Mechanisms for the biological activity of Gastrodia elata Blume and its constituents: A comprehensive review on sedative-hypnotic, and antidepressant properties.

BACKGROUND: Insomnia and depressive disorder are two common symptoms with a reciprocal causal relationship in clinical practice, which are usually manifested in comorbid form. Several medications have been widely used in the treatment of insomnia and depression, but most of these drugs show non-negligible side effects. Currently, many treatments are indicated for insomnia and depressive symptom, including Chinese herbal medicine such as Gastrodia elata Blume (G. elata), which has excellent sedative-hypnotic and antidepressant effects in clinical and animal studies. PURPOSE: To summarize the mechanisms of insomnia and depression and the structure-activity mechanism for G. elata to alleviate these symptoms, particularly by hypothalamic-pituitary-adrenal (HPA) axis and intestinal flora, aiming to discover new approaches for the treatment of insomnia and depression. METHODS: The following electronic databases were searched from the beginning to November 2023: PubMed, Web of Science, Google Scholar, Wanfang Database, and CNKI. The following keywords of G. elata were used truncated with other relevant topic terms, such as depression, insomnia, antidepressant, sedative-hypnotic, neuroprotection, application, safety, and toxicity. RESULTS: Natural compounds derived from G. elata could alleviate insomnia and depressive disorder, which is involved in monoamine neurotransmitters, inflammatory response, oxidative stress, and gut microbes, etc. Several clinical trials showed that G. elata-derived natural compounds that treat depression and insomnia have significant and safe therapeutic effects, but further well-designed clinical and toxicological studies are needed. CONCLUSION: G. elata exerts a critical role in treating depression and insomnia due to its multi-targeting properties and fewer side effects. However, more clinical and toxicological studies should be performed to further explore the sedative-hypnotic and antidepressant mechanisms of G. elata and provide more evidence and recommendations for its clinical application. Our review provides an overview of G. elata treating insomnia with depression for future research direction.

Chromosome-level genome of Entada phaseoloides provides insights into genome evolution and biosynthesis of triterpenoid saponins.

As a medicinal herbal plant, Entada phaseoloides has high levels of secondary metabolites, particularly triterpenoid saponins, which are important resources for scientific research and medical applications. However, the lack of a reference genome for this genus has limited research on its evolution and utilization of its medicinal potential. In this study, we report a chromosome-scale genome assembly for E. phaseoloides using Illumina, Nanopore long reads and high-throughput chromosome conformation capture technology. The assembled reference genome is 456.18 Mb (scaffold N50 = 30.9 Mb; contig N50 = 6.34 Mb) with 95.71% of the sequences anchored onto 14 pseudochromosomes. E. phaseoloides was estimated to have diverged from the Leguminosae lineage at ~72.0 million years ago. With the integration of transcriptomic and metabolomic data, gene expression patterns and metabolite profiling of E. phaseoloides were determined in different tissues. The pattern of gene expression and metabolic profile of the kernel were distinct from those of other tissues. Furthermore, the evolution of certain gene families involved in the biosynthesis of triterpenoid saponins and terpenes was analysed and offers new insights into the formation of these two metabolites. Four CYP genes, one UGT gene and related transcription factors were identified as candidate genes contributing to regulation of triterpenoid saponin biosynthesis. As the first high-quality assembled reference genome in the genus Entada, it will not only provide new information for the evolutionary study of this genus and conservation biology of E. phaseoloides but also lay a foundation for the formation and utilization of secondary metabolites in medicinal plants.

Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway.

We investigated the liver protective activity of dandelion polyphenols (DP) against acetaminophen (APAP; Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups (n = 9 per group): Control, APAP, APAP + DP (100 mg·kg-1), APAP + DP (200 mg·kg-1), and APAP + DP (400 mg·kg-1) groups. Mice were pretreated with DP (100, 200, and 400 mg·kg-1) by oral gavage for 7 d before being treated with 350 mg·kg-1 APAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics (aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance (superoxide dismutase, SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-1ß, IL-1ß). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

Novel application of neural network modelling for multicomponent herbal medicine optimization.

The conventional method for effective or toxic chemical substance identification of multicomponent herbal medicine is based on single component separation, which is time-consuming, labor intensive, inefficient, and neglects the interaction and integrity among the components; therefore, it is necessary to find an alternative routine to evaluate the components more efficiently and scientifically. In this study, sodium aescinate injection (SAI), obtained from different manufacturers and prepared as "components knockout" samples, was chosen as the case study. The chemical fingerprints of SAI were obtained by high-performance liquid chromatography to provide the chemical information. The effectiveness and irritation of each sample were evaluated using anti-inflammatory and irritation tests, and then "Gray correlation" analysis (GCA) was applied to rank the effectiveness and irritability of each component to provide a preliminary judgment for product optimization. The prediction model of the proportions of the expected components was constructed using the artificial neural network. The results of the GCA showed that the irritation sorting of each SAI component was in the order of B > A > G > J > I > H > D > F > E > C and the effectiveness sorting of SAI components was in the order of D > C > B > A > F > E > H > I > G > J; the predictive proportion of SAI was optimized by the BP neural network as A: B: C: D: E: F = 0.7526: 0.5005: 5.4565: 1.4149: 0.8113: 1.0642. This study provided a scientific, accurate, reliable, and efficient approach for the proportion optimization of multicomponent drugs, which has a good prospect of popularization and application in product upgrading and development of herbal medicine.

Anti-inflammatory and blood stasis activities of essential oil extracted from Artemisia argyi leaf in animals.

Artemisia argyi leaf is a well-known species in traditional Chinese medicine. However, the anti-inflammatory and activating blood stasis activities of its essential oil (AAEO) have not been explored in vivo. The present study measured the contents of three chemical components by gas chromatography (GC). The anti-acute inflammatory effects of AAEO were investigated in dimethyl benzene, glacial acetic acid and carrageenan-induced animals through skin administration or by oral gavage, respectively. The effects of AAEO on haemorheology were studied in a rat acute blood stasis model. The contents of eucalyptol, camphor and borneol in AAEO were 254.4, 51.6 and 58.7 mg/g, respectively. All dosages of AAEO by skin administration significantly decreased the swelling in dimethyl benzene-induced ear oedema and carrageenan-induced paw oedema, and reduced the permeability in glacial acetic acid-induced abdominal blood capillary (p < 0.01). Meanwhile, haemorheology indexes such as whole blood viscosity and the erythrocyte aggregation index significantly decreased only in the high dosage group. In addition, the effects of AAEO by oral gavage were weaker than skin administration at the medium dose in the experiments. It suggests that AAEO has better absorption bioavailability and pharmacological effects through skin administration due to the better skin permeability of essential oil than gastrointestinal absorption.

Analgesic effect of total flavonoids from Sanguis draxonis on spared nerve injury rat model of neuropathic pain.

BACKGROUND: Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (D. cochinchinensis). The active components of total flavonoids from SD (SDF) have analgesic effect. AIM: The aim of this study is to evaluate the analgesic effects and potential mechanism of SDF on mechanical hypersensitivity induced by spared nerve injury (SNI) model of neuropathic pain in the rat. METHODS: SNI model in rats was established and then the rats were treated with SDF intragastric administration for 14 days. Paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and days 1, 3, 5, 7, 9, 11, 14 after operation, respectively. After 14 days, we measured the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-10 (IL-10) in the spinal dorsal horn. In addition, the expression of fibroblast growth factor receptor 3 (FGFR3), phosphorylated cyclic AMP response element-binding protein (p-CREB) and glial fibrillary acidic protein (GFAP) of the spinal dorsal horn was evaluated by western blotting and an immunofluorescence histochemical method, respectively. RESULTS: Intragastric administration of SDF (100, 200, 400 mg/kg) alleviated significantly SNI-induced mechanical hypersensitivity, as PMWT increased in a dose-dependent manner. Moreover, SDF not only reduced the level of NO, NOS, TNF-α and IL-1ß, but also upregulated the level of IL-10 in the spinal dorsal horn of SNI rats. At the same time, SDF (100, 200, 400 mg/kg) could inhibit the expression of FGFR3, GFAP and p-CREB in the spinal dorsal horn. CONCLUSION: SDF has potentially reduced mechanical hypersensitivity induced by SNI model of neuropathic pain which may be attributed to inhibition of astrocytic function (like release pro-inflammatory cytokines) and NO release as well as p-CREB activation in the spinal dorsal horn.

[Molecular identification of Tibetan medicine Qianghuoyu by CO I].

The CO I gene sequences of Qianghuoyu, Pachytriton labiatus and Gehyra mutilata were achieved by PCR amplification and bi-directional sequencing. Furthermore, a pair of specific primers SJYW1 and SJYW2 in the non-conservative district were designed through sequence alignment. The PCR reaction condition was established by changing the annealing temperature and cycle numbers. The results showed that 350 bp DNA fragment was amplified from Qianghuoyu in PCR with annealed temperature at 54 °C and the cycle number was 25 cycles, whereas not any DNA fragment was amplified from P. labiatus and G. mutilata under the same reaction condition. This method is well-performed in the identification of Qianghuoyu for its excellent specificity and repeatability.

Phenolic glycosides from Glycosmis pentaphylla.

Three new phenolic glycosides, named as glycopentosides A-C (1-3), along with nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis pentaphylla. Their structures were determined by using spectroscopic and chemical methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide production in lipopolysaccharides-stimulated RAW 264.7 cells with IC50 value of 12.14 µM.

Triterpene saponins from the stems of Entada phaseoloides.

Ten new triterpene saponins (1-10) have been isolated from the stems of Entada phaseoloides. Their structures were elucidated by spectroscopic analysis and chemical methods. Among these compounds, the aglycons of 6-10 are being reported for the first time, in this study, including 3ß,15α,16α-trihydroxy-11α,12α-epoxy olean-28,13ß-olide (6), 3ß,15α,16α-trihydroxy-11-oxo-olean-12-en-28-oic acids (7 and 8), and 3ß,15α,16α-trihydroxy-oleana-11,13(18)-dien-28-oic acids (9 and 10). The cytotoxic activities of all of these compounds were evaluated against HepG-2, A549, and Ec-1 cell lines.

Lycojaponicuminol A-F: cytotoxic serratene triterpenoids from Lycopodium japonicum.

Six new serratene triterpenoids (1-6), together with nine known triterpenoid compounds were isolated from the extract of club moss Lycopodium japonicum. The structures of isolated compounds were established by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against three human cancer cell lines in vitro by MTT assay. Compounds 2, 6-8 and 11 exhibited moderate activities against all three cell lines with IC50 values of 2.28-11.81 µg/mL.

Relaxant effect of 1-butanol fraction from Elaeagnus pungens leaf through inhibiting L-type Ca2+ channel on guinea pig tracheal smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf of Elaeagnus pungens thunb. (Family Elaeagnaceae) has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional Chinese medicine. In the past years, only a few of preliminary studies reported the chemical constituents and pharmacology effects of the herb, but their action on the tracheal relaxation has not been investigated. AIM OF THE STUDY: To investigate the relaxing effect and mechanism of the extracts from Elaeagnus pungens leaves on guinea pig tracheal smooth muscle and bronchi smooth muscle cells. MATERIALS AND METHODS: Four fractions of different polarities from Elaeagnus pungens leaves were tested to the tracheal strips on the resting tension or pre-contracted by histamine (20 µM) and acetylcholine (20 µM). Inhibitory effects of the 1-butanol fraction (400mg/ml) on cumulative histamine and acetylcholine (0.2-20 µM) induced contraction were measured. In order to determine the mediators on the 1-butanol fraction effect, the relaxing effect of the 1-butanol fraction was evaluated in the absence and presence of ß-adrenoceptor antagonists (1 µM propranolol), K(+) channels-blockers (4-aminopyridine (2mM), tetraethylammonium chloride (5mM) or glibenclamide (10 µM)), the cyclooxygenase inhibitor (indomethacin, 10 µM), nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester, 100 µM) or L-type Ca(2+) channel inhibitor (nifedipine, 1 µM). Moreover, [Ca(2+)]i in bronchi smooth muscle cells was analyzed by measuring the fluorescence intensity with confocal system. RESULTS: 1-Butanol fraction induced the highest relaxant effect among four fractions of different polarities from Elaeagnus pungens leaves, and significantly relaxed the tracheal strip in the concentration-dependent manner on the resting tension and pre-contracted by histamine phosphate and acetylcholine. It also produced an unparallel rightward shift of the cumulative concentration-response curve of histamine or acetylcholine. Furthermore, the relaxant effect of 1-butanol fraction was not affected by propranolol, glibenclamide, tetraethylammonium chloride, 4-aminopyridine, indomethacin and Nω-nitro-L-arginine methyl ester. However, 1-butanol fraction-induced relaxation decreased after adding nifedipine. It also concentration-dependently inhibited CaCl2-induced contraction in the Ca(2+)-free, 60mM K(+)-containing solution. Additionally, [Ca(2+)]i in the BSMCs significantly reduced after administration of the 1-butanol fraction. CONCLUSIONS: The 1-butanol fraction from Elaeagnus pungens leaves resulted in a relaxation in the non-precontracted and pre-contracted tracheal strips. The relaxant effect was not related to K(+) channels, NO, cGMP or ß-adrenoceptors, but related to the inhibition of Ca(2+) influx through L-type Ca(2+) channels.

Two new flavonol glycosides from the leaves of Elaeagnus pungens.

The leaves of Elaeagnus pungens were extracted with 70% ethanol and successively purified by column chromatography. Seven constituents were obtained and characterized, all of which belong to the class of flavonol glycosides. Their structures were elucidated on the basis of spectroscopic methods including 1D/2D NMR and MS analysis techniques. The seven flavonol glycosides were determined as kaempferol 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 6)-[α-l-rhamnopyranosyl(1 â†’ 2)]-ß-d-galactopyranoside (1), isorhamnetin 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-galactopyranoside (2), together with five known compounds, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu-m bromide assay in vitro showed that the isolated flavonol glycosides showed no proliferation activity in the asthma airway smooth muscle cells, comparing with solvent as the control group.

Anti-inflammatory and anticancer activities of ethanol extract of pendulous monkshood root in vitro.

AIM: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. MATERIALS AND METHODS: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. RESULTS: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti- inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 µg/mL. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. CONCLUSION: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.

Two new flavanols from Glycosmis pentaphylla.

Two new flavanols, glycoflavanones A (1) and B (2), which were found to possess α-pyrone moiety, together with five known compounds 4'-O-methylgallocatechine (3), ß-sitosterol (4), alphitol (5), 3,4-dimethoxy-5-hydroxy-trans-cinnamyl alcohol (6), and oxyresveratrol (7), were isolated from the stems of Glycosmis pentaphylla by normal-phase and reverse-phase silica gel column chromatography. Their structures were determined on the basis of chemical and spectroscopic analyses.

[Comparative identification research on different extracts of Dai Medicine "Pokou" and its processed product by FTIR].

OBJECTIVE: To study identification methods of different extracts of Dai Medicine "Pokou" (the rhizome of Homalomena gigantea Engl. ) and its processed product made by immersing it in water, and provide reference for identification of the drug in further researches and applications. METHODS: FTIR technique was used for identifying the features of different extracted parts of this crude drug and its processed product. RESULTS: Compared with the crude drug, the petroleum ether-extracted parts of processed product turned out to have no obvious distinction in the FTIR. There was a large difference in the ethyl acetate-extracted parts, and the n-butanol-extracted parts also had certain discrepancy. A preliminary analysis was made on the chemical fundamentals which caused the changes in the FTIR before and after the drug's processing. CONCLUSION: The results provide an infrared spectral identification method for the drug and its applications.

[Comparative identification on Dai medicine "Pokou" and its processing product].

OBJECTIVE: To research identification methods of the Dai Medicine "Pokou" (the rhizome of Homalomena gigantea) and its processing product, and provide basis for identification of the drug in further research and application. METHODS: Macroscopic, microscopic observation and TLC and FTIR techniques were used to authenticate this raw medicine and its processing product. RESULTS: There were certain differences in the macroscopic features. The TLC result and infrared spectra of the samples had also obvious differences. The methods for identification of this raw medicine and its processing product were established, The detailed tissue and powder of this medicine were drawn. CONCLUSION: The results provided the basis for identification of the medicine and establishment of its quality standard.

Sulfur-containing amides from Entada phaseoloides.

To study the chemical constituents of the Entada phaseoloides (L.) Merr., seeds of Entada phaseoloides were extracted with 70% ethanol at room temperature. Isolation and purification were performed by silica gel, reversed-phase silica gel column chromatography and semi-preparative HPLC. Structures of the pure compounds were established on the basis of spectral analysis. Four sulfur-containing amide compounds were isolated from the n-BuOH-soluble fraction and identified as entadamide A-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranoside (1), entadamide A (2), entadamide A-beta-D-glucopyranoside (3) and clinacoside C (4). Compound 1 is a new compound. Compound 4 is isolated from the genus Entada for the first time.

Chemical constituents with free-radical-scavenging activities from the stem of Microcos paniculata.

The free-radical-scavenging activities of various solvent extracts of Microcos paniculata were evaluated through in vitro model systems, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and Co (II) EDTA-induced luminol chemiluminescence by flow injection. In all three of these systems the ethyl acetate (EtOAc) extract showed the highest free-radical-scavenging activity compared with the other three (n-BuOH, water and petroleum ether) extracts. Free-radical-scavenging assay-guided chromatographic separation of the EtOAc extract, using a normal-phase and reverse-phase silica gel column chromatography yielded five compounds: a new triterpene named methyl 3beta-O-p-hydroxy-E-cinnamoyloxy-2alpha,23-dihydroxyolean-12-en-28-oate (1), whose spectral data are presented for the first time, together with four known compounds, epicatechin (2), 3-trans-feruloyl maslinic acid (3), maslinic acid (4) and sucrose (5). All of the compounds were isolated from Microcos paniculata for the first time. The compounds were identified by spectroscopic methods. Among them, compound 2 displayed significant free-radical-scavenging activity which is similar to that of standard antioxidant ascorbic acid (V(C)) and therefore may be a promising natural antioxidant.

[Study on acute toxicity and animal gastrointestinal activity of crude and processed products of Entada phaseoloides].

OBJECTIVE: To study the acute toxicity of the crude and processed products of Entada phaseoloides and their effects on gastrointestinal movement in mice. METHODS: Using the method of intragastric administration, to observe the acute toxicity of the crude and processed products of Entada phaseoloides in mice and determine their LD50. With the methods of charcoal propulsion of small intestine and methyl orange colorimetry of gastric emptying, to study the impact of the crude and processed products of Entada on gastrointestinal movement in mice. RESULTS: The oral LD50 of crude Entada phaseoloides, No. 1 and No. 2 processed products of Entada phaseoloides in mice were 27.17, 35.13, 42.18 g/kg body weight. Crude and processed products of Entada phaseoloides can significantly promote the enteric propulsion of normal mice, and can significantly counteract the depressing status induced by atropine, but have no influence on the overactive status induced by neostigmine. The high, middle and low-dose of groups showed significant inhibition of the gastric emptying in normal mice. CONCLUSION: Processed Entada phaseoloides showed effects on the enteric propulsion of normal and depressing mice, can restrain the gastric emptying under normal mice, but its safety is better than crude Entada phaseoloides.

A new chromone derivative from Berchemia lineata.

To study the chemical constituents from the root of Berchemia lineata (L.) DC., nine compounds were isolated from the EtOAc extract by using silica gel, RP-C18 silica gel column chromatography and preparative HPLC. Based on the spectroscopic analysis, their structures were identified as 5-hydroxy-7-(2'-hydroxypropyl)-2-methyl-chromone (1), (-)-(1'R, 2'S)-erythro-5-hydroxy-7-(1', 2'-dihydroxypropyl)-2-methyl-chromone (2), naringenin (3), eriodictyol (4), (+)-aromadendrin (5), (+)-taxifolin (6), (+)-catechin (7), (+)-epigallocatechin (8) and quercetin (9). Among them, compound 2 is a new chromone derivative. Compound 1 is a known chromone derivative and isolated from this genus for the first time. Compounds 3-9 are known flavonoids and isolated from this plant for the first time.