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ARCHIVES OF MICROBIOLOGY · 2024 ·Vol. 206 ·期 4 ·1-10 · IF 2.3

Biotransformation approach to produce rare ginsenosides F1, compound Mc1, and Rd2 from major ginsenosides

Diao Mengxue,Chen Yanchi,Meng Lijun,Li Jianxiu,Xie Nengzhong

The stems and leaves of Panax notoginseng contain high saponins, but they are often discarded as agricultural waste. In this study, the predominant ginsenosides Rg1, Rc, and Rb2, presented in the stems and leaves of ginseng plants, were biotransformed into value-added rare ginsenosides F1, compound Mc1 (C-Mc1), and Rd2, respectively. A fungal strain YMS6 ( Penicillium sp.) was screened from the soil as a biocatalyst with high selectivity for the deglycosylation of major ginsenosides. Under the optimal fermentation conditions, the yields of F1, C-Mc1, and Rd2 were 97.95, 68.64, and 79.58%, respectively. This study provides a new microbial resource for the selective conversion of protopanaxadiol-type and protopanaxatriol-type major saponins into rare ginsenosides via the whole-cell biotransformation and offers a solution for the better utilization of P . notoginseng waste.

研究领域: 药用植物学 · 微生物学 · 天然产物化学
✓ 已验证 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Identification of key pharmacodynamic markers of American ginseng against heart failure based on metabolomics and zebrafish model

Dong Rong,Zhang Yougang,Chen Shanjun,Wang Huan,Hu Kaiqing,Zhao Huanxin,Tian Qingping,Zeng Kewu,Wang Songsong,Han Liwen

Background: American ginseng (Panax quinquefolium L., AG) is a traditional Chinese medicine with multiple cardiovascular protective properties. Many bioactive components have been discovered in AG over these years. However, the understanding of these key pharmacodynamic components of activity against heart failure is insufficient.Methods: A heart failure model was established using AB line wild-type zebrafish (Danio rerio) to evaluate the anti-heart failure activity of AG. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap-mass spectrometry technology (UHPLC-QE-Orbitrap-MS) was performed to screen differential components from AG samples. The potential active components were verified using the zebrafish model. Simultaneously, network pharmacology and molecular docking techniques were used to predict the possible mechanism. Finally, the key targets of six key pharmacodynamic components were verified in zebrafish using quantitative real-time-polymerase chain reaction (Q-PCR) techniques.Results: The heart failure model was successfully established in 48 h of post-fertilization (hpf) zebrafish larvae by treating with verapamil hydrochloride. The zebrafish assay showed that the anti-heart failure effects of AG varied with producing regions. The result of the herbal metabolomic analysis based on UHPLC-QE-Orbitrap-MS indicated that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, L-argininosuccinic acid, 3-methyl-3-butenyl-apinosyl (1→6) glucoside, pseudoginsenoside F11, and annonaine were differential components, which might be responsible for variation in efficacy. Further analysis using zebrafish models, network pharmacology, and Q-PCR techniques showed that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic acid, and pseudoginsenoside F11 were the pharmacodynamic markers (P-markers) responsible for anti-heart failure.Conclusion: We have rapidly identified the P-markers against heart failure in AG using the zebrafish model and metabolomics technology. These P-markers may provide new reference standards for quality control and new drug development of AG.

研究领域: 药理学 · 心脏病学 · 代谢组学 · 斑马鱼模型
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY · 2020 · IF 2.365

Panax quinquefolium saponin liposomes prepared by passive drug loading for improving intestinal absorption

Bing Zhang,Wenli Pan,Yaxin Deng,Haibing He,Jingxin Gou,Yanjiao Wang,Yu Zhang,Tian Yin,Dongchun Liu,Xing Tang

Panax quinquefolium saponin (PQS) composed of 45% pseudo-ginsenoside F11 (PF11), is a natural mixture of sterol compounds obtained from the American ginseng plant, having numerous promising benefits for health. However, low solubility and permeability limit the development of PQS as a therapeutic agent for oral administration. In this study, PQS liposomes (PQS-Lips) were prepared by thin layer hydration, an in situ single-pass intestinal perfusion (SPIP) model was used to verify the improvement of membrane permeability of PQS-Lips. PQS-Lips had a high encapsulation efficiency (EE) of 65%∼70%, a particle size about 100.0 nm, and a zeta potential of −60 mV with regular spherical surface. FTIR and DSC showed the PQS in liposomes were amorphous, indicating that hydrogen bonds formed between one or several hydroxyl groups in PQS and C-O group at the phospholipid polar terminal. In addition, PQS-Lips showed sustained release in vitro than PQS at pH 1.2 and pH 6.8, and PQS-Lips had good stability in simulated gastric and intestinal fluid. Then, the absorption rate (Ka) and effective permeability coefficient (Peff) of PQS-Lips in the whole small intestine were significantly higher than those in PQS solution (PQS-Sol), which proved that the PQS-Lips could significantly increase the membrane permeability of PQS and promote its absorption in the small intestine. From the experimental results, it could be known that liposome technology could effectively improve the absorption of PQS in the small intestine.

CAS / MDL: 9002-07-7
研究领域: 药剂学 · 生物药剂学 · 中药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2024 ·Vol. 108 ·期 1 ·1-13 · IF 3.9

Novel glycosidase from Paenibacillus lactis 154 hydrolyzing the 28-O-β-d-glucopyranosyl ester bond of oleanane-type saponins

Wu Zongzhan,Dou Wenyu,Yang Xiaolin,Niu Tengfei,Han Zhuzhen,Yang Li,Wang Rufeng,Wang Zhengtao

Abstract Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase Pl GH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli . Sequence analysis revealed that Pl GH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of Pl GH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p -nitrophenyl- β - d -glucopyranoside as a substrate, respectively. The K m and k cat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s −1 , respectively. Pl GH3 exhibits a highly specific activity on hydrolyzing the 28- O - β - d -glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus . This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. Key points • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis.

研究领域: 生物化学 · 药理学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

A Versatile β-Glycosidase from Petroclostridium xylanilyticum Prefers the Conversion of Ginsenoside Rb3 over Rb1, Rb2, and Rc to Rd by Its Specific Cleavage Activity toward 1,6-Glycosidic Linkages

Wenqi Xu,Cuicui Duan,Fumin Ma,Dan Li,Xiaolei Li

To convert ginsenosides Rb1, Rb2, Rb3, and Rc into Rd by a single enzyme, a putative β-glycosidase (Pxbgl) from the xylan-degrading bacterium Petroclostridium xylanilyticum was identified and used. The kcat/Km value of Pxbgl for Rb3 was 18.18 ± 0.07 mM–1/s, which was significantly higher than those of Pxbgl for other ginsenosides. Pxbgl converted almost all Rb3 to Rd with a productivity of 5884 μM/h, which was 346-fold higher than that of only β-xylosidase from Thermoascus aurantiacus. The productivity of Rd from the Panax ginseng root and Panax notoginseng leaf was 146 and 995 μM/h, respectively. Mutants N293 K and I447L from site-directed mutagenesis based on bioinformatics analysis showed an increase in specific activity of 29 and 7% toward Rb3, respectively. This is the first report of a β-glycosidase that can simultaneously remove four different glycosyls at the C–20 position of natural PPD-type ginsenosides and produce Rd as the sole product from P. notoginseng leaf extracts with the highest productivity.

研究领域: 生物化学 · 生物技术 · 药理学 · 微生物学
✓ 已验证 DOI PubMed 高影响因子
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Food Frontiers · 2025 · IF 6.9

Synergistic Effects of Ginsenoside Rb3 and Rc From Panax notoginseng Leaf on Alleviating Neuroinflammation via PACAP in Depression

Shu-zhen Ran,Rui Peng,Qin-wan Guo,Li-juan Ma,Jian-bo Wan,Jun-qing Huang,Zi-ying Wang,Gang Chen

Panax notoginseng Leaf (PNL), an edible-medicinal botanical resource, shows potential as functional ingredients for alleviating depression, owing to their unique saponin composition. This study investigates the regulatory effects of PNL-derived saponins on pituitary adenylate cyclase-activating polypeptide (PACAP) and their related antidepressant mechanisms. Our findings demonstrate that PNL supplementation significantly alleviates depressive-like behaviors. Mechanistically, PNL upregulates PACAP expression in the hippocampus and activates the downstream CREB and mTOR signaling pathways, leading to increased expression of synaptic plasticity markers, including BDNF and PSD95, while concurrently inhibiting microglial activation and the production of pro-inflammatory cytokines. Among the major saponins in PNL, ginsenosides Rb3 and Rc were found to synergistically enhance PACAP expression in the cultured PC12 cells. These results underscore the potential of PNL for novel functional food ingredients, highlighting the antidepressant synergism of its naturally occurring ginsenosides (Rb3/Rc), and provide a natural antidepressant strategy.

CAS / MDL: 50-22-6
研究领域: 药理学 · 神经科学 · 植物学 · 生物化学 · 精神病学
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WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY · 2011 ·Vol. 28 ·期 3 ·857-863 · IF 1.214

Effects of external calcium on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7

Ye Li,Zhang Chunyan,Li Jiyang,Shi Xunlong,Feng Meiqing

Calcium is a known signalling molecule in eukaryotic cells and plays a central role in the regulation of many cellular processes. In the following study, we report on the effect of external calcium treatments on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7. We observed that the intracellular calcium content of P . bainier 229-7 mycelia was increased in response to exposure to high external Ca 2+ concentrations. Both ginsenoside Rd biotransformation and β-glucosidase activity were both found to be dependent on the external calcium concentration. At an optimal Ca 2+ concentration of 45 mM, maximal ginsenoside Rd bioconversion rate of 92.44% was observed and maximal β-glucosidase activity of 0.1778 U was reached in a 72-h biotransformation. The Ca 2+ channel blocker Verapamil blocked the trans-membrane influx of calcium and decreased ginsenoside Rd biotransformatiom. In addition, β-glucosidase activity and ginsenoside Rd content decreased by 36.0 and 29.2% respectively after a 72-h incubation in the presence of 0.05 mM Calmodulin (CaM) antagonist Perphenazine. These results suggest that both Ca 2+ channels and CaM are involved in ginsenoside Rd biotransformation via regulation of β-glucosidase activity. This is the first report regarding the effects of calcium signal transduction on biotransformation and enzyme activity in fungi.

CAS / MDL: 100-02-7
研究领域: 药理学 · 微生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY · 2019 · IF 3.202

Various Multicharged Anions of Ginsenosides in Negative Electrospray Ionization with QTOF High-Resolution Mass Spectrometry

Nan Zhao,Mengchun Cheng,Shuai Huang,Dan Liu,Qiang Zhao,Yunpeng Bai,Xiaozhe Zhang

When characterizing components from ginseng, we found a vast number of multicharged anions presented in the liquid chromatography–mass spectrometry (LC-MS) chromatograms. The source of these anions is unclear yet, while ginsenosides, the major components of ginseng, are the main suspected type of molecules because of their sugar moiety. Our investigation using 14 pure ginsenosides affirmed that the multicharged anions were formed by ginsenosides rather than other types of ingredients in ginseng. Various anions could be observed for each ginsenoside. These anions contain ions ([M-2H]2−, [M+Adduct]2−), as well as those formed by polymerization of at least two ginsenosides, such as [nM-2H]2−, [nM-H+Adduct]2−, and [nM-3H]3−. The presence of so different types of ions from a ginsenoside explains the reason for the large number of anions in the LC-MS analysis of ginseng. We further found that formation of [nM-2H]2− ions was influenced by the number of sugar chains: ginsenosides containing two sugar chains produced all [nM-2H]2− ion types, whereas ginsenosides containing one sugar chain did not produce [2M-2H]2−. Thus, [2M-2H]2− and [3M-2H]2− can be utilized to rapidly identify monodesmosidic and/or bidesmosidic ginsenosides as joint diagnostic anions. The position of the glycosyl radical might be the key factor affecting the formation of multicharged multimer ions from monodesmosidic ginsenosides. Consequently, three groups of ginsenoside isomers were differentiated by characteristic [nM-2H]2− anions. Using concentration-dependent characteristics and collision-induced dissociation (CID), we confirmed that [nM-2H]2− ions are non-covalently bound multimers whose aggregation has marked distinction between monodesmosidic and bidesmosidic ginsenosides, accounting for the differentiated formation of [nM-2H]2− between them.

研究领域: 分析化学 · 药物分析 · 质谱学 · 天然产物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2020 ·Vol. 25 ·期 20 ·4815 · IF 3.267

Ginsenoside Rb3 Inhibits Pro-Inflammatory Cytokines via MAPK/AKT/NF-κB Pathways and Attenuates Rat Alveolar Bone Resorption in Response to Porphyromonas gingivalis LPS

Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du

Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides

CAS / MDL: 7440-17-7
研究领域: 药理学 · 牙科 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Science and Technology · 2020 · IF 1.443

Improved bioactivity and composition of Cordyceps militaris cultured with Panax ginseng

LI Li,ZUO Jin-Hui,YI Fan,YANG Yun-Li,DONG Yin-Mao,LI Qin-Yu,LI Min-Hui

Cordyceps militaris is a commonly used edible and medicinal fungus in East Asia. Preparation of the mycelium and fermentation liquid by submerged fermentation using additives such as Panax ginseng for skin whitening applications has attracted wide attention. In the present study, we screened traditional Chinese medicines as additives to the liquid fermentation medium for C. militaris and performed systematical research on the changes of bioactivity and ginsenoside levels during the fermentation process. Total polysaccharide contents, cordycepin content, and polysaccharide molecular weight in the fermentation products were measured by UV spectrophotometry, high-performance liquid chromatography-diode array detection (HPLC/DAD), and gel permeation chromatography-multi angle laser light scattering (GPC-MALLS), respectively. In addition, the ginsenosides Rb1, Re, Rd, Rg1, and pseudoginsenoside F11 in the fermentation products were quantitatively analyzed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). Panax ginseng significantly increased the cordycepin and total sugar contents, and the average molecular weight of polysaccharides in the fermentation liquid and the mycelium of C. militaris. At the same time, C. militaris enhanced the production of ginsenoside pseudoginsenoside F11, which is a unique component of Panax quinquefolium. The research provides scientific evidence for the application of C. militaris and P. ginseng as raw materials for food and medicines.

CAS / MDL: 9002-10-2
研究领域: 药用真菌学 · 生物化学 · 中药学
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Journal of Ginseng Research · 2021 · IF 6.06

Evaluation of storage period of fresh ginseng for quality improvement of dried and red processed varieties

Na Zhang,Xin Huang,Yun-Long Guo,Hao Yue,Chang-Bao Chen,Shu-Ying Liu

Background Dried and red ginseng are well-known types of processed ginseng and are widely used as healthy food. The dried and red ginseng quality may vary with the storage period of raw ginseng. Therefore, herein, the effect of the storage period of fresh ginseng on processed ginseng quality was evaluated through multicomponent quantification with statistical analysis. Methods A method based on ultrahigh performance liquid chromatography coupled to triple quadrupole mass spectrometry in multiple-reaction monitoring mode (UPLC-MRM-MS) was developed for quantitation of ginsenosides and oligosaccharides in dried and red ginseng. Principal component analysis and partial least squares discriminant analysis were conducted to evaluate the dynamic distributions of ginsenosides and oligosaccharides after different storage periods. Results Eighteen PPD, PPT and OLE ginsenosides and nine reducing and nonreducing oligosaccharides were identified and quantified. With storage period extension, the ginsenoside content in the processed ginseng increased slightly in the first 2 weeks and decreased gradually in the following 9 weeks. The content of reducing oligosaccharides decreased continuously as storage time extending, while that of the nonreducing oligosaccharides increased. Chemical conversions occurred during storage, based on which potential chemical markers for the storage period evaluation of fresh ginseng were screened. Conclusion According to ginsenoside and oligosaccharide distributions, it was found that the optimal storage period was 2 weeks and that the storage period of fresh ginseng should not exceed 4 weeks at 0 °C. This study provides deep insights into the quality control of processed ginseng and comprehensive factors for storage of raw ginseng.

研究领域: 药用植物学 · 食品科学 · 中药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF FOOD PROPERTIES · 2022 · IF 3.388

Comparative metabolic profiling of root, leaf, fruit, and stem tissues of Panax notoginseng

Rui Shi,Bingjie Xiong,Shu He,Can Liu,Jiftah Ben-Asher,Abraham Rami Horowitz,Shu Wang,Xiahong He

Panax notoginseng is highly used in traditional Chinese medicine, and its root is valued for ginsenoside contents. However, evidence suggests that other plant parts such as fruit, leaves, and stem are also potential sources of bioactive compounds. Therefore, this study aimed at providing insight into the differential accumulation of metabolites in fruit, leaf, root, and stem tissues collected from P. notoginseng. A total of 808 metabolites from 11 major metabolite classes were identified. Furthermore, 32 Ginsenosides with six conserved Ginsenosides Rg1, Rf, St-3, R1, Ro, Rc, and five conserved notoginsenosides R1, K, M, E, Rb1, were identified with differential accumulation in fruit, leaf, stem, and root tissues. Several other metabolites known for their potential roles in human health were also identified as differentially accumulated in the tissues. Furthermore, the accumulation pattern of ginsenosides in different tissues is highly suggestive of utilizing fruit, leaf, and stem tissues along with roots for value addition of P. notoginseng.

CAS / MDL: 67-56-1
研究领域: 植物学 · 药用植物研究 · 代谢组学
✓ 已验证 产品关联 DOI 高影响因子
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