Production and pharmaceutical research of minor saponins in Panax notoginseng (Sanqi): Current status and future prospects.

Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal herb known as Sanqi or Tianqi in Asia and is commonly used worldwide. It is one of the main raw ingredients of Yunnan Baiyao, Fu fang dan shen di wan, and San qi shang yao pian. It is also a source of cardiotonic pill used to treat cardiovascular diseases in China, Korea, and Russia. Approximately 270 Panax notoginseng saponins have been isolated and identified as the major active components. Although the absorption and bioavailability of saponins are predominantly dependent on the gastrointestinal biotransformation capacity of an individual, minor saponins are better absorbed into the bloodstream and act as active substances than major saponins. Notably, minor saponins are absent or are present in minimal quantities under natural conditions. In this review, we focus on the strategies for the enrichment and production of minor saponins in P. notoginseng using physical, chemical, enzyme catalytic, and microbial methods. Moreover, pharmacological studies on minor saponins derived from P. notoginseng over the last decade are discussed. This review serves as a meaningful resource and guide, offering scholarly references for delving deeper into the exploration of the minor saponins in P. notoginseng.

Ginseng-Sanqi-Chuanxiong (GSC) extracts attenuate d-galactose-induced vascular aging in mice via inhibition of endothelial progenitor cells senescence.

Vascular aging is an independent risk factor for age-related diseases and a specific type of organic aging. Endothelial progenitor cells (EPCs), a type of bone marrow stem cell, has been linked to vascular aging. The purpose of this study is to investigate if Ginseng-Sanqi-Chuanxiong (GSC) extract, a traditional Chinese medicine, can delay aortic aging in mice by enhancing the performance and aging of EPCs in vivo and to analyze the potential mechanisms through a d-Galactose (D-gal)-induced vascular aging model in mice. Our study revealed that GSC extracts not only enhanced the aortic structure, endothelial function, oxidative stress levels, and aging in mice, but also enhanced the proliferation, migration, adhesion, and secretion of EPCs in vivo, while reducing the expression of p53, p21, and p16. To conclude, GSC can delay vascular senescence by enhancing the function and aging of EPCs, which could be linked to a decrease in p16 and p53/p21 signaling. Consequently, utilizing GSC extracts to enhance the function and senescence of autologous EPCs may present a novel avenue for enhancing autologous stem cells in alleviating senescence.

Root rot destabilizes the Sanqi rhizosphere core fungal microbiome by reducing the negative connectivity of beneficial microbes.

The stability of microbial communities, especially among core taxa, is essential for supporting plant health. However, the impacts of disease infection on the stability of rhizosphere fungal core microbiome remain largely unexplored. In this study, we delved into the effects of root rot infestation on the community structure, function, network complexity, and stability of Sanqi fungal core microbiomes, employing amplicon sequencing combined with co-occurrence network and cohesion analyses. Our investigation revealed that root rot disease led to a decrease in the α-diversity but an increase in the ß-diversity of the Sanqi fungal core microbiomes in the rhizosphere. Notably, Ilyonectria, Plectosphaerella, and Fusarium emerged as indicator species in the rhizosphere core microbiome of root rot-infected Sanqi plants, while Mortierella predominated as the dominant biomarker taxa in healthy soils. Additionally, root rot diminished the complexity and modularity of the rhizosphere networks by reducing the metrics associated with nodes, edges, degrees, and modularity. Furthermore, root rot resulted in a reduction in the proportion of negative connections in the network and the negative/positive cohesion of the entire core fungal microbiome. Particularly noteworthy was the observation that root rot infection destabilized the rhizosphere core fungal microbiome by weakening the negative connectivity associated with beneficial agents. Collectively, these results highlight the significance of the negative connectivity of beneficial agents in ensuring the stability of core microbial community.IMPORTANCERoot rot disease has been reported as the most devastating disease in the production process of artificial cultivated Sanqi ginseng, which seriously threatens the Sanqi industry. This study provides valuable insights into how root rot influences microbial relationships within the community. These findings open up opportunities for disease prevention and the promotion of plant health by regulating microbial interactions. In summary, the research sheds light on the ecological consequences of root rot on rhizosphere fungal microbiomes and offers potential strategies for managing soil-borne diseases and enhancing plant health.

Combined Metabolome and Transcriptome Analysis of Creamy Yellow and Purple Colored Panax notoginseng Roots.

Panax notoginseng (Burk.) F.H. Chen is a species of the Araliaceae family that inhabits southwestern China, Burma, and Nepal. It is cultivated on a commercial scale in Yunnan province, China, owing to its significance in traditional Chinese medicine. Panax notoginseng roots are usually yellow-white (HS); however, purple roots (ZS) have also been reported. The majority of P. notoginseng research has concentrated on the identification and production of natural chemicals in HS; however, there is little to no information about the composition of ZS. Using UPLC-MS/MS, we investigated the global metabolome profile of both ZS- and HS-type roots and discovered 834 metabolites from 11 chemical groups. There were 123 differentially accumulated metabolites (DAM) in the HS and ZS roots, which were classified as lipids and lipid-like molecules, polyketides, organoheterocyclic chemicals, and organooxygen compounds. We investigated the associated compounds in the DAMs because of the importance of anthocyanins in color and saponins and ginsenosides in health benefits. In general, we discovered that pigment compounds such as petunidin 3-glucoside, delphinidin 3-glucoside, and peonidin-3-O-beta-galactoside were more abundant in ZS. The saponin (eight compounds) and ginsenoside (26 compounds) content of the two varieties of roots differed as well. Transcriptome sequencing revealed that flavonoid and anthocyanin production genes were more abundant in ZS than in HS. Similarly, we found differences in gene expression in genes involved in terpenoid production and related pathways. Overall, these findings suggest that the purple roots of P. notoginseng contain varying amounts of ginsenosides and anthocyanins compared to roots with a creamy yellow color.

[Dong's extraordinary point needling technique combined with medication for postoperative complications of anal fistula: a randomized controlled trial].

OBJECTIVE: To observe the effect of Dong's extraordinary point needling technique on postoperative complications of anal fistula. METHODS: A total of 241 patients undergoing anal fistula surgery were randomly divided into an observation group (121 cases, 3 cases dropped off) and a control group (120 cases, 2 cases dropped off). The patients in the control group were treated with intramuscular injection of compound diclofenac sodium injection and oral administration of tamsulosin hydrochloride sustained release capsules. In addition to the treatment in the control group, the patients in the observation group were treated with Daoma needling technique at the "Sanqi points" (Qimen point, Qijiao point, and Qizheng point) combined with Dongqi needling technique at "Sanhuang points" (sub-Tianhuang point, Dihuang point, Renhuang point), with each session lasting 30 min. The treatment in the two groups both started on the first day after surgery, and was given once daily for 14 consecutive days. Visual analog scale (VAS) score was compared between the two groups on postoperative day 1, 7, and 14; bladder residual urine volume, spontaneous voiding volume, and urinary catheterization frequency were assessed after treatment on postoperative day 1; and anorectal dynamic indexes (anal canal resting pressure, rectal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold) were evaluated before surgery and on postoperative day 4. Clinical efficacy was assessed in both groups one month after surgery. RESULTS: On postoperative day 7 and 14, the VAS scores of both groups were lower than those on postoperative day 1 (P<0.05), and the VAS scores in the observation group were lower than those in the control group (P<0.05). The bladder residual urine volume and urinary catheterization frequency in the observation group were lower than those in the control group (P<0.05), while the spontaneous voiding volume was higher than that in the control group (P<0.05). On postoperative day 4, the anal canal resting pressure, maximum squeeze pressure of the anal canal, and the minimum rectal sensory threshold were lower than preoperative values (P<0.05), while the rectal resting pressure was higher than preoperative value (P<0.05) in both groups. The anal canal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold were lower than those in the control group, and the rectal resting pressure was higher than that in the control group (P<0.05). The effective rate was 93.2% (110/118) in the observation group, which was higher than 84.7% (100/118) in the control group (P<0.05). CONCLUSION: Dong's extraordinary point needling technique could reduce postoperative pain, alleviate urinary retention, and improve defecation in patients undergoing anal fistula surgery.

Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

Sanqi Qushi Granule Alleviates Proteinuria and Podocyte Damage in NS Rat: A Network Pharmacology Study and in vivo Experimental Validation.

Background: Nephrotic syndrome (NS) and its numerous complications remain the leading causes of morbidity and mortality globally. Sanqi Qushi granule (SQG) is clinically effective in NS. However, its potential mechanisms have yet to be elucidated. Methods: A network pharmacology approach was employed in this study. Based on oral bioavailability and drug-likeness, potential active ingredients were picked out. After acquiring overlapping targets for drug genes and disease-related genes, a component-target-disease network and protein-protein interaction analysis (PPI) were constructed using Cytoscape, followed by GO and KEGG enrichment analyses. Adriamycin was injected into adult male Sprague-Dawley (SD) rats via the tail vein to establish NS model. Kidney histology, 24-hr urinary protein level, creatinine (Cr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) level were assessed. Western blotting, immunohistochemistry, and TUNEL staining were applied. Results: In total, 144 latent targets in SQG acting on NS were screened by a network pharmacology study, containing AKT, Bax, and Bcl-2. KEGG enrichment analysis suggested that PI3K/AKT pathway was enriched primarily. In vivo validation results revealed that SQG intervention ameliorated urine protein level and podocyte lesions in the NS model. Moreover, SQG therapy significantly inhibited renal cells apoptosis and decreased the ratio of Bax/Bcl-2 protein expression. Moreover, we found that Caspase-3 regulated the PI3K/AKT pathway in NS rats, which mediated the anti-apoptosis effect. Conclusion: By combining network pharmacology with experimental verification in vivo, this work confirmed the treatment efficacy of SQG for NS. SQG protected podocyte from injury and inhibited kidney apoptosis in NS rats via the PI3K/AKT pathway at least partially.

Network pharmacology-based strategy for predicting therapy targets of Sanqi and Huangjing in diabetes mellitus.

BACKGROUND: A comprehensive literature search shows that Sanqi and Huangjing (SQHJ) can improve diabetes treatment in vivo and in vitro, respectively. However, the combined effects of SQHJ on diabetes mellitus (DM) are still unclear. AIM: To explore the potential mechanism of Panax notoginseng (Sanqi in Chinese) and Polygonati Rhizoma (Huangjing in Chinese) for the treatment of DM using network pharmacology. METHODS: The active components of SQHJ and targets were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database. The potential targets for the treatment of DM were identified according to the DisGeNET database. A comparative analysis was performed to investigate the overlapping genes between active component targets and DM treatment-related targets. We constructed networks of the active component-target and target pathways of SQHJ using Cytoscape software and then analyzed the gene functions. Using the STRING database to perform an interaction analysis among overlapping genes and a topological analysis, the interactions between potential targets were identified. Gene Ontology (GO) function analyses and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in DAVID. RESULTS: We screened 18 active components from 157 SQHJ components, 187 potential targets for active components and 115 overlapping genes for active components and DM. The network pharmacology analysis revealed that quercetin, beta-sitosterol, baicalein, etc. were the major active components. The mechanism underlying the SQHJ intervention effects in DM may involve nine core targets (TP53, AKT1, CASP3, TNF, interleukin-6, PTGS2, MMP9, JUN, and MAPK1). The screening and enrichment analysis revealed that the treatment of DM using SQHJ primarily involved 16 GO enriched terms and 13 related pathways. CONCLUSION: SQHJ treatment for DM targets TP53, AKT1, CASP3, and TNF and participates in pathways in leishmaniasis and cancer.

First Report of Sanqi (Panax notoginseng) Root Rot Caused by Pythium vexans in China.

Sanqi (Panax notoginseng (Burk.) F. H. Chen) is a precious traditional Chinese herbal medicine. During April of 2021, a root rot disease with approximate 15% incidence was observed on 2-year-old Sanqi plants in a field of Zhouning (27º12' N, 119°33' E), Fujian Province of China. The disease symptoms included severe stunting, leaf chlorosis, root rotting and necrosis, as the disease progressed, the whole plant gradually wilted and died. To recover the causal agent, symptomatic roots were excised, surface sterilized in 75% alcohol for 1.5 min, rinsed in sterilized water three times, dried, and placed on PARP selective medium (Jeffers and Martin 1986), and incubated at 20°C in dark. After 5 days, total of 26 Pythium-like isolates were obtained, and one representative isolate Py21-6 (available from the Institute of Plant Protection, Fujian Academy of Agricultural Sciences) was selected for further identification. Colonies of Py21-6 on PARP plate were white with dense, cottony, aerial, and transparent mycelia. Sporangia were terminal or intercalary, non-papillate, spherical, pyriform or ovoid, measuring 21.7 ± 2.8 × 19.3 ± 2.3 µm (n = 30). Zoospores were saucer-like, released out of sporangium after maturation, and dispersed quickly by swimming. Oogonia were spherical, terminal or occasionally intercalary. Oospores were globose, smooth and aplerotic. The dimensions of zoospores, oogonia, and oospores were 6.8 ± 0.7 µm, 21.6 ± 2.2 µm and 18.2 ± 2.7 µm (n = 30), respectively. Antheridia were bell-shaped or irregular, terminal, monoclinous, and usually one per oogonium. According to the morphological characteristics the isolate was initially identified as Pythium spp. (Van der Plaats-Niterink 1981, Yong et al. 2016). For further identification, DNA extracted from Py21-6, the cytochrome c oxidase subunit I (COI) gene and internal transcribed spacer (ITS) region were amplified and sequenced with primers FM55/FM52R (Long et al. 2012) and ITS1 /ITS4 (White et al. 1990), respectively. BLAST analysis of 680-bp COI (OM688194) and 728-bp ITS (OM663703) sequences revealed 99.86% and 99.99% similarity to Pythium vexans in GenBank (HQ708995 [COI], GU133572 [ITS]). Therefore, the pathogen was identified as P. vexans. In order to fulfill Koch's postulates, isolate Py21-6 was grown on Martin's liquid medium (Martin 1992) for 72 h to produce a spore suspensions of 106 oospores/ml, and the pathogenicity test was conducted by root-dip method. Three groups of 2-year-old Sanqi (15 plants per group) with root soaked for 20 min in oospore suspension were used for pathogenicity, and the other three groups (15 plants per group) with root dipped in sterilized water as control. All treated plants were replanted in (15-cm-diameter) pots (2 plants/pot) filled with mixture of sterilized soil: vermiculite: pearlite (2:1:1, v/v), maintained in greenhouse under 60% black shade cloth at 20 to 26°C with 80% relative humidity, and watered once every three days. After 21days, all inoculated plants showed the same symptoms observed on the original diseased plants in the field, whereas, the control plants remained symptomless. The same pathogen was successfully re-isolated from the inoculated plants, and identical to those of the originals based on morphological and sequence data. To our knowledge, this is the first report of P. vexans causing root rot on Sanqi in China (Farr and Rossman 2022). Root rot is one of the destructive diseases in Sanqi production, identification of the pathogen will be useful to develop effective field management strategies to control this disease.

The mechanism of the cytotoxic effect of Panax notoginseng extracts on prostate cancer cells.

INTRODUCTION: Panax notoginseng (Burkill) F.H. commonly referred to as Sanqi, is a Chinese herb that has long been used to treat various conditions including blood disorders and cardiovascular diseases. While Panax notoginseng has been used as an anti-cancer medicinal herb in recent years, how it achieves this therapeutic effect has not been thoroughly elucidated. The purpose of this study was to reveal more about the mechanism of the cytotoxic effect of Panax notoginseng on prostate cancer (PCa) cells. METHODS: Ethanol extract of Panax notoginseng root was authenticated using high-performance liquid chromatography (HPLC). The cytotoxic activity of this herb against PCa cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: The assessment of cellular metabolic activity demonstrated that Panax notoginseng reduces the viability of LNCaP and 22Rv1 cells in a dose-dependent manner. Annexin-V binding flow cytometry assay showed that Panax notoginseng induces apoptosis in PCa cells. Cell cycle analysis by quantification of DNA content using flow cytometry showed that Panax notoginseng arrests the cell cycle at the G2/M phase in both LNCaP and 22Rv1 cells. Moreover, ELISA demonstrated that Panax notoginseng-treated PCa cells secrete significantly less tumor-promoting cytokine interleukin-4 (IL-4) to the supernatant compared with controls. CONCLUSIONS: These results provide evidence for the cytotoxic effects of Panax notoginseng on PCa cell lines. This botanical is a promising candidate for the complementary and integrative medicine treatment of PCa and further studies are indicated to determine the anti-cancer mechanism of Panax notoginseng.

Sanqi Oral Solution Mitigates Proteinuria in Rat Passive Heymann Nephritis and Blocks Podocyte Apoptosis via Nrf2/HO-1 Pathway.

Idiopathic membranous nephropathy (IMN) is the most common pathological type in adult nephrotic syndrome where podocyte apoptosis was found to mediate the development of proteinuria. Sanqi oral solution (SQ), an effective Chinese herbal preparation clinically used in treatment of IMN for decades, plays an important role in reducing proteinuria, but the underlying mechanisms have not been fully elucidated yet. The current study tested the hypothesis that SQ directly lessens proteinuria in IMN by reducing podocyte apoptosis. To investigate the effects of SQ, we established the experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum in vivo and doxorubicin hydrochloride (ADR)-injured apoptotic podocyte model in vitro. SQ intervention dramatically reduced the level of proteinuria, together with the rat anti-rabbit IgG antibodies, complement C3, and C5b-9 deposition in glomerulus of PHN rats, accompanied by an elevation of serum albumin. Protein expression of synaptopodin, marker of podocyte injury, restored after SQ administration, whereas the electron microscopic analysis indicated that fusion of foot processes, and the pachynsis of glomerular basement membrane was markedly diminished. Further studies showed that SQ treatment could significantly inhibit podocyte apoptosis in PHN rats and ADR-injured podocytes, and protein levels of Cleaved Caspase-3 or the ratio of Bax/Bcl-2 were significantly decreased with SQ treatment in vivo or in vitro. Moreover, we found that the nuclear factor erythroid 2-related factor-2/heme oxygenase 1 (Nrf2/HO-1) pathway mediated the anti-apoptosis effective of SQ in podocyte. Thus, SQ mitigates podocyte apoptosis and proteinuria in PHN rats via the Nrf2/HO-1 pathway.

Blood circulation activating effect of Sanqi (Radix Notoginseng) on venous thromboembolism rat.

OBJECTIVE: To explore the blood circulation activating effect and mechanism of Sanqi (Radix Notoginseng) in vivo, using a venous thromboembolism (VTE) rat model. METHODS: We established the VTE rat model, and then intervened with low molecular weight heparin (LMWH), as well as low, medium and high doses of Sanqi (Radix Notoginseng), to observe the blood circulation activating effect of Sanqi (Radix Notoginseng) on VTE rats. RESULTS: After the treatment with high concentrations of Sanqi (Radix Notoginseng), the pulmonary thromboembolism was alleviated, and the lower limb thrombosis was markedly improved. Moreover, the expression quantities of plasma activated partial thromboplastin time, prothrombin time and D-dimer, as well as endothelin, von Willebrand factor, and plasminogen activator inhibitor-1 in thrombosis segment tissues were markedly down-regulated; while those of nitric oxide and tissue-type plasminogen activator were up-regulated. After low and medium concentration Sanqi (Radix Notoginseng) treatment, no obvious improvement was observed in each index. Moreover, the high concentration Sanqi (Radix Notoginseng) showed comparable efficacy to the positive drug LMWH. CONCLUSION: This data suggests that high concentration of Sanqi (Radix Notoginseng) is effective in preventing and treating VTE.

Potassium enhances cadmium resistance ability of Panax notoginseng by brassinolide signaling pathway-regulated cell wall pectin metabolism.

The mechanism of how potassium (K) attenuates cadmium (Cd)-induced demethylation and anabolism of cell wall (CW) pectin through the brassinolide (BR) signaling pathway was verified in Panax notoginseng (Burk.). The P. notoginseng pectin methylesterase gene (PnPME1) was cloned and functionally verified in tobacco. Pectin and BR metabolism, Cd content and the pectin methylation degree (PMD) were detected in response to K, 2,4-epibrassinolide (EBL), and brassinazole treatments of P. notoginseng and tobacco under Cd stress. Activity of the main root pectin methylesterase enzyme (PME) was promoted by 22.29% under the EBL treatment, and Cd content increased by 29.03% under Cd stress. Potassium reduced PME activity and Cd content in main root pectin by 61.03% and 50.73%, respectively, under the EBL and Cd co-treatment. Potassium inhibited the promoting effects of Cd stress on the expression of PnPME1 by 57.04%. Potassium also inhibited expression of BR synthesis genes PnDET2, PnROT3, PnCYP90A1, and PnBR6OX1 by 65.61%, 52.02%, 47.36%, and 55.16%, respectively, and reduced the accumulation of Cd. The PnPME1 was located in the CW. The activity of transgenic tobacco root PME was higher than that of the wild-type, while the PMD was significantly lower. The regulatory effects of K and EBL on tobacco root pectin metabolism were consistent with those in P. notoginseng. In conclusion, K downregulated the expression of BR synthesis genes in P. notoginseng roots under Cd stress and reduced the production of BRs, which inhibited PnPME1 expression. The reduction in PME activity increased the PMD, which reduced the accumulation of Cd.

Herb Sanqi-Derived Compound K Alleviates Oxidative Stress in Cultured Human Melanocytes and Improves Oxidative-Stress-Related Leukoderma in Guinea Pigs.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

Comparative pharmacokinetic analysis of raw and steamed Panax notoginseng roots in rats by UPLC-MS/MS for simultaneously quantifying seven saponins.

CONTEXT: After being steamed, the restorative effects of Panax notoginseng (Burk.) F. H. Chen (Araliaceae) will be strengthened. However, the underlying mechanism remains elusive. OBJECTIVE: To compare the pharmacokinetics of ginsenosides Rg1, Rb1, Rd, Re, Rg5, Rk1, notoginsenoside R1 (GRg1, GRb1, GRd, GRe, GRg5, GRk1 and NGR1) in the raw and steam-processed P. notoginseng (RPN and SPN). MATERIALS AND METHODS: The pharmacokinetics of seven components after oral administration of SPN and RPN extracts (1.0 g/kg) were investigated, respectively, in SD rats (two groups, n = 6) using UPLC-MS/MS. RESULTS: The approach elicited good linear regression (r2 > 0.991). The accuracy, precision and stability were all within ± 15%. The extraction recoveries and matrix effects were 75.0-100.8% and 85.1-110.3%, respectively. Compared with the RPN group, AUC0-t of GRg1 (176.63 ± 42.49 ng/h/mL), GRb1 (5094.06 ± 1453.14 ng/h/mL), GRd (1396.89 ± 595.14 ng/h/mL), and NGR1 (135.95 ± 54.32 ng/h/mL), along with Cmax of GRg1 (17.41 ± 5.43 ng/mL), GRb1 (361.48 ± 165.57 ng/mL), GRd (62.47 ± 33.65 ng/mL) and NGR1 (23.97 ± 16.77 ng/mL) decreased remarkably with oral administration of the SPN extracts, while GRe showed no significantly difference. Of note, GRg5 and GRk1 could not be detected in the plasma. CONCLUSIONS: Influence of the processing reduced the systemic exposure levels to GRg1, GRb1, GRd and NGR1. It is the first report of comparative pharmacokinetic study of multiple saponins analysis after oral administration of RPN and SPN extract, which might be helpful for further studies on its steam-processing mechanism.

Efficacy of Sanqi (Radix Notoginseng) in treating cerebral hemorrhage in rats with traumatic brain injury.

OBJECTIVE: To evaluate the protective efficacy of Sanqi (Radix Notoginseng) on cerebral hemorrhage in a rat model of traumatic brain injury (TBI) by investigating plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), nuclear factor-κB (NF-κB, p-p65), nitric oxide (NO), endothelin (ET), cluster differentiation (CD61CD62), and coagulation. METHODS: The free-fall method was used to create a rat model of TBI. Forty-eight rats were randomly divided into six groups: the blank group, sham group, model group, low-dose Sanqi (Radix Notoginseng) group, middle-dose Sanqi (Radix Notoginseng) group, and high-dose Sanqi (Radix Notoginseng) group. At 24 h after the model was created, we investigated brain MRI, brain tissue morphology using HE staining, flow cytometry, and immunohistochemical changes. RESULTS: Cerebral hemorrhage was aggravated in TBI rats (observed in brain specimens, brain MRI, and brain tissue HE). Cerebral immunohistochemistry results demonstrated that the expression of t-PA, PAI-1 and p-p65 increased significantly in TBI rats, while t-PA/PAI-1 had a significant decrease. In addition, CD61CD62, D2D, and ET were significantly increased in TBI rats, and PT and APTT were significantly prolonged; in contrast, NO was significantly decreased. Sanqi (Radix Notoginseng) decreased cerebral hemorrhage in TBI rats (observed in brain MRI and brain tissue HE), and increased t-PA/PAI-1, CD61CD62 significantly. It also significantly decreased the expression of t-PA, PAI-1, and p-p65 in brain immunohistochemistry and significantly decreased PT, APTT, D2D, and ET. However, there were no differences in NO between the model group and the Sanqi (Radix Notoginseng) group. CONCLUSION: Sanqi (Radix Notoginseng) can decrease the expression of p-p65, increase t-PA/PAI-1, and stem traumatic intracranial hemorrhage in a TBI rat model.

"Effects of extracts from Renshen (Radix Ginseng), Sanqi (Radix Notoginseng), and Chuanxiong (Rhizoma Chuanxiong) on F-actin in senescent microvascular endothelial cells".

OBJECTIVE: To investigate the effects of extracts from Renshen (Radix Ginseng), Sanqi (Radix Notoginseng), and Chuanxiong (Rhizoma Chuanxiong) on the endothelial actin cytoskeleton in senescent human cardiac microvascular endothelial cells (HCMECs), and to propose the possible mechanism underlying the actions. METHODS: Lentiviral mediated RNA interference was applied to a replicative senescent HCMEC model by knocking down heat shock protein 27 (HSP27) gene. Cells were treated with extracts from Renshen (Radix Ginseng), Sanqi (Radix Notoginseng), and Chuanxiong (Rhizoma Chuanxiong) at final concentrations of 50, 100, and 200 mg/L, respectively and with 10 µM resveratrol for 48 h. Untreated cells were used as controls. Senescence was detected by senescence ß-galactosidase staining and cell proliferation was analyzed by cell counting kit-8 assays. Secreted nitric oxide levels were detected by nitrate reductase. Morphological changes of F-actin and G-actin were observed by laser scanning confocal microscopy. Protein and gene expression of F- actin and HSP27 was detected by western blotting. RESULTS: Compared with the control group, the proportion of senescent HSP27 shRNA cells treated with the extracts was decreased and their proliferation was increased. In the extract intervention group, F-actin around the cell periphery became irregular and jagged fractures formed gradually and then dissipated. Moreover, some dynamic actin stress fiber filaments appeared. The G-actin stretched to the cell periphery and punctate staining was scattered in the cytoplasm. In addition, the mean optical density value of F/G-actin was decreased significantly and the protein expression of F-actin was downregulated. CONCLUSION: The extracts delayed microvascular endothelial cell senescence by downregulating the expression of F-actin through HSP27.

High performance liquid chromatography-tandem mass spectrometry method for residue determination of 39 plant growth regulators in root and rhizome Chinese herbs.

A simple, rapid, and effective method based on salting-out extraction and LC-MS/MS techniques was developed for the determination of 39 plant growth regulator (PGR) residues in two of the most common root and rhizome Chinese herbs, Codonopsis Radix (Dangshen) and Notoginseng Radix et Rhizoma (Sanqi). The extraction process was performed with acetonitrile-water (5:1) and citrate buffer extraction salt. The performance of the method was validated in accordance with the analytical quality control criteria of SANTE/11813/2017 guidelines. Analyte recoveries of 79.49-109.41% (Dangshen) and 80.17-102.81% (Sanqi) were achieved. The limit of quantifications (LOQs) were determined with the consideration of accuracy and precision. LOQs were lower than the lowest residue limits in EU pesticide regulation (10 µg/kg) for most PGRs. Moreover, the method was successfully applied in the analysis of 35 batches of Dangshen, and 60 batches of Sanqi products. The concentration of eleven PGRs were determined in analyzed samples.

Comparison of intramuscular and intravenous pharmacokinetics of ginsenosides in humans after dosing XueShuanTong, a lyophilized extract of Panax notoginseng roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Many bioactive constituents of Chinese herbal medicines have poor oral bioavailability. Besides oral administration, herbal medicines in China are also prepared for parenteral administration. Unlike for intravenous route, little is known about the intramuscular pharmacokinetics of herbal compounds. To facilitate rational use of herbal medicine, it is important to better understand such intramuscular pharmacokinetics. AIM OF THE STUDY: Bioactive constituents of XueShuanTong (a lyophilized extract of Panax notoginseng roots, extensively used in treatment of ischemic heart and cerebrovascular diseases) predominantly comprise ginsenosides Rb1 and Rd of 20(S)-protopanaxadiol-type and ginsenosides Rg1, and Re, and notoginsenoside R1 of 20(S)-protopanaxatriol-type; these saponins are poorly absorbed from the gastrointestinal tract. This study aimed to compare intramuscular and intravenous pharmacokinetics of these ginsenosides after dosing XueShuanTong. METHODS: Pharmacokinetics of ginsenosides was assessed in human volunteers receiving an intramuscular injection or 1.5-h intravenous infusion of XueShuanTong, both at 150 mg/person, and the plasma and urine samples were analyzed by liquid chromatography/mass spectrometry. RESULTS: Like after intravenous administration, the unchanged saponins were the major circulating forms after intramuscular administration, while their metabolites were poorly detected. These ginsenosides exhibited intramuscular bioavailability of 100%-112%, relative to the respective intravenous data. Similar to that after intravenous infusion, the 20(S)-protopanaxadiol-type ginsenosides after the intramuscular injection exhibited notably longer terminal half-lives (46-106 h) than the 20(S)-protopanaxatriol-type ginsenosides (1.1-1.4 h). CONCLUSIONS: Intramuscular route might be an effective alternative to intravenous route for XueShuanTong, from the pharmacokinetic perspective.