Salidroside, a phenolic compound isolated from various Rhodiola plants, is the principal active constituent of Traditional Chinese Medicine known for its adaptogenic properties. Due to the challenging environment of Rhodiola species, such as high altitude, high radiation, drought, and hypoxia, the source of salidroside is scarce. However, numerous studies have shown that salidroside has a range of biological activities, including cardiovascular and central nervous system activity, and anti-hypoxia, anti-inflammatory, and anti-aging activities. Although previous studies have partially summarized the pharmacological effects of salidroside, the overall pharmacological effects have not been analyzed. Hence, this review will systematically summarize the isolation, purification, synthesis, derivatization, pharmacological activity, pharmacokinetics, clinical application, and safety of salidroside. It is expected to provide new insights for the further research and pharmaceutical development of salidroside.

Introduction: Phlomoides rotata (Benth. ex Hook.f.) Mathiesen (syn. Lamiophlomis rotata (Benth. ex Hook.f.) Kudô) (P. rotate) is a traditional Tibetan medicine known for its hemostatic, analgesic, and anti-inflammatory effects, as well as its high content of 8-O-Acetyl Shanzhiside methyl ester (8-OaS). Clinical and experimental studies have reported gastrointestinal side effects, such as diarrhea, loose stools, even to black stools, associated with P. rotata. Given the bitter taste characteristic, laxative and antipyretic effects of iridoid glycosides, this study aims to investigate the antipyretic and anti-inflammatory effects of 8-OaS (the primary iridoid glycosides of P. rotate) on yeast-induced pyrexia in rats. Additionally, the role 8-OaS in modulating the intestinal flora composition and metabolome profile is explored.Methods: The pyretic rat model was established by injected subcutaneously with 20% dry yeast suspension. Serum, hypothalamic tissues and colon content were collected for the assessment of relevant indicators. The peripheral inflammatory factors and central thermoregulatory mediators were assessed using enzyme-linked immunosorbent assay (ELISA). The expressions of mRNA and protein in hypothalamic tissue were evaluated through polymerase chain reaction (PCR), immunohistochemistry, and western blotting. 16S rDNA sequencing and LC-MS/MS were performed to determine the alteration and correlation of the intestinal flora and neurotransmitters in the colonic contents and hypothalamus.Results and discussion: Results show that 8-OaS treatment reduced pyrogenic cytokines (such as IL-6, IL-1β), and down-regulated the level of central thermoregulatory mediators (PGE₂), via multiply involved in TLR4/NF-κB and HSP70/NF-κB signaling pathways. Crucially, 8-OaS treatment significantly reduced the relative abundance of Alistipes (P < 0.01), Odoribacter (P < 0.05) and Alistipes_finegoldii (P < 0.05) in the intestinal flora. The correlation analysis demonstrated that 8-OaS treatment significantly correlated with the increasing on the abundance of Alistipes and levels of 5-hydroxytryptamine (P < 0.01), and tryptamine (P < 0.01). Our findings indicate that 8-OaS exhibits significant antipyretic and anti-inflammatory properties, potentially mediated by intestinal flora and metabolites of neurotransmitters. The results of this study may help to elucidate the antipyretic and anti-inflammatory mechanism of 8-OaS based on intestinal flora and metabolomics analysis.

Hydrogen sulfide (H₂S), as a key gas signaling molecule, plays an important role in regulating various diseases, with appropriate concentrations providing antioxidative, anti-inflammatory, and anti-apoptotic effects. The specific role of H₂S in acute hypoxic injury remains to be clarified. This study focuses on the H₂S donor sodium hydrosulfide (NaHS) and explores its protective effects and mechanisms against acute hypoxic lung injury. First, various mouse hypoxia models were established to evaluate H₂S’s protection in hypoxia tolerance. Next, a rat model of acute lung injury (ALI) induced by hypoxia at 6500 m above sea level for 72 h was created to assess H₂S’s protective effects and mechanisms. Evaluation metrics included blood gas analysis, blood routine indicators, lung water content, and lung tissue pathology. Additionally, LC-MS/MS and bioinformatic analyses were combined in performing quantitative proteomics on lung tissues from the normoxic control group, the hypoxia model group, and the hypoxia model group with NaHS treatment to preliminarily explore the protective mechanisms of H₂S. Further, enzyme-linked immunosorbent assays (ELISA) were used to measure oxidative stress markers and inflammatory factors in rat lung tissues. Lastly, Western blot analysis was performed to detect Nrf2, HO-1, P-NF-κB, NF-κB, HIF-1α, Bcl-2, and Bax proteins in lung tissues. Results showed that H₂S exhibited significant anti-hypoxic effects in various hypoxia models, effectively modulating blood gas and blood routine indicators in ALI rats, reducing pulmonary edema, improving lung tissue pathology, and alleviating oxidative stress, inflammatory responses, and apoptosis levels.

Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl₂-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI.