant-derived isoflavones might be used as a dietary supplement to prevent the onset of Parkinson's disease in at-risk patients and to reduce neurodegeneration in the brains (de Rus Jacquet et al, 2021).…”

Section: Alzheimer's Diseasementioning

confidence: 90%

Mechanisms behind the pharmacological application of biochanin-A: a review

et al. 2023

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This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A need to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.

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Section: Alzheimer's Diseasementioning

confidence: 90%

Mechanisms behind the pharmacological application of biochanin-A: a review

et al. 2023

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“…Primary cultures were prepared via dissection of E17 embryos obtained from pregnant Sprague-Dawley rats (Harlan, Indianapolis, IN) as described [24][25][26]29 . All animal handling procedures were approved by the Purdue Animal Care and Use Committee.…”

Section: Preparation Of Rat Primary Culturesmentioning

confidence: 99%

“…Neuroprotective activities of botanical extracts and compounds were assessed as described previously [24][25][26]29 . Briefly, primary midbrain cultures (7 DIV) were incubated in the presence of extract or compound (or the corresponding vehicle) for 72 h. Next, the cultures were incubated in fresh media containing PQ (2.5 μM) or rotenone (25 nM) plus extract, compound, or vehicle for an additional 24 h. Control cultures were incubated in media without PQ, extract, or compound.…”

Section: Analysis Of Neuroprotective Activities Of Extracts and Compo...mentioning

confidence: 99%

“…An adenovirus encoding EGFP downstream of the SX2 (E1) enhancer and minimal promoter derived from the mouse heme oxygenase-1 (HO-1) gene [41][42][43] was prepared and used to monitor activation of the Nrf2 pathway in cortical astrocytic cultures and primary midbrain cultures as described 25,26,29 . Cells plated in a 96-well, black clear-bottom plate (see above) were transduced with ARE-EGFP reporter virus at an MOI of 6.25 twenty-four hours after plating (astrocytes), or at an MOI of 10 seven days after plating (midbrain cultures).…”

Section: Nrf2 Transcriptional Activity Assaymentioning

confidence: 99%

“…Polyphenols are naturally occurring molecules in plants and fruits that have been studied extensively for their potential therapeutic benefit in a number of diseases, including mild cognitive impairment 16,17 and various neurodegenerative disorders [18][19][20] . Our group and others have shown that polyphenols can alleviate neurotoxicity in preclinical models of PD, including flavonoids (a subclass of polyphenols) such as green tea polyphenols [21][22][23] , anthocyanins (ANC) [24][25][26][27] , and isoflavones [28][29][30] , as well as the phenolic acid derivative curcumin 31 and stilbenes such as resveratrol and oxyresveratrol 24,32 . Polyphenols have been shown to protect against oxidative stress in a variety of disease models by scavenging free radicals and up-regulating endogenous cytoprotective responses 33,34 .…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of polyphenol-rich extracts against neurotoxicity elicited by paraquat or rotenone in cellular models of Parkinson’s disease

Tambe

Jacquet

Strathearn

et al. 2023

Preprint

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Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O2 consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.

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Molecular mechanisms underlying the potential neuroprotective effects of Trifolium pratense and its phytoestrogen‐isoflavones in neurodegenerative disorders

Al‐Shami

Essawy

Elkader

2023

Phytotherapy Research

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Neurodegenerative disorders are heterogeneous, debilitating, and incurable groups of brain disorders that have common features including progressive degeneration of the structure and function of the nervous system. Phytoestogenic‐isoflavones have been identified as active compounds that can modulate different molecular signaling pathways related to the nervous system. The main aim is to shed the light on the molecular mechanisms followed by phytoestrogen‐isoflavones profound in the Trifolium pratense and discuss the latest pharmacological findings in the treatment of neurodegenerative disorders. Data were collected using different databases. The search terms used included “Phytoestrogens,” “Isoflavones,” “neurodegenerative disorders,” “Neuronal plasticity,” etc., and combinations of these keywords. As a result, this review article mainly demonstrates the potential neuroprotective properties of phystoestrogen‐isoflavones present in the Trifolium pratense (Red clover), particularly in neurodegenerative disorders. Phytochemical studies have shown that Trifolium pratense mainly includes more than 30 isoflavone compounds. Among them, phytoestrogen‐isoflavones, such as biochanin A, daidzein, formononetin, genistein (Gen), etc.,are characterized by potent neuroprotective properties against different neurodegenerative disorders. There are preclinical and clinical scientific evidence on their mechanisms of action involve molecular interaction with estrogenic receptors, anti‐inflammatory, anti‐oxidative, antiapoptotic, autophagic inducing, and so on. phytoestrogen‐isoflavones are the major bioactive components in the Trifolium pratense that exhibit therapeutic efficacy in the case of neurodegenerative disorders. This review provides detailed molecular mechanisms targeted by phytoestrogen‐isoflavones and experimental key findings for the clinical use of prescriptions containing Trifolium pratense‐derived isoflavones for the treatment of neurodegenerative disorders.

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Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently...

Cited by 18 publications

References 148 publications

Mechanisms behind the pharmacological application of biochanin-A: a review

Mechanisms behind the pharmacological application of biochanin-A: a review

Protective effects of polyphenol-rich extracts against neurotoxicity elicited by paraquat or rotenone in cellular models of Parkinson’s disease

Molecular mechanisms underlying the potential neuroprotective effects of Trifolium pratense and its phytoestrogen‐isoflavones in neurodegenerative disorders

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