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Medicinal herbs have a long history of use in the practice of traditional Chinese medicine and a substantial body of evidence has, over recent decades, demonstrated a range of important pharmacological properties. Western biomedical researchers are examining not only the efficacy of the traditional herbal products but, through the use of a range of bioassays and analytical techniques, are developing improved methods to isolate and characterize active components. This review briefly describes the different extraction methodologies used in the preparation of herbal extracts and reviews the utility of chromatography-mass spectrometry for the analysis of their active components. In particular, applications of gas or liquid chromatography with mass spectrometry for the isolation and characterization of active components of ginseng are critically assessed. The analysis of toxic substances from herb extracts with mass spectrometric techniques is also discussed along with the potential for mass spectrometric methods to investigate the proteomics of herbal extracts.

Ginseng is one of the most widely used Chinese herbal medicines. In this report, the relatively short-term effect of ginseng extract on the immunoglobulin production and cytokine production was studied. The ginseng extract was prepared by boiling the ground ginseng root in 50% ethanol. The specific pathogen-free mice were intraperitoneally (i.p.) injected with various doses of ginseng extract for 3 consecutive days. The results indicated that the serum levels of immunoglobulin (Ig)M, IgG and IgA were significantly elevated after the mice were i.p. injected with 4 g/kg/day of ginseng extract. Under in vitro condition, the lipopolysaccharide (LPS)-stimulated spleen cells showed a dose-dependent increase in secretion of IgM, IgG and IgA. However, at a higher dosage (4 g/kg/day), the amount of IgA secretion began to decline. The serum level of interleukin (IL)-2, interferon (IFN)-γ [T-helper (Th)1-type cytokines] and IL-4 and IL-10 (Th2-type cytokines) were significantly elevated after the mice were i.p. injected with 2 g/kg/day or higher doses of ginseng extract. The amount of cytokine secretion by concanavalin A (Con A)-stimulated spleen cells was also significantly enhanced after the mice were i.p. injected with 0.4 g/kg/day or higher dose of ginseng extracted. To further confirm the results from enzyme-linked immunosorbent assay (ELISA), the spleen cells were cultured for 36 hours in the presence of 1 μg/ml of Con A. Total mRNA was isolated and assayed for mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR). The results revealed that expression of IL-2 and IFN-γ mRNA were dose-dependently enhanced by the ethanol extract of ginseng. The levels of IL-4 and IL-10 mRNA expression were also elevated in the spleen cells of ginseng-treated mice in comparison with that of the control group. In addition, we observed that the concentrations of IgG1, IgG2a and IgG2b in culture supernatants of spleen cells were dose-dependently increased by in vivo treatment of ginseng extract, suggesting that both Th1- and Th2-type cytokines were involved in IgG production. Our observation in this study demonstrated that the Chinese herbal drug ginseng was able to regulate antibody production by augmenting Th1- (IL-2, IFN-γ) and Th2-type (IL-4, IL-10) cytokine production.

Sexual dysfunction is prevalent in both men and women. Although new pharmaceutical agents have been identified for male erectile problems, sexual desire and orgasm disorders, individuals with sexual dysfunction often seek alternative therapies, including traditional Chinese medicine. This article reviews currently used alternative therapies, such as herbal medications, L-arginine, acupuncture, biofeedback and others. Potential herb-drug interactions are also presented.

Hepatic fibrosis is an over-accumulation of extracellular matrix (ECM). It is a result of an imbalance between collagen synthesis and degradation. Matrix metalloproteinase (MMP) has degradative activity against collagen, but tissue inhibitors of metalloproteinase (TIMP) control the active forms of MMP by blocking the active site of MMP. In our study, we established the bile duct ligated model (BDL) in rats to evaluate anti-fibrotic potential of Chinese medicine sho-saiko-to (TJ-9). We assessed the drug's potential in inhibiting collagen accumulation, suppressing procollagen α1 types (I) and (III), and TIMP-1 mRNA expression. After administration of TJ-9, hyperbilirubinemia reduced approximately four-fold when compared with BDL-untreated group. TJ-9 also significantly reduced the collagen content and fibrogenic score, as well as downregulated elevated procollagen α1 types (I) and (III) and TIMP-1 mRNA level. Finally, we concluded that (1) TJ-9 significantly reduced cholestasis in rats with BDL, (2) TJ-9 markedly reduced the collagen content by 50%, and (3) TJ-9 exerted its antifibrogenic effect by downregulation of the mRNA expression of procollagen α1 types (I) and (III), and TIMP-1 in liver tissue.

The present study used in vivo rat heart to investigate (1) whether Shen-Fu (SF), a traditional Chinese formulation comprising Radix Ginseng (RG) and Radix Aconitum Carmichaeli (AC), is protective against myocardium damage due to ischemia-reperfusion injury, and (2) whether the cardioprotective effect of SF is related to scavenging of hydroxyl radicals. The model of ischemia-reperfusion injury was established by ligation of left anterior descending coronary artery for 60 minutes followed by reperfusion for 240 minutes in anesthetized rats. The size of infarction and the pathologic changes of myocardium were observed. Lactate dehydrogenase (LDH) and creatine kinase (CK) in serum, the amounts of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were measured at the end of the reperfusion period. Pretreatment groups with SF (10 mg/kg), RG (9 mg/kg) and AC (1 mg/kg) inhibited the rise in MDA and LDH as well as CK, increased SOD activity, reduced the size of infarction, and improved the pathologic changes of myocardium during ischemia-reperfusion compared with the control group. The effect of SF is better than that of RG and AC. These results indicate that SF, RG and AC protect obviously myocardium against damage due to ischemia-reperfusion in rats. The cardioprotective effect of SF injection may be in part related to scavenging of hydroxyl radicals or inhibition of lipid peroxidation. SF is more effective than its separated herbal extracts prepared from RG and AC.

Ginseng is a well-known medicinal plant used in traditional Oriental medicine. In recent decades, ginseng root has gained popularity as a dietary supplement in the United States. Ginseng has also been commonly used in Oriental medicine to treat diabetes-like conditions. The present review discusses the research on the anti-diabetic effects of ginseng and the possible mechanisms of its anti-diabetic actions.

Ginseng radix (Panax ginseng C.A. Meyer) is a popular herbal medicine in Oriental countries. We investigated the effect of long-term oral administration of ginseng extract on the antigen-specific antibody response. Male BALB/c mice were treated orally for 30 consecutive days with 2 g/kg of a 50% ethanol extract of ginseng root. Mice treated with ginseng and immunized with ovalbumin (OVA), resulting in an eight-fold increase in titers of anti-OVA immunoglobulin (Ig)G in the serum compared to the group receiving OVA immunization without ginseng treatment; the level of IgG was also significantly elevated in the mice treated with ginseng and immunized with OVA. Mice treated with ginseng without OVA immunization exhibited significantly reduced IgG and IgA production by spleen cells. However, IgG production was not affected in mice treated with ginseng and OVA immunization in spleen cells. Interleukin (IL)-2, interferon (IFN)-γ and IL-4 secretion by spleen cells from either ginseng-treated mice or OVA-immunized mice were down-regulated compared to that in the control group; while the production of IL-10 was unchanged. The percentage of CD8⁺ cells was significantly reduced in spleen cells from ginseng-treated, OVA-immunized mice. Thus, long-term oral administration of ginseng extract appears to potentiate humoral immune response but suppress spleen cell functions.

The perfect ginseng radix is collected when the ginseng root reaches a cultivation age of six years; this ensures the best mass quality and consistency of the plant's essential bioactive components. Since traditional means of authentication via physical appearance or smell are hardly reliable, an efficient analytical method that can determine the real cultivation age of dried ginseng radix in commercial products, especially ginseng products of various dosage forms, is urgently required. In the present study, chemical fingerprint by ¹H-NMR spectroscopy was used on dried ginseng radix samples with cultivation ages ranging from 1–6 years. The resulting dataset was then analyzed by using principle component analysis and cluster analysis to build up a distributive model that allows the identification of the real cultivation age of the ginseng radix based on a plant metabolomic strategy. This quality surveillance method was able to clearly discriminate the 6 years old ginseng radix from the other ages, and could be applied on the evaluation of the real cultivation age for the various dried white ginseng radix samples and commercial products accurately.

We previously reported the antiproliferative effect of panaxadiol (PD), an active compound in steamed ginseng, on human HCT-116 colorectal cancer cells, and that antioxidants might play a role in this effect. In this study, we observed that PD's antiproliferative effect was significantly enhanced by epicatechin (EC), a strong natural antioxidant in grape seed. Evidence for the synergistic antiproliferative effect was supported by the remarkable increase in the number of apoptotic cells.

The purpose of this investigation was to determine whether Panax ginseng extract intake would influence exercise-induced muscle damage and inflammation responses. Eighteen male college students were randomly assigned to either an RG intake group (RG, n = 9) or a placebo group (P, n = 9). All subjects performed a high-intensity uphill treadmill running task (two rounds of 45 min at 10 km/h speed with a 15 degree uphill slope separated by 5 min of rest). The RG group ingested 20 g/day of Korean red ginseng extract (mixed with 200 ml of water) three times/day for seven days prior to performing the uphill treadmill exercise test and for four days after the treadmill test, while the P group ingested 200 ml of water containing Agastachis Herba on the same schedule. Plasma creatine kinase activity (CK) and interlukin-6 (IL-6) levels were measured at pre-exercise and 24, 48, 72, and 96 h post-exercise; the IL-6 level was also measured at 1 and 2 h post-exercise. To evaluate insulin sensitivity, the oral glucose tolerance test (OGTT) was performed 24 h post-exercise. Plasma CK level in RG was significantly lower than that in P 72 h post-exercise (p < 0.05), and IL-6 level was significantly decreased in RG during the 2 h and 3 h recovery period compared to that of P (p < 0.05). Plasma glucose and insulin responses in RG were significantly reduced compared to those of P (p < 0.05). The results of this study suggest that RG supplementation could reduce exercise-induced muscle damage and inflammatory responses, resulting in improvements in insulin sensitivity.

Intestinal microbiota contribute to diverse mammalian processes including the metabolic functions of drugs. It is a potential new territory for drug targeting, especially for dietary herbal products. Because most herbal medicines are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered by intestinal microbiota. Ginseng is one of the most commonly used herbs and it is an attractive natural product to study its effect in the body. In this review, after briefly introducing the interactions of herbal products and gut microbiota, we discuss the microbiota-mediated metabolism of ginsenosides in ginseng and red ginseng. In particular, the major metabolite compound K and its pharmacological advances are described including anticancer, antidiabetic and anti-inflammatory effects. In summary, the intestinal microbiota may play an important role in mediating the metabolism bioactivity of herbal medicines.

In the United States, many patients, including cancer patients, concurrently take prescription drugs and herbal supplements. Co-administration of prescription medicines and herbal supplements may have negative outcomes via pharmacodynamic and pharmacokinetic herb-drug interactions. However, multiple constituents in botanicals may also yield beneficial pharmacological activities. Botanicals could possess effective anticancer compounds that may be used as adjuvants to existing chemotherapy to improve efficacy and/or reduce drug-induced toxicity. Herbal medicines, such as ginseng, potentiated the effects of chemotherapeutic agents via synergistic activities, supported by cell cycle evaluations, apoptotic observations, and computer-based docking analysis. Since botanicals are nearly always administrated orally, the role of intestinal microbiota in metabolizing ginseng constituents is presented. Controlled clinical studies are warranted to verify the clinical utility of the botanicals in cancer chemoprevention.

Diabetes is a major medical problem that imperils public health. Over two thousand years ago, Traditional Chinese Medicine (TCM) called diabetes-related symptoms "Xiaoke" disease. In ancient China, TCM and Chinese herbal medicines were used widely in treating Xiaoke and abundant experience has been accumulated. This article discusses the TCM theory on diabetes and its achievements in the prevention and treatment of diabetes in the past. Using Chinese herbal medicine, recent progress in diabetes therapeutics, including data from clinical trials, are presented. Mechanistic studies from basic research are discussed. Yin-yang balance and a holistic approach of TCM may complement diabetes treatment in Western medicine. With continuous efforts, TCM could play a more important role in fighting this disease.

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov, identifier: NCT01483430.)

Angiogenesis is a regulated process integral to many physiological and pathological situations, including carcinogenesis and tumor growth. The majority of the angiogenic processes are related to inflammation. The interplay is not only important in the case of pathogen entry but also influential in chronic inflammatory diseases, tumor growth and tissue regeneration. Modulating the interaction between inflammation and angiogenesis could be an important target for cancer treatment and wound healing alike. Ginseng has a wide range of pharmacological effects, including anti-inflammatory and angiogenesis-modulating activities. This paper presents the recent research progresses on the inhibition of angiogenesis by ginseng and its active constituents, with a particular focus on processes mediated by inflammation. The modulatory role of ginseng compounds in inflammation-mediated angiogenesis involving hypoxia and microRNAs are also discussed. With the potential to modulate the angiogenesis at the transcriptional, translational and protein signaling level via various different mechanisms, ginseng could prove to be effective in cancer therapeutics.

Chinese Herbal Formulation, supplement energy and nourish lung (SENL), effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multi-drug resistance (MDR) in lung cancer cells in vitro. The present study is designed to assess the effect of a New SENL (NSENL, modification of SENL) formulation on resistance to chemotherapy of cisplatin (DDP)-resistant human lung cancer cell line (A549/DDP) xenografts in nude mice. We assessed six constituents in NSENL by high performance liquid chromatography (HPLC). BALB/c nude mice harboring A549/DDP cell xenografts were established to assess the antitumor effect of NSENL and its impact on the expression of MDR related genes. The six constituents in NSENL, including ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rg3, astragaloside IV, ophiopogonin D and tetrandrine were quantitated simultaneously by HPLC. The combination of NSENL with DDP significantly inhibited tumor growth at a rate of up to 66.8% ($P<0.01$). In addition, NSENL as monotherapy or combined with DDP downregulated multidrug resistance-associated protein 1 (MRP1), basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) at both the mRNA and protein levels ($P<0.01$), reduced glutathione S-transferase π (GST-π) protein expression and tumor microvascular density as well as decreased phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) ($P<0.01$). These findings demonstrated that NSENL can reverse MDR in A549/DDP cells in vivo, an effect possibly associated with downregulation of MDR-associated genes as well as inhibition of bFGF/FGFR and phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathways.

Postoperative cognitive dysfunction (POCD) is one of the major complications in patients who have undergone surgeries. Reduction of surgery-induced inflammation and perioperative stress responses may prevent the development of POCD. As recent experimental data have suggested, Shenmai and Shenfu injections, two ginseng containing formulations, may improve cognition. We designed this study using aged rats as an experimental model to determine the effect of combined perioperative Shenmai injection and Shenfu injection in preventing the development of POCD and exploring the underlying mechanism of this intervention. Aged rats were randomized into one of the two groups. Rats in the experiment group received preoperative Shenmai injection and postoperative Shenfu injection while those of the control group did not receive this treatment. Study results indicate that the memory and cognitive ability of rats in the experiment group were significantly better than those of the control group at postoperative day 1 as well as at day 3. Plasma levels of neuron-specific enolase (NSE), S-100 $\beta$ protein, interleukin-6 (IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), cortisol (COR), aldosterone (ALD), and adenocorticotropic hormone (ACTH) were significantly lower in the experiment group than in those of the control group (day 1 postoperatively). The plasma level of NSE on postoperative day 3 remained lower in the experimental group than in those of the control group. Our experimental results indicate that preoperative Shenmai and postoperative Shenfu injections facilitate conscious recovery and prevent postoperative cognitive decline. This anti-POCD effect may be a result of minimizing surgery-induced inflammation and reduction of perioperative stress responses by these injections.

Korean red ginseng (KRG) is a traditional herbal medicine used to prevent several geriatric diseases due to its therapeutic effects on metabolic disorder, including type 2 diabetes and fatty liver disease. In this study, we investigated the effects of KRG on the progression of nonalcoholic steatohepatitis (NASH) in mice. NASH was induced by feeding a methionine- and choline-deficient high-fat or high-fat/high-sucrose diet for 6 or 13 weeks, respectively. Each diet group was also orally administered saline (group G0) or KRG extract (100, 200, or 400 mg/kg/day; groups G1, G2, and G4, respectively). KRG showed anti-inflammatory and antifibrogenic effects in the diet-induced NASH models. Furthermore, the expression levels of lipid metabolism-related genes were markedly decreased with KRG treatment in both diet-induced NASH groups. We next confirmed the expression levels of FABP4 in the liver and its ability to regulate inflammation and/or oxidative stress. We observed decreased levels of FABP4 mRNA and protein in the KRG-treated groups indicating that KRG affects the pathogenesis of NASH-related inflammatory responses by modulating FABP4 expression. Results of in vitro experiments showed similar patterns in cells treated with KRG, indicating that KRG treatment regulates the expression of FABP4 and subsequently reduces NASH related inflammation. Our findings suggest a novel role of KRG in NASH-related inflammatory responses via modulation of FABP4 expression in the liver. KRG may be a safe alternative therapy to prevent NASH progression.

The Chinese patent medicine She-Xiang-Xin-Tong-Ning (SXXTN) is a clinical medication for coronary heart disease (CHD) and angina pectoris. This study aimed to investigate pharmacological effects of SXXTN and elucidate the role in angiogenesis on human umbilical vein endothelial cells (HUVECs) and acute myocardial ischemia (AMI) rats. We prepared SXXTN to treat the cells to reveal their effects on oxidative stress-damaged cell viability, as well as cell proliferation, migration, and tube formation processes. SXXTN was also used to treat coronary artery ligation-induced acute myocardial ischemia rats to confirm whether it had positive effect on myocardial issues by hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining. We measured the levels of peroxidative damage-related enzymes in cytoplasm and serum by biochemical kits and detected vascular endothelial growth factor (VEGF), angiotensin II (Ang II), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1$\alpha$) levels in cells and rats by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that SXXTN protects HUVECs against oxidative stress damage and reversed the decrease of superoxide dismutase (SOD), glutathione (GSH) and increase of creatine kinase (CK), lactate dehydrogenase (LDH) caused by oxidative stress. SXXTN promoted angiogenesis through stimulating cell migration, tube formation, and activating VEGF/VEGFR2 and ERK1/2 pathways. Furthermore, SXXTN reduced infarct size and inhibited PGI2/TXA2 imbalance, preventing atherosclerosis plaque rupture leading to worsening coronary heart disease. Taken together, we report the first in vivo and in vitro evidence that SXXTN reduced oxidative stress-mediated damage and enhanced angiogenesis, which might be useful in treatment of myocardial infarction.

The loss of skeletal muscle mass and function is a serious consequence of chronic diseases and aging. BST204 is a purified ginseng (the root of Panax ginseng) extract that has been processed using ginsenoside-$\beta$-glucosidase and acid hydrolysis to enrich ginsenosides Rg3 and Rh2 from the crude ginseng. BST204 has a broad range of health benefits, but its effects and mechanism on muscle atrophy are currently unknown. In this study, we have examined the effects and underlying mechanisms of BST204 on myotube formation and myotube atrophy induced by tumor necrosis factor-$\alpha$ (TNF-$\alpha$). BST204 promotes myogenic differentiation and multinucleated myotube formation through Akt activation. BST204 prevents myotube atrophy induced by TNF-$\alpha$ through the activation of Akt/mTOR signaling and down-regulation of muscle-specific ubiquitin ligases, MuRF1, and Atrogin-1. Furthermore, BST204 treatment in atrophic myotubes suppresses mitochondrial reactive oxygen species (ROS) production and regulates mitochondrial transcription factors such as NRF1 and Tfam, through enhancing the activity and expression of peroxisome proliferator-activated receptor-$\gamma$ coactivator1$\alpha$ (PGC1$\alpha$). Collectively, our findings indicate that BST204 improves myotube formation and PGC1$\alpha$-mediated mitochondrial function, suggesting that BST204 is a potential therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.