Four new diterpenoids from the aerial parts of Leucas zeylanica (L.) R. Br.

Four new undescribed halimane- and labdane-type diterpenoids, named zeylleucapenoids E-H (1-4), along with four known analogues (5-8), were isolated from the aerial parts of Leucas zeylanica (L.) R. Br. Their structures were determined by comprehensive spectroscopic analysis and computational calculations. Compounds 1 and 2 are the highly modified halimane diterpenoids featuring a 6/6/6-fused tricyclic system with an unusual six-membered 6,11-ether ring. Compound 8 exhibits nontoxic effects for zebrafish embryo, while it displays efficient reduction against NO production in a dose-dependent manner and strongly suppresses the secretion of LPS-induced TNF-α and IL-6 cytokines in RAW264.7 macrophages. In addition, marked reductions of iNOS and COX-2 expression were observed. Molecular docking analysis indicated that 8 has high affinities with the target amino acid residues on protein-binding sites, which may be a possible mechanism contributing to the anti-inflammatory potential of this molecule.

[Chemical constituents with α-glucosidase inhibitory activities from seeds of Morinda citrifolia (Noni)].

The present study investigated the chemical constituents and inhibitory activities against α-glucosidase from the seeds of Morinda citrifolia(Noni) by the chromatographic technique and semi-preparative HPLC.Fifteen compounds were isolated from the ethyl acetate extract of the seeds, and their structures were identified on the basis of physiochemical characteristics and spectroscopic data as(9S,2E,4Z,7Z)-9-hydroxydeca-2,4,7-trienoic acid(1), azelaic acid(2), scopoletin(3), ursolic acid(4), quercetin(5), cyclo-(L-Leu-L-Ile)(6), cyclo-(L-Phe-L-Ile)(7), cyclo-(L-Phe-L-Val)(8), cyclo-(L-Leu-L-Val)(9), cyclo-(L-Phe-L-Leu)(10), caffeic acid(11), 3,4-dihydroxycinnamaldehyde(12), p-hydroxybenzoic acid(13), p-hydroxy-cinnamic acid(14), and p-hydroxyphenethyl alcohol(15).Among them, compound 1 was a new fatty acid and compounds 7-10 and 12 were isolated from Morinda plant in the Rubiaceae family for the first time.Compounds 1, 2 and 4-15 were isolated from the seeds of M.citrifolia(Noni) for the first time.All isolated compounds were evaluated for the inhibitory activities against α-glucosidase and compounds 3-5 showed potential inhibitory activity with IC_(50) values of 160, 133, and 120 µmol·L~(-1), respectively.

New alkaloids from the noni juice with potential α-glucosidase inhibitory activity.

Four new alkaloids, nonialkaloids A-D (1-4) and six known analogues (5-10) were isolated from the noni juice. Among the new compounds, 1 and 2 are indole alkaloids with a seven-membered fused N-heterocyclic ring, 3 and 4 are quaternary ammonium derivatives. The structures were elucidated by extensive NMR and MS analysis, while the absolute configurations of the stereogenic carbons were established based on quantum-chemical electronic circular dichroism calculations or the modified Mosher's method. All the isolates were tested for α-glucosidase inhibitory activities. Compounds 1 and 3 displayed potent inhibitory activity against α-glucosidase with the IC50 values of 413.7 and 364.4 µM, respectively.

Bioactive cyclohexene derivatives from a mangrove-derived fungus Cladosporium sp. JJM22.

Four new cyclohexene derivatives cladoscyclitols A-D (1-4) and one new ribofuranose phenol derivative 4-O-α-D-ribofuranose-2-pentyl-3-phemethylol (5) were obtained from the EtOAC extract of the mangrove-derived endophytic fungus Cladosporium sp. JJM22. The structures were elucidated by extensive NMR and MS analysis, while the absolute configurations of the stereogenic carbons were established based on quantum-chemical electronic circular dichroism calculations or comparison of the optical rotations with those of related compounds. Compounds 2 and 5 displayed potent inhibitory activity against α-glucosidase with the IC50 values of 2.95 and 2.05 µM, respectively.

Agarwood Alcohol Extract Ameliorates Isoproterenol-Induced Myocardial Ischemia by Inhibiting Oxidation and Apoptosis.

Agarwood is a traditional medicine used for treating some diseases, including painful and ischemic diseases. This study was carried out to investigate the potential cardioprotective effect of the whole-tree agarwood-inducing technique-produced agarwood alcohol extract (WTAAE) on isoproterenol- (ISO-) induced myocardial ischemia (MI) in rats and explore the underlying molecular mechanisms. Compared to the MI group, WTAAE pretreatment significantly improved ST wave abnormal-elevation, mitigated myocardial histological damage; decreased creatinine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST) levels; reduced hydrogen peroxide (H2O2) and lipid peroxide (LPO) production; and increased total antioxidant capacity (T-AOC) and catalase (CAT) activities. Moreover, agarwood alcohol extracts (AAEs) markedly enhanced the mRNA levels of Nrf2-ARE pathway, and Bcl-2 reduced the apoptotic Bax family mRNA expressions. In addition, the effect of WTAAE was greater than that of wild agarwood alcohol extract (WAAE) and burning-chisel-drilling agarwood alcohol extract (FBAAE). All of these data indicate that WTAAE exerted the protective effects of MI, and its mechanism was associated with upregulating Nrf2-ARE and suppressing Bcl-2 pathways.

Dalbergia odorifera: A review of its traditional uses, phytochemistry, pharmacology, and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia odorifera, a traditional herbal medicine, has long been used in China for dissipating blood stasis, regulating the flow of qi, and relieving pain. AIM OF THIS REVIEW: This review aims to provide comprehensive and up-to-date information about the traditional uses, phytochemistry, pharmacology, and quality control of D. odorifera. Additionally, perspectives for possible future investigations on D. odorifera are also discussed. MATERIALS AND METHODS: Information on D. odorifera was obtained from a library database and electronic searches (e.g., Elsevier, Springer, ScienceDirect, Wiley, Web of Science, PubMed, Google Scholar, China Knowledge Resource Integrated). RESULTS: According to classical Chinese herbal texts and the Chinese Pharmacopoeia, D. odorifera promotes blood circulation, relieves pain, and eliminates blood stasis, and it can be used to treat cardio-cerebrovascular diseases in traditional Chinese medicine prescriptions. The chemical constituents of D. odorifera have been well studied, with approximately 175 metabolites having been identified, including flavonoids, phenols, arylbenzofurans, and quinones. The species also contains well-studied volatile oil. Its flavonoids and volatile oil are generally considered to be essential for its pharmacological activity. Modern pharmacology research has confirmed that isolated components and crude extracts of D. odorifera possess wide-ranging pharmacological effects, including anti-inflammatory, anti-angina, anti-oxidative, and other activities. Additionally, there are few quality control studies on D. odorifera. CONCLUSIONS: To date, significant progress has been made in D. odorifera phytochemistry and pharmacology. Thus, modern pharmacological research has provided some evidence for local or traditional uses. D. odorifera also showed therapeutic potential in cardiovascular and coronary heart diseases. However, the present findings are insufficient to explain its mechanisms of action. Additionally, the mechanism of heartwood formation, artificial induction technology for heartwood production, and quality control of D. odorifera require further detailed research.

[Anti-inflammatory sesquiterpenes from agarwood produced via whole-tree agarwood-inducing technique of Aquilaria sinensis].

The present study is to investigate the chemical constituents and anti-inflammation of agarwood produced via whole-tree agarwood-inducing technique( Agar-Wit) from Aquilaria sinensis by column chromatographic technique and semi-preparation HPLC.Eleven sesquiterpenes were isolated from the agarwood produced by Agar-Wit,and their structures were identified on the basis of physiochemical characteristics and spectroscopic data analysis as baimuxinol( 1),5α,7α( H)-eudesm-11( 13)-en-4α-ol( 2),( 7 S,9 S,10 S)-( +)-9-hydroxy-selina-4,11-dien-14-al( 3),petafolia A( 4),7( 11)-eremophilen-8-one( 5),neopetasane( 6),petafolia B( 7),11-hydroxy-valenc-1( 10)-en-2-one( 8),( 4αß,7ß,8αß)-3,4,4α,5,6,7,8,8α-octahydro-7-[1-( hydroxymethyl) ethenyl]-4α-methylnaphthalene-1-carboxaldehyde( 9),12-hydroxy-4( 5),11( 13)-eudesmadien-15-al( 10),and( 4 R,5 R,7 S,9 S,10 S)-(-)-eudesma-11( 13)-en-4,9-diol( 11). Among them,compound 1 was a new natural product,and this is the first time to report its13 CNMR spectroscopic data. Compounds 4,9 and 10 were reported from Aquilaria for the first time,and all the compounds are firstly isolated by Agar-Wit from A. sinensis. The anti-inflammatory activity of RAW264. 7 cells with lipopolysaccharide-induced was evaluated.As a result,1,4 and 9 showed potential anti-inflammatory activities with IC50 values( 2. 5±0. 35),( 3. 2±0. 2),( 4. 3±0. 56) µmol·L-1,respectively. This work provided scientific foundation for quality evaluation of the agarwood produced by Agar-Wit.

Agarwood Extract Mitigates Intestinal Injury in Fluorouracil-Induced Mice.

Agarwood is used to treat gastrointestinal diseases. Although our previous studies demonstrated that agarwood ethanol extract produced by the whole-tree agarwood-inducing technique (WTAAE) improves intestinal peristalsis, the intestinal protective effect of WTAAE remains unclear. This study aimed to evaluate the protective effect of WTAAE on the intestinal injury induced by fluorouracil (5-FU) and explore its potential mechanism. Institute of Cancer Research (ICR) mice were given agarwood ethanol extracts (AAEs) (details in materials part), including WTAAE (0.71, 1.42 and 2.84 g/kg), wild agarwood ethanol extract (WAAE) and burning-chisel-drilling agarwood ethanol extract (FBAAE) (2.84 g/kg). A colon injury model was induced by 5-FU. After 14 d of treatment, the histopathology and biochemical and molecular parameters were measured. Our results indicated that WTAAE enhanced the intestinal advancing rate and alleviated the severity of colon injury similar the WAAE and better than FBAAE. Simultaneously, WTAAE reduced the nitric oxide (NO) concentration and increased the glutathione (GSH) and superoxide dismutase (SOD) levels. WTAAE also reduced the levels of interleukin-17 (IL-17) and IL-33 and elevated the level of IL-10. Furthermore, WTAAE upregulated the mRNA expression of the nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and downregulated the mRNA levels of the nuclear factor-kappaB (NF-κB) pathway. WTAAE had a mitigating effect on intestinal damage, suggesting that it could be used as an intestinal protective and adjuvant therapy drug for intestinal injury induced by chemical drugs.

Bioactive aporphine alkaloids from the stems of Dasymaschalon rostratum.

Three undescribed aporphine alkaloids dasymaroine A (1), 3-methoxyoxoputerine N-oxide (2), and dasymaroine B (3), along with nine known analogues (4-12) were isolated from the stems of Dasymaschalon rostratum Merr. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. Compound 1 is a rarely reported nitro aporphine alkaloid and its absolute configuration was defined based on negative specific rotation and single-crystal X-ray diffraction. Compound 2 represents the first example of oxoaporphine alkaloid N-oxide. All compounds were evaluated for their activities of six pathogenic bacteria, 1 exhibited significant inhibition against Escherichia coli and Saphylococcus aureus with MIC values of 1.2 and 2.5 µM, respectively. As well as compounds 1-5, 7, 10, 12 were evaluated for their anti-HIV activities with EC50 ranged from 1.93 to 9.70 µM.

Agarwood Essential Oil Ameliorates Restrain Stress-Induced Anxiety and Depression by Inhibiting HPA Axis Hyperactivity.

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspension (TS) test and the forced swimming (FS) test illuminated that AEO has an antidepressant effect with the immobility time decreased. Stress can cause cytokine and nitric oxide (NO) elevation, and further lead to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. AEO was shown to dose-dependently inhibit the levels of cytokines, including interleukin 1α (IL-1α), IL-1ß, and IL-6 in serum, significantly decrease the mRNA level of neural nitric oxide synthase (nNOS) in the cerebral cortex and hippocampus, and inhibit the nNOS protein level in the hippocampus. Concomitant measurements of the HPA axis upstream regulator corticotropin releasing factor (CRF) and its receptor CRFR found that AEO significantly decreases the gene expression of CRF, and significantly inhibits the gene transcription and protein expression of CRFR in the cerebral cortex and hippocampus. Additionally, AEO dose-dependently reduces the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) downstream of the HPA axis, as measured by ELISA kits. These results together demonstrate that AEO exerts anxiolytic and antidepressant effects which are related to the inhibition of CRF and hyperactivity of the HPA axis.

Chemical Constituents and Pharmacological Activity of Agarwood and Aquilaria Plants.

Agarwood, a highly precious non-timber fragrant wood of Aquilaria spp. (Thymelaeaceae), has been widely used in traditional medicine, religious rites, and cultural activities. Due to the inflated demanding and depleted natural resources, the yields of agarwood collected from the wild are shrinking, and the price is constantly rising, which restricts agarwood scientific research and wide application. With the sustainable planting and management of agarwood applied, and especially the artificial-inducing methods being used in China and Southeast Asian countries, agarwood yields are increasing, and the price is becoming more reasonable. Under this condition, illuminating the scientific nature of traditional agarwood application and developing new products and drugs from agarwood have become vitally important. Recently, the phytochemical investigations have achieved fruitful results, and more than 300 compounds have been isolated, including numerous new compounds that might be the characteristic constituents with physiological action. However, no one has focused on the new compounds and presented a summary until now. Alongside phytochemical advances, bioactivity screening and pharmacological investigation have also made a certain progress. Therefore, this review discussed the new compounds isolated after 2010, and summarized the pharmacological progress on agarwood and Aquilaria plants.

New phenylpropanoid and 6H-dibenzo[b,d]pyran-6-one derivatives from the stems of Dasymaschalon rostratum.

Three new phenylpropanoid derivatives, dasymaroacid A (1), dasymaroesters B and C (2 and 3), and one new polyoxygenated 6H-dibenzo[b,d]pyran-6-one derivative dasymarolactone D (4), together with seven known compounds (5-11), were isolated from the stems of Dasymaschalon rostratum Merr. Compounds 1 and 2 are unusual phenylpropanoid derivatives with a polymethyl substituted cyclopentene conjugated diketone as a substituent, and 3 is a unique cinnamic acid detective with a polymethyl substituted cyclohexene conjugated triketone as a substituent. Their structures were elucidated by extensive spectroscopic methods and chemical method, and 4 was further confirmed by the single crystal X-ray diffraction method. Compounds 1-4 and 7 showed weak anti-HIV-1 activities with EC50 values ranged from 16.44 to 25.91µM.

New clerodane diterpenoids from the roots of Polyalthia laui.

Five new clerodane diterpenoids, polylauiester A (1), (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-14-oic acid (2) and polylauiamides B-D (3-5), together with 11 known clerodane diterpenoids (6-16), were isolated from the roots of Polyalthia laui. Among them, polylauiester A (1) represents the first example of a novel norclerodane diterpenoid only containing 17 carbon atoms on the carbon skeleton, and polylauiamide B (3) is an unusual diterpenoid with a p-substituted benzene ring as a substituent. Their structures were elucidated by extensive spectroscopic methods, and the relative configuration of polylauiamide B (3) was further confirmed by the single crystal X-ray diffraction method. Biological evaluation of new compounds against human Hela, MCF-7 and A549 human cancer cell lines showed that all compounds displayed weak cytotoxicities against various human cancer cell lines in the range of IC50 at 25.01-39.31µM.