Pharmacokinetic profiling of the bioactive components of Sijunzi Decoction in a rat model of breast cancer: Insights into herb-drug interactions with cyclophosphamide.

Benzoylaconitine and ginsenoside Rb1 synergistically attenuate cardiac remodeling through dual enhancement of DLG1-dependent mitochondrial integrity.

Dissection of crucial components of Chinese medicinal formula for COPD treatment by combining cell-based assays, animal studies, and lung organoid platforms.

Ginsenoside Rb1 attenuates hyperoxia-induced lung injury in neonatal rats by inhibiting ferroptosis via the system Xc- pathway.

Rare ginsenoside Rk1 protects against cisplatin-induced auditory damage by regulating the MST1/LONP1 pathway.

A novel β-glucosidase from Lacticaseibacillus rhamnosus: Catalytic specificity and efficient production of high-value rare ginsenosides.

Shenfu injection ameliorates coagulopathy in sepsis-associated liver injury via dual inhibition of endothelial cell pyroptosis.

Panax notoginseng saponins (PNS) are bioactive constituents that can be biotransformed by gut microbiota. Anaerobic Bacteroides bacteria are considered the next-generation probiotics. However, little is known about PNS biotransformation by Bacteroides bacteria. The study identified a nonenterotoxigenic Bacteroides fragilis capable of biotransforming PNS. Three family 3 glycoside hydrolases from the strain were heterologously expressed and identified as β-glucosidases GE-270 and GE-710 and β-xylosidase GE-616. The two β-glucosidases catalyzed the conversion of the abundant protopanaxadiol-type ginsenosides Rb2, Rb3, and Rc present in P. notoginseng flowers and leaves to the rare ginsenoside compounds O, Mx1, and Mc1, respectively, and also converted ginsenoside Rb1 to F2. Furthermore, GE-270 converted the protopanaxadiol-type ginsenoside Rg3 to Rh2 and the protopanaxatriol-type notoginsenoside R1 to ginsenoside Rg1. The β-xylosidase GE-616 could convert the ginsenoside Rb3 to Rd. This research provides a novel anaerobic bacterium and its enzymes for PNS biotransformation.

Targeting Hsc70-mediated mitochondrial-lipid droplet crosstalk via Ginsenoside Rb2 promotes post-infarction cardiomyocyte regeneration.

This study employed a multiplatform approach to compare in vivo exposure of saponins across six ginseng species, namely Panax ginseng (PG), red ginseng (RG), P. quinquefolius (PQ), P. notoginseng (PN), P. japonicus (PJ), and P. japonicus var. major (PJm). A strategy combining in-source fragmentation tracing with liquid chromatography/mass spectrometry was developed, facilitating characterization of 242 ginsenoside prototypes and metabolites. Tissue distribution patterns were visualized through desorption electrospray ionization mass spectrometry imaging (DESI-MSI), revealing significant accumulation of specific ginsenosides in the heart and kidney of rats. Pharmacokinetics of eight ginsenosides were analyzed by scheduled multiple reaction monitoring. PN had the highest exposure to ginsenosides Rb1 and Rd, while PQ showed high ginsenoside Rb1 but low ginsenoside Re levels. PJ and PJm had low exposure to oleanolic acid-type ginsenosides. This study elucidated the in vivo behavior of ginsenosides simultaneously across six ginseng species, providing insights for their quality control and functional application.

Ischemic stroke is a leading cause of death and disability, yet effective pharmacological interventions remain limited. Ginsenoside Rb1, a principal bioactive compound of Panax ginseng, has demonstrated neuroprotective activity, but its metabolic mechanisms remain incompletely defined. Here, we combined lipid metabolomics with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to investigate the spatially resolved metabolic effects of Rb1 in a rat model of cerebral ischemia/reperfusion injury. Rb1 treatment significantly reduced infarct volume and improved neurological outcomes. Metabolomic profiling revealed that Rb1 reversed ischemia-induced disturbances in the glycerophospholipid and amino acid metabolism, while MSI demonstrated recovery of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine distributions in the ischemic cortex. These metabolic improvements were strongly correlated with reduced levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and oxidative stress marker malondialdehyde, along with increased superoxide dismutase activity. Rb1 also preserved blood-brain barrier integrity by enhancing the expression of tight-junction proteins ZO-1 and Occludin. Together, these findings indicate that Rb1 confers neuroprotection through metabolic reprogramming linked to anti-inflammatory and antioxidant actions, and they highlight the value of integrating metabolomics with MSI to elucidate spatially defined drug mechanisms in the brain.

Ginsenoside Rb1 as a multi-target modulator in heart failure: Mechanistic insights into extracellular remodeling and transcriptional pathways from network pharmacology, molecular dynamics, and binding free energy analyses.

The biotransformation of Panax notoginseng saponins (PNS) is pertinent to the effect of colitis mediated by gut microbiota, which has variant microbes and diversities in inflammatory bowel diseases (IBDs). However, the metabolic profiles of PNS mediated by gut microbiota are ambiguous under the pathological condition in vivo. Therefore, it is meaningful to explore the metabolic profiling of PNS mediated by gut microbiota undercolitis in vivo. In this study, an ultrahigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) method was employed to identify, and relatively quantify PNS and metabolites in rat feces with dextran sulfate sodium salt-induced colitis. The results showed that 89 metabolites were identified in the control group, whereas only 39 ones were detected in the colitis model group, indicating a significant reduction in Panax notoginseng saponin metabolites in the model group, particularly in deglycosylated products. Several main metabolites, such as ginsenoside Rb1, ginsenoside compound K, protopanaxatriol, and protopanaxadiol, were generated with relatively low yields in the colitis group. Simultaneously, the deglycosylation reactions as the main biotransformation pathways mediated by gut microbiota of PNS were significantly limited in the colitis group. The employed analytical method helpfully demonstrated that gut microbiota dysbiosis in colitis was associated with the metabolism variation of PNS in vivo.

Periurethral injection of hyaluronic acid-based hydrogel for stress urinary incontinence: Nursing care strategies for women enhancing management and quality of life.

Ginsenoside Rb1 alleviates cerebral ischaemia/reperfusion injury by suppressing oxidative stress and excessive autophagy via ATM-CHK2-Beclin 1 pathway.

The drug delivery for Alzheimer's disease (AD) faces substantial obstacles owing to the presence of the blood-brain barrier (BBB). This circumstance highlights the nose-brain route as pivotal for enhancing drug distribution to the brain. As the efficiency of brain entry is constrained by the physiological barrier of the nasal cavity, the development of strategies to efficiently traverse this barrier is imperative for enhancing the effectiveness of AD treatment. In the present study, a cell-penetrating peptide (CPPs) named LK4, which originates from mastoparan-L (MPL), was employed. Its capacity to efficiently penetrate the physiological barrier of the nasal cavity was demonstrated. LK4 was modified into polydopamine (PDA) nanoparticles to construct nanoparticles containing ginsenoside Rg1, ginsenoside Rb1, and notoginseng saponin R1 (TGS), designated as LK4-TGS-PDA. Experiment results reveal that the LK4-TGS-PDA drug delivery system can enhance the uptake of olfactory neurons and promote epithelial transport. In an in vitro nasal mucosal barrier model, LK4 modification increased the apparent permeability coefficients of R1, Rg1, and Rb1 by 1.2-, 1.2-, and 12-fold, respectively, compared to unmodified nanoparticles. Following nasal administration, the brain concentrations of R1, Rg1, and Rb1 increased by 19-fold, 30-fold, and 15-fold, respectively, and the relative brain bioavailability reached 933.1%, 1375.0%, and 1144.4%, respectively. In the model of AD induced by amyloid-beta 1-42 (Aβ1-42), it was confirmed that LK4-TGS-PDA NPs can significantly improve cognitive dysfunction, with escape latency reduced by 30.3%, platform crossings increased by 5.4-fold, and target quadrant time extended by 2.4-fold, as well as reduce the effects of inflammation in the brain, with IL-1β, IL-6, and TNF-α decreased by 44.05%, 53.49%, and 84.40%, respectively. The present investigation outcomes reveal that the engineered LK4-TGS-PDA NPs demonstrates effectiveness and efficiency as a drug delivery approach for the nose-brain pathway, offering valuable insights and prospects for enhancing AD treatment.

Panax vietnamensis Ha et Grushv. (Vietnamese ginseng) is a plant of the Panax genus, Araliaceae family. It is a rare medicinal plant found in China and Vietnam, known for its structurally diverse ginsenosides, and holds significant value in the pharmaceutical and health food sectors. As market demand and its value continue to rise, the P. vietnamensis industry has developed rapidly. However, since Vietnamese ginseng is difficult to distinguish from other Panax materials based on appearance, especially Panax notoginseng, there is a lack of relevant standards for quality control. In this study, UPLC-Q/TOF-MS technology was employed for the qualitative identification and comparative analysis of ginsenosides in different parts of P. vietnamensis and three other Panax species. Additionally, an UFLC-MS/MS method was established to determine the content of 21 ginsenosides in P. vietnamensis. Based on the UPLC-Q/TOF-MS analysis, 55 ginsenosides were preliminarily identified, including 30 protopanaxadiol-type, 21 protopanaxatriol-type, 3 ocotillol-type, and 1 oleanane-type ginsenosides. Further comparative analysis revealed variations in the ginsenosides of P. vietnamensis and three Panax species, identifying 41 components present in all species, while 14 saponins were detected only in some species. Compared to three Panax species, the main roots of P. vietnamensis contained characteristic components such as majonoside R2, majonoside R1, and vinaginsenoside R2. Quantitative analysis of 21 ginsenosides in different Panax species indicated that P. vietnamensis and P. notoginseng contained higher levels of ginsenoside Rg1, Rd, Rb1, and notoginsenoside R1. For instance, the average content of ginsenoside Rg1 in P. vietnamensis was 25.57 mg/g. Quantitative analysis of ginsenosides in different parts of P. vietnamensis revealed that the taproots and fibrous roots had a diverse array of ginsenosides with higher concentrations, while the stems and leaves contained fewer ginsenosides with lower levels. Significantly, certain components such as notoginsenoside Re and ginsenoside Rd, Re, and Rb2 were present at higher concentrations in the leaves. Based on the qualitative and quantitative analysis results of ginsenosides from different parts of P. vietnamensis, it was concluded that the main roots, fibrous roots, and leaves all have potential for development and utilization.

Ginsenoside Rb1 downregulates proinflammatory cytokines expression via the Tlr2/Tlr4 signaling pathway in mice with experimental autoimmune myocarditis.

SIRT4-mediated debutyrylation of SUCLG1 rescues myocardial energy failure in HFpEF: Ginsenoside Rb3 as a novel SIRT4-interacting regulator.

The core pathogenic mechanism of coronary microvascular injury is endothelial damage following ischemic injury, subsequently triggering inflammatory responses and oxidative stress damage. This study investigated the interaction mechanism between SIRT5 and DNA-PKcs in regulating coronary microvascular endothelial injury and further validated the therapeutic potential in mitochondrial homeostasis dysregulation. We used single-cell sequencing analysis to identify dysregulation of mitochondrial homeostasis as a key regulatory phenotype in endothelial injury. The synergistic regulation of Ginsenoside Rb2 (GS-Rb2) on mitochondrial function in endothelial cells was confirmed by Western blot, RT-PCR, and other techniques. The interaction mechanism between SIRT5 and DNA-PKcs was finally identified invitro and invivo. By promoting the overexpression of SIRT5 and the downregulation of DNA-PKcs, GS-Rb2 intervention was able to restore heart function and reverse coronary microvascular damage during ischemia-reperfusion. Elevated DNA-PKcs expression can exacerbate microvascular endothelium inflammatory injury and disrupt endothelial cell mitochondrial homeostasis and redox balance stability. Endothelium pyroptosis was activated by SIRT5 loss, which led to a marked reduction in mitophagy and mitochondrial biogenesis. The aforesaid alterations were restored by transgenic therapy of SIRT5 and DNA-PKcs deletion, which also raised mitophagy levels, prevented excessive endothelial pyroptosis activation, and preserved microvascular cell homeostasis. At the cellular level, GS-Rb2 can boost autophagy, prevent the excessive release of DNA-PKcs in the nucleus, and improve endothelial cell activity following injury. Through SIRT5, GS-Rb2 can control DNA-PKc activity and restore mitochondrial homeostasis in the endothelium following hypoxic stress. A viable therapy approach for coronary microvascular damage was proposed.