Lipid mediators are a superfamily of bioactive molecules that are crucially involved in immune responses, regulating all stages of inflammation. Panax (P.) ginseng has pleiotropic pharmacological effects, including anti-cancer, anti-diabetic, and anti-inflammatory properties. Ginsenosides, unique triterpenoid glycosides from the plant's root, are proposed as active ingredients responsible for the immunomodulating potential of P.ginseng. Here, we comprehensively screened 23 ginsenosides for manipulating the lipid mediator network in various primary human innate immune cells. Several ginsenosides selectively inhibited 5-lipoxygenase (5-LOX)-mediated formation of pro-inflammatory leukotriene B4, but not of prostaglandins, in monocyte-derived macrophages and polymorphonuclear leukocytes by a unique irreversible mechanism. Structure-activity relationships revealed (i) higher anti-5-LOX activity of PPD-type ginsenosides, (ii) correlation with lipophilicity (R2 = 0.91), and (iii) eudysmic ratios favoring the 20S-epimers. Our findings highlight ginsenosides as immunomodulatory principles of P. ginseng and reveal abrogation of leukotriene formation rather than interference with prostaglandins as immediate anti-inflammatory mechanism.

Background/Objectives: Major depressive disorder (MDD) is a major global health concern that is intimately linked to neuroinflammation, oxidative stress, mitochondrial dysfunction, and complicated metabolic abnormalities. Traditional antidepressants frequently fall short, highlighting the urgent need for new, safer, and more acceptable therapeutic techniques. Phytochemicals, i.e., natural antidepressants derived from plants, are emerging as powerful plant-based therapies capable of targeting many pathogenic pathways at the same time. Summary: This narrative review synthesizes evidence from preclinical and clinical studies on the efficacy of phytochemicals such as curcumin, polyphenols, flavonoids, and alkaloids in lowering depressed symptoms. Consistent data show that these substances have neuroprotective, anti-inflammatory, and antioxidant properties, altering neuroimmune interactions, reducing oxidative damage, and improving mitochondrial resilience. Particularly, polyphenols and flavonoids have great therapeutic potential because of their capacity to penetrate the blood-brain barrier, inhibit cytokine activity, and encourage neuroplasticity mediated by brain-derived neurotrophic factor (BDNF). Despite promising results, the heterogeneity in study designs, phytochemical formulations, and patient demographics highlights the importance of thorough, standardized clinical studies. Conclusions: This review identifies phytochemicals as compelling adjuvant or independent therapies in depression treatment, providing multimodal mechanisms and enhanced tolerability. Additional research into improved dosage, pharmacokinetics, long-term safety, and integrative therapy approaches is essential. Using phytotherapeutics could considerably improve holistic and customized depression care, encouraging new research routes in integrative neuroscience and clinical psychiatry.

The endophytic microbiome serves a crucial function as a secondary line of defense against pathogen invasion in plants. This study aimed to clarify the mechanism of action of the ginseng plant growth-promoting rhizobacteria (PGPR) Bacillus vallismortis SZ-4 synergizing with endophytic microorganisms in the prevention and control of root rot.

Ginseng root samples from a susceptible group (CK) with a disease level of 0-2 and a biocontrol group (BIO) treated with strain SZ-4 were collected. We employed high-throughput sequencing to examine the microbial community structure of ginseng roots at different disease levels, explore beneficial endophytic bacteria, and evaluate the efficacy of strain SZ-4 in mitigating root rot through synergistic interactions with ginseng endophytic flora.

The application of the PGPR B. vallismortis SZ-4 biocontrol fungicide has been found to help ginseng resist Fusarium solani by modulating the richness and structure of endophytic microbial populations. The endophytic bacteria HY-43 and HY-46 isolated from ginseng roots treated with B. vallismortis SZ-4 were identified as Bacillus velezensis based on morphological, physiological, and biochemical characteristics, as well as 16S rDNA and gyrB sequencing analyses. The endophytic bacteria HY-43 and HY-46 were combined with strain SZ-4 to generate the bacterial consortia CS4-43 and CS4-46, respectively. Both CS4-43 and CS4-46 significantly enhanced the inhibitory effects of the single strain SZ-4, as well as HY-43 and HY-46, against ginseng root rot, while also promoting plant growth.

These findings offers a theoretical foundation for studying the microecological prevention and control of ginseng diseases as well as new insights for conducting research on the efficient and precise management of plant diseases.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease characterized by progressive mucosal damage. The incidence rate of UC is rising rapidly, which makes the burden of medical resources aggravated. In UC, due to various pathogenic factors such as mucosal immune system disorders, gene mutations and environmental factors disrupting the mucosal barrier function, the midgut pathogenic bacteria and exogenous antigens translocate into the lamina propria, thereby aggravating the inflammatory response and further damages the mucosal barrier. During the progression of UC, Th17 populations that cause inflammation generally increase, while Tregs that suppress Th17 activity decrease. Among them, Th17 mediates immune response, Treg mediates immunosuppression, and the coordinated balance of the two plays a key role in the inflammation and immune process of UC. Natural plant components can regulate biological processes such as immune inflammation from multiple levels of proinflammatory cytokines and signaling pathways. These characteristics have unique advantages and broad prospects in the treatment of UC. In immunomodulation, there is substantial clinical and experimental evidence for the modulatory role of natural plant products in restoring balance between Th17/Treg disturbances in UC. This review summarizes the previous studies on the regulation of Th17/Treg balance in UC by natural plant active ingredients, extracts, and traditional Chinese medicine prescriptions, and provides new evidence for the development and design of lead compounds and natural new drugs for the regulation of Th17/Treg balance in the future, and then provides ideas and evidence for future clinical intervention in the treatment of UC immune disorders and clinical trials.

Ulcerative colitis (UC), a chronic and challenging condition, necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications. Traditional Chinese medicine (TCM), known for its multi-stage and multi-targeted approach, has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment. Panax ginseng (P. ginseng), a commonly used remedy for UC in TCM, exemplifies this potential, although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated, highlighting the need for further research to unlock its full potential as a treatment option.

To investigate the key constituents and biological pathways through which P. ginseng exerts therapeutic effects on UC.

Network pharmacology investigated the UC-alleviating mechanism of P. ginseng, including "active ingredient-target-disease" network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Panaxadiol (PD; active ingredient of P. ginseng) was tested in a mouse model of 3% dextran sulfate sodium-induced UC, with assessments of body weight, Disease Activity Index scores, and colon length. Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining, immunohistochemistry, real time-quantitative PCR, and western blotting.

By integrating and analyzing the targets of P. ginseng and UC, 15 critical hub genes were discovered. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling. Among the 10 main active ingredients identified as potentially effective, PD was most abundant and was validated in vivo to mitigate weight loss, reduce Disease Activity Index scores, and prevent colon shortening. PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators. In addition, PD increased expression of mucin and tight junction proteins. Ultimately, PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK, while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.

PD alleviates colitis and aids intestinal barrier repair, partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways. These findings also suggest new research methods for treatment of UC with TCM.

Ginseng, a well-known herbal supplement, is widely recognized for its pharmacological properties, including anti-inflammatory, antioxidant, and immune-modulatory effects. This review explores the potential therapeutic benefits of ginseng, particularly its active compounds, ginsenosides, in promoting nasal mucosa health. The nasal mucosa plays a crucial role in respiratory defense, acting as a barrier to pathogens and particulate matter, while also orchestrating immune responses. Ginseng's bioactive compounds have shown promise in modulating inflammation, reducing oxidative stress, and enhancing immune functions, which could be beneficial in conditions such as allergic rhinitis, chronic rhinosinusitis, and viral infections. Histological studies highlight the impact of ginseng on nasal mucosal cells, particularly in regulating immune responses and promoting tissue resilience. Research demonstrates that ginseng can reduce inflammation in the nasal passages by inhibiting pro-inflammatory cytokines and pathways like NF-κB, while enhancing the activity of immune cells such as natural killer cells and macrophages. Furthermore, ginseng's antioxidant properties help protect nasal tissue from oxidative damage, which is common in chronic nasal conditions. Although promising, the evidence base is still developing, with many studies limited by small sample sizes and variations in ginseng preparations. Further clinical trials are needed to substantiate ginseng's efficacy, optimal dosage, and delivery methods for treating nasal conditions. This review provides insights into the potential of ginseng as a complementary therapeutic approach for enhancing nasal mucosa health and improving respiratory outcomes.

Natural toxins are toxic substances produced by living microorganisms and cause harmful effects to other creatures, but not the organisms themselves. Based on the sources, they are classified into fungal, microbial, herbal, algae, and animal biotoxins. Metals, the oldest toxicants, are not created or destroyed by human industry as elements, just concentrated in the biosphere. An antidote can counteract the toxic effects of a drug or toxin or mitigate the adverse effects of a harmful substance. The potential antidote effects of Panax ginseng in organ toxicity have been proved by many scientific research projects. Herein, we are going to gather a comprehensive mechanistic review of the antidotal effects of ginseng and its main constituents against natural toxins and metal toxicity. In this regard, a literate search has been done in PubMed/Medline, Science Direct, and Scopus from 2000 until 2024. The gathered data showed the protective impacts of this golden plant and its secondary metabolites against aflatoxin, deoxynivalenol, three-nitro propionic acid, ochratoxin A, lipopolysaccharide, nicotine, aconite, domoic acid, α-synuclein, amyloid β, and glutamate as well as aluminum, cadmium, chrome, copper, iron, and lead. These antidotal effects occur by multi-functional mechanisms. It may be attributed to antioxidant, anti-inflammatory, and anti-apoptotic effects. Future research directions on the antidotal effects of ginseng against natural toxins and metal toxicity involve broadening the scope of studies to include a wider range of toxins and metals, exploring synergistic interactions with other natural compounds, and conducting more human clinical trials to validate the efficacy and safety of ginseng-based treatments.

Research suggests that traditional Chinese medicine (TCM) holds promise in offering innovative approaches to tackle neurodegenerative disorders. In our endeavor, we conducted a comprehensive bibliometric analysis to delve into the landscape of TCM research within the realm of neurodegenerative diseases, aiming to uncover the present scenario, breadth, and trends in this field. This analysis presents potentially valuable insights for the clinical application of traditional Chinese medicine and provides compelling evidence supporting its efficacy in the treatment of neurodegenerative conditions.

The incidence of neurodegenerative diseases is on the rise, yet effective treatments are still lacking. Research indicates that TCM could offer novel perspectives for addressing neurodegenerative conditions. Nonetheless, the literature on this topic is intricate and multifaceted, with existing reviews offering only limited coverage. To gain a thorough understanding of TCM research in neurodegenerative diseases, we undertook a bibliometric analysis to explore the current status, scope, and trends in this area.

A literature search was carried out on April 1, 2024, utilizing the Web of Science Core Collection (WoSCC). Visualization and quantitative analyses were then performed with the assistance of CiteSpace, VOSviewer, and R software.

A total of 6856 articles were retrieved in the search. Research on TCM for neurodegenerative diseases commenced in 1989 and has exhibited a notable overall growth since then. Main research contributors include East Asian countries like China, as well as the United States. Through our analysis, we identified 15 highly productive authors, 10 top-tier journals, 13 citation clusters, 11 influential articles, and observed a progression in keyword evolution across 4 distinct categories. In 2020, there was a significant upsurge in the knowledge base, collaboration efforts, and publication output within the field. This field is interdisciplinary: network pharmacology emerges as the cutting-edge paradigm in TCM research, while Alzheimer's disease remains a prominent focus among neurodegenerative conditions due to its evolving etiology. A burst detection analysis unveils that in 2024, the focal points of research convergence between TCM and neurodegenerative diseases lie in two key biological processes or mechanisms: autophagy and microbiota.

For the first time, this study quantitatively and visually captures the evolution of TCM in addressing neurodegenerative diseases, showcasing a notable acceleration in recent years. Our findings underscore the pivotal role of interdisciplinary collaboration and the necessity for increased global partnerships. Network pharmacology, leveraging the advancements of the big data era, embraces a holistic and systematic approach as a novel paradigm in exploring traditional Chinese medicine and unraveling their fundamental mechanisms. Three ethnomedical plants-Tianma, Renshen, and Wuweizi-demonstrate the promise of their bioactive compounds in treating neurodegenerative disorders, bolstered by their extensive historical usage for such ailments. Moreover, our intricate analysis of the evolutionary trajectories of key themes such as targets and biomarkers substantially enriches our comprehension of the underlying mechanisms involved.

Panax ginseng (P. ginseng) C. A. Meyer. has been used extensively globally as a medicine. It has a therapeutic effect on sleep and is an attractive alternative for patients with insomnia. The United States Patent of Invention has approved the use of P. ginseng alcohol extract (GAE) in nutraceuticals or food to improve sleep. It has shown promise as an effective therapeutic agent for improving sleep and cognition. However, its mechanism of action is not yet fully understood.

To investigate the therapeutic benefits of GAE on sleep and cognition and its underlying mechanism in aged sleep-deprived rats, with a focus on orexin-mediated autophagy function.

We conducted in vivo tests in an aged sleep-deprivation rat model produced using p-chlorophenylalanine (PCPA) coupled with modified multi-platform method to examine the therapeutic effects and mechanisms of GAE. A pentobarbital sodium-induced sleep test and water maze were used to assess sleep and cognitive performance, respectively. An enzyme-linked immunosorbent assay was used to determine orexin levels and aging and sleep markers in serum and hypothalamic tissues. Hematoxylin-eosin staining and Nissl staining were used to assess histopathological changes, and autophagy levels were assessed using transmission electron microscopy, immunofluorescence. Western blot and immunohistochemical staining were performed to detect the levels of orexin, orexin-receptor proteins, and autophagy-associated proteins to study the effects of GAE on hippocampal neurons, and the underlying mechanisms.

In aged sleep-deprived rats, GAE treatment prolonged sleep duration, improved cognitive function, prevented hippocampal neuronal damage, increased the number of Nissl bodies, improved aging and sleep markers, and enhanced the LC3A/B expression in autophagosomes and neurons. The amount of orexin in serum and hypothalamic tissue and OX1R, OX2R, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) proteins also reduced, which resulted in the inhibition of the PI3K/Akt/mTOR pathway and activation of the autophagy process.

GAE may reduce hypothalamic orexin secretion and interact with orexin receptors to inhibit the PI3K/Akt/mTOR signalling network and activate autophagy. This may be a potential mechanism of action of GAE in regulating sleep-related cognitive function.

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.

Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders. The majority of KYNA is produced by the aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little is known about the consequences of deleting the KYN enzyme gene.

In CRISPR/Cas9-induced aadat knockout (kat2-/-) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and urine of 8-week-old males compared to wild-type mice.

Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, and indole-3-acetic acid levels were lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase were lower, but kynurenine 3-monooxygenase was higher; and oxidative stress and excitotoxicity indices were higher. Transgenic mice displayed depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-hydroxykynurenine pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite.

This is the first evidence that deleting the aadat gene induces depression-like behaviors uniquely linked to experiences of despair, which appear to be associated with excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in despair-based depression, a better understanding of these complex conditions, and more effective therapeutic strategies by elucidating the relationship between Trp metabolism and PTSD pathogenesis.

Korean Red Ginseng and ginsenosides have been studied for their efficacy against various diseases, including those related to aging. However, most aging studies use D-galactose to induce aging, which often does not accurately represent natural aging. This study aimed to verify improvements in auditory, cognitive, and liver function through administering red ginseng to an 18-month-old naturally aging mouse model.

Auditory function was assessed using Auditory Brainstem Response (ABR) and Auditory Middle Latency Response (AMLR). Cognitive function was evaluated electrophysiologically with P300 and mismatch negativity (MMN), and behaviorally using the Y-maze. Additionally, biochemical tests and histological analysis were conducted to assess liver function. The effects of red ginseng on gene expression regulation were also examined in the cochlea, auditory cortex, and liver, focusing on age-related disease processes.

Red ginseng significantly decreased hearing thresholds and improved central auditory function. It also enhanced cognitive behavior and function in response to external stimulation. Furthermore, red ginseng regulated alkaline phosphatase (ALP), albumin (Alb), and total protein (TP) levels, notably decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hematoxylin and eosin (H&E) staining of liver tissue showed significant improvement in fat droplets. These effects appear to be mediated by the regulation of aging-related genes Dec, c-Jun, Stat5b, and Lims2.

These results suggest that red ginseng improves auditory, cognitive, and liver functions in a naturally aged mouse model.

Ginseng (Panax ginseng C. A. Meyer), a traditional Chinese medicine, and the rare ginsenosides contained in it have various physiological activities. 25-OH-PPT (T19) is a rare natural dammarane-type ginseng sapogenin. Pharmacological studies have shown that T19 has good hypoglycemic, antioxidant, and anti-inflammatory activities. In the research, we optimized the T19 enrichment process and explored the potential mechanism of T19 in myocardial oxidative stress. Firstly, we studied a hydrolysis process on ginseng stems and leaves ginsenosides. Optimization factors include acid types, acid concentrations, ultrasound time, and ultrasound temperature. To develop safer preparation conditions more suitable for production scaleup, we studied the difference in hydrolysis between inorganic acid and food acids. The results show that using hydrochloric acid to hydrolyze ginsenosides in ginseng stems and leaves can increase the content of T19 to 12.16%. When using edible citric acid, the maximum content of T19 is 1.9%. However, using citric acid for hydrolysis has higher safety and non-toxic properties. Meanwhile, the myocardial protective effect of T19 was evaluated, indicating that T19 could effectively reduce isoproterenol (ISO)-induced oxidative stress injury by reducing the levels of LDH and CK-MB and regulating the contents of antioxidant enzymes SOD, lipid peroxidation product MDA, and non-enzymatic antioxidant GSH in cardiomyocytes. Further study demonstrated that regulation of fibrosis markers Collagen I, Collagen III, and α-SMA was involved in the potential mechanism of T19 efficiency.

Panax ginseng (P. ginseng) C.A. Meyer. Has been studied for decades for its various biological activities, especially in terms of immune-regulatory properties. Traditionally, it has been known that root, leaves, and fruits of P. ginseng were eaten for improving body's Qi and homeostasis. Also, these were used to protect body from various types of infectious diseases. However, molecular mechanisms of immunomodulatory activities of ginseng berries have not been systemically studied as often as other parts of the plant.

The aim of this research is to discover the regulatory effects of P. ginseng berries, more importantly, their ginsenosides, on innate immune responses and to elucidate the molecular mechanism.

Ginseng berry concentrate (GBC) was orally injected into BALB/c mice for 30 days, and spleens were extracted for evaluation of immune-regulatory effects. Murine macrophage RAW264.7 cells were used for detailed molecular mechanism studies. Splenic natural killer (NK) cells were isolated using the magnetic-activated cell sorting (MACS) system, and the cytotoxic activity of isolated NK cells was measured using a lactate dehydrogenase (LDH) release assay. The splenic immune cell population was determined by flow-cytometry. NF-κB promoter activity was assessed by in vitro luciferase assay. Expression of inflammatory proteins and cytokines of the spleen and RAW264.7 cells were evaluated using western blotting and real-time PCR, respectively.

The GBC enhanced cytotoxic activity of NK cells and the immune-regulation-related splenic cell population. Moreover, GBC promoted NF-κB promoter activity and stimulated the NF-κB signaling cascade. In spleen and RAW264.7 cells, expression of pro-inflammatory cytokines was increased upon GBC application, while expression of anti-inflammatory cytokines decreased.

These results suggest that P. ginseng berry can stimulate innate immune responses and help maintain a balanced immune condition, mostly due to the action of its key ginsenoside Re, along with other protopanaxadiol- and protopanaxatriol-type ginsenosides. Such finding will provide a new insight into the field of well-being diet research as well as non-chemical immune modulator, by providing nature-derived and plant-based bioactive materials.

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann's work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann's findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD.

The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer's disease (AD) remains unknown.

This study investigates the effects and mechanism of RSSW for ameliorating AD.

Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA.

Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced β-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking.

Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

This study was conducted to investigate the differences in chemical composition between red (RGBs) and yellow ginseng berries (YGBs) and their whitening and anti-aging skincare effects. The differences in the chemical composition between RGB and YGB were analyzed by ultra-high-performance liquid chromatography tandem quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-Q-Exactive-MS/MS) combined with multivariate statistics. An aging model was established using UVB radiation induction, and the whitening and anti-aging effects of the two ginseng berries were verified in vitro and in vivo using cell biology (HaCaT and B16-F10 cells) and zebrafish model organisms. A total of 31 differential compounds, including saponins, flavonoids, phenolic acids, and other chemical constituents, were identified between the two groups. Superoxide dismutase (SOD) activity was more significantly increased (p < 0.05) and malondialdehyde (MDA) content was more significantly decreased (p < 0.01) in RGB more than YGB induced by UVB ultraviolet radiation. In terms of whitening effects, YGB was more effective in inhibiting the melanin content of B16-F10 cells (p < 0.01). The results of zebrafish experiments were consistent with those of in vitro experiments and cell biology experiments. The DCFH fluorescence staining results revealed that both ginseng berries were able to significantly reduce the level of reactive oxygen species (ROS) in zebrafish (p < 0.01). Comparison of chemical composition and skin care activities based on RGB and YGB can provide a theoretical basis for the deep development and utilization of ginseng berry resources.

Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity.

At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research.

PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies.

This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

Black ginseng is the processed product of ginseng, and it has been found that the content and types of rare ginsenosides increased after processing. However, there is limited research on the ginsenoside differences between cultivated and forest ginseng before and after processing and among various plant parts. This study investigated the effects of processing on ginsenosides in different parts of cultivated and forest ginseng. After processing, the contents of Re, Rg1, S-Rg3, Rg5, R-Rh1, Rk1, Rk3, and F4 were significantly increased or decreased, the growth age of forest ginseng was not proportional to the content of ginsenosides, and the differences in ginsenoside content in ginseng from different cultivation methods were relatively small. Chemometric analysis identified processing biomarkers showing varying percentage changes in different parts. Network pharmacology predicted the EGFR/PI3K/Akt/mTOR pathway as a potential key pathway for the anti-cancer effect of black ginseng.

We aimed to examine the association between the use of specific types of dietary supplements and frailty using cross-sectional, nationally representative survey data. Adults aged ≥50 years in the Korea National Health and Nutrition Examination Survey 2018-2020 were included. We calculated a 46-item frailty index to assess frailty. In total, 27,384 older adults were included (mean age: 62.47 years; median frailty index: 0.12). Among them, 72% used at least one dietary supplement. The prevalence of dietary supplement use was higher among women than among men and in participants with higher socioeconomic status. Compared to non-users, users of dietary supplements had a healthier diet and nutrient intake, and lower levels of frailty. After adjusting for socioeconomic and dietary factors, users of vitamin C, red ginseng or calcium were found to be significantly less frail. Our findings indicate promising results concerning dietary supplement intake in managing frailty among older Korean adults.

There is a need for an efficient and long-lasting treatment due to the population's increasing prevalence of neurodegenerative disorders. In an effort to generate fresh ideas and create novel therapeutic medications, scientists have recently started to investigate the biological functions of compounds derived from plants and herbs. Ginseng, famous Chinese herbal medicine, has therapeutic value by virtue of its compounds ginsenosides or panaxosides, which are triterpene saponins and steroid glycosides. Research revealed positive impacts on ameliorating various disease conditions and found it as a possible drug candidate. Several neuroprotection mechanisms followed by this compound are inhibition of cell apoptosis, oxidative stress, inflammatory, and tumor activity. It has been demonstrated that controlling these mechanisms enhances cognitive performance and safeguards the brain against neurodegenerative disorders. The main objective of this review is to give a description of the most recent studies on ginsenoside's possible therapeutic application in the treatment of neurodegenerative diseases. Using organic compounds like ginseng and its various components may create new avenues for innovative treatment approaches development for neurological diseases. However, further research is necessary to confirm the stability and effectiveness of ginsenosides for neurodegenerative disease.

Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1β in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.

Welcome to Biomedicines' 10th Anniversary Special Issue, a journey through the human mind's labyrinth and complex neurological pathways [...].

Total ginsenosides (TG), the major active constituents of ginseng, have been proven to be beneficial in treatment of Alzheimer's disease (AD). However, the underlying mechanism of TG remains unclear.

APP/PS1 mice and N2a/APP695 cells were used as in vivo and in vitro model, respectively. Morris water maze (MWM) was used to investigate behavioral changes of mice; neuronal pathological changes were assessed by hematoxylin and eosin (H&E) and nissl staining; immunofluorescence staining was used to examine amyloid beta (Aβ) deposition; Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of relative amyloidogenic genes and proteins. Moreover, the antagonist of PPARγ, GW9662, was used to determine whether the effects of TG on Aβ production were associated with PPARγ activity.

TG treatment increased the spatial learning and memory abilities of APP/PS1 mice while decreasing the Aβ accumulation in the cortex and hippocampus. In N2a/APP695 cells, TG treatment attenuated the secretion of Aβ1-40 and Aβ1-42 acting as an PPARγ agonist by inhibiting the translocation of NF-κB p65. Additionally, TG treatment also decreased the expression of amyloidogenic pathway related gene BACE1, PS1 and PS2.

TG treatment reduced the production of Aβ both in vivo and in vitro. Activating PPARγ might be a potential therapeutic target of TG in facilitating Aβ clearance and ameliorating cognitive deficiency in APP/PS1 mice.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Neuroscience, neurology, and psychiatry are rapidly evolving fields that aim to understand the complex mechanisms underlying brain function and dysfunction, as well as to develop effective interventions for various neurological and psychiatric disorders [...].

Type 1 diabetes (T1D) is a specific autoimmune disease related to genetic and autoimmune factors. Recent studies have found that the intestinal flora is one of the important environmental factors in the development of T1D. The gut microbiota is the largest microbiota in the human body and has a significant impact on material and energy metabolism. Related studies have found that the intestinal floras of T1D patients are unbalanced. Compared with normal patients, the abundance of beneficial bacteria is reduced, and various pathogenic bacteria are significantly increased, affecting the occurrence and development of diabetes. Medicinal and food homologous traditional Chinese medicine (TCM) has a multicomponent, multitarget, and biphasic regulatory effect. Its chemical composition can increase the abundance of beneficial bacteria, improve the diversity of the intestinal flora, reduce blood sugar, and achieve the purpose of preventing and treating T1D by regulating the intestinal flora and its metabolites. Therefore, based on a review of T1D, intestinal flora, and TCM derived from medicine and food, this review describes the relationship between T1D and the intestinal flora, as well as the research progress of TCM interventions for T1D through regulation of the intestinal flora. Medicine and food homologous TCM has certain advantages in treating diabetes and regulating the intestinal flora. It can be seen that there is still great research space and broad development prospects for the treatment of diabetes by regulating the intestinal flora with drug and food homologous TCM.

Activation of NOD-like receptor protein 3 (NLRP3) inflammasome exacerbates liver inflammation and fibrosis in nonalcoholic steatohepatitis (NASH), suggesting that development of inflammasome inhibitor can become leading candidate to ameliorate NASH. Panax ginseng (P. ginseng) contains numerous bioactive natural components to reduce inflammation. This study aims to identify inhibitory components of P. ginseng for NLRP3 inflammasome activation. We separated polar and non-polar fractions of P. ginseng and tested modulation of NLRP3 inflammasome, and then identified pure component for inflammasome inhibitor which ameliorates diet-induced NASH. Non-polar P. ginseng fractions obtained from ethyl acetate solvent attenuated IL-1β secretion and expression of active caspase-1. We revealed that panaxydol (PND) is pure component to inhibit NLRP3 inflammasome activation. PND blocked inflammasome cytokines release, pyroptotic cell death, caspase-1 activation and specking of inflammasome complex. Inhibitory effect of PND was specific to NLRP3-dependent pathway via potential interaction with ATP binding motif of NLRP3. Moreover, in vivo studies showed that PND plays beneficial roles to reduce tissue inflammations through disruption of NLRP3 inflammasome and to ameliorate the development of NASH. These results provide new insight of natural products, panaxydol, for NLRP3 inflammasome inhibitor and could offer potential therapeutic candidate for reliving NASH.

Toxoplasmosis is a worldwide distributed zoonosis caused by Toxoplasma gondii (T. gondii), an obligate intracellular protozoan. The infection in immunocompetent hosts usually progresses with mild or no symptoms. However, in immunocompromised individuals, this disease can cause severe or fatal symptoms.

Sulfadiazine and pyrimethamine are two drugs used as standard therapies for human toxoplasmosis. Although they do not cause chronic infection, they may cause hematological toxicity, hypersensitivity, intolerance, teratogenic effects, gastrointestinal disorders, and bone marrow suppression.

The limited effect, significant toxicity, and emerging resistance to current drugs available to treat T. gondii infections require investigating other effective, nontoxic, and well-tolerated alternatives. Medicinal plants are, traditionally, the most promising sources used to treat infectious diseases Conclusion: This review provides data on new therapeutic and prophylactic methods for T. gondii infection based on the use of extracts and/or compounds derived from natural products, which have been reported to be useful as alternative treatment options in the last 20 years.

Panax ginseng C.A. Meyer (P. ginseng) is one of the more common traditional Chinese medicines (TCMs). It contains numerous chemical components and exhibits a range of pharmacological effects. An enormous burden is placed on people's health and life by Alzheimer's disease (AD), a neurodegenerative condition. Recent research has shown that P. ginseng's chemical constituents, particularly ginsenosides, have a significant beneficial impact on the prevention and management of neurological disorders. To understand the current status of research on P. ginseng to improve AD, this paper discusses the composition of P. ginseng, its mechanism of action, and its clinical application. The pathogenesis of AD includes amyloid beta protein (Aβ) generation and aggregation, tau protein hyperphosphorylation, oxidant stress, neuroinflammation, mitochondrial damage, and neurotransmitter and gut microbiota disorders. This review presents the key molecular mechanisms and signaling pathways of the active ingredients in P. ginseng involved in improving AD from the perspective of AD pathogenesis. A P. ginseng-related signaling pathway network was constructed to provide effective targets for the treatment of AD. In addition, the application of spatial metabolomics techniques in studying P. ginseng and AD is discussed. In summary, this paper discusses research perspectives for the study of P. ginseng in the treatment of AD, including a systematic and in-depth review of the mechanisms of action of the active substances in P. ginseng, and evaluates the feasibility of applying spatial metabolomics in the study of AD pathogenesis and pharmacological treatment.

In recent years, the phenomenon of acute poisoning and organ damage caused by organophosphorus pesticides (OPs) has been a frequent occurrence. Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides. The main active components of ginseng stems and leaves are total ginseng stem-and-leaf saponins (GSLSs), which have various biological effects, including anti-inflammatory, antioxidant and anti-tumor activities. We speculate that these could have great potential in the treatment of severe diseases and the relief of organophosphorus-pesticide-induced side effects; however, their mechanism of action is still unknown. At present, our work aims to evaluate the effects of GSLSs on the antioxidation of CPF in vivo and in vitro and their potential pharmacological mechanisms. Mice treated with CPF (5 mg/kg) showed severe intestinal mucosal injury, an elevated diamine oxidase (DAO) index, the decreased expression of occlusive protein-1 (ZO-1) and occlusive protein, an impaired intestinal mucosal oxidation system and intestinal villi relaxation. In addition, chlorpyrifos exposure significantly increased the contents of the inflammatory factor TNF-α and the oxidative-stress-related indicators superoxide dismutase (SOD), catalase (CAT), glutathione SH (GSH), glutathione peroxidase (GSH-PX), reactive oxygen species (ROS) and total antioxidant capacity (T-AOC); elevated the level of lipid peroxide malondialdehyde (MDA); reversed the expression of Bax and caspase; and activated NF-κB-related proteins. Interestingly, GSLS supplementation at doses of 100 and 200 mg/kg significantly reversed these changes after treatment. Similar results were observed in cultured RAW264.7 cells. Using flow cytometry, Hoechst staining showed that GSLSs (30 μg/mL, 60 μg/mL) could improve the cell injury and apoptosis caused by CPF and reduce the accumulation of ROS in cells. In conclusion, GSLSs play a protective role against CPF-induced enterotoxicity by inhibiting NF-κB-mediated apoptosis and alleviating oxidative stress and inflammation.

With the ageing of society's population, neurodegenerative diseases have become an important factor affecting the quality of life and mortality in the elderly. Since its physiopathological processes are complex and the authorized medications have recently been shown to have several adverse effects, the development of safe and efficient medications is urgently needed. In this study, we looked at how ginsenoside Rg1 works to postpone neural stem cell ageing and brain ageing, giving it a solid scientific foundation for use as a therapeutic therapy for neurodegenerative diseases.

Genetic and molecular knowledge of a species is crucial to its gene discovery and enhanced breeding. Here, we report the genetic and molecular dissection of ginseng, an important herb for healthy food and medicine. A mini-core collection consisting of 344 cultivars and landraces was developed for ginseng that represents the genetic variation of ginseng existing in its origin and diversity center. We sequenced the transcriptomes of all 344 cultivars and landraces; identified over 1.5 million genic SNPs, thereby revealing the genic diversity of ginseng; and analyzed them with 26,600 high-quality genic SNPs or a selection of them. Ginseng had a wide molecular diversity and was clustered into three subpopulations. Analysis of 16 ginsenosides, the major bioactive components for healthy food and medicine, showed that ginseng had a wide variation in the contents of all 16 ginsenosides and an extensive correlation of their contents, suggesting that they are synthesized through a single or multiple correlated pathways. Furthermore, we pair-wisely examined the relationships between the cultivars and landraces, revealing their relationships in gene expression, gene variation, and ginsenoside biosynthesis. These results provide new knowledge and new genetic and genic resources for advanced research and breeding of ginseng and related species.

Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal.

Aging is a complex process of impaired physiological integrity and function, and is associated with increased risk of cardiovascular disease, diabetes, neurodegeneration, and cancer. The cellular environment of the aging brain exhibits perturbed bioenergetics, impaired adaptive neuroplasticity and flexibility, abnormal neuronal network activity, dysregulated neuronal Ca²⁺ homeostasis, accumulation of oxidatively modified molecules and organelles, and clear signs of inflammation. These changes make the aging brain susceptible to age-related diseases, such as Alzheimer's and Parkinson's diseases. In recent years, unprecedented advances have been made in the study of aging, especially the effects of herbal/natural compounds on evolutionarily conserved genetic pathways and biological processes. Here, we provide a comprehensive review of the aging process and age-related diseases, and we discuss the molecular mechanisms underlying the therapeutic properties of herbal/natural compounds against the hallmarks of brain aging.