Botany, traditional usages, phytochemistry, pharmaceutical analysis, and pharmacology of Eleutherococcus nodiflorus (Dunn) S.Y.Hu: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus nodiflorus (Dunn) S.Y.Hu (Araliaceae), also called Eleutherococcus gracilistylus, Acanthopanax gracilistylus, and Xi-zhu-wu-jia (Wujiapi or Nan Wujiapi) in Chinese, is a widely used traditional Chinese herb with the effects of dispelling pathogenic wind and eliminating dampness, nourishing liver and kidney, diuresis and detumescence, promoting blood circulation for removing blood stasis, and strengthening the bones and tendons according to the theory of Traditional Chinese Medicine (TCM). It has been used as medicine for the treatment of paralysis, arthritis, rheumatism, lameness, body asthenia, fatigue, edema, beriberi, and liver diseases. Meanwhile, E. nodiflorus (EN, thereafter) has ginseng-like activities known as "ginseng-like herb". AIMS OF THE REVIEW: This review aims to present comprehensive information for the research progress of EN, including taxonomic position, botany, traditional usages, phytochemistry, pharmaceutical analysis, pharmacology and toxicology. Among them, phytochemical and pharmacological studies are mainly focused. MATERIALS AND METHODS: Relevant literature was acquired from scientific databases including Web of Science, PubMed, Google Scholar, Baidu Scholar, SciFinder and Chinese national knowledge infrastructure (CNKI). Monographs and Chinese pharmacopeia were also utilized as references. RESULTS: In the past decade, a great number of phytochemical and pharmaceutical analyses, as well as pharmacological studies on EN have been carried out. Several kinds of chemical compositions have been reported, including essential oil, sesquiterpenes, diterpenes, triterpenes, phenylpropanoids, lignans, caffeoyl quinic acids, flavonoids, steroids, fatty acids, ceramides as well as other compounds, among which, diterpenes and triterpenes were considered to be the most active components. The fingerprint chromatography, qualitative and quantitative analysis were used for the methods of quality control of EN. Considerable pharmacological experiments in vitro and in vivo have demonstrated that EN possessed hypoglycemic, anti-inflammatory, anticancer, anti-ageing, anti-fatigue, immunomodulatory, hepatoprotective, antioxidant, anti-AChE, anti-BuChE, anti-hyaluronidase, and antiobesity activities. CONCLUSIONS: As an important TCM, a large number of investigations have proved that EN and terpenoids isolated from EN have markedly therapeutic efficacy on diabetes, inflammation, and cancer disorders. These research findings provide modern scientific evidence for the traditional uses of EN. Moreover, more novel and active secondary metabolites from EN, as well as the in vivo and clinical in-depth tests are required in the future.

Acanthopanax henryi: Review of Botany, Phytochemistry and Pharmacology.

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Comprehensive HPTLC Fingerprinting for Quality Control of an Herbal Drug - The Case of Angelica gigas Root.

The quality of herbal drugs is usually controlled using several tests recommended in a monograph. HPTLC is the method of choice for identification in many pharmacopoeias. If combined with a suitable reference material for comparison, HPTLC can provide information beyond identification and thus may simplify quality control. This paper describes, as a proof of concept, how HPTLC can be applied to define specifications for an herbal reference material and to control the quality of an herbal drug according to these specifications. Based on multiple batches of cultivated Angelica gigas root, a specific HPTLC method for identification was optimized. This method can distinguish 27 related species. It also can detect the presence of mixtures of A. gigas with two other Angelica species traded as "Dang gui" and is suitable as well for quantitative assessment of samples in a test for minimum content of the sum of decursin and decursinol angelate. The new concept of "comprehensive HPTLC fingerprinting" is proposed: HPTLC fingerprints (images), which are used for identification, are converted into peak profiles and the intensities of selected zones are quantitatively compared to those of the corresponding zones of the reference material. Following a collaborative trial involving three laboratories in three countries, the method was applied to check the quality of further candidates for establishing an appropriate reference material. In conclusion, this case demonstrates that a single HPTLC analysis can provide information about identity, purity, and minimum content of markers of an herbal drug.

Lupane Triterpenes from the Leaves of Acanthopanax gracilistylus.

The phytochemical study on the leaves of Acanthopanax gracilistylus (Araliaceae) resulted in the discovery of a new lupane-triterpene compound, acangraciligenin S (1), and a new lupane-triterpene glycoside, acangraciliside S (2), as well as two known ones, 3α,11α-dihydroxy-lup-20(29)-en-23,28-dioic acid (3) and acankoreoside C (4). Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The chemical structures of the new compounds 1 and 2 were determined to be 1ß,3α-dihydroxy-lup-20(29)-en-23, 28-dioic acid and 1ß,3α-dihydroxy-lup-20(29)-en-23,28-dioic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl] ester, respectively. The anti-neuroinflammatory activity of the selective compounds, 1 and 3, were evaluated with lipopolysaccharide (LPS)-induced BV2 microglia. The tested compounds showed moderate inhibitory effect of nitric oxide (NO) production.

Inhibitory effects of lupane­type triterpenoid saponins from the leaves of Acanthopanax gracilistylus on lipopolysaccharide-induced TNF­α, IL­1ß and high­mobility group box 1 release in macrophages.

Acanthopanax gracilistylus (AGS) has long been used in traditional Chinese medicine for the treatment of various inflammatory diseases. 3­O­ß­D­glucopyranosyl 3α, 11α­dihydroxylup­20(29)­en­28­oic acid, acantrifoside A, acankoreoside D, acankoreoside B and acankoreoside A are major lupane­type triterpenoid saponins derived from AGS. In the present study, these five saponins were isolated from AGS by chromatography and their anti­inflammatory activities were investigated in lipopolysaccharide (LPS)­treated RAW264.7 macrophages. Cell viability was evaluated by MTT assay. Tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and NF­κB p65 were measured by ELISA. The gene expression levels of TNF­α and IL­1ß was detected by reverse­transcription polymerase chain reaction. And high­mobility group box 1 (HMGB1) were analyzed by western blotting. The results demonstrated that these five saponins significantly suppressed LPS­induced expression of TNF­α and IL­1ß at the mRNA and protein level in RAW264.7 cells. Further analysis revealed that acankoreoside A and acankoreoside B were able to reduce the secretion of HMGB1 and NF­κB activity induced by LPS in RAW264.7 macrophages. Taken together, these results suggested that the anti­inflammatory activity of AGS­derived saponins may be associated with the downregulation of TNF­α and IL­1ß, and the 'late­phase' proinflammatory cytokine HMGB1, via negative regulation of the NF­κB pathway in RAW264.7 cells.

Inhibitory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid on lipopolysaccharide-induced TNF-α, IL-1ß, and the high mobility group box 1 release in macrophages.

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.

Development of Chemical Fingerprints for Quality Control of Xiong Ma Tang and its Related Preparations by High-Performance Liquid Chromatography.

Xiong Ma Tang (XMT), one of the ancient herbal prescriptions, has been used in treatment of migraine disease. In this study, efficient high-performance liquid chromatographic fingerprints were developed for identification of 11 major marker components, named 1-(ß-D-ribofuranosyl)-1H-1,2,4-triazone, gastrodin, ligustrazine, 3,4-bihydroxy benzaldehyde, p-hydroxy benzaldehyde, p-hydroxybenzoic acid, benzoic acid, vanillin, ferulic acid, caffeic acid and senkyunolide I, respectively, in XMT and three related preparations. The analysis of 11 marker compounds was carried out using a Kromasil C18 reserved-phase column (5 µm, 4.6 × 250 mm) and gradient elution with methanol and aqueous phosphoric acid (0.1%, v/v). The flow rate was 1.0 mL/min and the detector wavelength was set at 276 nm. Mean chromatograms and correlation coefficients of samples were calculated by the software "Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine". The correlation coefficients of XMT and three related preparations ranged from 0.935 to 0.986, 0.909 to 0.949, 0.900 to 0.926 and 0.937 to 0.988, respectively. It was the first time 11 peaks of XMT and three related preparations were identified by comparing with standard compounds. These results have shown that the developed method was efficient for the quality evaluation of XMT and its related preparations.

Chemical constituents from aerial parts of Caryopteris incana and cytoprotective effects in human HepG2 cells.

An ethyl acetate fraction of the aerial parts of Caryopteris incana (Verbenaceae) showed potent cytoprotective effects against damage to HepG2 cells induced by tert-butylhydroperoxide (t-BHP). To search for hepatoprotective components of C. incana, various chromatographic separations of the ethyl acetate soluble fraction of C. incana led to isolation of three phenylpropanoid glycosides, 6‴-O-feruloylincanoside D, 6‴-O-sinapoylincanoside D and caryopteroside, and two iridoid glycosides, incanides A and B, together with 17 known compounds. Structures of these compounds were determined by spectroscopic analyses. The absolute stereochemistry of the caryopteroside was established with the help of circular dichroism data and in comparison with literature data. All isolated substances were determined for their cytoprotective effects against t-BHP-induced toxicity in HepG2 cells. Among the tested compounds, 6'-O-caffeoylacteoside exhibited the most potent cytoprotective activity with an IC50 value of 0.8±0.1 µM against t-BHP-induced toxicity. Structure-activity relationships of the assay results indicated an important role of the catechol moiety in phenylpropanoid, iridoid and flavonoid derivatives in eliciting cytoprotective effects.

Cytotoxicity and anti-inflammatory effects of root bark extracts of Acanthopanax henryi.

AIM: To investigate the cytotoxicity, anti-inflammatory activity, and action mechanism of root bark extracts of Acanthopanax henryi. METHOD: The hot methanol extract of the root bark of A. henryi was subjected to XAD-4 column chromatography eluting with a gradient of methanol in water. The cytotoxicity and anti-inflammatory effects of the MeOH fractions were evaluated on the inhibition on lipopolysaccharide (LPS)-induced nitric oxide, prostaglandin E2, interleukin-1ß, and interleukin-6 production in RAW 264.7 macrophages. RESULTS: The 80% MeOH fraction was a better inhibitor of LPS-induced NO, PGE2, IL-1ß, and IL-6 production, and expression of inducible nitric oxide synthase (iNOS) at the protein levels in a concentration-dependent manner. CONCLUSION: The 80% MeOH fraction of A. henryi root bark has significant anti-inflammatory activity. This provides a pharmacological basis for clinical application for the treatment of inflammation.

A new diarylheptanoid glycoside from the stem bark of Alnus hirsuta and protective effects of diarylheptanoid derivatives in human HepG2 cells.

To search for secondary metabolites of Alnus hirsuta (Betulaceae), various chromatographic separations of the ethyl acetate soluble fraction of the stem bark of A. hirsuta led to the isolation of a new diarylheptanoid glycoside, (3R)-1,7-bis-(4-dihydroxyphenyl)-3-heptanol 3-O-beta-D-glucopyranosyl(1-->3)-beta-D-xylopyranoside (13) and twelve diarylheptanoid derivatives, namely, oregonin (1), rubranoside A (2), hirsutanonol 5-O-beta-D-glucopyranoside (3), rubranoside B (4), rubranoside C (5), hirsutanonol (6), hirsutenone (7), (5S)-O-methylhirsutanonol (8), platyphylloside (9), platyphyllonol 5-O-beta-D-xylopyranoside (10), aceroside VII (11) and platyphyllenone (12). Isolates were assessed for their hepatoprotective effects against tert-butylhydroperoxide (t-BHP)-induced toxicity in HepG2 cells. Of these isolates, compounds 1-8 showed significant hepatoprotective effects on t-BHP-induced damage to HepG2 cells, with 8 exhibiting the greatest protective effect (50.7 + or - 3.7% at a concentration of 10 microM).

Lupane glycosides from the leaves of Acanthopanax koreanum.

Three new lupane-type saponins, acankoreosides F--H (1--3) were isolated from the methanol extract of the leaves of Acanthopanax koreanum NAKAI. The structures of these three saponins were established by chemical and spectroscopic analysis as 3alpha,30-dihydroxylup-20(29)-en-23,28-dioic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester (1), 3alpha,30-dihydroxylup-23-al-20(29)-en-28-oic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester (2), and (20S) 3alpha-hydroxylup-23-al-28,29-dioic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester (3), respectively. The effects of the isolates (1-3) on the lipopolysaccharide-induced production of nitric oxide and prostaglandin E2 were evaluated in RAW 264.7 macrophages.

Effect of concentration of catalpol and 5-hydroxymethyl-2-furaldehyde from processing of Rehmanniae Radix / 中国中药杂志

<p><b>OBJECTIVE</b>To study on effect of concentration of catalpol and 5-hydroxy methyl-2-furaldehyde (5-HMF) from Rehmanniae Radix at various processing.</p><p><b>METHOD</b>The Rehmanniae Radix was dried and prepared from the steaming process with 10% ethanol, 50% ethanol at 90 degrees C and 100 degrees C each other. And the changes of catalpol and 5-HMF was determinated. The extraction of 5-HMF and catalpol was sonicated in 30% methanol for 2 h. The analysis of 5-HMF and catalpol was conducted by HPLC with reversed-phase C-18 column and detected under UV 284 nm, 204 nm. Elution was carried out at 1.0 mL min(-1) with 3% acetonitrile.</p><p><b>RESULT</b>From this analysis, we found out that the content of catalpol was decreased with the number of processing times, and content of 5-HMF was increased with the number of processing times at various processing. The temperature and concentration of ethanol can effect on content of catalpol and 5-HMF at processing. The Cooked Rehmanniae Radix processed at 100 degrees C, 10% ethanol is best. And the content of 5-HMF processed for more than 7 times was accorded with standard of Korea phamcopoetia.</p><p><b>CONCLUSION</b>Analyze the effect of concentration of catalpol and 5-HMF from Rehmanniae Radix at various processing, and provide the foundation for further study.</p>

New oleanene glycosides from the leaves of Acanthopanax japonicus.

The structures of 6 new oleanene glycosides (1--6) isolated from the leaves of Acanthopanax japonicus FRANCH et. SAVART (Araliaceae) were elucidated by mass, 1D, and 2D NMR spectroscopy. The structures of 1--6 were established as 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester of 3beta,23-dihydroxy-olean-12-en-28,29-dioic acid, 3beta,30-dihydroxy-olean-12-en-23,28-dioic acid, 3beta,29-dihydroxy-olean-12-en-23,28-dioic acid (=dianic aicd), 3beta-dihydroxy-olean-12-en-23,28-dioic acid (=gypsogenic acid), 3beta,29-dihydroxy-23-oxo-olean-12-en-28-oic acid, and 3beta-hydroxy-23-oxo-olean-12-en-28,29-dioic acid, designated acanjaposide D (1), E (2), F (3), G (4), H (5), and I (6), respectively.

A new lupane glycoside from the leaves of Acanthopanax koreanum.

A new lupane-type saponin, named acankoreoside E (1), was isolated from the methanol extract of the leaves of Acanthopanax koreanum, and its structure was established through chemical and spectroscopic analyses as (20S) 3alpha-hydroxy-30-oxolupan-23,28-dioic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester.

Random amplified polymorphic DNA analysis of genetic relationships among Acanthopanax species.

Random amplified polymorphic DNA (RAPD) analysis was used to determine the genetic relationships among seventeen species of the Acanthopanax species. The DNA isolated from the leaves of the samples was used as template in polymerase chain reaction (PCR) with twenty random decamer primers in order to distinguish plant subspecies at the level of their genomes. The RAPD patterns were compared by calculating pairwise distances using Dice similarity index, and produced to the genetic similarity dendrogram by unweighted pair-group method arithmetic averaged (UPGMA) analysis, showing three groups; a major cluster(twelve species), minor cluster (4 species) and single-clustering species. The results of RAPD were compatible with the morphological classification, as well as the chemotaxonomic classification of the Acanthopanax species. The Acanthopanax species containing 3,4-seco-lupane type triterpene compounds in their leaves corresponded to the major cluster, another species having oleanane or normal lupane type constituents to minor clusters, and one species not containing triterpenoidal compound to single-cluster.

Lupane-triterpene glycosides from the leaves of Acanthopanax gracilistylus.

A novel lupane-triterpene glycoside, called wujiapioside B (1), was isolated from the leaves of Acanthopanax gracilistylus (Araliaceae) together with three known lupane-triterpene glycosides, acankoreoside C (2), acantrifoside A (3) and 3-epibetulinic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (4). Based on spectroscopic data, the chemical structure of 1 was determined as 3alpha,23-dihydroxy-lup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester. Compounds 2-3 were obtained for the first time from this plant and compound 4 has not been isolated from Acanthopanax genus yet.

A new lupane-triterpene glycoside from the leaves of Acanthopanax gracilistylus.

A new and two known lupane-triterpene glycosides were isolated from the hot MeOH fraction of the leaves of Acanthopanax gracilistylus W. W. Smith. Based on the physical properties and spectroscopic data, their chemical structures were determined as acankoreoside A (1), acankoreoside D (2), and 3alpha-hydroxy-lup-23-al-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), respectively. To our best knowledge, compound 3 appears to be novel, which was named as wujiapioside A.