Potential Wound Healing and Anti-Melanogenic Activities in Skin Cells of Aralia elata (Miq.) Seem. Flower Essential Oil and Its Chemical Composition.

Aralia elata (Miq.) Seem. (AES; family Araliaceae) is a medicinal plant and has been reported to have various bioactivities, including anticancer and hepatotoxicity protective activities. However, no studies have investigated the biological activities of AES or its extracts on skin. To address this, we aimed to explore the effect of AES-flower-derived absolute-type essential oil (AESFEO) on skin-related biological activities, especially skin wound healing and whitening-related responses in skin cells (human-derived keratinocytes [HaCaT cells] and melanocytes [B16BL6 cells]) and to identify the components of AESFEO. Cell biological activities were analyzed using WST and BrdU incorporation assays, ELISA, or by immunoblotting. In HaCaT cells, AESFEO promoted proliferation, type IV collagen production, and enhanced the phosphorylations of Erk1/2, p38 MAPK, JNK, and Akt. In B16BL6 cells, AESFEO reduced serum-induced proliferation, α-MSH-stimulated increases in melanin synthesis and tyrosinase activity, and α-MSH-induced increases in MITF, tyrosinase, TRP-1, and TRP-2 expressions. In addition, AESFEO inhibited the phosphorylation of Erk1/2, p38 MAPK, and JNK in α-MSH-stimulated B16BL6 cells. Eighteen compounds were identified in AESFEO by GC/MS. These results suggest that AESFEO has beneficial effects on keratinocyte activities related to skin wound healing and melanocyte activities related to inhibition of skin pigmentation. AESFEO may serve as a useful natural substance for developing agents that facilitate skin wound healing and inhibit melanogenesis.

A mini-review of isolation, purification, structural characteristics and bioactivities of polysaccharides from Aralia elata (Miq.) Seem.

In recent years, the isolation, purification, structural characterization of plant polysaccharides from natural resources have arrested widespread attention. Aralia elata (Miq.) Seem (A. elata) belongs to the Aralia genus of the Araliaceae family, which is one of the most popular edible mountain vegetables in East Asia. A. elata has been widely distributed in China, particularly in Liaoning, Jilin, and Heilongjiang provinces in northeast China, in which it has been used as a traditional herbal medicine for thousands of years to treat various diseases, such as hepatitis and rheumatoid arthritis. A. elata polysaccharides (AEPs) are one of the major active ingredients of A. elata, the monosaccharide composition of which consist primarily of Gal, Glc, Man, Ara, and Rha, with molecular weights ranging from 1.56 × 104 Da to 1.12 × 105 Da. AEPs have attracted worldwide attention owing to their various biological activities, including antioxidant activity, antitumor activity and hepatoprotection. The present review aims to comprehensively summarize the research advances on the polysaccharides isolated from A. elata, including the extraction, separation, physical-chemical properties, structural characteristics, and bioactivities over the past few decades. This review would establish a solid foundation for further development and application in the field of AEPs.

Reversible ON- and OFF-switch receptors Clec4G and Rab1A reveal the hormetic effects of a pectin polysaccharide in Aralia elata (Miq.) Seem.

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.

Functional identification of AeHMGR gene involved in regulation of saponin biosynthesis in Aralia elata.

Aralia elata (Miq.) Seem, a significant tree species in the Araliaceae family, has medicinal and edible properties. Saponins are the primary active components of A. elata. The 3-hydroxy-3-methylglutaryl- CoA reductase (HMGR) is the initial rate-limiting enzyme of the major metabolic pathway of saponins in A. elata. In this study, the AeHMGR gene was identified through screening of transcriptome data. Through the qRT-PCR analysis, it was determined that the expression level of AeHMGR gene is highest in the somatic embryo and stem of A. elata. Heterologous transformation in tobacco revealed that ectopic expression of the AeHMGR gene leads to a significant reduction in the expression levels of the NtSS, NtFPS, and NtSE genes in transgenic tobacco lines, with a minimum expression level of 0.24 times that of the wild type. In the overexpressed callus lines of A. elata, the expression levels of the AeFPS, AeSE, AeSS, and Aeß-AS genes were also significantly lower compared to the wild type, with a minimum expression level of approximately 0.3 times that of the wild type. Interestingly, the overexpression of the AeHMGR gene in A. elata somatic embryos led to a substantial decrease in the expression levels of AeFPS and AeSS, while the expression levels of AeSE and Aeß-AS increased. Among the transgenic somatic embryo strain lines, line 7 exhibited the highest expression levels of AeSE and Aeß-AS, with fold increases of 11.51 and 9.38, respectively, compared with that of the wild-type. Additionally, a high-performance liquid chromatography method was established to detect five individual saponins in transgenic A. elata. The total saponin content in line 7 somatic embryos was 1.14 times higher than that of wild-type materials, but only 0.30 times that of wild-type cultivated leaves. Moreover, the content of oleanolic acid saponin in line 7 was 1.35 times higher than that of wild-type cultivated leaves. These indicate that HMGR can affect triterpene biosynthesis.

Research progress in pharmacological effects of Aralia elata. / è¾½ä¸œæ¥¤æœ¨è¯ç†ä½œç”¨ç ”ç©¶è¿›å±•.

The traditional Chinese medicine Aralia elata (Miq.) Seem., also known as Aralia mandshurica, has the effect of "tonifying Qi and calming the mind, strengthening the essence and tonifying the kidneys, and dispelling wind and invigorating blood circulation". It is used in the treatment of neurasthenia, Yang deficiency and Qi deficiency, kidney Qi deficiency, spleen Yang deficiency, water-dampness stagnation, thirst, and bruises. Aralia elata saponins are the main components for the pharmacological effects. From the perspective of modern pharmacological science, Aralia elata has a wide range of effects, including anti-myocardial ischaemia and alleviation of secondary myocardium ischemic reperfusion injury by regulating ionic homeostasis, anti-tumor activity by inhibiting proliferation, promoting apoptosis and enhancing immunity, hypoglycemia and lipid lowering effects by regulating glucose and lipid metabolism, and hepato-protective, neuroprotective, anti-inflammatory/analgesic effects. The studies on pharmacological mechanisms of Aralia elata will be conducive to its development and application in the future. This article reviews the research progress of Aralia elata domestically and internationally in the last two decades and proposes new directions for further research.

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.

Total saponins of Aralia elata (Miq.) Seem. alleviate myocardial ischemia-reperfusion injury by promoting NLRP3-inflammasome inactivation via PI3K/Akt signaling.

Total saponins of Aralia elata (Miq.) Seem. (TSAE) have been shown to play a significant role in cardiovascular protection, anti-tumor, liver protection, anti-oxidant stress, and anti-inflammation. However, the specific mechanisms of TSAE in myocardial ischemia-reperfusion injury (MIRI) remain largely elusive. Hearts from male Wistar rats were used to establish the isolated heart MIRI model. Using a multichannel physiological recorder, the whole course heart rate (HR), left ventricular development pressure (LVDP), and maximum rise/decrease rate of left ventricular pressure (±dp/dtmax ) were recorded. 2,3,5-triphenyl-2H-tetrazolium chloride staining observed the infarct area, while hematoxylin & eosin staining detected pathological changes in myocardial tissue. Creatine kinase, lactate dehydrogenase, total superoxide dismutase, and malondialdehyde concentrations were determined by enzyme-linked immunosorbent assay. Immunohistochemistry, quantitative PCR, and western blot assay were used to assess the amounts of IL-18 and IL-1ß, NLR family protein (NLRP3) inflammasome- and apoptosis-related proteins, respectively. Treatment with TSAE or MCC950 (NLRP3-specific inhibitor) significantly reduced the myocardial infarction area, alleviated pathological changes in myocardial tissues, enhanced LVDP and ±dp/dtmax levels, prevented myocardial oxidative damage, and inhibited NLRP3 inflammasome formation. In addition, TSAE enhanced Akt and GSK3ß phosphorylation, and LY29004 co-reperfusion markedly diminished the protective role of TSAE reperfusion on cardiac function, oxidative damage, and inflammatory responses. Collectively, TSAE treatment exhibited a protective effect on I/R-triggered inflammatory responses, cell necrosis, and oxidative stress injury by stimulating PI3K/Akt signaling-mediated NLRP3 inflammasome inhibition.

Research progress in pharmacological effects of Aralia elata / 浙江大学学报·医学版

The traditional Chinese medicine Aralia elata (Miq.) Seem., also known as Aralia mandshurica, has the effect of "tonifying Qi and calming the mind, strengthening the essence and tonifying the kidneys, and dispelling wind and invigorating blood circulation". It is used in the treatment of neurasthenia, Yang deficiency and Qi deficiency, kidney Qi deficiency, spleen Yang deficiency, water-dampness stagnation, thirst, and bruises. Aralia elata saponins are the main components for the pharmacological effects. From the perspective of modern pharmacological science, Aralia elata has a wide range of effects, including anti-myocardial ischaemia and alleviation of secondary myocardium ischemic reperfusion injury by regulating ionic homeostasis, anti-tumor activity by inhibiting proliferation, promoting apoptosis and enhancing immunity, hypoglycemia and lipid lowering effects by regulating glucose and lipid metabolism, and hepato-protective, neuroprotective, anti-inflammatory/analgesic effects. The studies on pharmacological mechanisms of Aralia elata will be conducive to its development and application in the future. This article reviews the research progress of Aralia elata domestically and internationally in the last two decades and proposes new directions for further research.

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.

Identification and analysis of CYP450 and UGT supergene family members from the transcriptome of Aralia elata (Miq.) seem reveal candidate genes for triterpenoid saponin biosynthesis.

BACKGROUND: Members of the cytochrome P450 (CYP450) and UDP-glycosyltransferase (UGT) gene superfamily have been shown to play essential roles in regulating secondary metabolite biosynthesis. However, the systematic identification of CYP450s and UGTs has not been reported in Aralia elata (Miq.) Seem, a highly valued medicinal plant. RESULTS: In the present study, we conducted the RNA-sequencing (RNA-seq) analysis of the leaves, stems, and roots of A. elata, yielding 66,713 total unigenes. Following annotation and KEGG pathway analysis, we were able to identify 64 unigenes related to triterpenoid skeleton biosynthesis, 254 CYP450s and 122 UGTs, respectively. A total of 150 CYP450s and 92 UGTs encoding > 300 amino acid proteins were utilized for phylogenetic and tissue-specific expression analyses. This allowed us to cluster 150 CYP450s into 9 clans and 40 families, and then these CYP450 proteins were further grouped into two primary branches: A-type (53%) and non-A-type (47%). A phylogenetic analysis of 92 UGTs and other plant UGTs led to clustering into 16 groups (A-P). We further assessed the expression patterns of these CYP450 and UGT genes across A. elata tissues, with 23 CYP450 and 16 UGT members being selected for qRT-PCR validation, respectively. From these data, we identified CYP716A295 and CYP716A296 as the candidate genes most likely to be associated with oleanolic acid synthesis, while CYP72A763 and CYP72A776 were identified as being the most likely to play roles in hederagenin biosynthesis. We also selected five unigenes as the best candidates for oleanolic acid 3-O-glucosyltransferase. Finally, we assessed the subcellular localization of three CYP450 proteins within Arabidopsis protoplasts, highlighting the fact that they localize to the endoplasmic reticulum. CONCLUSIONS: This study presents a systematic analysis of the CYP450 and UGT gene family in A. elata and provides a foundation for further functional characterization of these two multigene families.

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.

Protective Effects of Total Saponins of Aralia elata (Miq.) on Endothelial Cell Injury Induced by TNF-α via Modulation of the PI3K/Akt and NF-κB Signalling Pathways.

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of Aralia elata (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya Aralia chinensis L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process.

Cholesterol-lowering effect of Aralia elata (Miq.) Seem via the activation of SREBP-2 and the LDL receptor.

BACKGROUND: Hyperlipidemia causes arteriosclerosis, a risk factor for coronary heart disease. Prevention of hyperlipidemia by improving dietary habits has recently attracted attention. In this regard, we investigated whether Aralia elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and modulate the cellular signaling pathway. METHODS: To determine AE's cholesterol regulating mechanism, we measured cholesterol level, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol regulating-related gene expression in HepG2 cells and in high-fat diet (HFD)-induced mice using ELISA and RT-PCR assay. RESULTS: The AE extract reduced cholesterol levels and HMG-CoA reductase activity in hepatocellular carcinoma HepG2 cells. In addition, it also reduced the plasma cholesterol concentrations in HFD-induced mice. Furthermore, the AE extract increased the gene expression of the LDL-receptor (LDL-R); sterol-regulatory-element binding protein-2 (SREBP-2); ATP-binding cassette, sub-family A, member 1 (ABCA1); and scavenger receptor class B member 1 (SR-B1) in a dose-dependent manner. However, the AE extract did not affect the gene expression of acetyl-coenzyme A acetyltransferase (ACAT) in either the HepG2 cells or mice. CONCLUSION: We demonstrated that the AE extract activated genes related to cholesterol metabolism, such as SREBP-2 and LDL-R, which resulted in hypocholesterolemic activities.

Structural modification and biological evaluation of monomeric compounds from Aralia elata / 中草药

Objective: To modify the structure of natural monomeric compound based on oleanolic acid-3-O-β-D-glucuronide from medicinal plant Aralia elata and to evaluate the myocardial protection activity of the derivatives. Methods: Taking oleanolic acid or ursolic acid as material, the target compounds were prepared by five steps of reactions and evaluated for myocardial protection effects by H9c2 cells in vitro. Results: Ten derivatives F1-F10 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that all of the compounds had the different levels potency of myocardial protection effects in cells. In particular, compounds F3 showed the significant myocardial protection activity compared to lead compound. Conclusion: The new compounds F1-F10 which show the potential of biological activity in myocardial protection, have not been reported in any literature and deserved further research.

Determination and pharmacokinetic study of two triterpenoid saponins in rat plasma after oral administration of the extract of Aralia elata leaves by UHPLC-ESI-MS/MS.

Aralia elata (Miq.) Seems (A. elata) grow in Northeast China and the total saponins of A. elata is used to auxiliary treatment for the acute hepatitis, chronic hepatitis and the transaminase on the high side. Aralia-saponinV and Aralia-saponinVI are the major bioactive saponins in A. elata leaves. A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of Aralia-saponinV and Aralia-saponinVI indwelling the extract in rat plasma in this article. The sample pretreatment involved a one-step extraction of 0.2mL plasma with methanol. Shengmaxinside C was used as internal standard (I.S.). The separation was carried out on an Agilent SB-C18 column (1.8µm, 50mm×2.1mm) at 30°C with a mobile phase of acetonitrile-5mM ammonium acetate (90:10, v/v) at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for Aralia-saponinV, Aralia-saponinVI and I.S. were 1103.2/941.2, 1119.2/957.0 and 707.0/647.1, respectively. The current UHPLC-MS/MS assay method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability, and it was suitable for the pharmacokinetic studies of the two saponins after oral administration of extract of A. elata leaves. The lower limits of quantification were 5.70ng/mL for Aralia-saponinV and 6.15ng/mL for Aralia-saponinVI. Intra-day and inter-day precisions were less than 7.4% and the accuracy range was from 1.19% to 8.60%. The mean extraction recoveries of analytes and I.S. from rat plasma were all more than 89.5%. This paper described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of Aralia-saponinV and Aralia-saponinVI in rat plasma after oral administration of the extract of A. elata leaves, and investigated on their pharmacokinetic studies as well.