Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8+ T cell proportion in tumor-bearing mice through the USP9X signaling pathway.

The management of colorectal cancer (CRC) poses a significant challenge, necessitating the development of innovative and effective therapeutics. Our research has shown that notoginsenoside Ft1 (Ng-Ft1), a small molecule, markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8+ T cells in tumor-bearing mice, thus restraining tumor growth. Investigation into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X, undermining its role in shielding ß-catenin. This leads to a reduction in the expression of downstream effectors in the Wnt signaling pathway. These findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC, working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8+ T cell prevalence within the tumor environment.

Identifying biomarkers of ginseng medicines with different natures on heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: The nature of Chinese medicine is a unique index to measure its efficacy. Generally, treating the hot syndrome with cold nature medicine and vice versa. Ginseng medicines, a renowned Chinese medicine known for its qi tonifying action, encompasses various herbal materials such as ginseng, red ginseng, and black ginseng (GS, RG, and BG, respectively), ginseng leaves (GL), and American ginseng (AG), which exhibited different natures, thought contained similar ginsenosides. This traditional effect of GS and RG "reinvigorate the pulse for relieving qi depletion". It is closely linked to anti-heart failure (HF), HF is a clinical manifestation of deficiency of "heart-qi". However, the elucidation of the mechanism underlying the anti-HF effects of ginseng medicines with different natures remains a significant challenge. AIM OF THE STUDY: To elucidate pharmacological mechanisms underlying the effect of ginseng medicines on HF, and to identify biomarkers associated with their various natures. Furthermore, it provides the basis for the different applications of ginseng medicines with various natures. MATERIALS AND METHODS: This study established a rat model of HF induced by isoproterenol (ISO) combined with a specific diet. Four representative hot/cold herbs were selected as compared references for the medicine natures. The divergent effects of these herbs on the HF model were investigated by analyzing RNA-seq data to identify genes expressed differentially. Additionally, pathways associated with medicine natures were obtained using KEGG. Furthermore, UPLC-QqQ-MS/MS, as well as ELISA, were used to measure indexes associated with the nervous system, energy metabolisms, and endocrinology systems, such as BNP, CK, IL-1, T3, T4, cAMP, cGMP, AD, adrenal hormones (DOC, CORT, and COR), progestogens (pregnenolone, P, 17-OH-PR, and 17-OH-P), androgens (DHEA, A4, and T), and estrogens hormones (E2). RESULTS: All ginseng medicines demonstrated varying levels of efficacy in alleviating HF and GS exhibited a significant protective effect on HF. The ginseng medicines with qi tonifying primarily achieve their effect by enhancing the levels of adrenal hormones (DOC, CORT, and COR), T4, elevation of cAMP/cGMP, and activation of AchE. Warm nature qi tonifying ginseng medicines increased the levels of 17-OH-PR and P while decreasing 17-OH-P and the ratio of E2/T. On the other hand, cold nature qi tonifying ginseng medicines decreased the levels of A4 and T while increasing the ratio of E2/T. CONCLUSION: Overall, the effects of warm nature ginseng medicines are stronger on HF compared to cold nature ginseng medicines. Our research firstly reported that the E2/T ratio, progestogens (17-OH-PR, 17-OH-P, and P), and androgens (A4 and T) have been identified as significant biomarkers for discerning the mechanism differences of ginseng medicines with differences natures in treatment of HF.

Therapeutic effects of ginsenosides on osteoporosis for novel drug applications.

Osteoporosis (OP) is a metabolic bone disease with a high incidence rate worldwide. Its main features are decreased bone mass, increased bone fragility and deterioration of bone microstructure. It is caused by an imbalance between bone formation and bone resorption. Ginsenoside is a safe and effective traditional Chinese medicine (TCM) usually extracted from ginseng plants, having various therapeutic effects, of which the effect against osteoporosis has been extensively studied. We searched a total of 44 relevant articles with using keywords including osteoporosis, ginsenosides, bone mesenchymal cells, osteoblasts, osteoclasts and bone remodeling, all of which investigated the cellular mechanisms of different types of ginsenosides affecting the activity of bone remodeling by mesenchymal stem cells, osteoblasts and osteoclasts to counteract osteoporosis. This review describes the different types of ginsenosides used to treat osteoporosis from different perspectives, providing a solid theoretical basis for future clinical applications.

Ginsenosides from Panax ginseng as potential therapeutic candidates for the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestine, which significantly affects patients' quality of life. As a perennial plant with the homology of medicine and food, Panax ginseng is known for its substantial anti-inflammatory effects in various inflammatory disorders. Ginsenosides, the main bioactive compounds of P. ginseng, are recognized for their efficacy in ameliorating inflammation. PURPOSE: Over the past decade, approximately 150 studies have investigated the effects of P. ginseng and ginsenosides on IBD treatment and new issues have arisen. However, there has yet to be a comprehensive review assessing the potential roles of ginsenosides in IBD therapy. METHOD: This manuscript strictly adheres to the PRISMA guidelines, thereby guaranteeing systematic synthesis of data. The research articles referenced were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "ginsenoside", "IBD", "colitis", "UC", "inflammation", "gut microbiota", and "intestinal barrier". For image creation, Figdraw 2.0 was methodically employed. RESULTS: Treatment with various ginsenosides markedly alleviated clinical IBD symptoms. These compounds have been observed to restore intestinal epithelia, modulate cellular immunity, regulate gut microbiota, and suppress inflammatory signaling pathways. CONCLUSION: An increasing body of research supports the potential of ginsenosides in treating IBD. Ginsenosides have emerged as promising therapeutic agents for IBD, attributed to their remarkable efficacy, safety, and absence of side effects. Nevertheless, their limited bioavailability presents a substantial challenge. Thus, efforts to enhance the bioavailability of ginsenosides represent a crucial and promising direction for future IBD research.

Ginsenosides Inhibit the Proliferation of Lung Cancer Cells and Suppress the Rate of Metastasis by Modulating EGFR/VEGF Signaling Pathways.

Ginsenosides Rg3 and Rg5 obtained from Panax (ginseng) have shown significant anticancer activity via the PI3K-Akt signaling pathway. This study evaluated the anticancer and antimetastatic effects of a combination of Rg3 and Rg5 on lung cancer cells. A combination of Rg3 and Rg5 was treated for lung cancer cell line A549 and human lung tumor xenograft mouse model, and anti-metastatic effects on Matrigel plug implantation in mice. The combination of Rg3 and Rg5 showed potent antiproliferative effects on A549 cells with IC50 values of 44.6 and 36.0 µM for Rg3 and Rg5 respectively. The combination of Rg3 and Rg5 (30 µM each) showed 48% cell viability as compared to Rg3 (72% viability) and Rg5 (64% viability) at 30 µM concentrations. The combination of Rg3 and Rg5 induced apoptosis in A549 cells characterized by activation of caspase-9 and caspase-3 and cleavage of PARP, as well as suppression of the autophagic marker LC3A/B. The antitumoral potentials of the combination of Rg3 and Rg5 were ascertained in a lung tumor xenograft mouse model with high efficacy as compared to individual ginsenosides. The metastasislimiting properties of the combination of Rg3 and Rg5 were assessed in Matrigel plug implantation in mice which showed the potent efficacy of the combination as compared to individual ginsenoside. Mechanistically, the combination of Rg3 and Rg5 inhibited the expression of PI3K/Akt/mTOR and EGFR/VEGF signaling pathways in lung cancer cells. Results suggest that the combination of Rg3 and Rg5 suppressed the tumor cell proliferation in lung cancer cells and limited the rate of metastasis which further suggest that the combination has a significant effect as compared to the administration of single ginsenoside.

Inhibition of p38 MAPK/NF-κB p65 signaling pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced premature ovarian failure and KGN cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey., one of the most used herbs in the world, shows effective treatment in reproductive injury. Recent studies have proven that the processed product, red ginseng, which is more active than ginseng itself. Therefore, it is speculated that its main functional component, rare ginsenosides (heat-transformed saponin, HTS), may be effective in treating premature ovarian failure (POF), but its efficacy has not yet been experimentally confirmed. AIM OF THE STUDY: To evaluate whether HTS could attenuate cyclophosphamide-induced inflammation and oxidative damage in POF model rats and the human granulosa-like KGN cell line and protect granulosa cell proliferation. MATERIAL AND METHODS: HTS were isolated from ginsenosides and high performance liquid chromatography (HPLC) analysis was used to analyze the HTS components. Cyclophosphamide (CP) was used to establish a POF rat model and KGN cell injury model. Reactive oxygen species (ROS) and antioxidant enzyme production was determined using specific assays, while inflammatory cytokine secretion was measured by enzyme-linked immunosorbent assay (ELISA). The proliferative function of granulosa cells was assessed using high-content screening and immunohistochemistry to determine the Ki67 protein level. Protein expression in ovarian tissues and KGN cells was analyzed by Western blotting, quantitative real-time PCR (qRT-PCR) was used to determine the transcriptional changes in ovarian tissues and KGN cells. RESULTS: In CP-treated POF model rats, HTS significantly decreased malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels, increased glutathione oxidase (GSH) levels, and upregulated Ki67 expression in ovarian granulosa cells. In addition, HTS significantly increased cell survival and Ki67 expression levels in CP-treated cells, and superoxide dismutase (SOD) levels were significantly increased. HTS significantly downregulated IL-6, TNF-α, and interleukin-1ß (IL-1ß) mRNA expression and significantly inhibited nuclear factor kappa-B p65 (NF-κB p65) and p38 mitogen activated protein kinase (p38 MAPK) phosphorylation in POF model rats and KGN cells. Moreover, NF-κB p65 and p38 MAPK levels were significantly increased in ovarian granulosa cells. p65 and p38 protein and gene expression was significantly downregulated. CONCLUSION: HTS ameliorated CP-induced POF and human granulosa cell injury, possibly by inhibiting inflammation and oxidative damage mediated by the p38 MAPK/NF-κB p65 signaling pathway.

Phytochemistry of Red Ginseng, a Steam-Processed Panax ginseng.

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial.

Ginsenoside - a promising natural active ingredient with steroidal hormone activity.

Ginsenosides are a class of natural products with hormone-like activity of triterpenoid saponins and have a variety of pharmacological activities such as anti-aging, immune regulation and cognitive improvement. With the great research interest in alternative medicine and natural products, they are gradually becoming research hotspots. Ginsenosides have a four-ring rigid steroid backbone similar to steroid hormones, and a series of experimental studies have shown that they can exhibit hormone-like activity by binding to nuclear receptors or affecting hormone levels, thereby affecting a wide range of inflammatory conditions, cancers, and menopause-related diseases. This review summarizes the mechanisms and potential health effects of ginsenosides exhibiting estrogen-like, glucocorticoid-like and androgen-like activities, providing an important reference for the exploration of safe phytohormone replacement therapy.

The effect of vine tea (Ampelopsis grossedentata) extract on fatigue alleviation via improving muscle mass.

ETHNOPHARMACOLOGICAL RELEVANCE: Vine Tea (VT, Ampelopsis grossedentata), boasts a venerable tradition in China, with a recorded consumption history exceeding 1200 years. Predominantly utilized by ethnic groups in southwest China, this herbal tea is celebrated for its multifaceted therapeutic attributes. Traditionally, VT has been employed to alleviate heat and remove toxins, exhibit anti-inflammatory properties, soothe sore throats, lower blood pressure, and fortify bones and muscles. In the realm of functional foods derived from plant resources, VT has garnered attention for its potential in crafting anti-fatigue beverages or foods, attributed to its promising efficacy and minimal side effects. Currently, in accordance with the Food Safety Standards set forth by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China, VT serves as a raw material in various beverages. AIM OF THE STUDY: VT has an anti-fatigue or similar effect in folk. However, the underlying molecular mechanisms contributing to VT's anti-fatigue effects remain elusive. This study endeavors to investigate the influence of Vine Tea Aqueous Extract (VTE) on fatigue mitigation and to elucidate its operative mechanisms, with the objective of developing VTE as a functional beverage. MATERIALS AND METHODS: The preparation of VTE involved heat extraction and freeze-drying processes, followed by the identification of its metabolites using UPLC-QTOF-MS to ascertain the chemical composition of VTE. A fatigue model was established using a forced swimming test in mice. Potential molecular targets were identified through network pharmacology, transcriptome analysis, and molecular docking. Furthermore, RT-PCR and Western blot techniques were employed to assess mRNA and protein expressions related to the AMPK and FoxO pathways. RESULTS: VTE significantly prolonged the duration of swimming time in an exhaustive swimming test in a dose-dependent manner, while simultaneously reducing the concentrations of blood lactic acid (LA), lactate dehydrogenase (LDH), serum urea nitrogen (SUN), and creatine kinase (CK). Notably, the performance of the high-dose VTE group surpassed that of the well-recognized ginsenoside. VTE demonstrated a regulatory effect akin to ginsenoside on the AMPK energy metabolism pathway and induced downregulation in the expression of Gadd45α, Cdkn1a, FOXO1, and Fbxo32 genes, suggesting an enhancement in skeletal muscle mass. These findings indicate that VTE can improve energy metabolism and muscle mass concurrently. CONCLUSIONS: VTE exhibits significant anti-fatigue effects, and its mechanism is intricately linked to the modulation of the AMPK and FoxO pathways. Crucially, no caffeine or other addictive substances with known side effects were detected in VTE. Consequently, vine tea shows substantial promise as a natural resource for the development of anti-fatigue beverages within the food industry.

Research Progress on the Antitumor Molecular Mechanism of Ginsenoside Rh2.

Cancer has evolved into a substantial public health concern as the second-leading cause of mortality globally. Radiotherapy and chemotherapy have been the two most widely used cancer therapies in recent years; however, both have drawbacks. Therefore, the focus has shifted to the creation of herbal medicines, the extraction of active ingredients, replacement therapy, and the adverse effects of these medications. Ginsenoside Rh2, which is extracted from ginseng, has been identified in many cancer cells. The immune system of the body is strengthened by ginsenoside Rh2, which can also cause the proliferation, death, and differentiation of tumor cells through various pathways. For instance, it inhibits the expression of the NF-[Formula: see text]B signaling pathway and induces cell apoptosis, affects the expression levels of mitochondrial apoptosis proteins Bcl-2 and Bax, and cooperates with the PD-1 blockade to reactivate T cells to promote an antitumor immune response. Furthermore, ginsenosides Rh2 has the effect of reversing the toxic effect of chemotherapy drugs on normal cells, reducing myocardial damage, and relieving bone marrow function suppression. For clinical applications, it is mainly used as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer. This paper summarizes the pharmacological action and mechanism of ginsenosides Rh2 in all kinds of cancer and looks forward to its future development and application.

Exploration in the Mechanism of Ginsenoside Rg5 for the Treatment of Osteosarcoma by Network Pharmacology and Molecular Docking.

OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.

Ginsenoside RK3 promotes neurogenesis in Alzheimer's disease through activation of the CREB/BDNF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the ancient book "Shen Nong's Herbal Classic," Panax ginseng CA Mey was believed to have multiple benefits, including calming nerves, improving cognitive function, and promoting longevity. Ginsenosides are the main active ingredients of ginseng. Ginsenoside RK3 (RK3), a rare ginsenoside extracted from ginseng, displays strong pharmacological potential. However, its effect on neurogenesis remains insufficiently investigated. AIM OF THE STUDY: This study aims to investigate whether RK3 improves learning and memory by promoting neurogenesis, and to explore the mechanism of RK3 action. MATERIALS AND METHODS: The therapeutic effect of RK3 on learning and memory was determined by the Morris water maze (MWM) and novel object recognition test (NORT). The pathogenesis and protective effect of RK3 on primary neurons and animal models were detected by immunofluorescence and western blotting. Protein expression of cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway was detected by western blotting. RESULTS: Our results showed that RK3 treatment significantly improved cognitive function in APPswe/PSEN1dE9 (APP/PS1) mice and C57BL/6 (C57) mice. RK3 promotes neurogenesis and synaptogenesis in the mouse hippocampus. In vitro, RK3 prevents Aß-induced injury in primary cultured neurons and promotes the proliferation of PC12 as well as the expression of synapse-associated proteins. Mechanically, the positve role of RK3 on neurogenesis was combined with the activation of CREB/BDNF pathway. Inhibition of CREB/BDNF pathway attenuated the effect of RK3. CONCLUSION: In conclusion, this study demonstrated that RK3 promotes learning and cognition in APP/PS1 and C57 mice by promoting neurogenesis and synaptogenesis through the CREB/BDNF signaling pathway. Therefore, RK3 is expected to be further developed into a potential drug candidate for the treatment of Alzheimer's disease (AD).

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.

Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

Mechanism Research and Application for Ginsenosides in the Treatment of Hepatocellular Carcinoma.

Ginsenosides, the main active pharmacological ingredients of ginseng, have been widely used for the treatment of numerous carcinomas. Hepatocellular carcinoma (HCC) is 3rd leading malignant tumor in terms of mortality worldwide. Accumulating evidence indicates that ginsenosides play a vital role in the prevention and treatment of HCC. Ginsenosides can significantly improve the symptoms of HCC, and their anticancer activity is mainly involved in inhibiting proliferation and migration, inducing cell cycle arrest at the G0/G1 phase, promoting caspase-3 and 8-mediated apoptosis, regulating autophagy related to Atg5, Atg7, Atg12, LC3-II, and PI3K/Akt pathways, and lowering invasion and metastasis associated with decreased nuclear translocation of NF-κB p65 and MMP-2/9, increasing IL-2 and IFN-γ levels to enhance immune function, as well as regulating the gut-liver axis. In addition, ginsenosides can be used as an adjuvant to conventional cancer therapies, enhancing sensitivity to chemotherapy drugs, and improving efficacy and/or reducing adverse reactions through synergistic effects. Therefore, the current manuscript discusses the mechanism and application of ginsenosides in HCC. It is hoped to provide theoretical basis for the treatment of HCC with ginsenosides.

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signalling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78, 95% confidence interval 0.68-0.90), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for sodium-glucose cotransporter 2 (SGLT2) inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signalling through the PI3K/Akt/mTOR/HIF-1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF-1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signalling through SIRT1/AMPK/PGC-1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC-1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC-1α and RXRα abrogated the favourable effects of QLQX in the heart. Since PGC-1α/RXRα is also a downstream effector of Akt/mTOR signalling, the actions of QLQX on PGC-1α/RXRα may explain its favourable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX - astragaloside IV, ginsenosides, and tanshione IIA - share QLQX's effects on PGC-1α/RXRα/PPARα signalling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+ -K+ -ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials.

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease.

Lung cancer is the malignancy with the highest morbidity and mortality. Additionally, pulmonary inflammatory diseases, such as pneumonia, acute lung injury, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF), also have high mortality rates and can promote the development and progression of lung cancer. Unfortunately, available treatments for them are limited, so it is critical to search for effective drugs and treatment strategies to protect the lungs. Ginsenosides, the main active components of ginseng, have been shown to have anti-cancer and anti-inflammatory activities. In this paper, we focus on the beneficial effects of ginsenosides on lung diseases and their molecular mechanisms. Firstly, the molecular mechanism of ginsenosides against lung cancer was summarized in detail, mainly from the points of view of proliferation, apoptosis, autophagy, angiogenesis, metastasis, drug resistance and immunity. In in vivo and in vitro lung cancer models, ginsenosides Rg3, Rh2 and CK were reported to have strong anti-lung cancer effects. Then, in the models of pneumonia and acute lung injury, the protective effect of Rb1 was particularly remarkable, followed by Rg3 and Rg1, and its molecular mechanism was mainly associated with targeting NF-κB, Nrf2, MAPK and PI3K/Akt pathways to alleviate inflammation, oxidative stress and apoptosis. Additionally, ginsenosides may also have a potential health-promoting effect in the improvement of COPD, asthma and PF. Furthermore, to overcome the low bioavailability of CK and Rh2, the development of nanoparticles, micelles, liposomes and other nanomedicine delivery systems can significantly improve the efficacy of targeted lung cancer treatment. To conclude, ginsenosides can be used as both anti-lung cancer and lung protective agents or adjuvants and have great potential for future clinical applications.

American Ginseng for the Treatment of Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid ß-protein (Aß) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.

Improvement of Cognitive Function by Fermented Panax ginseng C.A. Meyer Berries Extracts in an AF64A-Induced Memory Deficit Model.

This study investigated the potential therapeutic properties of fermented ginseng berry extract (GBE) for Alzheimer's disease (AD). Fermented GBE was examined for its ginsenoside content and physiological properties, which have been suggested to have neuroprotective effects and improve cognitive function. The results showed that fermented GBE contains high levels of major active ginsenosides and exhibits antioxidant and acetylcholinesterase inhibitory activities. Post-fermented GBE demonstrated therapeutic potential in AF64A-induced damaged neural stem cells and an animal model of AD. These findings suggest that fermented GBE may hold promise as a candidate for developing new therapeutic interventions for memory deficits and cognitive disorders associated with AD and other neurodegenerative conditions. However, further studies are needed to evaluate the safety, tolerability, and efficacy of fermented GBE in human subjects and to determine its clinical applications. In conclusion, our study provides evidence that fermented GBE has potential as a natural product for the prevention and treatment of AD. The high levels of active ginsenosides and antioxidant and acetylcholinesterase inhibitory activities of fermented GBE suggest that it may be a promising therapeutic agent for improving cognitive function and reducing neurodegeneration.

Ginsenoside Rh2: A shining and potential natural product in the treatment of human nonmalignant and malignant diseases in the near future.

BACKGROUND: Ginseng is well-known as one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide including East, Russia, Southeast Asia, North America and some Western European countries. Ginsenosides, as one of the main high active components of Ginseng, have various pharmacological activities, such as anti-inflammatory, antianaphylaxis, anti-depression, and anticancer activities. Ginsenoside Rh2 (Rh2), one of the major bioactive ginsenosides in Panax ginseng, also exhibits versatile pharmacological activities, such as increasing non-specific resistance and specific immune response, improving cardiac function and fibrosis, anti-inflammatory effects and antitumor effects, which may serve as an excellent medicinal potential. PURPOSE: As one of hundreds of ginsenosides being identified from ginseng, Rh2 exerts a markedly pharmacological effect on various diseases without severe toxicity, it has attracted many researchers 'attention. Although Rh2 plays important roles in some animal models and cell lines to simulate human diseases, its underlying molecular mechanisms have yet to be determined. During the past ten years, nearly 450 studies on Rh2 in the treatment of complex disease have been reported, however, up to now, no comprehensive reviews about the roles of Rh2 in animal models and cellular lines of human nonmalignant and malignant diseases have been conducted. METHOD: We searched articles on ginsenoside-related diseases from December 2010 to February 2023 in peer-reviewed and nonclinical databases, which include Web of Science, Scopus, PubMed, China national knowledge internet and Medline, and using the following keywords: Ginsenoside Rh2, Human diseases, Cancer, Mechanisms, Chinese herbal medicine, Natural products and Signaling pathway. RESULTS: Therefore, in this review, we make a comprehensive summary on the roles of Rh2 and support the potential mechanisms of Rh2 according to the disease classification, including nonmalignant disease such as ulcerative colitis, neuropathic pain, Asthma, myocardial injury, depression and malignant disease such as breast cancer, colorectal cancer, hepatocellular carcinoma and gastric cancer. Finally, the combination therapy of Rh2 and other medications in human diseases are summarized, apart from that, there are other problems such as the bioavailability of oral administration Rh2 to be overcome in following research. CONCLUSION: These findings provide strong evidence that Ginsenoside Rh2 plays important roles in the treatment of nonmalignant and malignant diseases.

[Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer].

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 µmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.