BACKGROUND: Linderae Radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., is a traditional Chinese herbal medicine that has been used for thousands of years for promoting Qi circulation, soothing the liver, and treating diarrhea and dysentery. Previous studies have found that ethanol extract of LR plays an anti-ulcerative colitis (UC) role by regulating Th17/ Treg balance. Water extract is the classic clinical application form of LR, but the effect of water extract of LR (LRWE) on UC and its underlying mechanism is still unclear.
OBJECTIVE: Purpose: UC is a gastrointestinal disease characterized by intestinal inflammation, mucosal injury, and fibrosis, and it is one of the high-risk factors for colon cancer. However, there is still a lack of remedies with satisfactory effects. This study aimed to investigate the efficacy and the potential mechanism of LRWE against UC.
METHODS: LRWE samples were prepared using a reflux extraction method. Colitis in mice was induced by administering 2.5 % DSS water solution to evaluate the therapeutic effect of LRWE by assessing disease activity score, colon length, and fecal morphology. H&E staining, TEM, Masson staining, and AB-PAS staining were applied to observe histopathological changes in the colon tissues. Differentially expressed genes in colon tissues were analyzed by transcriptomics. Cell apoptosis was detected by TUNEL staining. The expression of inflammatory factors such as IL-6 and IL-1β, as well as the expression of p-STAT1, p-JAK2, p-STAT3, Bax, and Bcl-2, were detected by immunofluorescence and immunohistochemistry. The expression of occludin, Bcl-2, Bax, and JAK/STAT signaling pathway-related vital proteins were quantified by Western blot (WB).
RESULTS: LRWE alleviated body weight loss, colon shortening, DAI scores, pathological changes, and ultrastructural features of colon tissue in mice with colitis. It also inhibited the increase of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) and increased IL-10 levels. Additionally, it protected the intestinal barrier by upregulating the expression of Occludin and Mucin-2. Mechanistically, LRWE could inhibit the activation of JAK-STAT signaling pathway by reducing the protein expression of p-JAK2, p-STAT3, p-STAT1, Bcl2, and Bax, thus reducing the inflammatory responses and inhibiting cell apoptosis.
CONCLUSIONS: LRWE has a protective effect on DSS-induced UC. This effect is related to the inhibition of the JAK-STAT signaling pathway, the improvement of intestinal inflammation, and the reduction of intestinal epithelial cell apoptosis.

Gastric cancer remains a global health threat, particularly in Asian countries. Current treatment methods include surgery, chemotherapy, and radiation therapy. However, they all have limitations, such as adverse side effects, tumor resistance, and patient tolerance. Hyperthermia therapy uses heat to selectively target and destroy cancer cells, but it has limited efficacy when used alone. Linderae Radix (LR), a natural compound with thermogenic effects, has the potential to enhance the therapeutic efficacy of hyperthermia treatment. In this study, we investigated the synergistic anticancer effects of cotreatment with LR and 43 °C hyperthermia in AGS gastric cancer cells. The cotreatment inhibited AGS cell proliferation, induced apoptosis, caused cell cycle arrest, suppressed heat-induced heat shock responses, increased reactive oxygen species (ROS) generation, and promoted mitogen-activated protein kinase phosphorylation. N-acetylcysteine pretreatment abolished the apoptotic effect of LR and hyperthermia cotreatment, indicating the crucial role of ROS in mediating the observed anticancer effects. These findings highlight the potential of LR as an adjuvant to hyperthermia therapy for gastric cancer. Further research is needed to validate these findings in vivo, explore the underlying molecular pathways, and optimize treatment protocols for the development of novel and effective therapeutic strategies for patients with gastric cancer.

Neuroinflammation and synaptic damage are important etiologies associated with the progression of Alzheimer\'s disease (AD). Linderae Radix (LR) has antioxidant and anti-inflammatory properties. This study investigated whether LR attenuates microglia activation-mediated neuroinflammation and synaptic degeneration and improves AD pathological phenotypes induced by amyloid beta oligomers (AβO) or lipopolysaccharide (LPS) toxicity. For in vitro studies, we treated LR to AβO-stimulated HT22 cells or LR LPS-stimulated BV2 cells. For in vivo studies, we administered LR to mice and AβO was injected by stereotaxic to induce cognitive impairment, neuroinflammation, and synaptic loss. We found that LR increased the cell viability reduced by AβO. Moreover, LR inhibited pro-inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), and downregulated p38 mitogen-activated protein kinase (MAPK) signaling in BV2 cells. Behavioral assessments demonstrated that LR administration significantly improved cognitive decline induced by AβO-injection. Furthermore, we found that microglia activation increased, and the expression of synaptic proteins decreased in the hippocampus of the AβO-injected group, which was alleviated in the LR-treated group. These findings suggest that LR may be a potential candidate for protection against neuroinflammation and synaptic loss, and may prevent or delay AD progression.

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

Traditional treatments have a poor effect on alcoholic liver diseases. Linderae radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., has been frequently used in traditional Chinese medicine for treating various diseases, and has been shown to exhibit a protective effect on liver injury. In the present study, LR extracts were made using various solvents, and then administrated to rats to establish a model of ethanol-induced liver injury. The study aimed to investigate the therapeutic effects and potential mechanism of LR extracts on acute alcoholic liver injury. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycercide (TG), cholesterol (TC), methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) were determined using an automatic biochemistry analyzer. In addition, pathological examination was performed by hematoxylin-eosin staining. The levels of MDA and SOD, and the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in liver tissue were investigated immunohistochemically. The expression of cytochrome P450 2E1 (CYP2E1) mRNA was quantified by reverse transcription-quantitative polymerase chain reaction. The results indicated that LR extracts improved the histopathological status and decreased the serum levels of ALT, AST, TG, TC and MDA. Furthermore, the levels of MDA and inflammatory mediators (NF-κB, TNF-α and IL-1β) were decreased in liver tissues, and the overexpression of CYP2E1 mRNA induced by ethanol treatment. LR extracts exhibited a protective effect on alcoholic liver injury and the mechanism may be associated with the anti-inflammatory and anti-oxidative action.