Ginsenosides Rk1 Research Articles

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects.

Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

Ginsenoside Rk3 ameliorates Aβ-induced neurotoxicity in APP/PS1 model mice via AMPK signaling pathway

Alzheimer's disease (AD) has become a major public health problem affecting the elderly population, and there is currently no effective treatment. Although the pathogenesis of AD is unclear, neurotoxicity induced by oxidative stress plays an important role in the progression of AD. Ginseng, the root and rhizome of Panax ginseng C. A. Meyer, is used not only as an herbal medicine but also as a functional food to support bodily functions. Ginsenoside Rk3 (Rk3), the main bioactive component in ginseng, has a strong antioxidant effect and has not been reported in AD. In this study, we showed that Rk3 improved neuronal apoptosis, decreased intracellular reactive oxygen species (ROS) production and restored mitochondrial membrane potential in PC12 and primary neuronal cells. In vivo, we found that Rk3 improved spatial learning and memory deficit in precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. Additionally, Rk3 increases glutathione reductase (GSH) and superoxide dismutase (SOD) levels while inhibits malondialdehyde (MDA) production, apoptosis and activation of glial cells in APP/PS1 mice. Mechanistically, we found that the protective effect of Rk3 is in correlation with the activation of AMPK/Nrf2 signaling pathway. In conclusion, the findings of this study provide support for Rk3 as a new strategy for the treatment of AD.

Ginsenoside Rk3 Inhibits the Extramedullary Infiltration of Acute Monocytic Leukemia Cell via miR-3677-5p/CXCL12 Axis.

Acute monocytic leukemia belongs to type M5 of acute myeloid leukemia (AML) classified by FAB, which appears a high incidence of extramedullary infiltration (EMI) and poor prognosis. In this study, we observed the inhibitory effect of ginsenoside Rk3 on the EMI of monocytic leukemia cells and initially explored its related mechanism of targeting the miR-3677-5p/CXCL12 axis. The MTT assay and colony formation assay were used to detect the inhibitory effect of Rk3 on proliferation. Both cellular migration and invasion were observed by the Transwell assay. The expression levels of miR-3677-5p, CXCL12, and CXCR4 were detected by RT-qPCR and Western blot, as well as overexpression of miR-3677-5p by transfected with lentivirus and detection of a dual luciferase reporter gene. The expression of MMP2 and TIMP2 was detected by immunofluorescence. Rk3 effectively inhibits the proliferation, migration, and invasion associated with EMI of leukemia. The leukemia cells of M5 patients with EMI showed low expression of miR-3677-5p but high expression of the mRNA of CXCL12 and CXCR4. Overexpression of miR-3677-5p or intervention of CXCL12 effectively inhibited the proliferation, migration, and invasion of SHI-1 cells. The luciferase assay showed that CXCL12 was the downstream target gene of miR-3677-5p. After overexpression of miR-3677-5p or intervention of CXCL12 in combination with Rk3, the inhibitory effect on the proliferation, migration, and invasion of SHI-1 cells was more obvious. Importantly, Rk3 significantly regulated the expression levels of miR-3677-5p, CXCL12, CXCR4, and EMI-related functional proteins including MMP2 and TIMP2. Overexpression of miR-3677-5p or intervention of CXCL12 also regulated the expression of MMP2 and TIMP2. The leukemia cells of M5 patients with EMI appeared to have low expression of miR-3677-5p and high expression of the mRNA of CXCL12 and CXCR4, which may be used as indicators of EMI and poor prognosis. Rk3 is effective in inhibiting the EMI of SHI-1 cells by targeting the miR-3677-5p/CXCL12 axis.

Steamed Panax notoginseng and its Saponins Inhibit the Migration and Induce the Apoptosis of Neutrophils in a Zebrafish Tail-Fin Amputation Model.

Panax notoginseng (PN) is a Chinese medicinal herb that is traditionally used to treat inflammation and immune-related diseases. Its major active constituents are saponins, the types and levels of which can be changed in the process of steaming. These differences in saponins are causally relevant to the differences in the therapeutic efficacies of raw and steamed PN. In this study, we have prepared the extracts of steamed PN (SPNE) with 70% ethanol and investigated their immunomodulatory effect using a zebrafish tail-fin amputation model. A fingerprint-effect relationship analysis was performed to uncover active constituents of SPNE samples related to the inhibitory effect on neutrophil number. The results showed that SPNE significantly inhibited the neutrophil number at the amputation site of zebrafish larvae. And SPNE extracts steamed at higher temperatures and for longer time periods showed a stronger inhibitory effect. Ginsenosides Rh1, Rk3, Rh4, 20(S)-Rg3, and 20(R)-Rg3, of which the levels were increased along with the duration of steaming, were found to be the major active constituents contributing to the neutrophil-inhibiting effect of SPNE. By additionally investigating the number of neutrophils in the entire tail of zebrafish larvae and performing TUNEL assays, we found that the decreased number of neutrophils at the amputation site was due to both the inhibition of their migration and apoptosis-inducing effects of the ginsenosides in SPNE on neutrophils. Among them, Rh1 and 20(R)-Rg3 did not affect the number of neutrophils at the entire tail, suggesting that they only inhibit the migration of neutrophils. In contrast, ginsenosides Rk3, Rh4, 20(S)-Rg3, and SPNE did not only inhibit the migration of neutrophils but also promoted neutrophilic cell death. In conclusion, this study sheds light on how SPNE, in particular the ginsenosides it contains, plays a role in immune modulation.

Integration of multiplatform metabolomics and multivariate analysis for geographical origin discrimination of Panax ginseng

As the health food industry grows, the market for ginseng also expands globally. Korean ginseng (Panax ginseng C. A. Meyer) is cultivated in East Asian countries such as Korea, China, and Japan. The metabolic profile of plants can vary depending on the cultivation environment. As such, in this study, we aimed to compare the differences in the metabolic profiles of P. ginseng cultivated in Korea, China, and Japan, and to construct a library of these metabolite data. Using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), we profiled 62 types of secondary metabolites, ginsenosides, using optimized analysis conditions to separate peaks with a high-resolution for about 30 min. In addition, we selected ginsenosides showing differences between their origins were selected among the possible origins in the S-line plot of orthogonal partial least squares discriminant analysis (OPLS-DA), which we quantitatively analyzed using UPLC-tandem mass spectrometry (UPLC-MS/MS). The contents of ginsenosides Ra1, Ra2, Ra3, and Rk1 were high in Korean P. ginseng; the contents of ginsenosides Rb1, Rb2, and Rc were high in Japanese P. ginseng; and the contents of the ginsenoside Ro was high in Chinese P. ginseng. We also analyzed the primary metabolite contents using nuclear magnetic resonance (NMR) spectroscopy and gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). Japanese P. ginseng showed a high sucrose content and Korean P. ginseng showed high contents of most amino acids and organic acids. In the PLS-DA results of multivariate statistical analysis using the data obtained from each analysis instrument, we observed a clear clustering among the three origins. Although a genetically identical species, the metabolic profile substantially differs depending on the cultivation environment. Because ginsenoside, having many biological activities, showed origin-dependent origins, when P. ginseng is used for medicinal purposes, its content by origin should be considered. After disclosing the profiling results of these metabolites, we expect that they will be used in future ginseng research.

Anaphylactic Rare Saponins Separated from Panax notoginseng Saponin and a Proteomic Approach to Their Anaphylactic Mechanism.

In recent years, many traditional Chinese medicine injections based on Panax notoginseng saponin (PNS) have been reported to cause anaphylaxis. Previous studies on the anaphylactic saponins of PNS and their mechanism are inadequate. In this study, potential anaphylactic saponins were obtained by the separation of PNS and preparation of each individual component through comprehensive techniques, such as liquid chromatography, preparative chromatography, HPLC, NMR, and MS. The anaphylactic abilities of these saponins were tested using RBL-2H3 cells via a β-hexosaminidase release rate test. The results for the mechanism of anaphylaxis were obtained by a proteomic analysis using RBL-2H3 cells. The results indicate that, among all the saponins prepared, gypenoside LXXV and notoginsenoside T5 showed strong anaphylactic abilities and notoginsenoside ST-4 and ginsenoside Rk3 showed weak anaphylactic abilities. These 4 saponins can induce anaphylaxis via direct stimulation of effector cells. The gene oncology enrichment analysis results showed that, among these saponins, only gypenoside LXXV was related to organelles of the endoplasmic reticulum and Golgi apparatus and biological processes in response to organic cyclic compounds. Four proteins in RBL-2H3 cells with the accession numbers A0A0G2JWQ0, D3ZL85, D4A5G8, and Q8K3F0 were identified as crucial proteins in the anaphylactic process. This research will help traditional Chinese medicine injection manufacturers strengthen their quality control and ensure the safety of anaphylactic saponins.

Effect of γ -Cyclodextrin on the Dissolution of Ginsenosides Rg5 and Rk1 from Red Ginseng Chewable Tablets

This study aimed to assess the water solubility of Ginsenosides Rg5 and Rk1 released from chewable tablets containing Red Ginseng preparation HRG80 incorporated γ-cyclodextrin (GCD) complex compared with γ-cyclodextrin free drug preparation. The dissolution rate of Ginsenosides Rg5 and Rk1 was increased three times after γ-cyclodextrin inclusion. The relative solubility of Ginsenosides Rg5 and Rk1 calculated from the ratio of Area under the curve AUC 0 – 90 min was correspondingly 221% and 227%. This study for the first reports that Red Ginseng preparation HRG80 inclusion into GCD significantly improves (increases) the water solubility of active constituents Ginsenosides Rg5 and Rk1.

Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics.

Injection of total saponins from Panax notoginseng (ISPN) is a modern preparation derived from traditional Chinese medicine (TCM) and is widely applied in the treatment of cardiovascular, cerebrovascular, ophthalmology, and endocrine system diseases. With the increase in the clinical application of ISPN, its adverse drug reactions (ADRs) and related safety issues have attracted much attention. In the present study, a data-independent acquisition (DIA) strategy was proposed to comprehensively characterize the saponins contained in ISPN based on the ultra-high-performance liquid chromatography/quadrupole-Orbitrap MS (UHPLC/Q-Orbitrap MS) platform. As many as 276 saponins were detected, and 250 compounds were identified or tentatively identified based on the retention times and MS/MS data. Furthermore, a metabolomic strategy was utilized to discover the discriminative saponins between normal and ADR batches. The results showed that six saponins, including ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rg5, ginsenoside Rk1, ginsenoside Rg6, and 20(S)-ginsenoside Rh2, were significantly different between the two groups. According to cytotoxicity analysis and degranulation detection of RBL-2H3 cells, ginsenoside Rg5, ginsenoside Rk1, and 20(S)-ginsenoside Rh2 were considered the potential compounds responsible for clinical ADRs, ultimately. In addition, the quantitative analysis showed that the content of these three compounds in ISPN samples with ADRs was generally higher than that in samples without ADRs. This study demonstrated that it is advisable to screen out potential markers related to ADRs for developing the quality standard of ISPN by the integration of untargeted metabolomic analysis and cell biology study, and thus reduce its ADRs in the clinic.

Anti-Photoaging and Anti-Inflammatory Effects of Ginsenoside Rk3 During Exposure to UV Irradiation.

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics.

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up- or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

Ginsenoside Rk3 Suppresses Hepatocellular Carcinoma Development through Targeting the Gut-Liver Axis.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Our previous reports showed that ginsenoside Rk3 provided excellent efficacy in alleviating the intestinal inflammatory response and protecting the liver, but its mechanism for HCC prevention remains to be explored. Here, the results suggested that Rk3 displayed potent antitumor effects against a dimethyl nitrosamine- and CCl4-induced HCC mouse model. Results revealed that Rk3 application inhibited liver injury, fibrosis, and cirrhosis. In parallel, Rk3 lowered the inflammatory response by decreasing the expression of inflammatory cytokines, inducing apoptosis, and blocking the cell cycle. Meanwhile, Rk3 effectively ameliorated the gut microbiota dysbiosis. Furthermore, correlation analysis revealed that the LPS-TLR4 signaling pathway, which was inhibited by Rk3, plays a key role in preventing HCC. To conclude, our research provides valuable insights into how Rk3 application targets the gut-liver axis and suppresses HCC development, suggesting that Rk3 might be a promising candidate for clinical treatment of HCC.

Ginsenoside Rk3 alleviates gut microbiota dysbiosis and colonic inflammation in antibiotic-treated mice

Ginsenoside Rk3 is a natural prebiotic found in ginseng, has excellent pharmacological efficacy, especially antitumor effects, and can greatly benefit human health. Here, we investigated the impact of Rk3 intake on modulation of the gut microbiota and their metabolites as well as its effect on low-grade inflammation in mice. C57BL/6JFandd mice were administered different doses of Rk3 for two weeks after establishment of an antibiotic-mediated gut microbiota disturbance model. Interestingly, Rk3 intake induced substantial changes in the gut microbiota composition, enriched the Bacteroides, Alloprevotella and Blautia genera, and effectively ameliorated gut microbiota dysbiosis, with significantly decreased Firmicutes/Bacteroidetes ratios. These changes were accompanied by beneficial alterations in gut microbiota diversity and improved short-chain fatty acid levels. In addition, we found that Rk3 intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (ZO-1, Occludin and Claudin-1), reducing colonic inflammatory cytokine levels, and suppressing TNF-α, IL-1β, and IL-6 overproduction. In conclusion, Rk3 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, and these findings help elucidate host-microbe interactions.

Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults.

Red ginseng (RG) and black ginseng (BG, CJ EnerG) were prepared from fresh ginseng using one and nine cycles of steaming and drying, respectively. This process reduces the molecular weight (MW) of ginsenoside-active compounds in ginseng by removing sugar moieties from their dammaranes. We compared the pharmacokinetic characteristics of ginsenosides between BG comprising mainly low-MW ginsenosides (Rg3, Rg5, Rk1, and Rh1) and RG that predominantly contains high-MW ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1). The safety profiles and tolerability were also studied using a randomized, double-blind, single-dose, crossover clinical trial. A combination of Rb1, Rg1, and Rg3, well-known representative and functional RG components, exhibited a 1 h faster absorption rate (Tmax) and 58% higher exposure (24 h area under the concentration–time curve, AUC24) in BG than in RG. Furthermore, the combination of Rg3, Rg5, and Rk1, the major and most efficient components in BG, displayed 824% higher absorption (AUC24) in BG than in RG. The total ginsenoside showed a 5 h rapid intestinal absorption (Tmax) and 79% greater systemic exposure (AUC24) in BG than in RG. No clinically significant findings were observed in terms of safety or tolerability. Thus, BG extract was more effective than RG extract.

Pharmacokinetic studies of ginsenosides Rk1 and Rg5 in rats by UFLC–MS/MS

A rapid ultra-fast liquid chromatography tandem mass spectrometry method was developed and validated to determine ginsenosides Rk1 and Rg5, a pair of isomers, in rat plasma, which was successfully applied to their pharmacokinetic studies. Two ginsenosides were given to male Sprague-Dawley rats via intragastrical and intravenous routes, respectively, and the impact of double bond position on the pharmacokinetic features of the two ginsenosides was elucidated in rats. Ginsenoside Rg3 was used as internal standard and ethyl acetate was applied to extract analytes and internal standard. Chromatographic separation was carried out on a reverse-phase UPLC HSS T3 column (100 × 2.1 mm, 1.8 μm). The flow rate was set to 0.4 ml/min. The fragmentation transition was m/z 765.4 → m/z 101.1 for two ginsenosides. The mobile phases were composed of 0.1% formic acid aqueous solution and acetonitrile. The linear range was 2-1,000 ng/ml for the two ginsenosides. Intra- and inter-day precisions were <11.67%, and accuracy fluctuated from -7.44 to 6.78%. The extraction recovery, matrix effect and stability were within acceptable levels. After treatment with ginsenosides Rk1 and Rg5, some differences were found in their pharmacokinetic profiles in rats. The maximum plasma drug concentration and the area under the plasma drug concentration-time curve of ginsenoside Rg5 were about 5 times bigger than those of ginsenoside Rk1 after oral administration, and 3 times higher after intravenous administration. The oral bioavailabilities of ginsenosides Rk1 and Rg5 were 0.67 and 0.97%, respectively. The results indicated that ∆20(22) -ginsenosides showed better pharmacokinetic features than ∆20(21) -ginsenosides with the same glycosylation.

Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Regulating of Intestinal Flora and the TLR4/NF-κB Signaling Pathway in C57BL/6 Mice.

Obesity-induced colonic inflammation-stimulated colitis is one of the main causes of colorectal cancer. Dietary phytochemicals are considered to be an effective strategy for relieving obesity-induced inflammatory diseases such as diabetes and colitis. Ginsenoside Rk3 (Rk3) is the main bioactive component of ginseng. Our previous study has demonstrated that Rk3 can effectively alleviate obesity-induced type 2 diabetes, but whether it plays a beneficial role in obesity-induced colitis remains poorly understood. Here, we found that Rk3 intervention repaired the intestinal barrier dysfunction by increasing the expression of the tight junction proteins (zonula occludens-1, claudin, and occludin), and reduced colonic inflammatory cytokine levels, oxidative stress, and macrophage infiltration in high-fat diet-induced mice. Importantly, Rk3 effectively ameliorated the metabolic dysbiosis of intestinal flora with significantly decreased Firmicute/Bacteroidete ratios and suppressed the inflammatory cascade by inhibiting the TLR4/NF-κB signaling pathway. Taken together, our findings indicate that Rk3 can be used as a potential natural anti-inflammatory agent to reduce chronic obesity-induced colitis.

Dynamic changes in chemical compositions and anti-acetylcholinesterase activity associated with steaming process of stem-leaf saponins of Panax notoginseng.

Stem-leaf saponins (SLSs), the total saponins from aerial part of P. notoginseng, are by-products of notoginseng, a famous traditional Chinese medicine. SLSs have been used as a health functional food in China, but its mild effects limited clinical applications in diseases. Inspired by steaming of notoginseng to enhance its pharmacological activity, a steaming protocol was developed to treat SLSs. SLSs were steamed at 100, 120, and 140°C for 1, 2, 3, and 4 h, respectively. The ultra-performance liquid chromatography coupled with quadrupole time-of-flight MS and ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry were applied to analyze the dynamic changes in chemical compositions. The anti-acetylcholinesterase activity of steamed SLS were assessed in vitro by directly determining the metabolic product of acetylcholine/choline. The components of SLSs were significantly changed by steaming. A total of 117 saponins and aglycones were characterized, and 35 of them were newly generated. The anti-acetylcholinesterase activity of steamed SLSs gradually increased with the extension of steamed time and the increase of steamed temperature and reached the maximum after 140°C for 3 h. Furthermore, ginsenosides Rk1 and Rg5, the main components of steamed SLSs, showed dose-dependent anti-acetylcholinesterase activities with half maximal inhibitory concentration (IC50 ) values of 26.88 ± 0.53 μm and 22.41 ± 1.31 μm that were only 1.8- and 1.5-fold higher than that of donepezil with IC50 values of 14.93 ± 4.17 μM, respectively.

Hepatoprotective effects of ginsenoside Rk3 in acetaminophen-induced liver injury in mice by activation of autophagy.

Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently used in clinical practice for APAP, there is a need to develop new therapies that can provide extensive protection against AIALI. Ginsenoside Rk3 is a rare ginsenoside extracted from Panax notoginseng and a previous study has reported its excellent hepatoprotective function. In this study, we explored the therapeutic potential of ginsenoside Rk3 in APAP-induced acute liver injury. We found that ginsenoside Rk3 could reduce APAP-induced hepatotoxicity by reducing serum alanine aminotransferase and aspartate aminotransferase activity and pathological damage to the liver. Moreover, ginsenoside Rk3 could inhibit APAP-induced liver inflammation and oxidative stress by inhibiting the production of oxidative molecules, increasing the production of antioxidant molecules, and reducing the infiltration of inflammatory cells and the production of pro-inflammatory cytokines. Further mechanistic investigations revealed that the therapeutic effect of ginsenoside Rk3 was mainly dependent on the continuous activation of autophagy. Chloroquine, an autophagy inhibitor, was found to inhibit these protective effects. Therefore, ginsenoside Rk3 shows potential as a novel hepatoprotective agent to prevent drug-induced liver injury.

산삼 부정배양근의 진세노사이드 함량 증진과 성분 변환

Background: Culturing wild ginseng adventitious root using plant factory technology provides genetic safety and high productivity. This production technology is drawing attention in the fields of functional raw materials and product development. The cultivation method using elicitors is key technology for controlling biomass and increasing secondary metabolites.BRMethods and Results: Elicitor treatments using methyl jasmonate, pyruvic acid, squalene, β-sistosterol were performed to amplify total ginsenosides (Rb1, Rc, Rb2, Rb3, and Rd) of cultured wild ginseng adventitious root. Thereafter, fermentation and steaming processes were performed to convert total ginsenosides into minor molecular ginsenosides (Rg3, Rk1, and Rg5). The result indicated that methyl jasmonate minimizes the reduction in fresh weight of cultured wild ginseng adventitious root and maximizes total ginsenosides (sum of Rb1, Rc, Rb2, Rb3, and Rd). Ginsenoside conversion results showed a maximum degree of conversion of 131 ㎎/g.BRConclusions: In this study, we demonstrated that the optimal elicitor treatment method increased the content of total ginsenosides, while the steaming and fermentation processing method increased the content of minor ginsenosides.

Diversity of Ginsenoside Profiles Produced by Various Processing Technologies.

Ginseng is a traditional medicinal herb commonly consumed world-wide owing to its unique family of saponins called ginsenosides. The absorption and bioavailability of ginsenosides mainly depend on an individual’s gastrointestinal bioconversion abilities. There is a need to improve ginseng processing to predictably increase the pharmacologically active of ginsenosides. Various types of ginseng, such as fresh, white, steamed, acid-processed, and fermented ginsengs, are available. The various ginseng processing methods produce a range ginsenoside compositions with diverse pharmacological properties. This review is intended to summarize the properties of the ginsenosides found in different Panax species as well as the different processing methods. The sugar moiety attached to the C–3, C–6, or C–20 deglycosylated to produce minor ginsenosides, such as Rb1, Rb2, Rc, Rd→Rg3, F2, Rh2; Re, Rf→Rg1, Rg2, F1, Rh1. The malonyl-Rb1, Rb2, Rc, and Rd were demalonylated into ginsenoside Rb1, Rb2, Rc, and Rd by dehydration. Dehydration also produces minor ginsenosides such as Rg3→Rk1, Rg5, Rz1; Rh2→Rk2, Rh3; Rh1→Rh4, Rk3; Rg2→Rg6, F4; Rs3→Rs4, Rs5; Rf→Rg9, Rg10. Acetylation of several ginsenosides may generate acetylated ginsenosides Rg5, Rk1, Rh4, Rk3, Rs4, Rs5, Rs6, and Rs7. Acid processing methods produces Rh1→Rk3, Rh4; Rh2→Rk1, Rg5; Rg3→Rk2, Rh3; Re, Rf, Rg2→F1, Rh1, Rf2, Rf3, Rg6, F4, Rg9. Alkaline produces Rh16, Rh3, Rh1, F4, Rk1, ginsenoslaloside-I, 20(S)-ginsenoside-Rh1-60-acetate, 20(R)-ginsenoside Rh19, zingibroside-R1 through hydrolysis, hydration addition reactions, and dehydration. Moreover, biological processing of ginseng generates the minor ginsenosides of Rg3, F2, Rh2, CK, Rh1, Mc, compound O, compound Y through hydrolysis reactions, and synthetic ginsenosides Rd12 and Ia are produced through glycosylation. This review with respect to the properties of particular ginsenosides could serve to increase the utilization of ginseng in agricultural products, food, dietary supplements, health supplements, and medicines, and may also spur future development of novel highly functional ginseng products through a combination of various processing methods.

Anti-hyperglycemic and hypolipidemic effects of black ginseng extract containing increased Rh4, Rg5, and Rk1 content in muscle and liver of type 2 diabetic db/db mice.

Black ginseng (BG), which is produced by repeated steaming and drying of fresh ginseng, has various pharmacological and therapeutic properties. This study investigated the anti-hyperglycemic and hypolipidemic effects of BG ethanolic extract in type 2 diabetic db/db mice. The levels of fasting blood glucose, HbA1c, insulin levels and thiobarbituric acid reactive substances values were decreased in the groups fed BG extract (BG) (100 and 900mg/kg BW/day), compared to the control group (CON). In the BG compared with the CON, hepatic steatosis in the liver and the size of adipocytes in muscle tissue were improved. The administration of BG regulated the glucose transporter type (GLUT) 4 and 2, and peroxisome proliferator-activated receptor (PPAR) α and γ in muscle and liver. Moreover, ginsenosides (Rh4, Rg5, and Rk1), which profiled by HPLC, regulated the markers for lipid metabolism and glucose metabolism; PPARs and GLUTs in muscle and C2C12 rather than liver cells and tissue. These findings suggested that ginsenosides (Rh4, Rg5, and Rk1) from BG extract can ameliorate type 2 diabetes through their anti-hyperglycemic and hypolipidemic effects.