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Schematic illustration of biotransformation of major ginsenosides Rb1, Rb2, and Rc to Rd (⟶ major pathway; ⤏ minor pathway).
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It is well known that ginsenosides—major bioactive constituents of Panax ginseng—are attracting more attention due to their beneficial pharmacological activities. Ginsenoside Rd, belonging to protopanaxadiol (PPD)-type ginsenosides, exhibits diverse and powerful pharmacological activities. In recent decades, nearly 300 studies on the pharmacologica...
Context in source publication
Context 1
... content of ginsenoside Rd differs from different wild ginseng and parts of ginseng, and ranges from 0.02% to 1.66% [4]. Moreover, it is difficult and costly to isolate Rd from natural products; thus, a microbial enzymatic transformation has become the predominant conversion modality of ginsenoside Rd due to its distinct selectivity, mild reactive conditions, and environmental compatibility ( Figure 1). ...
Citations
... This protective function of Rd against apoptosis may also alleviate T2D, as demonstrated by the suppressed progression of cell death and pro-apoptotic proteins in cultured human pancreatic islets [57]. A recent study demonstrated that Rd ameliorates retinal endothelial damage under high-glucose conditions by upregulating AMPK and Sirtuin 1 expression and their mutual interaction [58,59]. Collectively, these findings suggest the Rd is a promising pharmacological agent for diabetic intervention. ...
Diabetes mellitus (DM) is a systemic disorder of energy metabolism characterized by a sustained elevation of blood glucose in conjunction with impaired insulin action in multiple peripheral tissues (i.e., insulin resistance). Although extensive research has been conducted to identify therapeutic targets for the treatment of DM, its global prevalence and associated mortailty rates are still increasing, possibly because of challenges related to long-term adherence, limited efficacy, and undesirable side effects of currently available medications, implying an urgent need to develop effective and safe pharmacotherapies for DM. Phytochemicals have recently drawn attention as novel pharmacotherapies for DM based on their clinical relevance, therapeutic efficacy, and safety. Ginsenosides, pharmacologically active ingredients primarily found in ginseng, have long been used as adjuvants to traditional medications in Asian countries and have been reported to exert promising therapeutic efficacy in various metabolic diseases, including hyperglycemia and diabetes. This review summarizes the current pharmacological effects of ginsenosides and their mechanistic insights for the treatment of insulin resistance and DM, providing comprehensive perspectives for the development of novel strategies to treat DM and related metabolic complications.
... Ginsenoside is a vital active pharmaceutical component isolated from the traditional Chinese medicine ginseng, and it has been utilized for therapeutic purposes due to as anti-inflammatory, anti-stress, anti-oxidation, and anti-tumor effects (9). Rg3 is considered one of the most biologically active extracts among ginsenosides (10). ...
... Gensenosides are the main active ingredients of ginseng, with good therapeutic effects on many diseases, including cardiovascular diseases, neurological disorders, and metabolic diseases [1]. The pharmacological activities of ginsenosides include improving immune function, antioxidation, anti-aggregation, and anti-inflammatory, anti-stress, and anti-fatigue effects [2]. Several studies have demonstrated that ginsenosides have excellent efficacy and safety in treating lung, gastric, liver, and pancreatic cancers [3]. ...
The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.
... [1] The pharmacological activities of ginsenosides include improving immune function, antioxidation, anti-aggregation, and antiinflammatory, anti-stress, and anti-fatigue effects. [2] Several studies have demonstrated that ginsenosides have excellent efficacy and safety in treating lung, gastric, liver, and pancreatic cancers. [3] Recent studies have also confirmed the potential of some ginsenosides as promising compounds for treating colorectal cancer; [4] for example, the treatment of hypoxic colorectal cancer cells with ginsenoside Compound K significantly blocked Nur77-mediated carcinogenic signaling, inhibiting the cancer stem-cell-like cells characteristics and metastasis in vitro and in vivo . ...
The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared to the model group. Immunofluorescence and TUNEL analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/ mTOR autophagy pathway and regulate JAK2/ STAT3 and Bax/ Bcl-2/ caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.
... Therefore, biotransformation methods with high conversion to target products, high specificity, mild reaction conditions, and environmentalfriendly properties have become popular. Bioconversion mainly includes enzymatic and microbial fermentation methods (Chang et al. 2014;Choi et al. 2011;Kim et al. 2006;Song et al. 2022). Microbial fermentation method for the preparation of rare ginsenosides is to obtain rare ginsenosides by hydrolyzing the glycosyl groups of the substrate ginsenosides through microbial fermentation with the help of one or more enzymes of the microorganisms. ...
Rare ginsenosides are the deglycosylated secondary metabolic derivatives of major ginsenosides, and they are more readily absorbed into the bloodstream and function as active substances. The traditional preparation methods hindered the potential application of these effective components. The continuous elucidation of ginsenoside biosynthesis pathways has rendered the production of rare ginsenosides using synthetic biology techniques effective for their large-scale production. Previously, only the progress in the biosynthesis and biotechnological production of major ginsenosides was highlighted. In this review, we summarized the recent advances in the identification of key enzymes involved in the biosynthetic pathways of rare ginsenosides, especially the glycosyltransferases (GTs). Then the construction of microbial chassis for the production of rare ginsenosides, mainly in Saccharomyces cerevisiae, was presented. In the future, discovery of more GTs and improving their catalytic efficiencies are essential for the metabolic engineering of rare ginsenosides. This review will give more clues and be helpful for the characterization of the biosynthesis and metabolic engineering of rare ginsenosides.
Key points
• The key enzymes involved in the biosynthetic pathways of rare ginsenosides are summarized.
• The recent progress in metabolic engineering of rare ginsenosides is presented.
• The discovery of glycosyltransferases is essential for the microbial production of rare ginsenosides in the future.
... Ginsenosides are the main active components of the traditional Chinese herbal medicine Panax ginseng C. A. Mey (Song, et al. 2022). At present, nearly 200 ginsenosides have been isolated and identified from the roots, stems, leaves, flower buds, and berries of Panax ginseng C. A. Mey. ...
Nephropathy is a general term for kidney diseases, which refers to changes in the structure and function of the kidney caused by various factors, resulting in pathological damage to the kidney, abnormal blood or urine components, and other diseases. The main manifestations of kidney disease include hematuria, albuminuria, edema, hypertension, anemia, lower back pain, oliguria, and other symptoms. Early detection, diagnosis, and active treatment are required to prevent chronic renal failure. The concept of nephropathy encompasses a wide range of conditions, including acute renal injury, chronic kidney disease, nephritis, renal fibrosis, and diabetic nephropathy. Some of these kidney-related diseases are interrelated and may lead to serious complications without effective control. In serious cases, it can also develop into chronic renal dysfunction and eventually end-stage renal disease. As a result, it seriously affects the quality of life of patients and places a great economic burden on society and families. Ginsenoside is one of the main active components of ginseng, with anti-inflammatory, anti-tumor, antioxidant, and other pharmacological activities. A variety of monomers in ginsenosides can play protective roles in multiple organs. According to the difference of core structure, ginsenosides can be divided into protopanaxadiol-type (including Rb1, Rb3, Rg3, Rh2, Rd and CK, etc.), and protopanaxatriol (protopanaxatriol)- type (including Rg1, Rg2 and Rh1, etc.), and other types (including Rg5, Rh4, Rh3, Rk1, and Rk3, etc.). All of these ginsenosides showed significant renal function protection, which can reduce renal damage in renal injury, nephritis, renal fibrosis, and diabetic nephropathy models. This review summarizes reports on renal function protection and the mechanisms of action of these ginsenosides in various renal injury models.
... Bioconversion, also known as biotransformation, may provide a strategy to enhance the pharmacological effects of natural extracts by modifying and generating the structure of bioactive compounds [32]. Previous studies have been implicated that bioconversion improved the anti-inflammatory, anti-cancer, and anti-angiogenic effects of herbal medicine, possible through enriching several compounds containing phenolic acid and flavonoid [33,23]. ...
... Bioconversion, also known as biotransformation, may provide a strategy to enhance the pharmacological effects of natural extracts by modifying and generating the structure of bioactive compounds [32]. Previous studies have been implicated that bioconversion improved the anti-inflammatory, anti-cancer, and anti-angiogenic effects of herbal medicine, possible through enriching several compounds containing phenolic acid and flavonoid [23,33]. ...
Akebia quinata, commonly called chocolate vine, has various bioactivities, including antioxidant and anti-obesity properties. However, the anti-obesity effects of bioconverted extracts of A. quinate have not been examined. In this study, A. quinata fruit extracts was bioconverted using the enzyme isolated from the soybean paste fungi Aspergillus kawachii. To determine whether the bioconversion process could influence the anti-obesity effects of A. quinata fruit extracts, we employed 3T3-L1 adipocytes and HFD-induced obese rats. We observed that the bioconverted fruit extract of A. quinata (BFE) afforded anti-obesity effects, which were stronger than that for the non-bioconverted fruit extract (FE) of A. quinata. In 3T3-L1 adipocytes, treatment with BFE at concentrations of 20 and 40 μg reduced intracellular lipids by 74.8 (p < 0.05) and 54.9% (p < 0.01), respectively, without inducing cytotoxicity in preadipocytes. Moreover, the oral administration of BFE at the concentration of 300 mg/kg/day significantly reduced body and adipose tissue weights (p < 0.01) in HFD-induced obese rats. Plasma cholesterol values were reduced, whereas HDL was increased in BFE receiving rats. Although FE could exert anti-obesity effects, BFE supplementation induced more robust effects than FE. These results could be attributed to the bioconversion-induced alteration of bioactive compound content within the extract.
... Among all GS monomers, Rd, Rb1, Rb2, Rc, Re, and Rg1 account for more than 80% of the total saponins, and are thus termed the main saponins. The contents of Rg3, Rg5, Rg2, Rh1, Rh2, Rh3, Rh4, and CK are rare, while their pharmacological efficacy are better than those of the main saponins (Song et al. 2022). Ginsenoside Rd (GSRd) is a main monomer extract of total saponins, which is low in Panax ginseng and high in Panax notoginseng (Karikura et al. 1992). ...
... The two glycosyl groups at C-3 position is the pharmacological basis of GSRd antioxidant activity (Yang et al. 2007). Gastrointestinal microbiota and metabolic enzymes are involved in the biotransformation of the main saponins Rb1, Rb2, and Rc into Rd (Ku et al. 2016;Song et al. 2022); therefore, Rd is one of the main forms of absorption and utilization of main saponins in the intestine after metabolism (Kim et al. 2013;Ye et al. 2008). Among the more than 50 types of GS, GSRd is the main active ingredient in broad-spectrum pharmacological actions of Panax ginseng. ...
Noise pollution has become one of the important social hazards that endanger the auditory system of residents, causing noise-induced hearing loss (NIHL). Oxidative stress has a significant role in the pathogenesis of NIHL, in which the silent information regulator 1(SIRT1)/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway is closely engaged. Ginsenoside Rd (GSRd), a main monomer extract from ginseng plants, has been confirmed to suppress oxidative stress. Therefore, the hypothesis that GSRd may attenuate noise-induced cochlear hair cell loss seemed promising. Forty-eight male guinea pigs were randomly divided into four groups: control, noise exposure, GSRd treatment (30 mg/kg Rd for 10d + noise), and experimental control (30 mg/kg glycerol + noise). The experimental groups received military helicopter noise exposure at 115 dB (A) for 4 h daily for five consecutive days. Hair cell damage was evaluated by using inner ear basilar membrane preparation and scanning electron microscopy. Terminal dUTP nick end labeling (TUNEL) and immunofluorescence staining were conducted. Changes in the SIRT1/PGC-1α signaling pathway and other apoptosis-related markers in the cochleae, as well as oxidative stress parameters, were used as readouts. Loss of outer hair cells, more disordered cilia, prominent apoptosis, and elevated free radical levels were observed in the experimental groups. GSRd treatment markedly mitigated hearing threshold shifts, ameliorated outer hair cell loss and lodging or loss of cilia, and improved apoptosis through decreasing Bcl-2 associated X protein (Bax) expression and increasing Bcl-2 expression. In addition, GSRd alleviated the noise-induced cochlear redox injury by upregulating superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, decreasing malondialdehyde (MDA) levels, and enhancing the activity of SIRT1 and PGC-1α messenger ribonucleic acid (mRNA) and protein expression. In conclusion, GSRd can improve structural and oxidative damage to the cochleae caused by noise. The underlying mechanisms may be associated with the SIRT1/PGC-1α signaling pathway.
... Ginsenosides are the main active components of traditional Chinese herbal medicine Panax ginseng C. A. Mey. (Song et al., 2022). At present, nearly 200 ginsenosides have been isolated and identified from the roots, stems, leaves, flowers buds, and berries of Panax ginseng C. A. Mey. . ...
Breast cancer (BC) is one of the most common malignant tumor, the incidence of which has increased worldwide in recent years. Ginsenosides are the main active components of Panax ginseng C. A. Mey., in vitro and in vivo studies have confirmed that ginsenosides have significant anti-cancer activity, including BC. It is reported that ginsenosides can induce BC cells apoptosis, inhibit BC cells proliferation, migration, invasion, as well as autophagy and angiogenesis, thereby suppress the procession of BC. In this review, the therapeutic effects and the molecular mechanisms of ginsenosides on BC will be summarized. And the combination strategy of ginsenosides with other drugs on BC will also be discussed. In addition, epigenetic changes, especially microRNAs (miRNAs) targeted by ginsenosides in the treatment of BC are clarified.
