Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

Xu, Fei; Wu, Qiaolan; Li, Lei; Gong, Jie; Huo, Ran; Cui, Weihong

doi:10.3389/fphar.2021.663776

Cited by 19 publications

(17 citation statements)

References 61 publications

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“…In addition, the long-term safety of many described drugs is also an area of concern. Therefore, further research to improve the clinical effect of these compounds is warranted ( Xu et al, 2021 ).…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease

et al. 2022

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Ageing is a progressive physiological process mediated by changes in biological pathways, resulting in a decline in tissue and cellular function. It is a driving factor in numerous age-related diseases including cardiovascular diseases (CVDs). Cardiomyopathies, hypertension, ischaemic heart disease, and heart failure are some of the age-related CVDs that are the leading causes of death worldwide. Although individual CVDs have distinct clinical and pathophysiological manifestations, a disturbance in cellular homeostasis underlies the majority of diseases which is further compounded with aging. Three key evolutionary conserved signalling pathways, namely, autophagy, mitophagy and the unfolded protein response (UPR) are involved in eliminating damaged and dysfunctional organelle, misfolded proteins, lipids and nucleic acids, together these molecular processes protect and preserve cellular homeostasis. However, amongst the numerous molecular changes during ageing, a decline in the signalling of these key molecular processes occurs. This decline also increases the susceptibility of damage following a stressful insult, promoting the development and pathogenesis of CVDs. In this review, we discuss the role of autophagy, mitophagy and UPR signalling with respect to ageing and cardiac disease. We also highlight potential therapeutic strategies aimed at restoring/rebalancing autophagy and UPR signalling to maintain cellular homeostasis, thus mitigating the pathological effects of ageing and CVDs. Finally, we highlight some limitations that are likely hindering scientific drug research in this field.

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Section: Limitations and Future Directionsmentioning

confidence: 99%

Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease

et al. 2022

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“…Icariside II (ICS), a type of flavonoid, is one of the main active ingredients of the traditional Chinese medicine Epimedium [ 20 ]. Extensive data have shown that ICS could exhibit a variety of biological and pharmacological properties, including anti-inflammatory [ 21 , 22 ], antioxidant [ 23 , 24 ], and anticancer [ 20 , 25 ] activities. Recent studies have also found that ICS has a protective effect against CNS damage.…”

Section: Introductionmentioning

confidence: 99%

Icariside II Attenuates Methamphetamine-Induced Neurotoxicity and Behavioral Impairments via Activating the Keap1-Nrf2 Pathway

Huang

Ding

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Chronic and long-term methamphetamine (METH) abuse is bound to cause damages to multiple organs and systems, especially the central nervous system (CNS). Icariside II (ICS), a type of flavonoid and one of the main active ingredients of the traditional Chinese medicine Epimedium, exhibits a variety of biological and pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. However, whether ICS could protect against METH-induced neurotoxicity remains unknown. Based on a chronic METH abuse mouse model, we detected the neurotoxicity after METH exposure and determined the intervention effect of ICS and the potential mechanism of action. Here, we found that METH could trigger neurotoxicity, which was characterized by loss of dopaminergic neurons, depletion of dopamine (DA), activation of glial cells, upregulation of α-synuclein (α-syn), abnormal dendritic spine plasticity, and dysfunction of motor coordination and balance. ICS treatment, however, alleviated the above-mentioned neurotoxicity elicited by METH. Our data also indicated that when ICS combated METH-induced neurotoxicity, it was accompanied by partial correction of the abnormal Kelch 2 like ECH2 associated protein 1 (Keap1)-nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and oxidative stress response. In the presence of ML385, an inhibitor of Nrf2, ICS failed to activate the Nrf2-related protein expression and reduce the oxidative stress response. More importantly, ICS could not attenuate METH-induced dopaminergic neurotoxicity and behavioral damage when the Nrf2 was inhibited, suggesting that the neuroprotective effect of ICS on METH-induced neurotoxicity was dependent on activating the Keap1-Nrf2 pathway. Although further research is needed to dig deeper into the actual molecular targets of ICS, it is undeniable that the current results imply the potential value of ICS to reduce the neurotoxicity of METH abusers.

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“…5 ICS II was proven to have antitumor efficacy by inducing cell-cycle arrest and inhibiting tumor-associated angiogenesis. 6…”

Section: Introductionmentioning

confidence: 99%

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis

Wen

et al. 2022

Journal of Cardiovascular Pharmacology

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:Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor–induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor–induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

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Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

Cited by 19 publications

References 61 publications

Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease

Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease

Icariside II Attenuates Methamphetamine-Induced Neurotoxicity and Behavioral Impairments via Activating the Keap1-Nrf2 Pathway

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis

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