HeiLongJiang ZBD Pharmaceutical Co., Ltd.

Schisandra chinensis (Turcz.) Baill, which is frequently used in health products and drinks, is recognized for its high content of essential oils that could have protective effects against PD, despite the lack of complete understanding of its pharmacological mechanisms. This research aims to examine how ESC can affect autophagy signaling pathways and activate the Nrf2/HO-1 pathway to effectively decrease oxidative damage, thus shedding light on the possible anti-PD effects of this treatment. The results demonstrated that ESC significantly reduced behavioral issues linked to Parkinson's disease in a mouse model that was induced by MPTP and safeguarded dopaminergic neurons that expressed tyrosine hydroxylase. Moreover, ESC boosted the antioxidant capability of Nrf2, assisted with autophagy processes, and finally decreased protein expression levels of Keap1, HO-1, MAPK, mTOR, and ERK. According to in vitro studies, ESC treatment had a significant reduction in H₂O₂-induced cytotoxicity and oxidative stress levels, which suggests that Nrf2 targets ESC after treatment. The activation of both autophagy and Nrf2 antioxidant pathways was assessed using western blotting. In conclusion, ESC exhibits the potential to suppress oxidative stress by activating Nrf2 in response to autophagy, which is positioned as a promising pharmaceutical candidate, especially for the management and treatment of PD and related disorders.

Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune condition, presents a substantial challenge to public health. Dictamnus dasycarpus Turcz. (D. dasycarpus) is a traditional Chinese medicinal plant recognized for its anti-inflammatory properties and is increasingly being utilized as a potential anti-RA agent, but the underlying mechanism is still unclear.

The objective of this research is to elucidate the potential active components and therapeutic properties of D. dasycarpus in experimental RA-induced DBA/1J mice, and to uncover the pharmacological basis of its action.

Surface plasmon resonance (SPR) was employed to ascertain the specificity of interactions between protein targets and D. dasycarpus active ingredients for treating RA. The extract of D. dasycarpus was obtained by HP-20 microresin column chromatography, and its chemical composition was assessed using UPLC-Orbitrap-MS. This study utilized a collagen-induced arthritis (CIA) mouse model for in vivo experimentation. Body weight, foot thickness measurements, arthritis scores, immune organ index, and serum antibody levels of mice were used as indicators to evaluate the effects of D. dasycarpus components in treating RA. The serum levels of inflammatory factors in mice were measured using a cytokine antibody microarray assay. Additionally, this study quantified the protein expression levels associated with inflammatory responses through a combination of immunohistochemical staining and western blotting analyses.

This research investigated the interaction between D. dasycarpus active components and target proteins, including PTPN14, using a BIACORE system. The screened active components were identified as alkaloids through mass spectrometry. The UPLC-Orbitrap-MS analysis revealed that alkaloids were the predominant constituents in the 60% EtOH extract of D. dasycarpus. Alkaloid components significantly reduced the arthritis index, foot swelling, and serum antibody levels of IgG1, IgG 2a, and IgG 2b in CIA mice. Histological staining results indicated that alkaloid components mitigate disease exacerbations in CIA mice. Bioinformatics analysis and protein level detection results show that the therapeutic mechanism of D. dasycarpus in managing RA could be attributed to the suppression of the IL-17 signaling pathway.

This study was based on clarifying the therapeutic effect of D. dasycarpus on RA, identifies its effective chemical components as alkaloids. It systematically elucidates the pharmacological mechanisms of alkaloids in treating RA, thereby laying a crucial theoretical foundation for further exploration of the active constituents of D. dasycarpus.

Schisandra chinensis (Turcz.) Baill (S. chinensis), first recorded in Shennong's Classic of the Materia Medica, is described as a "top grade medicine". As a traditional Chinese medicine of tonifying the kidneys and the brain, S. chinensis is widely used to treat diseases such as amnesia and dementia. Alzheimer's disease (AD) is a neurodegenerative disease, and ferroptosis is one of the essential causes of AD. Although previous studies have suggested that the lignans of S. chinensis (SCL) have neuroprotective effects, it is unclear whether SCL can alleviate AD pathology by inhibiting ferroptosis.

To investigate the effect of SCL on AD caused by ferroptosis and its possible molecular mechanism.

This study was based on SAMR1/SAMP8 mouse models along with Erastin-induced HT22 cell lines to examine the influence of SCL on ferroptosis in AD. The S. chinensis was extracted via 75% EtOH-H₂O and identified by HPLC/UPLC-QTOF-MS. MWM assessed spatial learning, while HE staining, biochemical detection, IHC, and WB analyzed AD pathology and iron metabolism. Mitochondrial changes were evaluated by TEM, and confocal imaging post-SCL treatment analyzed ROS, MMP, and Fe²⁺ levels in HT22 cells. IF determined the expression levels and localization of Nrf2 and FPN1. CETSA was deployed to study the interaction between SCL and Nrf2.

Treatment with SCL mitigated cognitive dysfunction and reduced p-Tau as well as neuronal loss in AD model mice. Additionally, the administration of SCL alleviated oxidative stress and maintained relatively intact mitochondrial ridges and membranes, decreased TFR and DMT1 protein expression, and upregulated FTH1. Consistent with the in vivo results, SCL inhibited Erastin-induced ferroptosis in HT22 cells. SCL promoted Nrf2 nuclear translocation and upregulated FPN1, SLC7A11, and GPX4 protein expressions while decreasing FACL4. The improvement of ferroptosis by SCL was associated with the regulation of the Nrf2/FPN1 signaling pathway.

The novel discoveries of this study suggest that SCL can suppress ferroptosis in the brains of AD model mice and exerts a partial protective effect against Erastin-induced ferroptosis in HT22 cells, in which the Nrf2/FPN1 signaling pathway plays a crucial role.