Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

Recent studies focused on the pharmacology and feasibility of herbal compounds as a potential strategy to target a variety of human diseases ranging from metabolic to brain disorders. Accordingly, bioactive ingredients which are found within a variety of herbal compounds are reported to produce both neuroprotective and psychotropic activities which may help to combat mental disorders such as depression, anxiety, sleep disturbances and cognitive alterations. In the present manuscript, we focus on three herbs which appear effective in mitigating anxiety or depression with favourable risk-benefit profiles, namely Scutellaria baicalensis (S. baicalensis), Hericium erinaceus (H. erinaceus) and Rhodiola rosea (R. rosea). These three traditional folk medicinal herbs target the main biochemical events that are implicated in mental disorders, mimicking, to some extent, the mechanisms of action of conventional antidepressants and mood stabilizers with a wide margin of tolerability. In detail, they rescue alterations in neurotransmitter and neuro-endocrine systems, stimulate neurogenesis and the synthesis of neurotrophic factors, and they counteract oxidative stress, mitochondrial dysfunction and inflammation. Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.

https://www.mdpi.com/2076-3921/9/3/234/pdf

Potential Antidepressant Effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea.

Non-polyphenolic natural inhibitors of amyloid aggregation.

Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review.

Salidroside (SAL) is a phenylpropanoid glycoside monomer extracted from Rhodiola at high altitudes. It has been proven to have protective effects on myocardial injury, liver cancer, renal fibrosis, and other organ diseases, as well as play neuroprotective roles in central nervous system (CNS) diseases. Specifically, SAL can inhibit a series of pathological reactions in CNS diseases and improve neurological dysfunction. This review elucidated the pharmacological effects of SAL on inflammation, oxidative stress, apoptosis, autophagy, and neuronal regeneration. Furthermore, how SAL affects various signaling pathways to regulate pathological processes in CNS diseases is also assessed. However, the relationship between various pathways and the mechanisms in different pathological stages remains unclear. Additionally, the appropriate dosage and side effects of SAL on the clinical outcomes of CNS diseases have not been fully determined due to the limited number of clinical studies on SAL. Therefore, the regulatory mechanisms and clinical applications of SAL still need to be further demonstrated. This review tracked and summarized studies from the past eight years reported in databases, including PubMed, ScienceDirect, and Google Scholar, filtered using the keywords "salidroside" and/or paired with "diseases" and "CNS diseases". 

Pharmacological effects of salidroside on central nervous system diseases.

Alzheimer's disease (AD) is one of the most frequent diseases in elderly people and causes high mortality. Its incidence is increasing annually and no effective therapeutic treatment currently exists. In the present study, salidroside, a major active ingredient of Rhodiola rosea, was able to protect PC‑12 cells from the toxicity and apoptosis induced by AD inducer amyloid (A)β1‑42. Salidroside significantly protected PC‑12 cells by inhibiting Aβ1‑42‑induced cytotoxicity and mitochondria‑mediated endogenous caspase apoptotic pathways. Mechanistic studies demonstrated that salidroside significantly activated the extracellular signal regulated kinase (ERK)1/2 and protein kinase B (AKT) signaling pathways. This observation was further confirmed using the ERK1/2 inhibitor PD98059 and the AKT inhibitor LY294002, which demonstrated that salidroside promoted PC‑12 cell survival and proliferation by activating the ERK1/2 and AKT signaling pathways. Salidroside is a therapeutic candidate for the treatment of AD and provides a basis for further drug development.

/pdf/salidroside-protects-pc-12-cells-against-amyloid-b-induced-3e4gh8hsan.pdf

Salidroside protects PC-12 cells against amyloid β-induced apoptosis by activation of the ERK1/2 and AKT signaling pathways.

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Salidroside protects PC-12 cells against amyloid β-induced apoptosis by activation of the ERK1/2 and AKT signaling pathways.