Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p<0.001; p<0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

The roots, leaves, and other parts of American ginseng contain ginsenosides and polyphenols, among other bioactive components. So far, reports on exploring the changes in bioactive components within its leaves after heat treatment have been limited. In the present study, we investigated the effects of far-infrared irradiation (FIR) heat treatment from 160 to 200 ℃ on the deglycosylation and dehydration rates of the bioactive components in American ginseng leaves. As the temperature was increased, the amounts of constant ginsenosides decreased while those of rare ginsenosides increased. After FIR heat treatment of the American ginseng leaves at an optimal 190 ℃, the highest total polyphenolic content and kaempferol content were detected, the antioxidant activity was significantly enhanced, and the amounts of rare ginsenosides F4, Rg6, Rh4, Rk3, Rk1, Rg3, and Rg5 were 41, 5, 37, 64, 222, 17, and 266 times higher than those in the untreated leaves, respectively. Moreover, the radical scavenging rates for 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and the reducing power of the treated leaf extract, were 2.17, 1.86, and 1.77 times higher, respectively. Hence, optimal FIR heat treatment at 190 ℃ is an efficient method for producing beneficial bioactive components from American ginseng leaves.

Background: The biofilm-forming bacteria Porphyromonas gingivalis (P. gingivalis) is primarily responsible for periodontal disorders, which continue to be a global health issue. Despite the widespread use of antibiotics like metronidazole, other potent therapeutic a crucial quorum sensing molecule implicated in the formation of P. gingivalis biofilm. Approaches are now being explored due to the growing challenge of antibiotic resistance. Objective: In particular, chemicals from Symphytum Officinale (S) and Panax Ginseng (G) plants will be examined in this study to assess if they have the ability to inhibit biofilm and to prevent the development of acylated homoserine lactones (AHLs), a quorum sensing molecule. Materials and Methods: With Metronidazole serving as a control, the antibacterial effects of these substances (Symphytum Officinale and Panax Ginseng) were examined against a standard strain and a clinical isolate of P. gingivalis. Dilutions of these plant extracts were used either alone (G+S) or in conjunction with metronidazole (G+S+F), to assess their antibacterial activity using antibacterial susceptibility test (inhibition zone), biofilm inhibition and disruption assay (optical density) and quorum sensing inhibition assay (AHL). Results: The combinations of Symphytum officinale, Panax Ginseng and metronidazole (S+G+F) showed the maximum effectiveness with highest zone of inhibition (25.000±0.001 mm) and biofilm inhibition (98.46%), and were comparable to G+S (inhibition zone of 24.341±0.593 mm and biofilm inhibition of 97.76%), and significantly different in the degree of biofilm inhibition with different treatment scenarios. Additionally, the plant's extracts and combinations are specific concentrations had a significant effect on the suppression of the generation of AHL (p < 0.05). Conclusion: According to preliminary research, these plant-derived substances, especially when paired with metronidazole, significantly inhibited the growth of P. gingivalis biofilm providing valuable information for the development of innovative therapeutic approaches for periodontitis and other biofilm-associated illnesses.

Background: The important periodontal disease pathogen Porphyromonas gingivalis produces large biofilms that increase its pathogenicity. Finding natural antimicrobial agents is crucial because of the rise in antibiotic resistance. Objective: The purpose of this study was to determine if plant extracts such as Symphytum officinale (S) and Panax ginseng (G) were effective against P. gingivalis separately and in combination with a common antibiotic Metronidazole (F). Materials and Procedures: Six different dilutions were produced the plant extracts and antibiotic separately and in combination with G and F and S and F using two-fold serial dilution technique. To evaluate the effects of these substances biofilm inhibition experiments were conducted. Plaque samples were collected from periodontitis patients to isolate P. gingivalis and standard strain of P. gingivalis (ATCC 33277) were bought. Additionally, Acylated Homoserine Lactones (AHLs) detection was carried out to look for any activity that would interfere with quorum sensing. GraphPad prism was used for statistical analysis with p value < 0.05. Results: The combinations of Symphytum Officinale and Metronidazole (S+F) showed the maximum effectiveness in biofilm inhibition (98.7%), which was better than G+F (98.2%) with substantial variations in biofilm inhibition levels in different treatment regimes. Notably, the isolate from the patient was more active than the standard strain. Additionally, the plant extracts and their combinations at particular dilutions had notable inhibitory effects on the generation of AHL (p <0.05). Conclusion: The study highlights the possibility of Symphytum Officinale and Panax Ginseng as effective treatments for P. gingivalis biofilm and AHLs, both on their own and in combination with Metronidazole. These organic substances may open the door to cutting-edge methods of treating periodontal disorders.

Panax ginseng C. A. Meyer (P. ginseng), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and possesses a variety of pharmacological activities. Alzheimer's disease (AD) is neurodegenerative disease that creates a huge burden on the lives and health of individuals. In recent years, studies have indicated that the chemical components of P. ginseng, especially ginsenosides, play a pronounced positive role in the prevention and treatment of neurological diseases. This review aimed to summarize currently studies on chemical components and the mechanisms action in AD intervention treatment of P. ginseng, especially ginsenosides. In this review, the components of P. ginseng and their respective active effects were first introduced. Then the key molecular mechanisms and signaling pathways of P. ginseng were introduced, and its different active ingredients in the prevention and treatment of Alzheimer's disease-related pathogenesis were also summarized from the pathogenesis of AD Aβ generation and aggregation, hyperphosphorylation of tau protein，oxidant stress，neuroinflammation，mitochondrial damage，disorder of neurotransmitter and gut microbiota. Signaling pathway networks related to the action of ginseng active ingredients was constructed, which could serve as a therapeutic target for Alzheimer's disease. In addition to a detailed report on P. ginseng in improving Alzheimer's disease-related pathogenesis, the application of the current technology, spatial metabonomics in AD therapeutics and diagnostics were later discussed. Spatial metabonomics could be applied to investigate the multi-target intervention of P. ginseng on Alzheimer's disease. Research perspectives for the study of P. ginseng in the treatment of Alzheimer's disease were provided for further studies.

Black ginseng is a type of processed ginseng that is traditionally used as herbal medicine in East Asian countries. It is prepared from fresh, white, or red ginseng by undergoing a process of steaming and drying nine times. However, the chemical differentiation of black ginseng with different processing levels is not well understood. The aim of this study is to propose a new method for discriminating and quantifying black ginseng. Six ginsenosides from black ginseng were accurately quantified, and based on this, the black ginseng samples were divided into uncompleted and completed black ginseng. Ultra-high-performance liquid chromatography-quadrupole-time of flight/mass spectrometry (UPLC-Q-TOF/MS) combined with a multivariate statistical analysis strategy was then employed to differentiate the two groups. A total of 141 ions were selected as analytical markers of black ginseng, with 45 of these markers being annotated by matching precise m/z and MS/MS data from prior studies.

Porcine epidemic diarrhea virus (PEDV) causes severe enteric disease in pigs, particularly neonatal piglets. Attempts to develop a safe and effective vaccine have been unsuccessful. Ginseng stem-leaf saponins (GSLS), a promising oral adjuvant candidate, can improve intestinal immune responses in poultry and mice. However, the low stability limits the further use. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable nanoparticle, have been widely used in biomedicine for stable and targeted drug delivery. In this study, we developed GSLS-PLGA nanoparticles (GSLS-NPs) and evaluated the mucosal adjuvant efficacy in vitro and in vivo. GSLS-NPs significantly enhanced antigen internalization and pro-inflammatory cytokine secretion by DC2.4 cells. Mice orally administered GSLS-NPs before intramuscular inoculation generated CD11b+CD8α- and CD11b-CD103+ dendritic cells in the spleen and draining mesenteric lymph nodes, respectively, which are the types mainly responsible for antigen presentation. Additionally, enhanced neutralizing and non-neutralizing antibody responses and expanded activities of specific effector and memory CD4+ and CD8+ T cells were also observed in mice immunized with PEDV vaccines plus GSLS-NPs compared to mice receiving the vaccines alone. Furthermore, GSLS-NPs showed a good safety profile and presented great advantages over GSLS aqueous solution. Collectively, our results highlight the potential of GSLS-NPs as a mucosal adjuvant and provide an attractive vaccination strategy for combatting PEDV. Further study is required to evaluate the efficacy of this mucosal adjuvant in swine.

Atopic dermatitis (AD) is a chronic and allergic skin disease, however, there is no cure for the disease. Many studies have shown anti-AD potentials of red ginseng, while red ginseng marc (RGM) remained after the ginseng extraction is discarded as industrial waste. However, it is recently reported that RGM, particularly fermented RGM (fRGM), still contains the bioactive properties. Thus, anti-allergic effects of fRGM were examined in 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. The treatments of fRGM alleviated the skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion, however, increased glutathione contents, with down-regulated gene expressions for inflammatory mediators. The histopathological analyses demonstrated that fRGM suppressed the epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved the anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph node. The beneficial effects were observed in the dexamethasone and fRGM groups, however, the antioxidant effects were evident only in the fRGM treatments. These provide useful information for developing fRGM as therapeutic sources for AD.

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major "rare" ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10-4 to 10-18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10-6 M to 10-18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10-4 M. Network pharmacology analyses of genes expression profiles using Ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, loss of concentration, and during recovery. According to ancient records, Red Ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their level in blood is shallow - at concentrations from 10-6 to 10-18 M. In the present study, we compared the effects of Red Ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/ml with effects of White Ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression of isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially various effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10000 to 0.01 ng/ml. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

This study was aimed at investigating the effects of roasting and cryogenic milling on particle size, water solubility, and amount of bioactive components in ginseng root. Samples were pulverized by cryogenic milling, and one treatment condition was selected for each size range (10-50 μm, and >50 μm). The selected samples were roasted at different temperatures (160-200 °C) followed by cryogenic milling. Powdered samples were analyzed for their physicochemical characteristics. Results revealed that roasted samples exhibited significantly smaller particle size than controls (not roasted, p<0.05), and the particle size of roasted samples decreased with increase in roasting temperature until flocculation occurred around 180-190 °C. With decrease in particle size of ginseng; water solubility index, antioxidant activity, total polyphenol content, and total polysaccharide content were observed to increase. Ginseng samples showed an increasing trend in antioxidant activity with decreasing particle size (p>0.05) with significantly higher values for all roasted samples compared to the controls (p<0.05). Non-polar ginsenosides such as Rg2(S), Rg2(R), Rg3(S), Rg3(R), and Rh1(S) showed an increase in temperature-dependent manner. This study revealed that roasting at certain temperature range with cryogenic milling has positive effects on ginseng by reducing its particle size, and increasing water solubility and bioactive components.

This study aimed to decrease the particle size of ginseng by roasting and cryogenic milling to increase its water solubility and physiological activity. The samples were roasted for different times (9–21 min) and generated in different sizes (10–50, and > 50 μm). All roasted samples revealed significantly smaller particle sizes than did non-roasted samples based on Sauter mean diameter (D [3,2], p < 0.05). Further, the particle sizes of roasted samples decreased till roasting up to 15 min. In terms of the water solubility index (WSI), antioxidant activity, total polyphenol content (TPC), and total polysaccharides according to particle size, 10-20 μm-sized samples showed the highest values when compared with >50 μm-sized samples. Based on roasting time, WSI values of all samples roasted for up to 15 min were higher than those of the control (not roasted) (p < 0.05). Antioxidant activity and TPC also increased with increasing roasting time. Total polysaccharide content was the highest upon roasting for 15 min except for the 10-20 μm sample. Ginsenoside content of roasted samples >20 μm size was higher than that of the control (not roasted) except after 15 min of roasting. Therefore, roasting and cryogenic milling are effective in producing ginseng root powder.

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.

Astragalus membranaceus (AM) and Panax ginseng (PG) are two herbal products with a long history of clinical usage in traditional Chinese medicine (TCM), used in treating a variety of diseases especially in stimulating or inhibiting the immune system. To elucidate the immunity effect of these two traditional Chinese medicine on animal model, four pharmacodynamic indexes (spleen index, thymus index, splenic lymphocyte proliferation and cytotoxic activity of natural killer (NK) cells) were observed on mice. Furthermore, metabolic profiles of plasma were also analyzed by ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS, LC-MS) method. All mice were intragastric administrated at three doses (low dose, moderate dose and high dose) once daily for 30 days. Principal components analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA) were performed on LC-MS spectra of plasma, showing that all administration groups developed the disturbance of internal milieu, compared to the blank control (BC) group. Besides, correlation analysis was conducted between pharmacodynamic index and metabolic index. It indicated that uracil, lysoPC(18:3(6Z,9Z,12Z)), sphinganine, LPA(0:0/16:0), UDP-glucuronate, PC(14:0/18:0) were five main endogenous substances, much closely related to four immunological indexes. Glycerophospholipid metabolism was found in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were closely regulated in AM groups. Energy metabolism (starch and sucrose metabolism, Pentose and glucuronate interconversions, together with glycerolipid metabolism) and glycerolipid metabolism were found in PG groups. These findings could contribute to the understanding of mice plasmatic metabolic profiling after long-term administration. Comparative immune-related metabolomic analysis of AM and PG was obtained on the base of pathway analysis of immune-related biomarkers. PG groups trended to have effect on cytotoxic activity of NK cells. AM groups trended to effect thymus index. Our work provides a detailed interpretation of immunological characteristics in different traditional Chinese medicine on metabonomic level.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.