Siberian Ginseng (Eleutherococcus)

Acanthopanax (A.) henryi (Oliv.) Harms contain many bioactive compounds commonly used in traditional Chinese medicine. The objective of the present study was to investigate the antibacterial activity of the single constituent, Eleutheroside K (ETSK) isolated from the leaves of A. henryi (Oliv.) Harms, against methicillin-resistant Staphylococcus (S.) aureus (MRSA). Broth microdilution assay was used to measure the minimal inhibitory concentration (MIC) and the MIC values of ETSK against eight clinical S. aureus strains were all 50 µg ml-1 . At sub-inhibitory concentrations, a synergistic effect between oxacillin (OXA) and ETSK was confirmed using checkerboard dilution assay and time-kill curve analysis. The bacteriostatic effect became more pronounced when ETSK was used in combination with detergent (Triton X-100) or ATPase inhibitor (N, N'-dicyclohexylcarbodiimide). According to western blot analysis, the down-regulated expression of Penicillin-binding protein 2a (PBP2a) further validated that the bacterial activity was inhibited when treated with ETSK in a dose-dependent manner. Results based on our study verified that ETSK significantly suppressed MRSA infections and emphasized the potential application of ETSK as a novel anti-MRSA natural drug. © 2020 The Society for Applied Microbiology.

The objective of the present study was to investigate the antibacterial activity of a single constituent, ursolic acid 3-O-α-L-arabinopyranoside (URS), isolated from the leaves of Acanthopanax henryi (Oliv.) Harms, alone and in combination with oxacillin (OXA) against methicillin-resistant Staphylococcus aureus (MRSA). A broth microdilution assay was used to determine the minimal inhibitory concentration (MIC). The synergistic effects of URS and OXA were determined using a checkerboard dilution test and time-kill curve assay. The mechanism of action of URS against MRSA was analyzed using a viability assay in the presence of a detergent and an ATPase inhibitor. Morphological changes in the URS-treated MRSA strains were evaluated via transmission electron microscopy (TEM). In addition, the producing penicillin-binding protein 2a (PBP2a) protein level was analyzed using western blotting. The MIC value of URS against MRSA was found to be 6.25 µg/ml and there was a partial synergistic effect between OXA and URS. The time-kill growth curves were suppressed by OXA combined with URS at a sub-inhibitory level. Compared to the optical density at 600 nm (OD600) value of URS alone (0.09 µg/ml), the OD600 values of the suspension in the presence of 0.09 µg/ml URS and 0.00001% Triton X-100 or 250 µg/ml N,N'-dicyclohexylcarbodiimide reduced by 56.6 and 85.9%, respectively. The TEM images of MRSA indicated damage to the cell wall, broken cell membranes and cell lysis following treatment with URS and OXA. Finally, an inhibitory effect on the expression of PBP2a protein was observed when cells were treated with URS and OXA compared with untreated controls. The present study suggested that URS was significantly active against MRSA infections and revealed the potential of URS as an effective natural antibiotic.

OBJECTIVE: To investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48/80 (C48/80). METHODS: Rats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion/damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehvde were determined. RESULTS: C48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage/secretion, C48/80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2-receptor antagonist commonly used to treat gastric ulcers. CONCLUSION: ASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

BACKGROUND: Generally accepted, but insufficiently proved, the concept of synergy is based on an assumption that combining of two biologically active substances is justified because the combination is more active and less harmful than the ingredients. HYPOTHESIS: Analysis of RNA microarray of isolated neuroglia cells and the comparison the number of genes deregulated by plant extracts and their fixed herbal formulation might be a useful tool/method for assessment of synergistic and antagonistic interactions of herbal extracts in human organism. AIM: The primary aim of this study was to extend a new method of assessment of synergistic and antagonistic interactions of herbal extracts in isolated human neuroglia cells when they applied in the form of fixed combinations. The secondary aim of the study was to predict possible effects of Herba Andrographidis (APE), Radix Eleutherococci (ESE) genuine extracts and their fixed combination Kan Jang (KJ) on cellular and physiological functions and associated diseases. The third task of the study was to find evidences that justify the hypothesis that these plants extracts in combination are more useful than the monodrugs. METHODS: Gene expression profiling was performed on the human neuroglia cell line T98G after treatment with APE, ESE, KJ and total number of more than two fold-deregulated genes from all experiments were compared by Venn diagram. Interactive pathways downstream analysis was performed with data sets of significantly up- or down-regulated genes and predicted effects on cellular functions and diseases were identified by Ingenuity IPA database software. RESULTS: ESE and APE significantly deregulate 207 and 211 genes correspondingly; 36 deregulated genes were common for both extracts. In total of 382 deregulated genes was expected to be deregulated by their fixed combination KJ. However, it was found only 250 genes deregulated by KJ. Among these 250 genes, 111 genes were unique for the KJ combination and not affected by ESE and APE. This is presumably due to synergistic interactions of molecular networks affected by ESE and APE. Meanwhile, 170 genes deregulated by ESE, and 55 genes deregulated by APE when teste

Combination therapy had become very popular currently for the diabetes mellitus and its complications, because of long term unreasonable drug use and adverse reaction to human body. In this study, a polysaccharide (ASP) from the roots of Acanthopanax senticosus was evaluated as an adjuvant with metformin for antidiabetic therapy in alloxan-induced diabetic rats. The result identified ASP plus metformin had a more beneficial promotion for relieving the symptoms of diabetes and reversing liver and kidney damage to normal level than only metfomin administration to diabetic rats. The blood glucose, blood lipid (TC and TG), thiobarbituric acid reactive substances (TBARS), AST, ALT, ALP, total bilirubin, creatinine and urea levels in diabetic rats were decreased by combination of ASP and metformin. Furthermore, the body weight, liver glycogen formation, antioxidant substance (GSH) and antioxidant enzyme (SOD and GPX) levels increased evidently in diabetic mice treated with both ASP and metformin. In particular, sometimes ASP plus metformin could significantly reverse the pathophysiologic parameters of diabetic rats to normal level than only metformin administration. Therefore ASP could be developed to a new adjuvant combined with metformin for diabetes mellitus therapy in the future.

Acanthopanax senticosus HARMS (AS) is used as a Chinese herbal medicine and as a health supplement in Japan. However, little is known about the interaction between AS and other drugs. In this study, we investigated the effect of AS extract on intestinal drug transporter (P-glycoprotein, or P-gp) and peptide transporter activities in Caco-2 cells. Caco-2 cells were cultured on a culture dish and a permeable membrane for 1-3 weeks. The apical-to-basolateral (A-to-B) transport of digoxin, a P-gp substrate, was significantly increased by the addition of AS extract in a concentration-dependent manner. In contrast, the A-to-B transport of cephalexin, a peptide transporter substrate, was significantly decreased by the addition of AS extract in the same manner. The effects of AS extract addition on the kinetics of the uptake of rhodamine 123, a P-gp substrate, and Gly-Sar, a peptide transporter substrate, were investigated. V (max) for rhodamine 123 uptake was significantly increased by AS extract addition compared with the control, whereas that for Gly-Sar uptake was significantly decreased. On the other hand, K (m) and K (d) for rhodamine 123 and Gly-Sar uptake were not affected. We conducted further investigations to clarify the effect of AS extract addition on P-gp activity. When AS extract was added to the apical side, B-to-A transport of rhodamine 123 was significantly decreased compared with the control. Furthermore, the amount of intracellular rhodamine 123 was increased by AS extract addition compared with the control. These results suggest that P-gp and peptide transporter activities are suppressed by AS extract addition in a non-competitive manner.

Asian ginseng, Siberian ginseng, and Indian Ayurvedic medicine Ashwagandha demonstrated modest interference with serum digoxin measurements by the fluorescent polarization immunoassay (FPIA). Recently, Abbott Laboratories marketed a new digoxin immunoassay, Digoxin III for application on the AxSYM analyzer. We studied potential interference of these herbal supplements on serum digoxin measurement by Digoxin III assay in vitro and compared our results with the values obtained by Tina-quant assay. Aliquots of drug-free serum pool were supplemented with various amounts of Asian ginseng, Siberian ginseng, or Ashwagandha approximating expected concentrations after recommended doses and overdoses of these herbal supplements in serum. Then digoxin concentrations were measured by the Digoxin III and Tina-quant (Roche Diagnostics) assay. We also supplemented aliquots of a digoxin pool prepared from patients receiving digoxin with various amounts of these herbal supplements and then measured digoxin concentrations again using both digoxin immunoassays. We observed modest apparent digoxin concentrations when aliquots of drug-free serum pool were supplemented with all three herbal supplements using Digoxin III assay (apparent digoxin in the range of 0.31-0.57 ng/ml), but no apparent digoxin concentration (except with the highest concentration of Ashwagandha supplement for both brands) was observed using the Tina-quant assay. When aliquots of digoxin pool were further supplemented with these herbal supplements, digoxin concentrations were falsely elevated when measured by the new Digoxin III assay. For example, we observed 48.2% (1.63 ng/ml digoxin) increase in digoxin concentration when an aliquot of Digoxin pool 1 (1.10 ng/ml digoxin) was supplemented with 50 microl of Asian ginseng extract (Brand 2). Measuring free digoxin does not eliminate the modest interferences of these herbal supplements in serum digoxin measurement by the Digoxin III assay.

The regulatory requirements for assessing potential interactions between herbal medicinal products and other medicines can cause specific, additional phytopharmaceutical problems. In this short review we assess the state of our knowledge for herbal extracts commonly used as over the counter (OTC) products for upper respiratory infections and which in many cases are considered to have immunomodulatory effects. Overall, the data on the safety of these products is still limited and only in the case of Echinacea preparations can preliminary conclusions be drawn. The available evidence points to weak cytochrome P450 inhibition which is unlikely to be of clinical relevance.

High-performance liquid chromatography coupled with solid phase extraction method was developed for determination of isofraxidin in rat plasma after oral administration of Acanthopanax senticosus extract (ASE), and pharmacokinetic parameters of isofraxidin either in ASE or pure compound were measured. The HPLC analysis was performed on a Dikma Diamonsil RP(18) column (4.6 mm x 150 mm, 5 microm) with the isocratic elution of solvent A (acetonitrile) and solvent B (0.1% aqueous phosphoric acid, v/v) (A : B = 22 : 78) and the detection wavelength was set at 343 nm. The calibration curve was linear over the range of 0.156-15.625 microg/ml. The limit of detection was 60 ng/ml. The intra-day precision was 5.8%, and the inter-day precision was 6.0%. The recovery was 87.30+/-1.73%. When the dosage of ASE is equal to pure compound caculated by the amount of isofraxidin, it has been found to have two maximum concentrations in plasma while the pure compound only showed one peak in the plasma concentration-time curve. The determined content of isofraxidin in plasma after oral administration of ASE is the total contents of free isofraxidin and its precursors in ASE in vitro. The pharmacokinetic characteristics of ASE showed the priority of the extract and the properities of traditional Chinese medicine.

Significant pharmacokinetic/pharmacodynamic interactions between various herbal products and warfarin have recently been reported. The aim of this study was to determine whether concomitant treatment of rats with Kan Jang (a standardized fixed combination of extracts from Andrographis paniculata and Eleutherococcus senticosus) and warfarin would lead to an alteration in the pharmacological effects of warfarin. Each day for 5 days a group of animals was treated orally with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active principle andrographolide (a daily dose some 17-fold higher than that recommended for humans): the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples taken. The concentration of warfarin in blood plasma was measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in blood plasma was measured using thromboplastin reagent. The concomitant application of Kan Jang and warfarin did not produce significant effects on the pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.

Anti-inflammatory factor (AIF) is a water soluble extract of three herbs, Panax notoginseng (Burk.) F. H. Chen, Rehmannia glutinosa Libosch and Eleutherococcus senticosus. The present study aimed to investigate the safety and efficacy of herb extracts, AIF, on Korean knee osteoarthritis patients for six weeks. Fifty seven patients with knee osteoarthritis, ranging from 43 to 73 years of age, who fulfilled the "American College of Rheumatology" (ACR) classification of idiopathic osteoarthritis of knee and radiographic criteria were randomly selected and enrolled for the study. After initial screening and resting period, two capsules each of AIF (Each capsule contains; 400 mg) and similar identical placebo were administered twice a day to both groups. Pain intensity at second, fourth, and sixth weeks of study as well as one week after discontinuation of drugs was assessed by using 100 mm visual analogue scale (VAS). Changes in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score were compared at the initiation and completion of the study. VAS assessed by patients were significantly reduced (at visit 2; 54.64+/-14.72, at visit 4, 37.32+/-16.58, p< 0.001) after AIF administration. Results showed an improvement in the physical function of K-WOMAC scale which was significantly higher (p=0.013) in AIF than placebo group, and decreases of total K-WOMAC score were also significantly higher (p=0.030) in AIF groups than placebo group. No serious adverse effect was observed, and there was no difference in incidence of adverse effect between AIF and placebo groups. In this population of Korean patients with knee osteoarthritis, AIF was found to be safe, tolerable and effective for symptomatic improvement of pain and physical function.

The purpose of this prospective randomized study was to investigate the effects of the extract of Acanthopanax senticosus (AS extract), a widely used oriental herb, on bone remodeling and bone mineral density in Korean postmenopausal women. A total of 81 postmenopausal women with osteopenia or osteoporosis, an age of less than 65 years, were enrolled in the study. Subjects were randomly assigned to two groups: (1) the control group (n = 40), calcium intake (500 mg per day), and (2) the treatment group (n = 41), calcium (500 mg per day) plus AS extract (3 g per day). After treatment with AS extract for 6 months, the AS extract group showed a significant increase in serum osteocalcin levels compared with the control group (P = 0.041). However, no significant changes in bone mineral density were observed by dual-energy X-ray absorptiometry (DXA). AS extract was generally well tolerated, and no differences were observed between the two groups in terms of adverse events. This study suggests that AS extract supplementation may have beneficial effects on bone remodeling in Korean postmenopausal women and that it has no significant adverse events.

CONTEXT: Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. OBJECTIVE: To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. RESULTS: In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29-1.48), DCR (RR = 1.15, 95% CI 1.12-1.19), QOL (RR = 1.71, 95% CI 1.54-1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. CONCLUSIONS: Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.

Adaptogens are synthetic compounds (bromantane, levamisole, aphobazole, bemethyl, etc.) or plant extracts that have the ability to enhance the body's stability against physical loads without increasing oxygen consumption. Extracts from Panax ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, Rhodiola rosea, and Schisandra chinensis are considered to be naturally occurring adaptogens and, in particular, plant adaptogens. The aim of this study is to evaluate the use of plant adaptogens in the past and now, as well as to outline the prospects of their future applications. The use of natural adaptogens by humans has a rich history-they are used in recovery from illness, physical weakness, memory impairment, and other conditions. About 50 years ago, plant adaptogens were first used in professional sports due to their high potential to increase the body's resistance to stress and to improve physical endurance. Although now many people take plant adaptogens, the clinical trials on human are limited. The data from the meta-analysis showed that plant adaptogens could provide a number of benefits in the treatment of chronic fatigue, cognitive impairment, and immune protection. In the future, there is great potential to register medicinal products that contain plant adaptogens for therapeutic purposes.

OBJECTIVES: Shuganjieyu capsule is a pure herbal pharmaceutical product for depression. Our objective was to explore the effectiveness and safety of Shuganjieyu capsule for the treatment of major depressive disorder in adults. METHOD: Eight computerized databases were searched. In addition, randomized controlled trials (RCTs) on Shuganjieyu capsule were hand-searched on seven key Chinese journals. Data were extracted and evaluated by two reviewers independently. Analysis was performed by intention-to-treat where possible. Prespecified subgroup analyses were different-dose regimens, patient spectrum, publication status, and treatment duration. RESULTS: Seven RCTs with 595 participants were included. Shuganjieyu capsule was superior than placebo in terms of response rate (RR = 2.42, 95% CI: 1.55-3.79; P = 0.0001), remission rate (RR = 4.29, 95% CI: 1.61-11.45; P = 0.004), the scores of the mean change from baseline of the HAM-D17 (MD = -4.17, 95% CI: -5.61 to -2.73; P < 0.00001) and from baseline of traditional Chinese medicine (TCM) syndrome score scale scores (MD = -6.00, 95% CI: -8.25 to -3.75; P < 0.00001). In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate (RR = 1.56, 95% CI: 1.29-1.88; P < 0.00001) and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores (MD = -0.74, 95% CI:-1.12 to -0.35; P = 0.0002) than venlafaxine alone. CONCLUSION: Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone. Due to the considerable risk of bias in majority of trials, recommendations for practice should be cautious, and additional, well-designed RCTs are needed in next step.

BACKGROUND: Acute ischaemic stroke is a common cause of death and disability. A number of studies published in China have shown that acanthopanax is beneficial for acute ischaemic stroke. OBJECTIVES: To assess the efficacy and safety of acanthopanax in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched January 2008), the Chinese Stroke Trials Register (last searched March 2008), and the Trials Register of the Cochrane Complementary Medicine Field (last searched January 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), CINAHL (1982 to March 2008), AMED (1985 to March 2008), and nine Chinese databases, including the China Biological Medicine Database (CBM-disc) (1979 to March 2008). We handsearched three Chinese journals and searched reference lists, relevant clinical trials registers and research databases. In an attempt to identify further published, unpublished, and ongoing trials, we contacted a pharmaceutical company, researchers and study authors. SELECTION CRITERIA: We included randomised controlled trials comparing acanthopanax with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors selected trials for inclusion, assessed trial quality and extracted the data independently. MAIN RESULTS: We included 13 trials (962 participants); the period of follow up in all included trials ranged from 10 to 30 days. None of the trials reported the pre-specified primary outcome death or dependency during the follow-up period. The outcome measure in all included trials was the improvement of neurological deficit after treatment; acanthopanax was associated with a significant increase in the number of participants whose neurological impairment improved (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.15 to 1.29). Two trials reported adverse events; five trials reported no adverse events. AUTHORS' CONCLUSIONS: The risk of bias in all the included trials was high, and hence the data were

OBJECTIVE: To assess the efficacy of Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection. METHODS: Systematic review of the literature and meta-analysis of randomized controlled trials. Mean difference in the reduction in symptom severity scores between treatment and control groups was calculated to obtain an overall estimate of effect. RESULTS: Four studies met our inclusion criteria and were reviewed. A total of 433 patients reported in three trials were included in the statistical analysis. Andrographis paniculata fixed combination with Acanthopanax senticosus was more effective than placebo. The mean difference was 2.13 points (95% CI 1.00-3.26 points, P=0.0002) on the symptom severity score. The difference in effects between A. paniculata and placebo was 10.85 points (95% CI 10.36-11.34 points, P<0.0001) in favour of A. paniculata. CONCLUSION: Current evidence suggests that A. paniculata extract alone or in combination with A. senticosus extract may be more effective than placebo and may be an appropriate alternative treatment of uncomplicated acute upper respiratory tract infection.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease closely associated with aging, yet the contribution of cellular senescence to fibrotic remodeling and its therapeutic implications remain incompletely understood. Syringin, a phenylpropanoid glycoside derived from Acanthopanax senticosus, has been reported to possess anti-inflammatory and antioxidant activities, but its role in IPF has not been elucidated. In this study, bulk lung transcriptomic data from the GTEx project and nine IPF cohorts were integrated with IPF scRNA-seq data to characterize senescence-associated fibrotic programs. A systems-level compound prioritization strategy incorporating reversed gene expression scoring, network proximity analysis, drug-likeness and toxicity evaluation was applied to identify candidate

INTRODUCTION: Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. is an important medicinal shrub with increasing demand for its wild resources. However, the responses of its future habitat suitability and medicinal quality to global environmental change remain poorly understood. METHODS: Future climate projections under multiple Shared Socioeconomic Pathway (SSP) scenarios, land-use dynamics, HPLC fingerprint data, and ensemble species distribution models were integrated to evaluate the habitat suitability, medicinal quality, and conservation priorities of E. senticosus in Heilongjiang Province. RESULTS: Climate variables, particularly Bio18, Bio11, and Bio08, were identified as the dominant drivers of habitat suitability, whereas land-use change exerted comparatively limited effects on habitat dynamics. Future climate change was projected to expand the overall suitable habitat of E. senticosus in Heilongjiang Province while reducing the extent of highly suitable habitats. The areas with high contents of the five major bioactive compounds, namely coniferin, syringin, eleutheroside E, isofraxidin, and syringaresinol-4'-O-β-D-glucopyranoside, were all projected to increase under future climate scenarios. Priority conservation analysis based on habitat suitability showed that existing nature reserves covered only 12.899% of the identified priority conservation areas. Wild tending priority areas, identified by integrating habitat suitability and medicinal component distributions, were mainly concentrated in the Less

BACKGROUND: Adaptogens are primarily plant-derived bioactive compounds that enhance the body's resistance to physical, chemical, and biological stressors, thereby showing promise in managing stress-related disorders, neurodegenerative diseases, inflammation, and ageing, among others. This narrative review summarizes current evidence on the mechanisms, therapeutic applications, and clinical relevance of adaptogens, particularly in neurological and inflammatory disorders, and identifies limitations and future research directions. SUMMARY: This narrative review included peer-reviewed literature from PubMed and Scopus using keywords such as "adaptogens," "stress response," "HPA axis," "neuroprotection," and names of specific adaptogens. Both in vitro and in vivo studies, as well as human clinical trials, were considered. Studies indicate that adaptogens modulate multiple molecular pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, Nuclear Factor - kappa B (NF-κB), mitogen-activated protein kinase 9 (MAPK), and antioxidant defence systems, exerting neuroprotective, anti-inflammatory, immunomodulatory, endocrine-regulating, antifatigue, and mood-enhancing effects. Prominent adaptogens include Withania somnifera, Panax ginseng, Rhodiola rosea, Schisandra chinensis, and Eleutherococcus senticosus. Though pre-clinical findings are promising, clinical trials are often limited by small sample sizes, short durations, and heterogeneity in herbal preparations. KEY MESSAGES: Adaptogens demonstrate significant potential in stress management and as adjunctive therapy for chronic diseases. However, further large-scale, standardized clinical studies are needed to confirm their efficacy, elucidate mechanisms, and support integration into mainstream medicine. © The Author(s) 2026. Published by S. Karger AG.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim leaves (ESL) are consumed as tea or stir-fried dishes and exhibit neuroprotective activity. Their primary active components, triterpenoids, pose characterization challenges due to structural complexity and extensive isomerism. To address these challenges, we developed a novel integrated annotation strategy that incorporates polygonal mass defect filtering (p-MDF), molecular fingerprinting, molecular networks (MN) and ion mobility spectrometry (

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited intervention. This study developed a bidirectional fermentation system combining Tremella fuciformis and Acanthopanax trifoliatus (TF-AT) to enhance metabolite biotransformation and bioactivity. TF-AT showed stronger lipid-lowering effects than the unfermented controls in the free fatty acid (FFA)-induced human normal hepatocyte cell line (LO2 cells). Network pharmacology and targeted metabolomics were used to identify key phenolic metabolites and potential signaling pathways. The TF-AT fermentation product was fractionated into free phenolic fractions (TF-AT-1-TF-AT-6) and a crude polysaccharide fraction (TF-AT-PS). In vitro assays were performed in FFA-induced LO2 cells to assess lipid accumulation, cell viability, triglyceride (TG), total cholesterol (TC), and mRNA expression of MAPK pathway-related genes. Ten phenolic metabolites, including quercetin, myricetin, and luteolin, were identified, and the MAPK pathway was predicted as a potential signaling pathway associated with TF-AT activity. TF-AT, TF-AT-1, and TF-AT-PS significantly improved the cell viability, reduced lipid droplets, and lowered TG and TC

Age-related hearing loss (ARHL) is a pervasive sensorineural deficit lacking effective pharmacological interventions. Although Eleutherococcus senticosus fruit extracts exhibit otoprotective potential, their precise bioactive constituents and underlying molecular mechanisms remain elusive. Using network pharmacology and transcriptomic analysis as hypothesis-generating tools, followed by experimental validation, this study identifies chiisanoside (CSS) as a key bioactive compound mitigating d-galactose-induced cellular senescence and auditory impairment, with an optimal effective dose of 25 μM in vitro (HEI-OC1 cells) and 50 mg/kg/day in vivo (oral gavage in C57BL/6 mice). Mechanistically, the in vitro and in vivo models demonstrate that CSS suppresses age-related auditory decline primarily by targeting the SESN2/AMPK signaling axis. Specifically, CSS upregulates SESN2 to activate AMPK, which not only enhances autophagy via the mTOR/ULK1 pathway but also concurrently inhibits the HIF-1α/TFRC/FTH1 cascade. These findings provide mechanistic insights supporting the potential of CSS as a therapeutic candidate in ARHL. © 2026 American Chemical Society.

BACKGROUND: Ulcerative colitis (UC) is a long-term, recurrent inflammatory condition marked by bloody feces and mucosal damage. Its rising global incidence and socioeconomic burden necessitate safer long-term interventions. Edible and medicinal herbs (EMHs) are prospective alternatives due to their multi-targ

BACKGROUND: This study investigates the core molecular mechanisms by which the rootstock of Eleutherococcus sessiliflorus (E.sessiliflorus) regulates the stem growth of Eleutherococcus senticosus (E.senticosus), using E.senticosus as the scion. METHODS: Grafted plants with E.sessiliflorus as the rootstock served as the primary research subjects, while self-rooted E.senticosus plants were utilized as controls. An integrated approach, combining physiological and biochemical assays, transcriptomics, and metabolomics, was employed to analyze the mechanisms, with verification by qRT-PCR. RESULTS: Physiological and biochemical analyses showed that self-grafting had no significant effect on E. senticosus stems. By contrast, cross-root grafting did not significantly alter moisture content, total ash, or extractive content. However, it significantly enhanced nutrient accumulation and antioxidant defense capacity in the stems, thereby promoting secondary metabolite accumulation. Transcriptomic and metabolomic analyses further revealed that grafting significantly regulates the biosynthesis pathways of unsaturated fatty acids and amino acids. Differential expression of key enzymes, such as SCD, FAD2, icd, and PK, facilitates metabolic specialization and collaborative adaptation between rootstock and scion. CONCLUSIONS: This study elucidates potential core targets and molecular mechanisms underlying the influence of grafting on E.senticosus, providing valuable theoretical references and research directions for variety improvement, high-quality cultivation, and the sustainable utilization of rare medi

INTRODUCTION: Eleutherococcus senticosus, a medicinal plant of significant value in China, currently faces habitat degradation and inconsistent quality. To establish a theoretical foundation for its effective conservation and utilization, this study takes Liaoning Province as the research area to investigate the distribution dynamics of this species under current and future climate scenarios, as well as the intrinsic mechanisms underlying habitat quality formation. METHODS: This study integrated the Ultra-Performance Liquid Chromatography (UPLC), Maximum Entropy (MAXENT) and the coupled Maximum Entropy-Geographical Detector model (MAXENT-GD). Ecological Suitability and Quality of this species were analyzed under current and future climate scenarios. Model accuracy was evaluated using four validation metrics: coefficient of determination, ROC curve (AUC), Kappa coefficient, and True Skill Statistic (TSS). RESULTS: Ten key environmental variables governed E. senticosus distribution: average precipitation in July (prec7), average precipitation in November (prec11), vegetation type (zblx), warmth index (index_ci), standard deviation of seasonal temperature variation (bio4), soiltype, average temperature in November (tmean11), aspect, altitude, and slope. Quality was primarily driven by interactive effects of precipitation, temperature, and topography. The overall accuracy, AUC value, Kappa coefficient, and TSS value of the MAXENT-GD model were 85.00%, 0.885, 0.700, and 0.7692, and the MAXENT model (82.00%, 0.862, 0.646, and 0.7231), indicating that the former possesses higher simulation accuracy. Under current climate conditions, the predicted suitable habitat area was 9.4129 × 104 km² (MAXENT) and 7.1375 × 104 km² (MAXENT-GD). Under future scenarios, the projected habitat change ra

Acanthopanax has therapeutic efficacy against vertigo; however, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism by which Acanthopanax treats vertigo through integrated network pharmacology and molecular docking techniques, and retrieved all target genes of Acanthopanax for vertigo treatment from July to October 2025. Vertigo-related target genes were subsequently identified from public databases, including GeneCards and Online Mendelian Inheritance in Man. The intersection between Acanthopanax-derived targets and vertigo-related targets was analyzed to identify candidate target genes. Using the STRING platform, we constructed protein-protein interaction networks for the identified candidate targets and mined the core functional modules within these networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on candidate targets via the clusterProfiler package. A carp bile poisoning-liver injury target-pathway network was constructed via Cytoscape 3.8.2 software, network topology analysis was conducted, and the core components and targets were screened. The results found that A total of 295 candidate targets for the treatment of vertigo caused by Eleutherococcus senticosus were identified. Pathway enrichment an

The genus Triozidus Li, 1994 stat. rev., sensu novo has a complex history. Here we redefine the genus as a natural group with two new species from Taiwan, Triozidus burckhardti Liao & Percy sp. nov. from the southernmost peninsula, and Triozidus yangorum Liao & Percy sp. nov. from the central and northern mountain region. In addition, we redescribe the type species, Triozidus stackelbergi (Loginova, 1967) comb. nov. and Triozidusukogi (Shinji, 1940) comb. nov., and we propose new combinations for a further two species as follows: Triozidus ceratophorus (Li, 2005) comb. nov. and Triozidus eleutherococci (Konovalova, 1980) comb. nov.; all new combinations except the latter are transferred from Heterotrioza Dobreanu & Manolache, and T. eleutherococci from Trioza Foerster. All but one Triozidus species with confirmed host plants are known to produce enclosed galls on Eleutherococcus (Araliaceae): Triozidus stackelbergi produces round galls on the leaf surface of Eleutherococcus sessiliflorus or more variably on leaf petioles, flowers, fruits and twigs of E. divaricatus; T. ukogi produces spindle-shaped galls on the leaf petioles or petiolules of E. spinosus; and T. yangorum produces round galls on the petiolules of the compound leaves or leaf bases of Eleutherococcus trifoliatus; T. burckhardti appears to share the same host plant a

Bioactive phenolic compounds from plants are valuable natural products with significant health benefits. Eleutherococcus senticosus (E. senticosus) fruit, a typically discarded resource, is a promising source of bioactive phenolics. Deep eutectic solvents (DESs) have emerged as a green solvent due to their low toxicity, biodegradability, and tunable properties. This study established an efficient ultrasound-microwave-assisted extraction using a tailored DES, followed by macroporous resin (HPD-600) purification. The purified extract (P-CF) achieved a 17-fold enrichment of polyphenols, reaching 537.9 mg/g, and was characterized to contain syringin, eleutheroside E, and isofraxidin. Molecular docking revealed that these compounds had strong affinities to α-amylase and α-glucosidase. In vitro assays demonstrated that P-CF possessed significant antioxidant and hypoglycemic activities, inhibiting α-amylase/α-glucosidase. In vivo validation using a hyperglycemic zebrafish model confirmed its efficacy in reducing blood g

BACKGROUND: Cholestatic liver injury (CLI) is mainly driven by intrahepatic cholestasis, a pathological condition characterized by systemic and intrahepatic accumulation of bile acids. Ciwujianoside B (CWB), the active constituent of Eleutherococcus senticosus, has demonstrated protective effects in various hepatic pathologies, but its functional role in CLI has not yet been investigated. PURPOSE: This study aims to evaluate the therapeutic potential of CWB against CLI and investigate its mechanism. METHODS: CLI was induced via bile duct ligation, and the protective effects of CWB were assessed through H&E, Sirius red, and immunohistochemical staining. Inflammatory cytokines in serum were measured by ELISA. Integrated analysis of 16S rDNA sequencing, serum metabolomics, and fecal microbiota transplantation was performed to investigate the interactions between gut microbiota and host metabolism. Trimethylamine oxide (TMAO) was supplemented to evaluate its impact on the hepatoprotective effects of CWB. In AML-12 cells, flavin-containing monooxygenase 3 (FMO3) was knockdown or overexpressed to assess TMAO levels, apoptosis, reactive oxygen species (ROS) content, and endoplasmic reticulum (ER) stress. The interaction between CWB and FMO3 was evaluated with molecular docking and molecular dynamics simulations. RESULTS:

Renal ischemia-reperfusion injury (IRI) drives acute kidney injury (AKI) and its progression to chronic kidney disease (CKD), currently lacking effective treatments. This study identifies chiisanogenin, the key bioactive component from Eleutherococcus sessiliflorus fruit extract, as a potent nephroprotective agent. Mechanistically, chiisanogenin targets the mixed lineage kinase domain-like pseudokinase (MLKL)-lysosome axis. It inhibits the pathological translocation of MLKL to the lysosomal membrane, thereby preserving lysosomal integrity. This action promotes the nuclear translocation of transcription factor EB to restore the autophagic flux. Concurrently, it prevents the leakage of cathepsin B into the cytosol, thus suppressing NLRP3 inflammasome activation and subsequent pyroptosis. In vivo and in vitro models confirm that chiisanogenin attenuates IRI-induced acute damage and retards the AKI-to-CKD fibrotic transition. These findings highlight chiisanogenin as a promising therapeutic candidate for treating ischemic renal injury.

Neurodegenerative diseases are closely linked to oxidative stress-induced neuronal damage, yet effective therapies remain limited. This study evaluated the protective effects of GMAS-01, an herbal formulation comprising Eleutherococcus sessiliflorus, Pinus densiflora, and Phragmites australis against H2O2-induced oxidative stress in SH-SY5Y cells. HPLC analysis identified catechin, p-coumaric acid, and acanthoside D as major bioactive compounds. Molecular docking indicated strong binding affinities of these compounds to apoptosis and inflammation-related targets, including NF-κB, APP, Bax, Bcl-2, caspase-3, and caspase-9. GMAS-01 pre-treatment significantly improved cell viability, reduced apoptotic features, and preserved mitochondrial membrane potential. Additionally, it attenuated ROS generation and restored antioxidant enzyme activities (SOD, GPx, and CAT). Gene expression analysis revealed modulation of apoptosis-related markers and suppression of NF-κB signalling. These findings demonstrate that GMAS-01 mitigates oxidative stress-induced neuronal damage and highlight its potential as a therapeutic candidate for neurodegenerative disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. is a well-established traditional adaptogen traditionally used to strengthen muscles and bones, suggesting potential relevance in muscle wasting conditions. However, its stems remain underutilized compared with the roots. As a sustainable aerial resource, the stem represents a practical target for standardized ethnopharmacological development. Therefore, this study aimed to evaluate the anti-atrophic efficacy of a standardized E. sen

One undescribed triterpenoid and four novel triterpenoid saponins, elesestriterpenoids A-E (1-5) were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Their chemical structures were determined using spectroscopic data analysis, with their corresponding absolute configurations measured using single-crystal X-ray diffraction, electronic circular dichroism calculations, and DP4+ technologies. Notably, elesestriterpenoid A (1) represents the first reported lupane-type triterpenoid with a 5/7/6/6/5-fused ring system from nature, and elesestriterpenoids B-E (2-5) feature an unprecedented 7/6/6/5-fused carbon skeleton. The neuroprotective potential of these isolates was evaluated using an in vitro model of oxidative stress in l-glutamate-induced HT22 mouse hippocampal neuron cells. The results revealed significant neuroprotective activity for compounds 1, 3, and 4. Particularly noteworthy, compound 1 demonstrated pronounced efficacy in mitigating oxidative damage through modulation of the Keap1/Nrf2/HO-1 signaling pathway in HT22 cells, indicating its potential for treating nerve injuries.

This study aims to investigate the therapeutic effect of ethanol extract from fermented broth of Acanthopanacis senticosi Radix et Rhizoma seu Caulis-Ganoderma applanatum (EEA-GF) on IM and clarify its active material basis and mechanism of action. Insomnia (IM) model mice were established by induction with p-chlorophenylalanine (PCPA). The IM status was evaluated through a pentobarbital sodium-induced righting reflex test, hematoxylin-eosin (H&E) staining, and biochemical index detection. The composition of EEA-GF and its blood-migrating components were analyzed based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology. Core active components were screened by combining weighted gene co-expression network analysis (WGCNA), network pharmacology, and molecular docking technology. Animal experiments have shown that EEA-GF exhibits excellent therapeutic efficacy in the treatment of IM. A total of 19 compounds were identified from the serum of mice administered with EEA-GF via gavage using UPLC-MS/MS technology. Through WGCNA, HIF1A, REN, NFE2L2, and PARP1 were determined as core targets. Gene Ontology (GO) enrichment analysis yielded 87 results. In addition to cancer-related pathways, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis mainly included pathways such as the thyroid hormone signaling pathway and neuroactive ligand-receptor interaction. Molecular docking results showed that five components including kaempferol exhibited good binding activity with the aforementioned core targets, indicating that

BACKGROUND: The interaction between endophytic fungi and medicinal plants plays a crucial role in the production of secondary metabolites; however, the metabolic interplay between Eleutherococcus senticosus (E. senticosus) and Penicillium oxalicum (P. oxalicum) remains inadequately studied. This research employed both targeted and non-targeted metabolomics to elucidate the metabolic reprogramming induced by P. oxalicum in the leaves of E. senticosus. Targeted analysis utilizing UPLC-MS quantified five medicinal compounds, including syringin and oleanolic acid, along with 19 phenolic metabolites. Additionally, GC-MS-based non-targeted profiling identified 127 primary metabolites. RESULTS: The results demonstrated a distinct dose-dependent modulation pattern: optimal concentrations of P. oxalicum (low, CL; medium, CM) enhanced the biosynthesis of phenolic compounds, with significant accumulation of C6C1- and C6C3C6-type phenolics. In contrast, high concentrations (CH) suppressed the accumulation of most primary and secondary metabolites. Alterations in primary metabolism primarily involved carbohydrate and amino acid pathways, such as alanine, aspartate, and glutamate metabolism, indicating a reallocation of carbon and nitrogen from primary metabolism to defense

BACKGROUND: Inflammation is closely linked to depression, and natural compounds show promise for treating inflammatory depression, though their mechanisms remain unclear. Eleutheroside B (EB), a key bioactive component of the classic Araliaceae plant Eleutherococcus senticosus with various central protective effects, but its antidepressant properties remain to be explored. OBJECTIVE: The aim of this research

Trevesia palmata (Roxburgh ex Lindley) Visiani 1842 is a distinctive and visually striking plant species belonging to the family Araliaceae. Commonly known as the 'Snowflake Aralia' or 'Spider Leaf Tree', it is native to the subtropical and tropical regions of Southeast Asia. This study exhibits a complete chloroplast genome of T. palmata, alongside a phylogenetic analysis involving 23 additional species from Araliaceae. The chloroplast genome has a length of 156,541 bp and an overall GC content of 37.9%, which is structurally composed of a large single-copy (LSC) region (86,460 bp), a small single-copy (SSC) region (18,119 bp), and a pair of inverted repeat (IRs) regions (25,981 bp). At the gene level, this chloroplast genome harbors a total of 133 genes, comprising of 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. The phylogram showed that T. palmata shares a close evolutionary affinity with Brassaiopsis and Eleutherococcus. The chloroplast genome annotated and displayed below will lay a favorable foundation for the species relationship identification and evolutionary research of Trevesia. © 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus senticosus fruit (ESF) originates from the mature fruit of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim, which is effective in treating essential hypertension (EH). However, the incomplete comprehension of how ESF antihypertensives impedes its further development. AIM OF THE STUDY: This study aims to elucidate the potential molecular

Eleutherococcus senticosus, a medicinally important woody plant, is widely used in pharmaceuticals and functional foods due to its bioactive compounds. Its wild populations are facing severe threats due to over-harvesting. To inform scientific conservation and sustainable utilization strategies, this study aimed to comprehensively assess its genetic background. We developed 13 highly polymorphic expressed sequence tag-simple sequence repeat (EST-SSR) markers from full-length transcriptome data, with an average polymorphism information content (PIC) of 0.52. Using these markers, we systematically evaluated the genetic diversity of 405 individuals from 22 natural populations across Northeast China. The results indicate that E. senticosus maintains moderate genetic diversity at the species level (mean expected heterozygosity He = 0.43), but substantial variation exists among populations. The Linjiang population showed the highest diversity (He = 0.58), whereas peripheral populations such as Tonghua (He = 0.31) and Huinan (He = 0.32) exhibited lower diversity. Analysis of molecular variance (AMOVA) revealed that genetic variation primarily resided within populations (66.3%

Background/Objectives: Adaptogens are plant-derived substances that enhance the body's nonspecific resistance to physical, chemical, biological, and psychological stressors by normalizing physiological functions. This article discusses the molecular mechanisms of action of seven key plant adaptogens-Rhodiola rosea, Schisandra chinensis, Withania somnifera, Eleutherococcus senticosus, Panax ginseng, Ocimum tenuiflorum, and Bacopa monnieri-in the context of chronic stress and lifestyle-related diseases. Methods: A review of the scientific literature is performed, including preclinical in vitro and in vivo studies, randomized placebo-controlled clinical trials, and studies employing network pharmacology analyses, molecular docking, and genomic techniques such as gene expression profiling. The interactions of active constituents with signaling pathways, molecular targets, and synergistic mechanisms were analyzed based on publications from the years 2010-2025. Results: Adaptogens exhibit pleiotropic activity: they regulate the HPA axis (Hypothalamic-Pituitary-Adrenal axis); induce Hsp70/Hsp16 expression; modulate SAPK/JNK, FOXO, and NF-κB pathways; and demonstrate antioxidant and mitoprotective effects. Specific mechanisms include: salidroside from R. rosea activating PI3K/Akt; schizandrin B from S. chinensis stimulating Hsp70; withanolides from W. somnifera inhibiting PDE4D; ginsenosides from P. ginseng suppressing FKBP51; and bacosides from B. monnieri enhancing acetylcholine synthesis. Clinical studies confirm reductions in cortisol levels (14-30%), decreased fatigue, and improved cognitive function without adverse effects. Conclusions: Understanding the molecular mechanisms of adaptogens supports their application in integrative medicine for the treatment of stress-related disorders, depression, anxiety, and neurodegenerative diseases. Further clinical studies are needed to optimize dosages and standardize extracts.

Acute myocardial infarction can lead to ventricular remodelling, which affects ventricular function and survival prognosis. Therefore, improving ventricular remodelling has become a focus of research. This study aims to investigate the effect of Acanthopanax senticosus leaf saponins (ASS) on cardiac function and left ventricular remodelling in a rat model of myocardial infarction, and explore its potential mechanism. Coronary artery ligation was used to establish a rat model of myocardial infarction, and ASS was administered orally for 28 days. After 28 days, cardiac function was evaluated by hemodynamic detection, and the levels of myocardial enzymes, inflammatory cytokines, oxidative stress and fibrosis-related factors were detected. The degree of fibrosis was evaluated by immunohistochemical detection of collagen I and collagen III deposition. The expression levels of MMP-2, MMP-9 and TIMP-1 were checked by Western blot. Compared with the Sham group, the cardiac function of the Model group was significantly impaired, and ASS administration could improve this change. In addition, compared with the Model group, ASS significantly alleviated myocardial injury, reduced the release of inflammatory cytokines TNF-α and IL-β, improved the oxidative stress state, reduced the release of NT-propBNP, Ang II, ET-1 and inhibited myocardial fibrosis. Moreover, ASS could reduce the expression of MMP-2 and MMP-9, and increase the expression level of TIMP-1. In conclusion, ASS may inhibit left ventricular remodelling by reducing the expression of MMP-2 and MMP-9.