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In this study, we evaluated antihyperglycemic effects of American ginseng berry extract in diabetic ob/ob mice. Animals received daily intraperitoneal (IP) injections of the extract 150 mg/kg for 12 days. On days 5 and 12, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to day 0 (both p < 0.05). Glucose tolerance improved significantly, which was shown by overall glucose excursion, calculated as area under the curve (AUC) during the two-hour IP glucose tolerance test. The AUC decreased by 31.8% on day 12 compared to day 0 (p < 0.01). In addition, after 12 days of the berry extract treatment, a significant reduction in body weight (p < 0.01 compared to day 0) and a significant increase in body temperature (p < 0.01 compared to day 0) was noticeable. Our results support in vivo antihyperglycemic and antiobese activity of American ginseng berry extract that may prove to be of clinical importance in the prevention and treatment of Type 2 diabetes.

Nausea and vomiting are significant adverse effects of chemotherapeutic agents like cisplatin, and cause significant patient morbidity. Cisplatin treatment results in oxidant gut injury, which is postulated to be the primary cause of nausea and vomiting. We evaluated the effects of two antioxidant herbs, Scutellaria baicalensis and American ginseng berry, on cisplatin-induced nausea and vomiting using a rat model. Rats react to emetic or nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by increased kaolin consumption (pica). We measured pica in rats to quantify cisplatin-induced nausea. We observed that pretreatment of rats with S. baicalensis or ginseng berry extracts resulted in a significant reduction in cisplatin-induced pica. The in vitro free radical scavenging ability of the herbal extract observed in the study, further confirmed the antioxidant action of the herb. We conclude that herbal antioxidants may have a role in attenuating cisplatin-induced nausea and vomiting.

Cardiovascular disease continues to be the leading cause of death in the US. Recent studies found that reactive oxygen species (ROS) have been incriminated in the pathogenesis of both acute and chronic heart diseas. Many botanicals possess antioxidant properties, and these herbal antioxidants may protect against cardiovascular diseases by contributing to the total antioxidant defense system of the human body. In this article, we reviewed the antioxidant components and properties of four putative antioxidant botanicals (i.e., grape seeds, green tea, Scutellaria baicalensis, and American ginseng), and their potential role in treating cardiovascular illness. The antioxidant activities of the herbal active constituents, and the relationship between their chemical structures and biological functions were also discussed. Further investigations are needed on the mechanisms of action of these botanicals as they affect salient cellular and molecular pathways involved in major diseases. Data obtained from future studies will have the potential for translation into practical benefits for human health.

Colorectal cancer remains one of the most prevalent cancer and a leading cause of cancer related death in the US. Many currently used chemotherapeutic agents are derived from botanicals. Identifying herbal sources, including those from ginseng family, to develop better anti-cancer therapies remains an essential step in advancing the treatment of the cancer. In this article, potential roles of ginseng herbs, especially American ginseng and notoginseng, in colorectal cancer therapeutics are presented. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified as protopanaxadiol and protopanaxatriol groups. Structure-activity relationship between their chemical structures and pharmacological activities are discussed. In addition, various steaming temperature and time treatment of the ginseng herbs can change ginsenoside profiles, and enhance their anti-cancer activities. This heat treatment process may increase the role of ginseng in treating colorectal cancer.

American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied. We used an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) method to determine 15 ginsenosides and/or metabolites and their bioavailability in humans. Six healthy human subjects received a single oral dose of 10 g of American ginseng root powder, after which samples of their blood were collected at 0, 2, 4, 7, 9 and 12 h for measurement of ginsenoside/metabolite levels in plasma. Ginsenosides Rb1, Rd, Rg2 and compound K (C-K) were detected in human plasma samples at different time points. The Rb1 concentration peak was 19.90 ± 5.43 ng/ml at 4 h. C-K was detected from 7 h to 12 h with 7.32 ± 1.35 ng/ml at 12 h. Since the last time point was at 12 h, C-K peak level was not observed. The areas under the concentration curves (AUC) from 0 to 12 h were 155.0 ± 19.5 ng⋅h/ml for Rb1 and 26.4 ± 6.4 ng⋅h/ml for C-K, respectively. The gradual decrease of Rb1 levels and the delayed increase in levels of C-K observed in human subjects supported previous reports that enteric microbiota played a key role in transforming Rb1 to C-K.

Natural products play an important role in cancer therapeutics, and lately more attentions have been paid to the prevention of major lethal malignancies, such as colorectal cancer (CRC). After oral ingestion, botanicals' parent compounds can be converted to their metabolites by the enteric microbiome, and these metabolites may have different bioactivities and variable bioavailability. In this study, we used an active ginseng metabolite, protopanaxadiol (PPD), as an example to assess its colon cancer preventive effect by comparing its effect with the treatment effect of fluorouracil (5-FU). A xenograft tumor nude mouse model with human colon cancer cell inoculation was used. After preventive PPD or treatment 5-FU administration with the same dose (30 mg/kg), tumor growth inhibition was evaluated by both a Xenogen bioluminescence imaging technique and manual tumor size measurement. Our data showed that preventive PPD very significantly inhibited the tumor growth compared to 5-FU (p < 0.01). Our data suggest that the PPD is a promising cancer prevention agent. More studies are needed to explore the chemopreventive actions of PPD and its potential clinical utility.

Ginseng has beneficial effects in cancer, diabetes and aging. There are two main varieties of ginseng: Panax ginseng (Korean ginseng) and Panax quinquefolius (American ginseng). There are anecdotal reports that American ginseng helps reduce body temperature, whereas Korean ginseng improves blood circulation and increases body temperature; however, their respective effects on body temperature and metabolic parameters have not been studied. We investigated body temperature and metabolic parameters in mice using a metabolic cage. After administering ginseng extracts acutely (single dose of 1000 mg/kg) or chronically (200 mg/kg/day for four weeks), core body temperature, food intake, oxygen consumption and activity were measured, as well as serum levels of pyrogen-related factors and mRNA expression of metabolic genes. Acute treatment with American ginseng reduced body temperature compared with PBS-treated mice during the night; however, there was no significant effect of ginseng treatment on body temperature after four weeks of treatment. VO₂, VCO₂, food intake, activity and energy expenditure were unchanged after both acute and chronic ginseng treatment compared with PBS treatment. In acutely treated mice, serum thyroxin levels were reduced by red and American ginseng, and the serum prostaglandin E2 level was reduced by American ginseng. In chronically treated mice, red and white ginseng reduced thyroxin levels. We conclude that Korean ginseng does not stimulate metabolism in mice, whereas a high dose of American ginseng may reduce night-time body temperature and pyrogen-related factors.

In North America, a high proportion of pregnant women use herbal medications including North American ginseng. This medicinal plant contains high amounts of triterpene saponins (ginsenosides), which are the main bioactive compounds. It is important to assess ginseng’s impact on all reproductive functions to ensure the safety of pregnant women and fetuses. In this study, we defined the concentration-responsive effects of North American alcoholic and aqueous ginseng extracts on preimplantation development in vitro and on pregnancy and post-partum development in the mouse. Two-cell mouse embryos were cultured with 5 different concentrations of whole ginseng root extracts, or ginsenosides Rb1, Rg1 and Re alone, a combinatorial ginsenoside solution and a crude polysaccharide fraction solution. Embryonic development and recovery from each treatment was assessed. To investigate the in vivo effects of ginseng extracts, female mice were gavaged with 50mg/kg/day, 500mg/kg/day or 2000mg/kg/day of either extract (treatment) or water (sham) for 2 weeks prior to mating and throughout gestation. Gestation period, litter size, pup growth and pup sex ratio were evaluated. Oral ginseng consumption did not significantly affect fertility or pregnancy in the mouse. High doses of ginseng (2000mg/kg/day) decreased maternal weight gain. Direct treatment of preimplantation embryos in vitro demonstrated that ALC and AQ extract treatment reduced development in a concentration responsive manner, while only ALC extract effects were largely reversible. Treatments with individual or combinatorial ginsenosides, or the polysaccharide fraction solution alone did not impair preimplantation development, in vitro. In conclusion, maternal oral consumption of ginseng has little negative impact on pregnancy in the mouse, however, direct exposure to ginseng extract during mouse preimplantation development in vitro is detrimental.

American ginseng and Asian ginseng, which occupy prominent positions in the list of best-selling natural products in the West and East, are suitable for different indications in the traditional pharmacological uses. Currently, the effects of American ginseng and Asian ginseng in the protection against metabolic dysfunction and the differences between them are still unknown. Herein, an untargeted metabolomics based on liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was determined. The serum metabolomics and dynamic feces metabolomics revealed significant metabolic distinction between American ginseng and Asian ginseng in diet-induced obese (DIO) mice. The results show that American ginseng and Asian ginseng alleviate glucose and lipid metabolism disorder in DIO mice. A total of 45 differential metabolites were confirmed between the drug-naïve and American ginseng group, and 32 metabolites were confirmed between the drug-naïve and Asian ginseng group. Metabolic pathways analysis shows that these two ginsengs treatment dynamic rectifies metabolic disorder in DIO mice mainly via regulating linoleic acids metabolism, cysteine and methionine metabolism and biosynthesis of unsaturated fatty acid. Moreover, American ginseng’s specific function in monitoring the carnitines and taurine/hypotaurine metabolism might make it more effective in meliorating lipids metabolism disorder than Asian ginseng.

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng’s biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.

Ginseng-containing Shentao Ruangan granules (STR) have been a well-known Chinese medicine prescription for the treatment of hepatocellular carcinoma (HCC) in China for decades. This study aimed to establish an in silico experimental framework to decipher the underlying mechanism of STR in the treatment of HCC. Microarray analysis, network pharmacology, RNA-sequencing (RNA-seq), bioinformatics analysis, and in vivo and in vitro experiments were used as integrated approaches to uncover the effects and mechanisms of action of STR. The introduction of STR significantly suppresses the proliferation and metastasis of HepG2 and Huh7 cells. STR treatment notably suppressed the growth of transplanted Huh7 tumors. Furthermore, STR administration reduced the expression of various epithelial-to-mesenchymal transition (EMT)-related proteins including N-cadherin, vimentin, and $\beta$-catenin. By employing a systems biology approach, 21 common genes were identified across RNA-seq data, TCGA-HCC dataset, and network pharmacology analysis. Finally, of these genes nine were found to be associated with both OS and PFS in patients with HCC within the TCGA cohort. Validation of candidate genes by qPCR and WB identified a significant downregulation in the expression of pGSK3$\beta$ and RELA protein with increasing concentrations of STR. These results elucidated the mechanism by which STR inhibits tumor growth and EMT of HCC may be related to the GSK3$\beta$/RELA pathway.