Ginsenosides from Panax ginseng: Their mechanisms, microbiome determinants, and translational strategies in therapeutic activity against cancer

Objectives : This study was performed to investigate the applications of 47 prescriptions containing Ginseng Radix and Aconiti Lateralis Preparata Radix in Dongeuibogam. Methods : 47 prescriptions containing Ginseng Radix and Aconiti Lateralis Preparata Radix which have been used separately or concurrently in Oriental Medicine for a long time as a treatment for various disease in Dongeuibogam were studied through order of frequency, symptoms, dosages, etc. Results : 1. 17.02 % prescriptions are used in cold chapter with the 8 frequency, 14.89% in fatigue chapter with the 7 frequency, 10.64% in stool and wind chapter each with the 5 frequency, and 6.38% in children chapter with the 3 frequency. 2. Cold-diarrhea, Yang deficiency treating herbs, General fatigue treating herbs are most used chapters and articulation pain, severe cold, convulsion chapters are following frequency among 38 symptoms in prescriptions including Ginseng Radix and Aconiti Iateralis Preparata Radix. 3. In the prescriptons which has used more Ginseng Radix than Aconiti Lateralis Preparata Radix, the dosage ratio between Ginseng Radix and Aconiti Lateralis Preparata is ranged from 2.5 puns:1.5 puns ~ 1 jeon:7 puns. Among the range, 1 jeon:5 puns is recorded 2 times(33.33%), the rests are 1 time(16.67%). 4. In the prescriptons which has used same amount Ginseng Radix and Aconiti Lateralis Preparata Radix, the dosage ratio Ginseng Radix and Aconiti Lateralis Preparata is ranged from 2 puns ~ 1 nyangs each. Among the range, 1 jeon is recorded 12 times(41.38%), 1.25 jeon and 5 jeons are 3 times(10.34%) each, 0.5 jeon, 0.7 jeons and 3 jeons each are recorded 2 times (6.90%), the rests are 1 time(3.45%). 5. In the prescriptons which has used less Ginseng Radix than Aconiti Lateralis Preparata Radix, the dosage ratio between Ginseng Radix and Aconiti Lateralis Preparata is ranged from 3 puns:1 jeon ~ 1 nyang:3 nyangs. Among the range, 5 jeons:1 nyang is recorded 2 times(25.00%), the rests are 1 time(12.50%). 6. 5 jeons:1 piece are used 2 times(50.00%), the rests are 1 time(25.00%) each used among 3 prescriptions including Ginseng Radix and Aconiti Lateralis Preparata Radix. Conclusions : The 47 prescriptions including Ginseng Radix and Aconiti Iateralis Preparata Radix in Dongeuibogam are mainly composed of Samboo-tang, Sayeok-tang, Eejoong-tang, Samool-tang, Sagoonja-tang and Gobangpoong-tang, Bowon-tang, etc.

Objective To investigate the clinical effect of liquorice ginseng decoction combined with omeprazole in patients with upper gastrointestinal hemorrhage (UGIH), and to analyze the effect on serum TNF-α and IL-2 levels. Methods A total of 80 UGIH patients admitted to our hospital from March 2016 to August 2018 were randomly divided into two groups according to the number table method, namely control group (40 cases treated with omeprazole) and observation group (40 cases treated with liquorice ginseng decoction and omeprazole). After four weeks of continuous treatment, the two groups were compared in terms of treatment efficiency, changes before and after treatment, adverse reactions, and the effects on TNF-α and IL-2 levels. Results The total effective rate of the observation group (92.50%, 37/40) was significantly higher than that of the control group (80%, 32/40), with statistically significant difference (P<0.05). After treatment, the incidence of adverse reactions such as nausea, vomiting, hematemesis, dizziness, blood in the stool, and melena in the observation group were significantly lower than those in the control group (P<0.05). After treatment, TNF-α level, IL-2 level, and TNF-α/IL-2 ratio in the observation group were significantly lower than those in the control group [(105.06±13.17) ng/ml vs.(296.84±16.57) ng/ml, (10.23±6.10) ng/ml vs.(24.54±8.73) ng/ml, (8.55±4.52) vs.(12.81±3.16)] (P<0.05). Conclusion Liquorice ginseng decoction combined with omeprazole can effectively improve the treatment efficiency of UGIH patients, correct the levels of IL-2 and TNF-α cytokines in the body, which can provide a basis for the treatment of UGIH in clinical treatment. Key words: Liquorice ginseng decoction; Omeprazole; Upper gastrointestinal hemorrhage (UGIH); TNF-α; IL-2

To investigate the effects of ginseng polysaccharide on T-lymphocytes of enteric mucosal lymphocytes in rats with collagen induced arthritis (CIA). The peyer’s patche lymphocyte (PPL), intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) of SD rats were isolated. The PPL, IEL and LPL were checked with flow cytometry and these lymphocytes were co-cultured with ginseng polysaccharide separately at different dosages. ELISA measured the expression levels of TNF-α and IFN-γ in supernatants. The results showed thatginseng polysaccharide could increased the protein expression of TNF-α and IFN-γ in the supernatant of PPL on normal rats, and it could lower the protein expression of TNF-α while increase the IFN-γ protein level in the supernatant of PPL on CIA rats. Ginseng polysaccharide could lower the protein levels both TNF-α and IFN-γ in the supernatant of LPL on normal rats. And it could lower the protein levels of TNF-α and IFN-γ in the supernatant of both IEL and LPL on CIA rats. Ginseng polysaccharide could decrease the expression of TNF-α and IFN-γ, regulate the function of Lymphocytes in enteric mucosal immune system in CIA rats, which indicate that Ginseng polysaccharide could be used in the treatment of autoimmune disease. Key words: Ginseng polysaccharide, collagen induced arthritis, lymphocyte, enteric mucosal immunity, TNF-α, IFN-γ.

Objective To evaluate the effect of modified Renshen decoction plus routine western medicine on chronic congestive heart failure. Methods The selected 75 candidate patients were divided into control group with 37 patients and treatment group with 38 patients. The patients of control group received routine western medicine and treatment group received modified Renshen decoction plus routine western medicine. After 2 weeks of treatment, the effect of both group were evaluated with indictors of clinical heart function, BNP and traditional Chinese syndrome. Results There were significantly statistical difference, of total effective ratio of clinical heart function (χ2=4.343, P<0.05)between the treatment group (92.1%,35/38)and control group (73.0%, 27/37), and of total effective ratio of traditional Chinese syndrome (χ2=4.649, P<0.05) between the treatment group (94.7%, 36/38) and control group (73.0%, 27/37). The BNP levels of both group decreased significantly (P<0.05), and the significant statistical difference between two groups was also observed 1 477.1 ± 316.7 pg/ml vs. 2 256.9 ± 521.3 pg/ml; t=7.853, P<0.01). Conclusions The Modified Renshen decoction plus routine western medicine could improve chronic congestive heart failure patients' the heart function, reduce BNP and attenuate the symptoms. Key words: Heart failure; Modified Renshen decoction; Natriuretic peptide,brain; Integrated Chinese traditional and western medicine therapy

Panax ginseng (PG) has been commonly used as medicinal herb for the treatment of various diseases in Eastern Asia for thousands of years. This study was designed to investigate the protective effect of PG against paracetamol-(N-acetyl-p-amino­phenol; APAP)-induced liver damage in rats. Thirty-two albino Wistar rats were divided into four groups: Group C (control); Group APAP (gavaged orally with APAP (APAP, 2 g/kg, single dose); Group PG 100 mg/kg + APAP or 200 mg/kg + APAP (these two groups were treated by gavaging with PG (100 or 200 mg/kg) for 30 days following a single dose of APAP). APAP treatment alone induced hepatotoxicity, evidenced by significant increases in malondialdehyde (MDA) level and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α). In addition, the level of GSH in the liver was significantly reduced, as were the activities of superoxide dismutase (SOD) and catalase (CAT). Liver histopathological examination showed that APAP administration induced centrilobular necrosis and infiltration of lymphocytes. However, these biochemical and histological changes were prevented by PG pretreatment. In conclusion, our results suggest that PG may be considered a protective medicinal herb against APAP-induced liver injury. Key words: Panax ginseng, N-acetyl-p-amino­phenol, liver, oxidative damage, rat.

Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease

Panax Ginseng C. A. Mey. is a traditional Chinese herb with a long history of application and significant activity in Asia. Modern studies have confirmed that the traditional efficacy of ginseng is closely related to metabolic diseases. Metabolic diseases are a globally increasing disease, involving the immune, digestive, and nervous systems. Research shows that pyroptosis may be a new entry point for the prevention and treatment of metabolic diseases. P. ginseng has shown great pharmacodynamics in the treatment of metabolic diseases such as diabetes mellitus (DM) and obesity. DM is a type of immune disease characterized by metabolic disorders and chronic inflammatory response, which is always a core problem in the medical community because it is often accompanied by some serious complications. Current research has made remarkable progress in P. ginseng targeting pyroptosis in the treatment of DM-related metabolic diseases, but there is still a long way to go to further explore the pathogenesis of metabolic diseases. However, the current specific drugs for metabolic diseases have obvious limitations, which are not conducive to the promotion and long-term use. This review summarizes the published research about P. ginseng and its active ingredients in the treatment of DM-related metabolic diseases. It fully demonstrates that P. ginseng targeting pyroptosis has a good application prospect in the treatment of DM-related metabolic diseases, providing a new perspective for the prevention and treatment of metabolic diseases in the future.

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein–protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

The book “Nei Wai Shang Bian Huo Luen” written by Dong-Yuan Li records the differences of diseases caused by internal and external factors as well as the treatment of diseases caused by internal factors. The 46 main prescriptions contained inside the book demonstrate Dong-Yuan Li’s style and reasoning when composing an herbal prescription. This article reviewed the main prescriptions of “Nei Wai Shang Bian Huo Luen” with “Tan Ye Ben Cao” written by Hao-Gu Wang, and statistically analyzed the formulas according to: frequency of use of the various herbs, grouping of herbs, up-lifting and down-bearing nature, channel entry and therapeutic mechanism. As a result, herbs are used in the main prescriptions for 398 times. The most frequently used herbs are Gan Cao (Glycyrrhiza glabra), Chen Pi (Citrus reticulata), Huang Qi (Atractylodes macrocephala) and Ren Shen (Panax ginseng). These herbs all belong to the “Dampness transforming” group which was also the most frequently showing pharmacological group of herbs with 147 occurrences. Most main prescriptions of the book are up-lifting in nature. The three most common channels used were the stomach channel (48.9%), spleen channel (22.5%) and lung channel (12%). The main therapeutic mechanism used is “Removal of lodged pathogenic influences”. So the most frequently showing pharmacological group of herbs is the “Dampness transforming” group. Most main prescriptions of the book are up-lifting in nature. “Nei Wai Shang Bian Huo Luen” was found to be mostly associated with the stomach (removal of food accumulation) and spleen(supplementing Qi) with the two channels associated to 70% of all prescriptions. Furthermore, the lung channel prescriptions were related to febrile diseases. After analyzing the book, we found Dong-Yuan Li treated diseases caused by internal factors primarily through removal of food accumulation, and secondarily through supplementing Qi. His treatments hence focus on the digestive system.

Panax ginseng is one of the most widely prescribed herbal medicines for the treatment of cancer, diabetes, chronic inflammation, and neurodegenerative and cardiovascular diseases. Since the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions, we investigated the possible genotoxicity of a water-soluble form of the dry root of P. ginseng (2.5, 5.0 or 10.0 mg/mL) and its ability to protect against the genotoxicity of doxorubicin (DOX; 0.125 mg/mL) by using the Drosophila melanogaster wing somatic mutation and recombination test (SMART) with standard and high-bioactivation crosses of flies. Panax ginseng was not genotoxic at the concentrations tested, whereas DOX-induced genotoxicity in marker-heterozygous flies resulted mainly from mitotic recombination. At low concentrations, P. ginseng had antirecombinogenic activity that was independent of the concentration of extract used. Recombination events may promote cancer, but little is known about the ability of P. ginseng to inhibit such recombination or modulate DNA repair mechanisms.

Background: Ginsenoside Rg3 is a steroidal saponin extracted from Panax ginseng with various anti-tumor effects. While very few studies have focused on exploring the cytotoxic effects of Ginsenoside Rg3 in lung cancer treatment via Notch/hairy and enhancer of split 1 (HES1) pathway. We examined the underlying mechanism of action and the anti-tumor effects of Ginsenoside Rg3 in lung cancer cells and attempted to develop it as a systemic treatment strategy for non-small cell lung cancer (NSCLC). Methods: NCI-H1650, H520 and H1963 cells were used for experiment. MTT assay was used to detect cell proliferation. Annexin V/PI assay was used to detect cell apoptosis. Western blotting was used to detect the level of Notch1, Notch2, HES1, p38 MAPK, Caspase-3 and Caspase-9 expressions. Results: Ginsenoside Rg3 inhibited the proliferation of NCI-H1650, H520 and H1963 cells in a time and dose-dependent manner. Furthermore, Ginsenoside Rg3 induced significant cell apoptosis. The level of Notch1, Notch2 and HES1 expressions decreased but the level of p38 MAPK, Caspase-3 and Caspase-9 expressions increased with Ginsenoside Rg3 treatment. Conclusions: Ginsenoside Rg3 could target the Notch/HES1 pathway to cause apoptosis leading to inhibit the proliferation of lung cancer cells and the results suggested a therapeutic potential of Ginsenoside Rg3 in clinical use for lung cancer treatment.

A growing number of technologies are being developed in order to produce different high added value products, such as phytochemicals, ethanol and other chemicals from biomass, representing an important trend that needs to be evaluated. The use of pressurized-fluid technologies to obtain phytochemicals from certain biomasses has shown encouraging results in terms of selectivity, enabling its use prior bioenergy generation since generally only a small part of the solid material is extracted. The phytochemical compound which is most financially interesting to extract from the Brazilian Ginseng (Pfaffia glomerata) roots is ecdysterone (beta-ecdysone), an ecdysteroid. Ecdysteroids are a class of natural steroids acting as hormones and beta-ecdysone is the most important steroid employed in cosmetic formulations. It is also used in other industries such as the food and pharmaceutical industry. Due to its health properties, large amounts of Pfaffia glomerata roots are being exported from Brazil to countries that use phytochemical therapies widely. This work is part of a project that aims to present a solution to perform phytochemicals recovery step in Brazil envisioning decentralized local-scale production. In this study, first the influence of the extraction temperature (353-413 K) and static extraction time (5-15 min) using pressurized ethyl acetate as extracting solvent on the beta-ecdysone recovery was experimentally evaluated and compared with literature results employing other pressurized fluids. Afterwards, an economical analysis was done for comparison using ASPEN PLUS software and OSMOSE platform. It was observed that the relationship of the beta-ecdysone recovery, extraction temperature and static extraction time was linear. An increase in temperature and static time resulted in enhancement of the beta-ecdysone recovery from the biomass. On the other hand, the increase of the extraction temperature beyond 373 K possibly might enhance the degradation of the beta-ecdysone extracted decreasing its relative amount in the extract. Since for the economical analysis performed the former response variable (beta-ecdysone recovery) is most important than the latter, it was calculated the net present value of this process considering high extraction temperatures. Considering an installation time of two years, a lifetime of 25 years and an interest rate of 15 % the obtained net present value for the different pressurized extracting solvents were in the following order: ethyl acetate &gt; ethanol &gt; CO2-ethanol mixture. The results demonstrate that the inclusion of a pressurized fluid-based process using ethyl acetate or ethanol for beta-ecdysone recovery prior further bioenergy production is very promising.

Panax ginseng (Panax ginseng C.A. Meyer) is a classic herbal medicine widely utilized in dermatological management, yet its precise therapeutic mechanisms have only recently begun to be fully elucidated. This review systematically synthesizes the pharmacological roles of ginseng's active components, including ginsenosides, polysaccharides, and gintonin, in maintaining skin homeostasis and treating various cutaneous pathologies. Emerging evidence suggests that the efficacy of ginseng extends beyond direct molecular interactions, exhibiting the distinct characteristics of "indirect pharmacology." Specifically, parent ginsenosides function primarily as natural prodrugs that require microbial biotransformation into high-affinity active metabolites, such as Compound K and Rh2, to exert potent therapeutic effects. Functionally, these components regulate skin health by mobilizing endogenous host defense systems, particularly through the activation of the Nrf2/ARE antioxidant pathway and the suppression of inflammatory cascades via the NF-κB, MAPK, and IL-1 signaling networks. Furthermore, they remodel the systemic microenvironment through the gut-skin axis, facilitating metabolic homeostasis to improve skin barrier function. Notably, biotransformation rates and ultimate therapeutic efficacy are highly dependent on individualized variables, such as host age, dietary patterns, and baseline disease states. This systemic regulation has demonstrated robust efficacy in intervening in complex pathologies, including atopic dermatitis, psoriasis, and skin cancer. Additionally, this article addresses the translational bottleneck of low bioavailability and evaluates recent advances in novel skin delivery systems, specifically those utilizing ginseng-derived exosomes. Collectively, this review provides a scientific framework for understanding the systemic actions of ginseng, supporting its development as a precision botanical therapy for dermatological applications.

Panax ginseng is an important herb that has clear effects on the treatment of diverse diseases. Until now, the natural peptide constitution of this herb remains unclear. Here, we conduct an extensive characterization of Ginseng peptidome using MS-based data mining and sequencing. The screen on the charge states of precursor ions indicated that Ginseng is a peptide-rich herb in comparison of a number of commonly used herbs. The Ginseng peptides were then extracted and submitted to nano-LC-MS/MS analysis using different fragmentation modes, including CID, high-energy collisional dissociation, and electron transfer dissociation. Further database search and de novo sequencing allowed the identification of total 308 peptides, some of which might have important biological activities. This study illustrates the abundance and sequences of endogenous Ginseng peptides, thus providing the information of more candidates for the screening of active compounds for future biological research and drug discovery studies.

Protective effect of oligosaccharides isolated from Panax ginseng C. A. Meyer against UVB-induced skin barrier damage in BALB/c hairless mice and human keratinocytes