This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.
Mice ; Male ; Animals ; Ginsenosides/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; Panax/genetics* ; Lipopolysaccharides/adverse effects* ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Mice, Inbred C57BL ; Acute Lung Injury/genetics* ; Lung/metabolism* ; Superoxide Dismutase/metabolism* ; Plant Leaves/metabolism* ; RNA, Messenger

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
Animals ; Male ; Rats ; Caspase 3/metabolism* ; Collagen ; Disease Models, Animal ; Hypertension, Pulmonary/drug therapy* ; Monocrotaline/adverse effects* ; Panax notoginseng/chemistry* ; Proliferating Cell Nuclear Antigen/pharmacology* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/metabolism* ; Rats, Sprague-Dawley ; Receptor, Notch3/genetics* ; RNA, Messenger ; Saline Solution ; Signal Transduction ; Saponins/pharmacology*

OBJECTIVETo investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX).

METHODSMice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot.

RESULTSIn response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05).

CONCLUSIONSPDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.

Animals ; Antineoplastic Agents ; adverse effects ; Cell Proliferation ; drug effects ; Cyclophosphamide ; adverse effects ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; GATA1 Transcription Factor ; metabolism ; Ginsenosides ; pharmacology ; therapeutic use ; Hematopoiesis ; drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Myeloid Cells ; drug effects ; pathology ; Panax ; chemistry ; Pancytopenia ; chemically induced ; drug therapy ; pathology ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-kit ; metabolism ; Saponins ; pharmacology ; Up-Regulation ; drug effects

Traditional Chinese medicine (TCM)-based herbal therapies have gained increasing popularity worldwide, raising concerns of its efficacy, safety profile and potential interactions with Western medications. Antithrombotic agents are among the most common prescription drugs involved in herb-drug interactions, and this article focused on aspirin, one of the most widely used antiplatelet agents worldwide. We discussed herbs that have potential interactions by exploring Western and TCM approaches to thrombotic events. Common TCM indications for these herbs were also highlighted, including possible scenarios of their concurrent usage with aspirin. With greater awareness and understanding of potential herb-drug interactions, TCM and Western physicians may collaborate more closely to identify, treat and, most importantly, prevent adverse drug events.
Aspirin ; therapeutic use ; Carthamus ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; therapeutic use ; Herb-Drug Interactions ; Humans ; Medicine, Chinese Traditional ; Panax ; Physicians ; Platelet Aggregation Inhibitors ; therapeutic use ; Salvia ; Thrombosis ; drug therapy

Local healthcare providers often question the possible steroidal activity of traditional Chinese medicine (TCM) herbs or herbal products and implicate them as a cause for adrenal insufficiency or Cushing's syndrome in patients with a history of TCM intake. We conducted a comprehensive database search for evidence of potential glucocorticoid, mineralocorticoid, androgenic or oestrogenic activity of herbs or herbal products. Overall, there are not many herbs whose steroidal activity is well established; among these, most cases were based on preclinical studies. Liquorice root may cause pseudoaldosteronism through interference with the steroidogenesis pathway. Although ginseng and cordyceps have some in vitro glucocorticoid activities, the corroborating clinical data is lacking. Deer musk and deer antler contain androgenic steroids, while epimedium has oestrogenic activity. On the other hand, adulteration of herbal products with exogenous glucocorticoids is a recurrent problem encountered locally in illegal products masquerading as TCM. Healthcare providers should stay vigilant and report any suspicion to the relevant authorities for further investigations.
Androgens ; analysis ; Animals ; Cordyceps ; Databases, Factual ; Deer ; Drugs, Chinese Herbal ; adverse effects ; analysis ; Epimedium ; Estrogens ; analysis ; Fatty Acids, Monounsaturated ; Glucocorticoids ; analysis ; Glycyrrhiza uralensis ; Humans ; Medicine, Chinese Traditional ; adverse effects ; Mineralocorticoids ; analysis ; Panax ; Plant Preparations ; analysis ; Risk ; Singapore ; Steroids ; adverse effects ; analysis ; Tissue Extracts

Red ginseng is a well-known alternative medicine with anti-inflammatory activity. It exerts pharmacological effects through the transformation of saponin into metabolites by intestinal microbiota. Given that intestinal microflora vary among individuals, the pharmacological effects of red ginseng likely vary among individuals. In order to produce homogeneously effective red ginseng, we prepared probiotic-fermented red ginseng and evaluated its activity using a dextran sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of intestinal damage indicated that the administration of probiotic-fermented red ginseng significantly decreased the severity of colitis, compared with the control and the activity was higher than that induced by oral administration of ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL-6 and TNF-α, inflammatory biomarkers that are increased at the initiation stage of colitis, were significantly decreased in probiotic-fermented red ginseng-treated groups in comparison to the control group. The levels of inflammatory cytokines and mRNAs for inflammatory factors in colorectal tissues were also significantly decreased in probiotic-fermented red ginseng-treated groups. Collectively, oral administration of probiotic-fermented red ginseng reduced the severity of colitis in a mouse model, suggesting that it can be used as a uniformly effective red ginseng product.
Administration, Oral ; Animals ; Colitis ; chemically induced ; drug therapy ; immunology ; Colon ; drug effects ; immunology ; Dextran Sulfate ; adverse effects ; Disease Models, Animal ; Female ; Fermentation ; Humans ; Interleukin-6 ; immunology ; Lactobacillus plantarum ; metabolism ; Mice ; Mice, Inbred BALB C ; Panax ; chemistry ; metabolism ; microbiology ; Plant Extracts ; administration & dosage ; chemistry ; metabolism ; Powders ; administration & dosage ; metabolism ; Probiotics ; metabolism ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo investigate the effects of Korean red ginseng (KRG) on semen parameters in male infertility patients in a randomized, double-blind, placebo-controlled study.

METHODSA total of 80 male infertility patients with varicocele were recruited from April 2011 to February 2012. The subjects were then divided into the following four groups: non-varicocelectomy (V)+placebo (P) group, V+P group, non-V+KRG group (1.5-g KRG daily), and V+KGR group (1.5-g KRG daily). Semen analysis was performed and hormonal levels were measured in each treatment arm after 12 weeks.

RESULTSAll groups but not the non-V+P group, showed significant improvements in sperm concentrations, motility, morphology, and viability at the end of the study. However, there were no significant differences in serum follicle-stimulating hormone, luteinizing hormone, and testosterone among groups. The incidence of adverse events was low, and all events were assumed to be unrelated to the treatments administered.

CONCLUSIONSAlthough the exact mechanism by which KRG improves spermatogenesis remains unclear, KRG may be a useful agent for the treatment of male infertility. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed.

Adult ; Double-Blind Method ; Hormones ; metabolism ; Humans ; Infertility, Male ; drug therapy ; Male ; Panax ; chemistry ; Placebos ; Plant Extracts ; adverse effects ; pharmacology ; therapeutic use ; Semen ; drug effects ; metabolism

BACKGROUNDFatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS).

METHODSThe study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme.

RESULTSThe fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks.

CONCLUSIONSOur results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group.

Adult ; Double-Blind Method ; Fatigue ; drug therapy ; Humans ; Inositol ; therapeutic use ; Middle Aged ; Panax ; chemistry ; Plant Extracts ; chemistry ; Taurine ; adverse effects ; therapeutic use ; Thiamine ; therapeutic use ; Treatment Outcome ; Ursodeoxycholic Acid ; adverse effects ; therapeutic use

Acupuncture Therapy ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Eye ; innervation ; Female ; Herpes Zoster ; drug therapy ; physiopathology ; therapy ; Humans ; Panax ; adverse effects ; chemistry ; Trigeminal Nerve ; drug effects ; physiopathology

In traditional Chinese medicine (TCM), the human body is divided into Yin and Yang. Diseases occur when the Yin and Yang balance is disrupted. Different herbs are used to restore this balance, achieving the goal of treatment. However, inherent difficulties in designing experimental trials have left much of TCM yet to be substantiated by science. Despite that, TCM not only remains a popular form of medical treatment among the Chinese, but is also gaining popularity in the West. This phenomenon has brought along with it increasing reports on herb-drug interactions, beckoning the attention of Western physicians, who will find it increasingly difficult to ignore the impact of TCM on Western therapies. This paper aims to facilitate the education of Western physicians on common Chinese herbs and raise awareness about potential interactions between these herbs and warfarin, a drug that is especially susceptible to herb-drug interactions due to its narrow therapeutic range.
Animals ; Carthamus tinctorius ; chemistry ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Ginger ; chemistry ; Ginkgo biloba ; chemistry ; Glycyrrhiza ; chemistry ; Herb-Drug Interactions ; Humans ; Lycium ; chemistry ; Medicine, Chinese Traditional ; methods ; Panax ; chemistry ; Prunus persica ; chemistry ; Salvia miltiorrhiza ; chemistry ; Singapore ; Warfarin ; administration & dosage ; adverse effects ; therapeutic use