Medicinal plants are fundamental sources of natural products with high chemical diversity and specificity as novel lead compounds with diverse pharmacological activities. Ruta graveolens L. is an important traditional Chinese medicine used to treat fever caused by cold, wind-fire toothache, headache, bruises and sprains, irregular menstruation, and infantile eczema. Although various traditional uses and chemical constituent activity evaluations have been reported, no systematic review and future perspective of R. graveolens has been published. A total of 113 literature about R. graveolens were collected from online scientific databases, including SciFinder, PubMed, CNKI, Web of Science, and Google Scholar. Additional information was obtained from other sources of literature, such as the Chinese Pharmacopoeia, Flora of China, classical Chinese herbal books and local prints and scripts. Herein, we comprehensively review the traditional uses, phytochemistry, pharmacology, and toxicology of R. graveolens, and provide critical comments and meaningful perspectives for the future development of this medicinal plant.

Graveoline exhibits various biological activities. However, only limited studies have focused on its hepatoprotective properties. This study evaluated the anti-inflammatory and hepatoprotective activities of graveoline, a minor 2-phenylquinolin-4-one alkaloid isolated from Ruta graveolens L., in a liver injury model in vitro and in vivo. A network pharmacology approach was used to investigate the potential signaling pathway associated with the hepatoprotective activity of graveoline. Subsequently, biological experiments were conducted to validate the findings. Topological analysis of the KEGG pathway enrichment revealed that graveoline mediates its hepatoprotective activity through genes associated with the hepatitis B viral infection pathway. Biological experiments demonstrated that graveoline effectively reduced the levels of alanine transaminase and aspartate transaminase in lipopolysaccharide (LPS)-induced HepG2 cells. Graveoline exerted antihepatitic activity by inhibiting the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and elevated the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) in vitro and in vivo. Additionally, graveoline exerted its hepatoprotective activity by inhibiting JAK1 and STAT3 phosphorylation both in vitro and in vivo. In summary, graveoline can attenuate acute liver injury by inhibiting the TNF-α inflammasome, activating IL-4 and IL-10, and suppressing the JAK1/STAT3 signaling pathway. This study sheds light on the potential of graveoline as a promising therapeutic agent for treating liver injury.

Dayuanyin decoction is a traditional Chinese medicine formulation that is commonly used in modern clinical practice to treat viral infections such as viral pneumonia, viral fever, influenza, and hepatitis. Although the usage rate of Dayuanyin decoction is gradually increasing in clinical practice, its pharmacological constituents are still unclear. This study comprehensively characterized the chemical constituents in Dayuanyin decoction using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular networking. The overall strategy involved retrieving structural information, such as fragment ions and precursor ion masses, from self-built databases to identify the target constituents of the Dayuanyin decoction extract. The identification of non-targeted constituents was achieved by analyzing different categories, fragment pathways, mass spectrometry data, and the relationships between clusters of structures in molecular networking. Unannotated constituents were inferred from secondary mass spectrometry similarity and molecular weight differences and annotated constituents in the same constituent cluster. A few predicted constituents were selected and validated by comparing them to reference standards under identical mass spectrometry conditions. This study preliminarily identified 216 constituents, including flavonoids, amino acids, alkaloids, triterpenes, steroidal saponins, phenylpropanoids, and other constituents. This integrated strategy using UPLC-QTOF-MS and molecular networking lays the foundation for clinical research on pharmacologically active substances in Dayuanyin decoction and could be popularized for the comprehensive profiling of chemical constituents of other traditional Chinese medicines.

Kokusaginine is a bioactive ingredient extracted from Ruta graveolens L., which has a range of biological activities. Its pharmacokinetic (PK) properties are particularly important for clinical applications; however, they have not been fully elucidated. In addition, the effect of sex differences on drug metabolism is increasingly being recognized, but most studies have ignored this important factor. This study aims to fill this knowledge gap by taking an in-depth look at the PK properties of kokusaginine and how gender affects its metabolism and distribution in the body. It also lays the foundation for clinical drug development. In this study, a sensitive ultra-high-performance liquid chromatography (UPLC) method was developed and validated for quantifying kokusaginine in Sprague Dawley (SD) rat plasma and tissue homogenates. Metabolic stability was evaluated in vitro using gender-specific liver microsomes. Innovatively, we incorporated sex as a variable into both in vitro and in vivo PK studies in SD rats, analyzing key parameters with Phoenix 8.3.5 software. The developed UPLC method demonstrated high sensitivity and precision, essential for PK analysis. Notably, in vitro studies revealed a pronounced sex-dependent metabolic variability (p < 0.05). In vivo, gender significantly affected the Area Under the Moment Curve (AUMC)_(0-∞) of the plasma PK parameter (p < 0.05) and the AUMC_(0-t) of brain tissue (p < 0.0001), underscoring the necessity of sex-specific PK assessments. The calculated absolute bioavailability of 71.13 ± 12.75% confirmed the favorable oral absorption of kokusaginine. Additionally, our innovative tissue-plasma partition coefficient (K_p) analysis highlighted a rapid and uniform tissue distribution pattern. This study presents a sex-inclusive PK evaluation of kokusaginine, offering novel insights into its metabolic profile and distribution. These findings are instrumental for informing clinical medication practices, dosage optimization, and a nuanced understanding of drug efficacy and safety in a sex-specific context.

Objectives: Moringa oleifera (M. oleifera) Lam (Moringaceae) is a perennial plant broadly used in South Asia and Africa as a traditional folk medicine to treat many ailments such as paralysis, helminthiasis, sores and skin infections. The review provides a critical and comprehensive evaluation of the botany, traditional uses, phytochemistry, pharmacology, toxicity, agricultural economy and dietary benefit of M. oleifera and its future perspectives. Key findings: In this review, the entire plant of M. oleifera, containing diverse phytochemicals, is summarized. The 163 chemical components, included flavonoids, carbamates, glucosinolates, phenols, and so on with various bioactivities, such as anti-tumour, antioxidant, anti-inflammatory, and so on. Additionally, M. oleifera is toxic at certain doses; and overuse can cause genotoxicity. Summary: Although M. oleifera has been widely used in traditional medicine, the pharmacological studies that have been conducted so far are not sufficient for its use in the setting of evidence-based medicine. Little relevant data from clinical trials of M. oleifera have been reported. The majority of studies of its constituents, such as carbamates and glucosinolates, have been conducted only in vitro. Owing to a lack of available data, the pharmacology, toxicity, agricultural economy and dietary benefit of its constituents and extracts require further evaluation.

Diabetic nephropathy (DN) is a major complication of diabetes. Moringa oleifera seeds are recognized as a source of bioactive compounds with potential health benefits, prompting investigation into their specific components and effects on DN. This study aimed to isolate bioactive compounds from M. oleifera seeds and evaluate their renoprotective effects and underlying mechanisms of action against high-glucose-induced diabetic nephropathy. Four cyanoglycosides and one cyanoaglycone were isolated from M. oleifera seeds using chromatographic techniques. The renoprotective effects of these compounds were then evaluated using an in vitro model of high-glucose-induced diabetic nephropathy in HBZY-1 mesangial cells. Mechanistic studies further investigated the compounds' effects on oxidative stress, inflammation, mitochondrial function, expression of the glycolysis-related protein PFKFB3, and the TGF-β1/Smad signaling pathway. Two previously undescribed cyanoglycosides were isolated alongside three known compounds. All five compounds demonstrated significant renoprotective effects in the high-glucose-induced HBZY-1 cell model. Mechanistically, these effects were achieved by suppressing oxidative stress and inflammation, protecting mitochondrial function, modulating the expression of the glycolysis-related protein PFKFB3, and inhibiting the TGF-β1/Smad signaling pathway, collectively contributing to beneficial metabolic reprogramming. This study isolated two novel cyanoglycosides from M. oleifera seeds. These compounds, alongside known ones, protect against high-glucose-induced renal injury. Their renoprotection involves metabolic reprogramming via suppressing oxidative stress/inflammation, preserving mitochondrial function, modulating PFKFB3, and inhibiting TGF-β1/Smad signaling. These findings offer insights for utilizing M. oleifera seeds and suggest these cyanoglycosides as potential diabetic nephropathy therapeutics.