Author: Nguepi Tsopmejio, Ivan Steve ; Wang, Zi ; Hu, Jun-Nan ; Liu, Jin-Hui ; Li, Wei ; Zhang, Jing ; Ren, Shen ; Zhang, Jing-Tian ; Zhu, Hong-Yan ; Liu, Shuang ; Tian, Zhao-Feng

ETHNOPHARMACOLOGICAL RELEVANCEAging contributes to various pathologies, including kidney injury, but the therapeutic potential of natural drugs in these contexts remains inadequately assessed. The roots of Panax ginseng C.A. Meyer, a widely used traditional Chinese medicine, are reputed for their anti-aging properties and life-prolonging effects, yet their specific medicinal components and mechanisms of action require further exploration.AIM OF STUDYThis study compared the pharmacological effects of ginsenoside Rg2 (Rg2), 20(S)-protopanaxatriol (PPT) and arginyl-fructosyl glucose (AFG) on aging-related kidney injury, aiming to identify their relative efficacy and potential mechanisms of action.MATERIALS AND METHODSSAMP8 mice, which exhibit an accelerated aging phenotype, were treated daily with Rg2, PPT or AFG for eight weeks. Kidney function markers were evaluated, and histopathological analysis was performed. Additionally, mRNA and protein expression levels were analyzed using Real-time qPCR and western blot methods to investigate the involvement of IGF-1/mTOR, PI3K/AKT and MAPK/ERK signaling pathways.RESULTSRg2, PPT and AFG all significantly improved kidney function and aging markers, ameliorated histological changes, and exhibited anti-inflammatory, antioxidant and anti-apoptotic effects. Among all compounds, Rg2 had the most significant effect on basic renal function indicators. In addition, Rg2 and PPT significantly affected AMPK family proteins, mTOR and IGF-1 transcription factors, highlighting their regulatory activities through insulin/IGF-1 and mTOR signaling pathways, and AFG significantly regulates PI3K/AKT signaling pathways.CONCLUSIONThe findings indicate that Rg2, PPT and AFG may prevent aging-related kidney diseases by targeting IGF-1/mTOR and PI3K/AKT signaling pathway. These results highlight their potential for further investigation to treat aging-related kidney diseases.

01 Apr 2025·Journal of Ethnopharmacology

Risk assessment of CYP3A induction by ginsenosides’ metabolites from oral Panax notoginseng (Sanqi) extract

Article

Author: Wang, Xiao-Lei ; Du, Jing ; Deng, Yang ; Chen, Ming ; Dong, Yan-Xi ; Wang, Le-Le ; Rao, Ying ; Du, Fei-Fei ; Wang, Feng-Qing ; Dong, Mei-Ling ; Hua, Yun-Fei ; Wu, Xiao-Lan ; Yang, Jun-Ling ; Li, Chuan ; Zeng, Yi-Mei ; He, Xin

ETHNOPHARMACOLOGICAL RELEVANCEIn China, the integration of Chinese traditional medicine with Western medicine for the treatment of multifactorial diseases provides notable therapeutic benefits. Given this integration involving co-administration of herbal medicines and synthetic drugs, it is critical to evaluate the potential for associated drug interactions.AIM OF THE STUDYThis investigation aimed to evaluate an oral extract of Panax notoginseng roots (Sanqi) for its potential to induce CYP3A activity, which may contribute to herb-drug interactions.METHODSHuman microbiota-associated (HMA) rats were used to determine whether repeated oral administration of Sanqi extract induces CYP3A activity. Cryopreserved primary rat and human hepatocytes were used to evaluate the ability of ginsenoside metabolites and their combinations to induce rat Cyp3a and human CYP3A. Fecal samples from HMA rats repeatedly treated with oral Sanqi extract were analyzed for microbial deglycosylation activity on ppt-type ginsenosides. Quantitative real-time polymerase chain reaction was used to measure mRNA levels of rat Cyp3a1 and Cyp3a2, and human CYP3A4 and CYP3A5. Liquid chromatography/mass spectrometry was used to quantify ginsenosides and their metabolites in rat samples and in vitro study samples. 16S rRNA gene sequencing was used to analyze intestinal microbiota composition.RESULTSRepeated oral administration of Sanqi extract did not induce hepatic Cyp3a expression in rats. Neither ginsenoside metabolites nor their combinations induced rat Cyp3a or human CYP3A in vitro. Systemic exposure to oxidized metabolites of 20(S)-protopanaxtriol showed significant accumulation in HMA rats following repeated administration of Sanqi extract. This accumulation pattern mirrored previous findings in humans. The increased systemic exposure to the oxidized metabolites was likely due to enhanced microbial deglycosylation activity resulting from repeated oral administration of the extract.CONCLUSIONSOral Sanqi extract exhibits a low propensity to induce CYP3A. This limited potential for drug interactions supports its safe use in cardiovascular therapies, particularly in polypharmacy settings.

01 Mar 2025·Phytomedicine

Harnessing natural saponins: Advancements in mitochondrial dysfunction and therapeutic applications

Review

Author: Lin, Xinyu ; Wang, Huan ; Wang, Jinlian ; Lan, Wenying ; Liu, Hongmei ; Xu, Min

BACKGROUNDMitochondrial dysfunction plays a crucial role in the development of a variety of diseases, notably neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, and cancer. Natural saponins, which are intricate glycosides characterized by steroidal or triterpenoid structures, have attracted interest due to their diverse pharmacological benefits, including anti-inflammatory, antiviral, and anti-aging effects.PURPOSEThis review synthesizes recent advancements in understanding mitochondrial dysfunction and explores how saponins can modulate mitochondrial function. It focuses on their potential applications in neuroprotection, cardiovascular health, and oncology.STUDY DESIGNThe review incorporates a comprehensive literature analysis, highlighting the interplay between saponins and mitochondrial signaling pathways. Specific attention is given to the effects of saponins like ginsenoside Rg2 and 20(S)-protopanaxatriol on mitophagy and their neuroprotective, anti-aging, and synergistic therapeutic effects when combined.METHODSWe conducted a comprehensive review of current research and clinical trials using PubMed, Google Scholar, and SciFinder databases. The search focused on saponins' role in mitochondrial function and their therapeutic effects, including "saponins", "mitochondria" and "mitochondrial function". The analysis primarily focused on articles published between 2011 and 2024.RESULTSThe findings indicate that certain saponins can enhance mitophagy and modulate mitochondrial signaling pathways, showing promise in neuroprotection and anti-aging. Additionally, combinations of saponins have demonstrated synergistic effects in myocardial protection and cancer therapy, potentially improving therapeutic outcomes.CONCLUSIONAlthough saponins exhibit significant potential in modulating mitochondrial functions and developing innovative therapeutic strategies, their clinical applications are constrained by low bioavailability. Rigorous clinical trials are essential to translate these findings into effective clinical therapies, ultimately improving patient outcomes through a deeper understanding of saponins' impact on mitochondrial function.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder	Preclinical	China	Jilin Agricultural University	10 Jul 2024

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