PgDDS Changes the Plant Growth of Transgenic Aralia elata and Improves the Production of Re and Rg3 in Its Leaves.

Aralia elata (Miq.) Seem is a medicinal plant that shares a common pathway for the biosynthesis of triterpenoid saponins with Panax ginseng. Here, we transferred the dammarenediol-II synthase gene from P. ginseng (PgDDS; GenBank: AB122080.1) to A. elata. The growth of 2-year-old transgenic plants (L27; 9.63 cm) was significantly decreased compared with wild-type plants (WT; 74.97 cm), and the leaflet shapes and sizes of the transgenic plants differed from those of the WT plants. Based on a terpene metabolome analysis of leaf extracts from WT, L13, and L27 plants, a new structural skeleton for ursane-type triterpenoid saponins was identified. Six upregulated differentially accumulated metabolites (DAMs) were detected, and the average levels of Rg3 and Re in the leaves of the L27 plants were 42.64 and 386.81 µg/g, respectively, increased significantly compared with the WT plants (15.48 and 316.96 µg/g, respectively). Thus, the expression of PgDDS in A. elata improved its medicinal value.

Identification and Quantitation of the Bioactive Components in Wasted Aralia elata Leaves Extract with Endothelial Protective Activity.

Aralia elata, a renowned medicinal plant with a rich history in traditional medicine, has gained attention for its potential therapeutic applications. However, the leaves of this plant have been largely overlooked and discarded due to limited knowledge of their biological activity and chemical composition. To bridge this gap, a comprehensive study was conducted to explore the therapeutic potential of the 70% ethanol extract derived from Aralia elata leaves (LAE) for the treatment of cardiovascular disease (CVD). Initially, the cytotoxic effects of LAE on human umbilical vein endothelial cells (HUVECs) were assessed, revealing no toxicity within concentrations up to 5 µg/mL. This suggests that LAE could serve as a safe raw material for the development of health supplements and drugs aimed at promoting cardiovascular well-being. Furthermore, the study found that LAE extract demonstrated anti-inflammatory properties in HUVECs by modulating the PI3K/Akt and MAPK signaling pathways. These findings are particularly significant as inflammation plays a crucial role in the progression of CVD. Moreover, LAE extract exhibited the ability to suppress the expression of adhesion molecules VCAM-1 and ICAM-1, which are pivotal in leukocyte migration to inflamed blood vessels observed in various pathological conditions. In conjunction with the investigation on therapeutic potential, the study also established an optimal HPLC-PDA-ESI-MS/MS method to identify and confirm the chemical constituents present in 24 samples collected from distinct regions in South Korea. Tentative identification revealed the presence of 14 saponins and nine phenolic compounds, while further analysis using PCA and PLS-DA allowed for the differentiation of samples based on their geographical origins. Notably, specific compounds such as chlorogenic acid, isochlorogenic acid A, and quercitrin emerged as marker compounds responsible for distinguishing samples from different regions. Overall, by unraveling its endothelial protective activity and identifying key chemical constituents, this research not only offers valuable insights for the development of novel treatments but also underscores the importance of utilizing and preserving natural resources efficiently.

Purification, characterization and bioactivities of a 4-O-methylglucuronoxylan from Aralia echinocaulis.

The discovery of active constituents from food plants is an important area of research in pharmaceutical sciences. Aralia echinocaulis is a medicinal food plant that is mainly used to prevent or treat rheumatoid arthritis in China. This paper reported the isolation, purification and bioactivity of a polysaccharide (HSM-1-1) from A. echinocaulis. Its structural features were analyzed according to the molecular weight distribution, monosaccharide composition, gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectra. The results indicated that HSM-1-1 was a new 4-O-methylglucuronoxylan mainly composed of xylan and 4-O-methyl glucuronic acid with the molecular weight of 1.6 × 104 Da. Furthermore, the antitumor and anti-inflammatory activities of HSM-1-1 in vitro were investigated, and the results showed that HSM-1-1 had potent proliferation inhibition activity on colon cancer cell SW480 with an inhibition rate of 17.57 ± 1.03 % at a concentration of 600 µg/mL, as measured via MTS methods. To our knowledge, this is the first report of a polysaccharide structure obtained from A. echinocaulis and its bioactivities, and its potential as an adjuvant natural product with antitumor effects is shown.

Saponin of Aralia taibaiensis promotes angiogenesis through VEGF/VEGFR2 signaling pathway in cerebral ischemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia taibaiensis is known for its ability to promote blood circulation and dispel blood stasis, activate meridians and remove arthralgia. The saponins of Aralia taibaiensis (sAT) are the main active components that are often used to treat cardiovascular and cerebrovascular diseases. However, it has not been reported whether sAT can improve ischemic stroke (IS) by promoting angiogenesis. AIM OF THE STUDY: In this study, we investigated the potential of sAT to promote post-ischemic angiogenesis in mice and determined the underlying mechanism through in vitro experiments. METHODS: To establish the middle cerebral artery occlusion (MCAO) mice model in vivo. First of all, we examined the neurological function, brain infarct volume, and degree of brain swelling in MCAO mice. We also observed pathological changes in brain tissue, ultrastructural changes in blood vessels and neurons, and the degree of vascular neovascularization. Additionally, we established the oxygen-glucose deprivation/reoxygenation (OGD/R) -human umbilical vein endothelial cells (HUVECs) model in vitro to detect the survival, proliferation, migration and tube formation of OGD/R HUVECs. Finally, we verified the regulatory mechanism of Src and PLCγ1 siRNA on sAT promoting angiogenesis by cell transfection technique. RESULTS: In the cerebral ischemia-reperfusion mice, sAT distinctly improved the cerebral infarct volume, brain swelling degree, neurological dysfunction, and brain histopathological morphology due to cerebral ischemia/reperfusion injury. It also increased the double positive expression of BrdU and CD31 in brain tissue, promoted the release of VEGF and NO and decreased the release of NSE and LDH. In the OGD/R HUVECs, sAT significantly improved cell survival, proliferation, migration and tube formation, promoted the release of VEGF and NO, and increased the expression of VEGF, VEGFR2, PLCγ1, ERK1/2, Src and eNOS. Surprisingly, the effect of sAT on angiogenesis was inhibited by Src siRNA and PLCγ1 siRNA in OGD/R HUVECs. CONCLUSION: The results proved that sAT promotes angiogenesis in cerebral ischemia-reperfusion mice and its mechanism is to regulate VEGF/VEGFR2 and then regulate Src/eNOS and PLCγ1/ERK1/2.

Ultrasound-Assisted Extraction of Total Saponins from Aralia taibaiensis: Process Optimization, Phytochemical Characterization, and Mechanism of α-Glucosidase Inhibition.

PURPOSE: Aralia taibaiensis, a medicinal food plant, and total saponins from its root bark extract inhibit α-glucosidase activity, which is associated with type 2 diabetes; however, the inhibitory mechanism is unknown. Furthermore, a green extraction technique superior to conventional hot reflux extraction (HRE) is needed for the rapid and easy extraction of A. taibaiensis total saponins (TSAT) to exploit and utilize this resource. Our aim was to develop a green extraction method for obtaining TSAT and to investigate the mechanism by which TSAT inhibits α-glucosidase. MATERIALS AND METHODS: In this study, the ultrasound-assisted extraction (UAE) process was optimized using a Box-Behnken design, and the extraction mechanism was investigated using scanning electron microscopy (SEM). High-performance liquid chromatography (HPLC) was used for qualitative and quantitative analyses of TSAT. In vitro glycosylation assays, enzyme kinetics, fluorescence spectroscopy measurements, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques were used to investigate the mechanism by which the A. taibaiensis active ingredients inhibit α-glucosidase. RESULTS: The optimal parameters for the extraction yield were obtained as an ethanol concentration of 73%, ultrasound time of 34 min, ultrasound temperature of 61 °C and solid-liquid ratio of 16 g/mL, which were better than HRE. The SEM analysis showed that UAE effectively disrupted plant cells, thus increasing the TSAT yield. In vitro α-glucosidase inhibition experiments showed that both TSAT and its active ingredient, araloside A, inhibited α-glucosidase activity by binding to α-glucosidase, thereby changing the conformation and microenvironment of α-glucosidase to subsequently inhibit enzyme activity. CONCLUSION: The optimal extraction conditions identified here established a basis for future scale-up of ultrasound extraction parameters with the potential for obtaining maximum yields. In vitro enzyme inhibition experiments investigated the mechanism of the TSAT interaction with α-glucosidase and further explored whether araloside A may be the main contributor to the good inhibition of α-glucosidase activity by TSAT.

Traditional uses, phytochemistry, pharmacology, toxicity and quality control of medicinal genus Aralia: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia, which belongs to Araliaceae family, is mainly distributed in Asia, such as China, Japan and South Korea. It has a long medicinal history and is widely used in the treatment of various diseases, such as hepatitis, rheumatoid arthritis, bruises, lumps and carbuncles. AIM OF THE STUDY: The purpose of this review is to systematically evaluate the traditional uses, phytochemistry, pharmacology, toxicity and quality control of main medicinal plants of Aralia, discusses the application of ethnic medicine, modern scientific research and the relationship between them, and put forward some suggestions to promote the further development and utilization of Aralia. MATERIALS AND METHODS: The relevant information on Aralia was collected through electronic databases (PubMed, Web of Science, Science Direct, Springer, CNKI and Wanfang), Chinese herbal classics, Ph.D. and M.Sc. dissertations, Chinese Pharmacopoeia. Plant names were verified by "The Plant List" (http://www.theplantlist.org). The literature cited in this review can be traced back to 1878 to 2021. RESULTS: More than 290 chemical constituents have been isolated from the genus Aralia, including triterpenoid saponins, terpenoids, organic acids, flavonoids, polyacetylenes, phenylpropanoids and other constituents. Pharmacological studies have shown that the extracts and compounds of Aralia have a wide range of pharmacological activities, including anti-inflammation, analgesic, anti-tumor, liver protection, protection of cardiovascular and nervous system, regulating substance metabolism, antibacterial, antiviral and antioxidation. CONCLUSIONS: The genus Aralia is not only an excellent traditional herbal medicine, but also a source of bioactive molecules with good application prospects. However, the structure-activity relationship, in vivo activity and action mechanism of its bioactive components need to be further studied. In addition, more toxicological and quality control studies are essential to evaluate the efficacy and safety of Aralia as medicine.

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma.

Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.

Phenolic Extract from Aralia nudicaulis L. Rhizomes Inhibits Cellular Oxidative Stresses.

UV-B and IR-A radiation are important inducers of biological changes in skin involving ROS generation. The overloading of antioxidant defense mechanisms by ROS production could lead to photoaging and photocarcinogenesis processes. Various traditional usages are reported for Aralia nudicaulis L. extracts, including treatment of dermatological disorders. Antioxidant and anti-inflammatory properties have already been reported for other Aralia species possibly due to the presence of phenolic compounds. However, the phenolic composition and the potential activity of A. nudicaulis rhizomes extract against oxidative stress and UV/IR damages have not been investigated. The main aims of this study were to prepare a fraction enriched in phenolic compounds (FEPC) from A. nudicaulis rhizomes, to identify its major phenolic compounds and to assess its potential for protective effects against oxidative stress induced by UV-B, IR-A or inflammation. A quantitative LC-MS study of FEPC shows that chlorogenic, caffeic and protocatechuic acids are the main phenolic compounds present, with concentrations of 15.6%, 15.3% and 4.8% of the total composition, respectively. With a validated analytical method, those compounds were quantified over different stages of the growing period. As for biological potential, first this extract demonstrates antioxidant and anti-inflammatory activities. Furthermore, ROS generation induced by IR-A and UV-B were strongly inhibited by A. nudicaulis extract, suggesting that Aralia nudicaulis L. rhizome extract could protect dermal cells against oxidative stress induced by UV-B and IR-A.

Ultrafiltration isolation, structures and anti-tumor potentials of two arabinose- and galactose-rich pectins from leaves of Aralia elata.

Two novel arabinose- and galactose-rich pectic polysaccharides, AELP-B5 (Mw, 4.25 × 104 g/mol) and B6 (Mw, 1.56 × 104 g/mol), were rapidly obtained from the leaves of Aralia elata (Miq.) Seem. with anion resin and sequenced ultrafiltration membrane columns. The structural backbone and branched chains of AELP-B5 and B6 were preliminarily elucidated by mild acid hydrolysis with HILIC-ESI--MS/MS. The planar structures and spatial configurations were further identified using UPLC-QDa and GC-MS for compositions, Smith degradation and methylation analysis, FT-IR, NMR (1H/13C, DEPT, HSQC, HMBC, COSY, NOESY and TOCSY) and SEC-MALLS-RID. (1) AELP-B5 possessed →4GalA1→ as smooth regions (HG) and a repeating disaccharide moiety of →4GalA1→2Rha1→ as hairy regions (RG-I) with a 1:5 molar ratio, whereas AELP-B6 had a distinguishing 1:1 molar ratio between the HG and RG-I; (2) complex side chains were constituted of T-α-Araf, 1,3-α-Araf, 1,5-α-Araf, T-ß-Galp, 1,3-ß-Galp, 1,4-ß-Galp, 1,6-ß-Galp, 1,3,4-ß-Galp and 1,3,4,6-ß-Galp connected at C-4 of the rhamnosyl units in RG-I of AELP-B5 and B6; and (3) both possessed highly branched and compact coil conformations. The CCK-8 assay illustrated that AELP-B6 possessed higher cytotoxicity against HepG2 and HT-29 than that of AELP-B5. Surface plasmon resonance showed the binding affinity of AELP-B6 to galectin-3 (6.488 × 10-5 M) was about 10 times stronger than that of AELP-B5 (4.588 × 10-4 M). The above findings provide a molecular structure and bioactivity basis for future potential applications of AELP in the food and medical industries.

A Review on a Medicinal and Edible Plant: Aralia elata (Miq.) Seem.

Aralia elata (Miq.) Seem. (Araliaceae), which is the key point of this review, is a precious wild vegetable that has served in the treatment of diabetes and rheumatoid arthritis in traditional folk medicine in East Asia (China, Japan, Korea, Russia). This review aims to overview the results of the current research related to Aralia elata (Miq.) Seem., with particular emphasis on chemical composition and biological activity. The existing research has been searched and summarized through the database, and it has been found that it has a certain therapeutic effecta on a variety of chronic diseases such as: malignant tumors, cardio-cerebrovascular disease, diabetes, and its complications, etc. Additionally, it is loved by people in East Asia due to its rich taste as a wild vegetable. In conclusion, it offers the possibility of developing innovative pharmacological drugs as well as healthy food. Thus, it is critical to prove its validity and clarify the exact action mechanisms that promote it as a pharmacological drug. This review is expected to provide direction for future research.

The evaluation of anti-breast cancer activity and safety pharmacology of the ethanol extract of Aralia elata Seem. leaves.

Aralia elata Seem. is a traditional folk Chinese medicinal plant and its leaves have been used to treat many diseases. We aimed to evaluate the anti-breast cancer activity and safety pharmacology of the ethanol extract of A. elata Seem. leaves (ELE). Cytotoxicity was evaluated on human tumor cell lines by MTT assay in vitro. A tumor bearing-nude mice model was used to assess antitumor activity in vivo. Cell apoptosis was determined by Hoechst 33258 staining, flow cytometry and TUNEL staining. The protein levels were determined by western-blotting and immunohistochemical staining. In safety evaluation, ICR mice and beagle dogs were orally administered ELE at different doses to determine its adverse effects on the central nervous system and cardiorespiratory system. ELE significantly inhibited tumor growth and induced cell apoptosis in MCF-7 cells in vitro and in vivo. The protein levels including caspase-3, caspase-9, bax, bcl-2, PARP, and cytochrome c were significantly changed. For the central nervous system, no treatment-related changes in behavior, motor activity or coordination were observed in mice. For the cardiorespiratory system, no significant differences in cardiorespiratory parameters including heart rate, PR interval, RR interval, P wave duration, QRS duration, QTcF interval, respiratory frequency, tidal volume, body temperature, and blood pressure were observed in beagle dogs between the ELE treatment and control group. In conclusion, ELE possessed anti-breast cancer activity by activating a mitochondrial-mediated apoptotic pathway with high biological safety in animals, which indicates it could be a potential therapeutic agent for treating human breast cancer in the future.

Polysaccharides and glycosides from Aralia echinocaulis protect rats from arthritis by modulating the gut microbiota composition.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia echinocaulis has been used in traditional medicines in China and exhibits good effects on rheumatoid arthritis (RA). AIM OF THE STUDY: Aralia echinocaulis is rich in polysaccharides and glycosides. This study aims to explore the effect of total polysaccharide and glycoside (TPG) from A. echinocaulis on an RA rat model and the role of alterations in gut microbes mediated by TPG. MATERIALS AND METHODS: In this study, a collagen-induced arthritis (CIA) rat model was constructed and used to evaluate the effects of TPG in vivo. 16S rRNA sequencing was used to detect the changes in the gut microbiota. A cooccurrence analysis was conducted by calculating Spearman's rank correlations. Microbial functions were predicted using PICRUSt with the KEGG and COG databases. RESULTS: The results showed that TPG from A. echinocaulis could inhibit arthritis, reduce serum IL-1ß and TNF-α levels, and improve synovial pathology in the RA rat model but failed to produce the same results in a pseudoaseptic RA rat model. 16S rRNA sequencing verified that TPG could modulate the gut microbiota community structure of RA rats. The cooccurrence analysis found 19 out of the 50 most abundant genera in a cooccurrence network, of which 16 showed a positive correlation and 3 showed a negative correlation. KEGG pathway and COG function analyses found that TPG-induced alterations in the gut microbiota might be correlated with the circulatory system, excretory system, metabolic diseases, signaling molecules and interactions, coenzyme transport and metabolism, and nucleotide transport and metabolism. CONCLUSIONS: TPG from A. echinocaulis had significant effects on the RA rat model, which are related to the modulation of the gut microbiota. These results are useful to better understanding the mechanisms of TPG in RA.

A high methyl ester pectin polysaccharide from the root bark of Aralia elata: Structural identification and biological activity.

In this study, a high methyl ester pectin polysaccharide, AER-A3 (Mw, 1.12 × 105 g/mol; O-methyl ester groups (wt%), 3.81%), was isolated and purified from the root bark of Aralia elata by ion exchange and gel-filtration chromatography. Its planar structure was investigated in combination with UPLC-ESI+-MS, FT-IR, HILIC-UPLC-ESI--HCD-MS/MS, GC-MS and NMR techniques. The main chain of AER-A3 was unambiguously determined to be smooth region and hairy region with a chain length ratio of 1:1, characterized by occurrence of (1 â†’ 2)-α-Rhap, (1 â†’ 2,3)-α-Rhap, (1 â†’ 2,4)-α-Rhap, (1 â†’ 2,3,4)-α-Rhap, and (1 â†’ 4)-α-GalpA, whereas the branched chain included T-α-Rhap, T-α-Araf, (1 â†’ 5)-α-Araf, (1 â†’ 3,5)-α-Araf, T-ß-Galp, (1 â†’ 3)-ß-Galp, (1 â†’ 3,4,6)-ß-Galp, (1 â†’ 4)-Glcp, (1 â†’ 3)-Glcp, and (1 â†’ 3)-Manp. Meanwhile, SEC-MALLS-RID, CD and Congo red assays showed that AER-A3 had no helical conformations but existed as a globular shape with branching. In addition, AER-A3 had good scavenging activities against DPPH, hydroxyl, and superoxide radicals. Anti-tumor assay investigated the effects of AER-A3 on human A549 and HepG2 cancer cell lines in vitro. These results provided a scientific basis for the use of the polysaccharides in A. elata root barks in pharmaceuticals.

Optimization of Extraction Conditions of Continentalic and Kaurenoic Acids from Aralia continentalis by HPLC/UV and Their Validation.

Aralia continentalis (AC) is a perennial herb that has long been used as a traditional medicine for many diseases. Continentalic acid (CA) and kaurenoic acid (KA) are major diterpenoids in AC, which are known to exert various pharmacological activities. This study focuses on the optimization of the extraction of CA and KA from dried AC roots by evaluating the influence of different extraction conditions on their yield. Five extraction variables were examined: sample weight, solvent concentration, extraction time, solid matrix and the number of repeated extractions. The analytical method used in this study was also validated in terms of linearity, limit of detection, limit of quantification, precision and accuracy. The CA and KA yields were measured by high-performance liquid chromatography analysis. The results show that CA and KA were the highest when unpulverized samples (3.75 g) were subjected to a single extraction for 5 h using 50% ethanol (300 mL) as the solvent. These conditions are proposed for the optimization of the extraction of CA and KA from AC.

SIRT1-Mediated Protective Effect of Aralia elata (Miq.) Seem against High-Glucose-Induced Senescence in Human Umbilical Vein Endothelial Cells.

Aralia elata (Miq.) Seem (AS) is widely been for treating many diseases, enhancing energy, and boosting immunity; however, its protective effects against high-glucose (HG)-triggered endothelial dysfunction and the potential underlying mechanisms have not been investigated. In this study, we determined the effect of AS on senescence in human umbilical vein endothelial cells (HUVECs) and elucidated the mechanisms underlying its anti-aging effects. The senescence model of endothelial cells (ECs) was established by culturing HUVECs in media containing HG (30 mM). We found that the proportion of senescent (senescence-associated ß-galactosidase+) cells in the HG group was significantly higher than that in the control group; however, this increase was suppressed by AS treatment. Moreover, cell cycle analysis revealed that AS (20 µg/mL) significantly recovered HG-induced cell cycle arrest in ECs, and Western blot revealed that AS prevented HG-induced decreases in silent information regulator 1 (SIRT1) level and endothelial nitric oxide synthase (eNOS) phosphorylation. These results show that AS delayed HG-induced senescence in ECs by modulation of the SIRT1/5' AMP-activated protein kinase and AKT/eNOS pathways.

Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo.

The aim of this study was to identify the active compound responsible for the pharmacological activities of Manchurian spikenard (Aralia continentalis Kitag.). Interleukin (IL)-1ß-stimulated human chondrocytes and monoiodoacetate (MIA)-induced osteoarthritic rats were treated with the 50% ethanolic extract of spikenard or its major components, such as continentalic acid (ent-pimara-8(14),15-diene-19-oic acid) and kaurenoic acid (ent-kaura-16-en-19-oic acid). The spikenard extract significantly inhibited IL-1ß-stimulated production of IL-6, IL-8, metalloproteinase (MMP)-1, MMP-13, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and prostaglandin(PG)E2 in a dose-dependent manner but not MMP-3 production. The extract also inhibited the IL-1ß-induced translocation of NF-κB/p65 into the nucleus and dose-dependent phosphorylation levels of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase. Continentalic acid exhibited significant anti-arthritic activity corresponding exactly to that of the extract containing an equivalent amount of continentalic acid. On the other hand, kaurenoic acid exhibited a compatible activity at about a 10-times higher molar concentration than that of continentalic acid. In vitro anti-arthritic activities of the spikenard extract and continentalic acid were also confirmed in MIA-induced osteoarthritic rats. The 50% ethanolic extract of Manchurian spikenard exhibited promising anti-arthritic activities in the in vitro and in vivo osteoarthritis models, and continentalic acid, not kaurenoic acid, was most probably responsible for those activities.

Chronic Alcohol Exposure Induced Neuroapoptosis: Diminishing Effect of Ethyl Acetate Fraction from Aralia elata.

An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neurodegeneration in chronic alcohol-induced mice. The neuroprotective effect was examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assays. As a result, AEEF reduced alcohol-induced cytotoxicity and oxidative stress. To evaluate the improvement of learning, memory ability, and spatial cognition, Y-maze, passive avoidance, and Morris water maze tests were conducted. The AEEF groups showed an alleviation of the decrease in cognitive function in alcohol-treated mice. Then, malondialdehyde (MDA) levels and the superoxide dismutase (SOD) content were measured to evaluate the antioxidant effect of AEEF in the brain tissue. Treatment with AEEF showed a considerable ameliorating effect on biomarkers such as SOD and MDA content in alcohol-induced mice. To assess the cerebral cholinergic system involved in neuronal signaling, acetylcholinesterase (AChE) activity and acetylcholine (ACh) content were measured. The AEEF groups showed increased ACh levels and decreased AChE activities. In addition, AEEF prevented alcohol-induced neuronal apoptosis via improvement of mitochondrial activity, including reactive oxygen species levels, mitochondrial membrane potential, and adenosine triphosphate content. AEEF inhibited apoptotic signals by regulating phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated protein kinase B (p-Akt), Bcl-2-associated X protein (BAX), and phosphorylated Tau (p-Tau). Finally, the bioactive compounds of AEEF were identified as caffeoylquinic acid (CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and chikusetsusaponin IVa using the UPLC-Q-TOF-MS system.

American Civil War plant medicines inhibit growth, biofilm formation, and quorum sensing by multidrug-resistant bacteria.

A shortage of conventional medicine during the American Civil War (1861-1865) spurred Confederate physicians to use preparations of native plants as medicines. In 1863, botanist Francis Porcher compiled a book of medicinal plants native to the southern United States, including plants used in Native American traditional medicine. In this study, we consulted Porcher's book and collected samples from three species that were indicated for the formulation of antiseptics: Liriodendron tulipifera, Aralia spinosa, and Quercus alba. Extracts of these species were tested for the ability to inhibit growth in three species of multidrug-resistant pathogenic bacteria associated with wound infections: Staphylococcus aureus, Klebsiella pneumoniae, and Acinetobacter baumannii. Extracts were also tested for biofilm and quorum sensing inhibition against S. aureus. Q. alba extracts inhibited growth in all three species of bacteria (IC50 64, 32, and 32 µg/mL, respectively), and inhibited biofilm formation (IC50 1 µg/mL) in S. aureus. L. tulipifera extracts inhibited biofilm formation (IC50 32 µg/mL) in S. aureus. A. spinosa extracts inhibited biofilm formation (IC50 2 µg/mL) and quorum sensing (IC50 8 µg/mL) in S. aureus. These results support that this selection of plants exhibited some antiseptic properties in the prevention and management of wound infections during the conflict.

Apoptotic effect of Aralia echinocaulis extract on fibroblast-like synoviocytes in rats with adjuvant-induced arthritis via inhibiting the Akt/Hif-1α signaling pathway in vitro.

Aralia echinocaulis is used for the treatment of rheumatoid arthritis by Tujia Minority in China. A previous study demonstrated that A. echinocaulis had a significant anti-arthritic effect on adjuvant arthritis (AA) rats in vivo. However, it remains unclear whether A. echinocaulis can induce the apoptosis of fibroblast-like synoviocytes (FLS) from AA rats and the underlying mechanism is unknown. In this paper, CCK-8 assay, Hoechst staining and flow cytometry were used to evaluate the apoptotic effect of an A. echinocaulis ethanol extract (AEE) on AA FLS. Western blotting analysis was performed to measure the protein expression levels of Bcl-2, Bax, cleaved caspase-3, Akt, p-Akt, and Hif-1α. The results revealed that AEE could inhibit FLS proliferation in a dose and time-dependent manner. After treatment with AEE, AA FLS displayed the classical apoptotic morphology, and the apoptosis rates were significantly increased. Furthermore, we found that AEE increased the protein levels of Bax, cleaved caspase 3, and decreased the protein levels of Bcl-2, Hif-1α and p-Akt, without affecting total Akt levels. Collectively, these results suggested that the apoptosis inducing effect of AEE on AA FLS was related to the regulation of the expression of apoptosis-related proteins and the inhibition of the Akt/Hif-1α signaling pathway.

The ethanolic extract of Aralia continentalis ameliorates cognitive deficits via modifications of BDNF expression and anti-inflammatory effects in a rat model of post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a disease associated with that the experience of traumatic stress. The traumatic experience results in the development of a prolonged stress response that causes impaired memory function and increased inflammation in the hippocampus. Currently, antidepressants are the only approved therapy for PTSD. However, the efficacy of antidepressants in the treatment of PTSD is marginal. The ethanol extract of Aralia continentalis (AC) is traditionally used in oriental medicine, and has been showed to possess pharmacological properties, including anti-inflammatory, anti-cancer, anti-atherosclerotic, and anti-diabetic effects. Nevertheless, the effects of AC on cognitive memory and its mechanism of action in PTSD remain unclear. Given the necessity of further treatment options for PTSD, we investigated the effect of AC on the spatial cognitive impairment caused by single prolonged stress (SPS) in a rat model of PTSD. METHODS: Male rats were treated with various intraperitoneal (i.p.) doses of AC for 21 consecutive days after inducing chronic stress with the SPS procedure. RESULTS: Cognitive impairment caused by SPS were inhibited after treatment with 100 mg/kg AC, as measured by the Morris water maze test and an object recognition test. Additionally, AC treatment significantly alleviated memory-related decreases in brain-derived neurotrophic factor (BDNF) mRNA and protein levels in the hippocampus. Our results suggest that AC significantly inhibited the cognitive deficits caused by SPS via increased expression of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6, in the rat brain. CONCLUSIONS: AC reversed the behavioral impairments and inflammation triggered by SPS-derived traumatic stress and should be further evaluated as a potential therapeutic drug for PTSD.