ABSTRACT
Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.
ABSTRACT
Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.
Subject(s)
Acetates , Asteraceae , Cadmium , Cyclopentanes , Oxylipins , Cadmium/metabolism , Plant Roots/metabolism , Polysaccharides/metabolism , Polysaccharides/pharmacology , Pectins/chemistry , Cell Wall/metabolism , Asteraceae/metabolismABSTRACT
BACKGROUND: Combined methylmalonic acidemia (MMA) and hyperhomocysteinemia, cobalamin C (cblC) type, also named cblC deficiency is a rare autosomal recessive genetic metabolic disease. It progressively causes neurological, hematologic, renal and other system dysfunction. The clinical manifestations are relatively different due to the onset time of disease. CASE PRESENTATION: This report describes a rare case of a 26 year old man with cblC deficiency who developed life-threatening aortic dissection and acute kidney injury (AKI) and showed neuropsychiatric symptoms with elevated serum homocysteine and methylmalonic aciduria. After emergent operation and intramuscular cobalamin supplementation therapy, the male recovered from aortic dissection, neurological disorder and AKI. Finally, two previously published compound heterozygous variants, c.482G > A (p.R161Q) and c.658_660del (p.K220del) in the MMACHC gene were detected in this patient and he was confirmed to have cblC deficiency. CONCLUSIONS: Poor cognizance of presenting symptoms and biochemical features of adult onset cblC disease may cause delayed diagnosis and management. This case is the first to depict a case of adult-onset cblC deficiency with aortic dissection. This clinical finding may contribute to the diagnosis of cblC deficiency.
Subject(s)
Acute Kidney Injury , Amino Acid Metabolism, Inborn Errors , Hyperhomocysteinemia , Adult , Male , Humans , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/diagnosis , Hyperhomocysteinemia/genetics , Vitamin B 12 , Amino Acid Metabolism, Inborn Errors/complications , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/genetics , Acute Kidney Injury/etiology , OxidoreductasesABSTRACT
Roscoea is an alpine or subalpine genus from the pan-tropical family Zingiberaceae, which consists of two disjunct groups in geography, namely the "Chinese" clade and the "Himalayan" clade. Despite extensive research on the genus, Roscoea species remain poorly defined and relationships between these species are not well resolved. In this study, we used plastid genomes of nine species and one variety to resolve phylogenetic relationships within the "Chinese" clade of Roscoea and as DNA super barcodes for species discrimination. We found that Roscoea plastid genomes ranged in length from 163,063 to 163,796 bp, and encoded 113 genes, including 79 protein-coding genes, 30 tRNA genes, four rRNA genes. In addition, expansion and contraction of the IR regions showed obvious infraspecific conservatism and interspecific differentiation. Plastid phylogenomics revealed that species belonging to the "Chinese" clade of Roscoea can be divided into four distinct subclades. Furthermore, our analysis supported the independence of R. cautleoides var. pubescens, the recovery of Roscoea pubescens Z.Y. Zhu, and a close relationship between R. humeana and R. cautloides. When we used the plastid genome as a super barcode, we found that it possessed strong discriminatory power (90%) with high support values. Intergenic regions provided similar resolution, which was much better than that of protein-coding regions, hypervariable regions, and DNA universal barcodes. However, plastid genomes could not completely resolve Roscoea phylogeny or definitively discriminate species. These limitations are likely related to the complex history of Roscoea speciation, poorly defined species within the genus, and the maternal inheritance of plastid genomes.
ABSTRACT
Four new 2-(2-phenethyl)chromone dimers (1-4) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria from Philippines. Their structures were elucidated by spectroscopic analysis (1D and 2D NMR, and HRESIMS) and comparison of the experimental and computed ECD curves. Compounds 1-4 exhibited inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range from 33.94 to 57.53 µM.
Subject(s)
Chromones , Thymelaeaceae , Chromones/pharmacology , Molecular Structure , Thymelaeaceae/chemistry , Magnetic Resonance Spectroscopy , Lipopolysaccharides , Flavonoids/chemistryABSTRACT
OBJECTIVES: To investigate the effect and efficacy of traditional Chinese and western medicine combined with lung rehabilitation training on pulmonary function in patients with chronic obstructive pulmonary disease(COPD) complicated with chronic cor pulmonale. METHODS: Totally 200 COPD patients with chronic cor pulmonale in our hospital were selected as research objects. The 100 patients in control group were managed by conventional western medicine combined with lung rehabilitation training, and another 100 patients in observation group were treated with traditional Chinese and western medicine combined with lung rehabilitation training. The pulmonary function (modified British Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Tests (CAT), BODE index (body-mass, airflow obstruction, dyspnea, and exercise capacity), pulmonary function-related indexes (FEV1, FVC, FEV1/FVC, and FEV1/Pred), and blood gas analysis indicators (paO2, PaCO2, SaO2 and PH value)) and curative effect (the effectiveness, Satisfaction Test, Quality of Life Score, and TCM Syndrome Integral) before and after treatment within or between groups were compared. RESULTS: Before treatment, the pulmonary function and curative effect (Quality of Life Score and TCM Syndrome Integral) parameters showed no significant difference between the two groups, which indicated there was a comparability between the two groups. After treatment, all parameters of pulmonary function and curative effect displayed better results in observation group than in control group. Compared with the results before treatment, pulmonary function and curative effect revealed better in both groups after treatment, and more visible improvement trends were found in observation group. CONCLUSIONS: Traditional Chinese and western medicine combined with lung rehabilitation training displayed better results on lung function and curative effect than conventional western medicine combined with lung rehabilitation training in patients with COPD complicated with chronic cor pulmonale (Tab. 8, Ref. 43). Text in PDF www.elis.sk Keywords: traditional Chinese and western medicine combined, lung rehabilitation training, chronic obstructive pulmonary disease, pulmonary function, curative effect.
Subject(s)
Cardiovascular Diseases , Pulmonary Disease, Chronic Obstructive , Pulmonary Heart Disease , Humans , Quality of Life , Pulmonary Heart Disease/complications , Lung , Pulmonary Disease, Chronic Obstructive/complications , DyspneaABSTRACT
Two new flavonoid glycosides scutelikiosides A and B (13 and 23), along with twenty-one known compounds from the 75% ethanol extract of roots of Scutellaria likiangensis Diels. Their structures were determined by the comprehensive analyses of the spectroscopic data (1D NMR, 2D NMR, HRESIMS, and CD) and physicochemical properties. Compounds 4-14, 17-19, 21, and 22 were evaluated for their in vivo antimalarial activities against Plasmodium yoelii BY265RFP in mice. Compound 17 exhibited significant activity close to artemisinin with an inhibition ratio of 29.2%, and compounds 6, 9-12, 14, 18, 19, and 22 exhibited moderate antimalarial activities with inhibition ratios ranging from 10.2% to 20.0% at a dose of 25 mg/kg/day. In addition, a summary of preliminary structure-activity relationship of isolated flavonoids for in vivo antimalarial activity was described.
Subject(s)
Antimalarials , Scutellaria , Mice , Animals , Flavonoids/chemistry , Antimalarials/pharmacology , Scutellaria/chemistry , Molecular Structure , Glycosides/pharmacologyABSTRACT
The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.
Subject(s)
Caenorhabditis elegans Proteins , Drugs, Chinese Herbal , Humans , Animals , Mice , Caenorhabditis elegans/metabolism , Longevity , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Drugs, Chinese Herbal/pharmacology , Oxidative Stress , Transcription Factors/metabolism , Doxorubicin/pharmacology , Forkhead Transcription Factors/metabolismABSTRACT
Celery seeds are commonly used as condiments and in herbal teas with high medicinal value. In the present study, we investigated the contents of extracts derived under different extraction conditions and determined the optimal conditions for only extracting flavone glycosides from celery seeds. The compositional analysis identified three primary flavone glycosides in the ethanolic extract, and apiin, graveobioside A, and graveobioside B were isolated. Apigenin, luteolin, and chrsyeriol were obtained by the acid hydrolysis of flavone glycosides under high-temperature conditions. Here we investigated the inhibitory activity of apigenin and apiin on xanthine oxidase by reducing the rate of oxidative cytochrome C and found that both apigenin and apiin reduced cytochrome C production, except for low concentrations of apiin. In vivo analysis with hyperuricemia mice and rats showed that apiin had excellent uric acid-lowering effects and high dose-dependence, while apigenin was relatively slightly uric acid-lowering. In addition, the flavone glycoside extracts from celery seeds exhibited similar effects of reducing uric acid with apiin. Surprisingly, in hyperuricemia rats, the uric acid-lowering effects of high-dose apiin and flavone glycoside extracts were almost comparable to that of allopurinol. Besides, our experimental results showed that apigenin could improve uric acid clearance by increasing the glomerular filtration capacity, which was reflected in reducing the renal function parameters SUN and SCr; also, apiin showed better results. This study also showed that celery seeds have a unique medicinal value in treating hyperuricemia and that the flavone glycoside extracts from celery seeds can be developed as medicine for hyperuricemia.
Subject(s)
Apium , Flavones , Hyperuricemia , Teas, Herbal , Allopurinol/analysis , Allopurinol/pharmacology , Allopurinol/therapeutic use , Animals , Apigenin/analysis , Apium/chemistry , Cytochromes c , Flavones/chemistry , Glycosides/chemistry , Hyperuricemia/drug therapy , Luteolin/analysis , Mice , Plant Extracts/chemistry , Rats , Seeds/chemistry , Teas, Herbal/analysis , Uric Acid , Xanthine OxidaseABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The plant Bauhinia brachycarpa Benth (BBB) has been traditionally used for treating muscle aches such as bone pain, and neuralgia for a long time, on account of its sedative and antinociceptive activities in Yunnan province of China. However, there was no experimental evidence to confirm its traditional medicinal use. AIM OF THE STUDY: The antinociceptive effect and possible mechanism of ethanolic extract of BBB on neuropathic pain was evaluated through a model of partial sciatic nerve ligation in mice. MATERIALS AND METHODS: A commonly employed animal model induced by partial sciatic nerve ligation (PSNL) in mice was established in the aim of studying neuropathic pain. Ethanolic extract of BBB (1000, 500, 250 mg/kg) and pregabalin (60 mg/kg) were intragastric administrated daily for 7 days post-PSNL. Mechanical and thermal hyperalgesia were assessed throughout the experimental period. After the experiment, the levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in serum were determined by ELISA. The mRNA expressions of ionized calcium binding adaptor molecule 1 (Iba-1), CD16, CD206, arginine-1 (Arg-1), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) in the spinal cord were detected by qPCR. The protein levels of Iba-1, CD16, CD206, and p38 phosphorylation in the spinal cord were detected by immunohistochemistry and western blotting. The phytochemical analysis of BBB was performed through the colorimetric test. RESULTS: Neuropathic pain induced by PSNL was significantly alleviated by BBB treatment, which decreased pro-inflammatory cytokines such as TNF-α, IL-1ß and iNOS, increased anti-inflammatory cytokine such as IL-10 and Arg-1, and attenuated p38 phosphorylation. BBB also reduced the number of Iba-1 and CD16 positive cells, but it enhanced the number of CD206 positive cells. n-Butanol portion that was partitioned from the ethanolic extract had the highest content of total flavonoids among all the portions, and the antinociceptive effect of n-butanol portion is better than that of other portions. CONCLUSIONS: Our findings indicate that the antinociceptive effect of BBB is mediated by inhibiting the inflammatory response and regulating the differentiation of microglia. The antinociceptive effect of BBB was related to the content of total flavonoids.
Subject(s)
Bauhinia , Neuralgia , 1-Butanol , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , China , Cytokines/metabolism , Flavonoids/therapeutic use , Hyperalgesia/drug therapy , Interleukin-10 , Mice , Neuralgia/drug therapy , Neuralgia/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sciatic Nerve/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16-0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58-2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: -1.11 to -0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.
ABSTRACT
Phloridzin is a lead compound of the prestigious antidiabetic gliflozins. The present study found that phloridzin highly accumulated in Malus rockii Rehder. The content of phloridzin in M. rockii was the highest among wild plants, with the percentage of 15.54% in the dry leaves. The structure of phloridzin was revised by proton exchange experiments and extensive 2D NMR spectra. Phloridzin exhibited significant hypolipidemic activity in golden Syrian hamsters maybe by increasing the expression of CYP7A1, at the doses of 50 mg/kg and 200 mg/kg. The total performance of anti-hyperlipidemic effect of phloridzin may be superior to that of lovastatin, though lovastatin was more active than phloridzin. In addition, phloridzin exhibited moderate antimalarial activity with inhibition ratio of 31.3 ± 10.9% at a dose of 25 mg/kg/day, and showed moderate analgesic activity with 28.0% inhibition at a dose of 50 mg/kg.
Subject(s)
Antimalarials , Malus , Sodium-Glucose Transporter 2 Inhibitors , Phlorhizin/pharmacology , Phlorhizin/chemistry , Malus/chemistry , Sodium-Glucose Transporter 2 Inhibitors/metabolism , Protons , Lovastatin/metabolismABSTRACT
The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.
Subject(s)
Aging, Premature/drug therapy , Antioxidants/pharmacology , Apiaceae/chemistry , Caenorhabditis elegans/growth & development , Doxorubicin/toxicity , Longevity , Plant Extracts/pharmacology , Aging, Premature/chemically induced , Aging, Premature/pathology , Animals , Antibiotics, Antineoplastic/toxicity , Caenorhabditis elegans/drug effects , Heat-Shock Response , Male , Mice , Mice, Inbred C57BL , Oxidative Stress , Plant Roots/chemistryABSTRACT
Four previously undescribed hydroxypropionylated d-glucose derivatives, astrabhotins A-D (1-4), along with ten known compounds α-d-glucose (5), ß-d-glucose (6), quebrachitol (7), 3-hydroxypropionic acid (8), oleic acid (9), isoliquiritigenin (10), liquiritigenin (11), odoratin (12), 7ß-hydroxysitosterol (13) and daucosterol (14), were isolated from the roots of Astragalus bhotanensis. Their structures were elucidated based on the analyses of extensive spectroscopic data and physicochemical properties. Astrabhotin A (1) reduced the writhing response remarkably with 52.5% inhibition by acetic acid induced writhing test. The analgesic effect of 1 was stronger than the standard drug aspirin. In addition, compounds 1 and 3 showed significant antioxidant activities with IC50 values of 9.9 ± 0.2 and 7.9 ± 0.4 µg/mL, and exhibited weak or moderate cytotoxicity against HepG2 cells with IC50 values of 106.6 ± 2.7 and 42.0 ± 0.9 µg/mL, respectively.[Figure: see text].
Subject(s)
Astragalus Plant , Glucose , Antioxidants/pharmacology , Plant Extracts , Plant RootsABSTRACT
Synthetic cannabinoids, as exemplified by SDB-001 (1), bind to both CB1 and CB2 receptors and exert cannabimimetic effects similar to (-)-trans-Δ9-tetrahydrocannabinol, the main psychoactive component present in the cannabis plant. As CB1 receptor ligands were found to have severe adverse psychiatric effects, increased attention was turned to exploiting the potential therapeutic value of the CB2 receptor. In our efforts to discover novel and selective CB2 receptor agonists, 1 was selected as a starting point for hit molecule identification and a class of 1H-pyrazole-3-carboxamide derivatives were thus designed, synthesized, and biologically evaluated. Systematic structure-activity relationship investigations resulted in the identification of the most promising compound 66 as a selective CB2 receptor agonist with favorable pharmacokinetic profiles. Especially, 66 treatment significantly attenuated dermal inflammation and fibrosis in a bleomycin-induced mouse model of systemic sclerosis, supporting that CB2 receptor agonists might serve as potential therapeutics for treating systemic sclerosis.
Subject(s)
Designer Drugs/chemistry , Drug Discovery , Receptor, Cannabinoid, CB2/agonists , Scleroderma, Systemic/drug therapy , Designer Drugs/pharmacokinetics , Humans , Structure-Activity RelationshipABSTRACT
The pollination drop (PD), also known as an ovular secretion, is a critical feature of most wind-pollinated gymnosperms and function as an essential component of pollination systems. However, the metabolome and small RNAs of gymnosperm PDs are largely unknown. We employed gas chromatography-mass spectrometry to identify a total of 101 metabolites in Ginkgo biloba L. PDs. The most abundant metabolites were sugars (45.70%), followed by organic acids (15.94%) and alcohols (15.39%) involved in carbohydrate metabolism, glycine, serine and threonine metabolism. Through pollen culture of the PDs, we further demonstrated that the metabolic components of PDs are indispensable for pollen germination and growth; in particular, organic acids and fatty acids play defensive roles against microbial activity. In addition, we successfully constructed a small RNA library and detected 45 known and 550 novel miRNAs in G. biloba PDs. Interestingly, in a comparative analysis of miRNA expression between PDs and ovules, we found that most of the known miRNAs identified in PDs were also expressed in the ovules, implying that miRNAs in PDs may originate from ovules. Further, combining with potential target prediction, degradome validation and transcriptome sequencing, we identified that the interactions of several known miRNAs and their targets in PDs are involved in carbohydrate metabolism, hormone signaling and defense response pathways, consistent with the metabolomics results. Our results broaden the knowledge of metabolite profiling and potential functional roles in gymnosperm PDs and provide the first evidence of extracellular miRNA functions in ovular secretions from gymnosperms.
Subject(s)
Ginkgo biloba , MicroRNAs , Gene Expression Regulation, Plant , Ginkgo biloba/genetics , MicroRNAs/genetics , Ovule , Pollen/genetics , PollinationABSTRACT
Eleven new angeloylated eudesmane sesquiterpenoids, dobinins D-N (2, 3, 5, 6, 8, 9, and 11-15), and four known compounds (1, 4, 7, and 10) were isolated from the roots of Dobinea delavayi. A new oxidation product (8a) was also obtained from dobinin H (8). Their structures were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses. Dobinins K-N (12-15) are the first examples of rearrangement noreudesmane analogue sesquiterpenoids with a unique 6/5-fused carbon skeleton. A putative biosynthetic pathway of compounds 12-15 is proposed. Compound 12 exhibited significant antimalarial activity superior to artemisinin with the inhibition ratio of 59.1%, and compounds 3, 5, and 15 exhibited moderate antimalarial activities against Plasmodium yoelii BY265RFP with inhibition ratios ranging from 14.5% to 18.5% at a dose of 30 mg/kg/day. In addition, the apoptosis of P. yoelii BY265RFP by the depolarization of mitochondrial membrane potential with striking ROS production, after parasitized erythrocyte lysis mediated by cytokines IL-12 and IFN-γ, may be a possible mechanism of antimalarial action of compound 12 against P. yoelii BY265RFP.
Subject(s)
Anacardiaceae/chemistry , Antimalarials/chemistry , Antimalarials/pharmacology , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Animals , Apoptosis/drug effects , Cytokines/physiology , Erythrocytes/parasitology , Malaria/drug therapy , Malaria/parasitology , Membrane Potential, Mitochondrial/drug effects , Mice , Molecular Structure , Plant Extracts/chemistry , Plant Roots/chemistry , Plasmodium yoelii/drug effects , Reactive Oxygen Species/metabolism , X-Ray DiffractionABSTRACT
Five new sesquiterpenoids (1-5), together with a known compound 6 was isolated from ethyl ether extract of agarwood. Their structures were elucidated on the basis of spectroscopic techniques (UV, IR, MS, 1D and 2D NMR), as well as by comparison with literature data. Compound 5 exhibited inhibitory activity against acetylcholinesterase with inhibition ratio of 48.33 ± 0.17% at the concentration of 50 µg/mL.
Subject(s)
Sesquiterpenes/chemistry , Thymelaeaceae/chemistry , Wood/chemistry , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/isolation & purification , Esters/chemistry , Molecular Structure , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Sesquiterpenes/isolation & purification , ThailandABSTRACT
Dodelates A-E (1-5), five angeloylated eudesmane sesquiterpenoid dimers were isolated from the roots of Dobinea delavayi. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. A possible biosynthetic pathway of these five compounds was proposed. Compounds 1 and 3 exhibited moderate antimalarial activities against Plasmodium yoelii BY265RFP.
Subject(s)
Antimalarials/pharmacology , Malaria/drug therapy , Plants, Medicinal/chemistry , Plasmodium yoelii/drug effects , Sapindaceae/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Animals , Antimalarials/chemistry , Antimalarials/isolation & purification , Crystallography, X-Ray , Dose-Response Relationship, Drug , Mice , Mice, Inbred Strains , Models, Molecular , Molecular Structure , Parasitic Sensitivity Tests , Plant Roots/chemistry , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/isolation & purification , Structure-Activity RelationshipABSTRACT
Astragalus ernestii has been used as a substitute for Radix Astragali (Huang-Qi) in southwest China. To better understand the chemical rationale for the medicinal usage, the phytochemistry of A. ernestii was recently studied. As a result, a novel aurone-phenylpropanoid adduct astrernestin (1), together with five known phenoloids calycosin-7-O-ß-D-glucopyranoside (2), 4,4'-dimethoxy-3'-hydroxy-7,9':7',9-diepoxylignan-3-O-ß-D-glucopyranoside (3), syringaresinol-4-O-ß-D-monoglucoside (4), hedyotol D 4â³-O-ß-D-glucopyranoside (5) and trifolirhizin (6), were isolated from the roots of A. ernestii. The structure of compound 1 was elucidated by extensive spectroscopic analysis and optical rotation calculation.