Expanding the therapeutic potential of Salvia miltiorrhiza: a review of its pharmacological applications in musculoskeletal diseases.

Salvia miltiorrhiz, commonly known as "Danshen" in Chinese medicine, has longstanding history of application in cardiovascular and cerebrovascular diseases. Renowned for its diverse therapeutic properties, including promoting blood circulation, removing blood stasis, calming the mind, tonifying the blood, and benefiting the "Qi", recent studies have revealed its significant positive effects on bone metabolism. This potential has garnered attention for its promising role in treating musculoskeletal disorders. Consequently, there is a high anticipation for a comprehensive review of the potential of Salvia miltiorrhiza in the treatment of various musculoskeletal diseases, effectively introducing an established traditional Chinese medicine into a burgeoning field. AIM OF THE REVIEW: Musculoskeletal diseases (MSDs) present significant challenges to healthcare systems worldwide. Previous studies have demonstrated the high efficacy and prospects of Salvia miltiorrhiza and its active ingredients for treatment of MSDs. This review aims to illuminate the newfound applications of Salvia miltiorrhiza and its active ingredients in the treatment of various MSDs, effectively bridging the gap between an established medicine and an emerging field. METHODS: In this review, previous studies related to Salvia miltiorrhiza and its active ingredients on the treatment of MSD were collected, the specific active ingredients of Salvia miltiorrhiza were summarized, the effects of Salvia miltiorrhiza and its active ingredients for the treatment of MSDs, as well as their potential molecular mechanisms were reviewed and discussed. RESULTS: Based on previous publications, Salvianolic acid A, salvianolic acid B, tanshinone IIA are the representative active ingredients of Salvia miltiorrhiza. Their application has shown significant beneficial outcomes in osteoporosis, fractures, and arthritis. Salvia miltiorrhiza and its active ingredients protect against MSDs by regulating different signaling pathways, including ROS, Wnt, MAPK, and NF-κB signaling. CONCLUSION: Salvia miltiorrhiza and its active ingredients demonstrate promising potential for bone diseases and have been explored across a wide variety of MSDs. Further exploration of Salvia miltiorrhiza's pharmacological applications in MSDs holds great promise for advancing therapeutic interventions and improving the lives of patients suffering from these diseases.

FXR/ASS1 axis attenuates the TAA-induced liver injury through arginine metabolism.

Previous studies demonstrated that arginine biosynthesis was frequently impaired in acute liver injury. However, the underlying mechanisms remain elusive. In this study, we found that Argininosuccinate synthetase 1 (ASS1), a rate-limiting enzyme in arginine metabolism, was downregulated in the TAA-induced liver injury model. Single-cell RNA-seq data found that ASS1 was highly enriched in the hepatocytes. The reduction of ASS1 was attributed to the decreased expression of Farnesoid X receptor (FXR), which is a bile acid-activated nuclear hormone receptor with high expression in the liver. Subsequent studies demonstrated that activation of FXR by its agonist obeticholic acid (OCA) directly promoted ASS1 transcription and enhanced arginine synthesis, leading to the alleviation of TAA-mediated liver injury. Further experiments found that OCA, ASS1, and arginine supplement can rescue TAA-mediated hepatocytes apoptosis by decreasing the protein levels of Cyto C, PARP, and Caspase 3. Taken together, our study illustrated a protective role of the FXR/ASS1 axis in TAA-induced liver injury by targeting arginine metabolism, which might shed light on the development of novel therapeutic approaches for acute liver injury.

Properties of selenium nanoparticles stabilized by Lycium barbarum polysaccharide-protein conjugates obtained with subcritical water.

Selenium nanoparticles (SeNPs) in an aqueous solution have poor stability and tend to aggregate when stored for a long time. In the present study, SeNPs were stabilized by using Lycium barbarum polysaccharide (LBP) and Lycium barbarum protein (LBPr) conjugates (LBPP) as a stabilizer and dispersing agent. Particularly, the LBPP1 was obtained with subcritical water treatment. In addition, the physical stability, re-dispersity and antitumor activity of LBPP1-SeNPs were investigated. The results showed the particle size of LBPP1-SeNPs was maintained at 111.5-117 nm, which was stable at PH 6, 4 °C and darkness for at least 40 days. Besides, the result of TEM showed that the dispersion of LBPP1-SeNPs had more clear layers and smoother surfaces. Moreover, LBPP1-SeNPs had excellent re-dispersibility and exhibited a significant inhibitory effect on HepG-2 cells and Caco-2 cells, respectively (p < 0.05). Therefore, LBPP1-SeNPs can be used as potential selenium nutritional supplements for food and medical applications.

Digestion and absorption properties of Lycium barbarum polysaccharides stabilized selenium nanoparticles.

In the present study, the digestion and absorption properties of Lycium barbarum polysaccharides stabilized selenium nanoparticles (LBP-SeNPs) were investigated. The results showed that selenium nanoparticles (SeNPs) exhibited a higher selenium release rate than LBP-SeNPs (p＜0.05) after being digested in the stages of oral cavity, stomach and intestine. During the digestion process, the particle size of the LBP-SeNPs and SeNPs were both significantly increased, but the particle size of LBP-SeNPs was significantly smaller than that of SeNPs. The results of TEM further indicated that LBP-SeNPs can better maintain the morphology and properties of nanoparticles. Besides, the experiments of the intestinal sac model showed that LBP-SeNPs can better promote the absorption of selenium in various parts (duodenum, jejunum and ileum) of the intestine. Therefore, the LBP can help to improve the structural stability of SeNPs in the digestion process and improve the bioavailability of selenium.

Synthesis, stability and anti-fatigue activity of selenium nanoparticles stabilized by Lycium barbarum polysaccharides.

Lycium barbarum polysaccharides (LBP) with different molecular weights (LBP1, LBP2 and LBP3) of 92,441 Da, 7714 Da, and 3188 Da were used as stabilizers and capping agents to prepare uniformly dispersed selenium nanoparticles (SeNPs), and determined the storage stability. In addition, the anti-fatigue activity of LBP-decorated SeNPs with the best stability (LBP1-SeNPs) was estimated by using forced swimming test. The results showed that LBP1-SeNPs exhibited smaller particle size and more excellent stability than those of LBP2-SeNPs and LBP3-SeNPs when the storage time was extended to 30 days, and the average particle size was maintained at about 105.4 nm. The exhaustion swimming time of all tested dose groups of LBP1-SeNPs was significantly longer than the control group (p < 0.05), and the high-dose group among them was even obviously longer than the positive group (p < 0.05). The results of glycogen, blood urea nitrogen (BUN), blood lactic acid (BLA), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were further confirmed that LBP1-SeNPs could relieve fatigue by increasing the reserve of glycogen, enhancing antioxidant enzyme levels and regulating metabolic mechanism. These results demonstrated that LBP1-SeNPs could be developed as a potential anti-fatigue nutritional supplement.

Alpha7 nicotinic acetylcholine receptor activation attenuated intestine-derived acute lung injury.

BACKGROUND: Intestinal ischemia-reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. RESULTS: Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity (P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury. CONCLUSIONS: α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung.

Development and application of a ruthenium(II) complex-based photoluminescent and electrochemiluminescent dual-signaling probe for nitric oxide.

A ruthenium(II) complex, [Ru(bpy)2(DA-phen)](PF6)2 (bpy: 2,2'-bipyridine; DA-phen: 5,6-diamino-1,10-phenanthroline), has been developed as a photoluminescent (PL) and electrochemiluminescent (ECL) dual-signaling probe for the highly sensitive and selective detection of nitric oxide (NO) in aqueous and biological samples. Due to the presence of electron transfer process from diamino group to the excited-state of the Ru(II) complex, the PL and ECL intensities of the probe are very weak. After the probe was reacted with NO in physiological pH aqueous media under aerobic conditions to afford its triazole derivative, [Ru(bpy)2(TA-phen)](2+) (TA-phen: 5,6-triazole-1,10-phenanthroline), the electron transfer process was inhibited, so that the PL and ECL efficiency of the Ru(II) complex was remarkably increased. The PL and ECL responses of the probe to NO in physiological pH media are highly sensitive with the detection limits at low micromolar concentration level, and highly specific without the interferences of other reactive oxygen/nitrogen species (ROS/RNS) and metal ions. Moreover, the probe has good cell-membrane permeability, and can be rapidly transferred into living cells for trapping the intracellular NO molecules. These features enabled the probe to be successfully used for the monitoring of the endogenous NO production in living biological cell and tissue samples with PL and ECL dual-modes.

A europium(III) chelate as an efficient time-gated luminescent probe for nitric oxide.

The first Eu(3+) chelate-based luminescent probe specific for nitric oxide (NO) has been designed and synthesized for highly sensitive and selective time-gated luminescence detection of NO. Based on the probe, a time-gated luminescence imaging technique was developed for imaging the endogenous NO production in living plant cells/tissues.