The Natural Alkaloid (-)-N-Hydroxyapiosporamide Suppresses Colorectal Tumor Progression as an NF-κB Pathway Inhibitor by Targeting the TAK1-TRAF6 Complex.

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.

Trichopsistides A and B: Two Highly Oxygenated Pentacyclic Polyketides with Promising Inhibitory Effects on the NF-κB Signaling Pathway from the Fungus Trichoderma koningiopsis WZ-196.

Two highly oxygenated pentacyclic polyketides with two new carbon skeletons, trichopsistide A (1) and trichopsistide B (2), were isolated from the plant endophyte Trichoderma koningiopsis WZ-196 derived from the leaf of Rubia podantha Diels. The structures of these polyketides with full configurations were determined by comprehensive spectroscopic analysis, computer-assisted structure elucidation software, computational calculation, and X-ray crystal diffraction. Among them, 1 represented the first example of an unprecedented 5/6/6/6/5 pentacyclic ketal-containing polyketide pyridine alkaloid, and 2 possessed a novel 6/6/6/6/5 pentacyclic ketal-containing polyketide scaffold fused with an α-pyrone. The plausible biosynthetic route for 1 and 2 was also proposed. Moreover, biological activity assays showed that 1 and 2 possessed inhibitory effects on the NF-κB signaling pathway with IC50 values of 14.77 and 8.58 µM, respectively. Furthermore, 1 and 2 could also inhibit the expression of IκBα and p65 phosphorylation, decrease the expression of MCP-1, E-selectin, and IL-8 at the mRNA level, and inhibit the TNF-α-induced nuclear translocation of p65.

Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing Klotho.

Renal fibrosis is an unavoidable end result of all forms of progressive chronic kidney diseases (CKD). Discovery of efficacious drugs against renal fibrosis is in crucial need. In a preliminary study we found that a derivative of artemisinin, dihydroartemisinin (DHA), exerted strong renoprotection, and reversed renal fibrosis in adenine-induced CKD mouse model. In this study we investigated the anti-fibrotic mechanisms of DHA, particularly its specific target in renal cells. Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) or oral administration of adenine (80 mg · kg-1), the mice received DHA (30 mg · kg-1 · d-1, i.g.) for 14 or 21 days, respectively. We showed that DHA administration markedly attenuated the inflammation and fibrotic responses in the kidneys and significantly improved the renal function in both the renal fibrosis mouse models. In adenine-treated mice, DHA was more effective than 5-azacytidine against renal fibrosis. The anti-fibrotic effects of DHA were also observed in TGF-ß1-treated HK-2 cells. In order to determine the target protein of DHA, we conducted pull-down technology coupled with shotgun proteomics using a small-molecule probe based on the structure of DHA (biotin-DHA). As a results, DNA methyltransferase 1 (DNMT1) was identified as the anti-fibrotic target of DHA in 3 different types of renal cell lines (HK-2, HEK293 and 3T3). We demonstrated that DHA directly bound to Asn 1529 and Thr 1528 of DNMT1 with a Kd value of 8.18 µM. In primary mouse renal tubular cells, we showed that DHA (10 µM) promoted DNMT1 degradation via the ubiquitin-proteasome pathway. DHA-reduced DNMT1 expression effectively reversed Klotho promoter hypermethylation, which led to the reversal of Klotho protein loss in the kidney of UUO mice. This subsequently resulted in inhibition of the Wnt/ß-catenin and TGF-ß/Smad signaling pathways and consequently conferred renoprotection in the animals. Knockdown of Klotho abolished the renoprotective effect of DHA in UUO mice. Our study reveals a novel pharmacological activity for DHA, i.e., renoprotection. DHA exhibits this effect by targeting DNMT1 to reverse Klotho repression. This study provides an evidence for the possible clinical application of DHA in the treatment of renal fibrosis.

Rubichaetoglobin A, a new cytochalasan alkaloid isolated from the plant endophytic fungus Chaetomium tectifimeti S104.

Rubichaetoglobin A (1), a new cytochalasan alkaloid, together with nine closely related known ones (2-10), were isolated from the ethyl acetate extracts of the endophytic fungus Chaetomium tectifimeti S104 harbored in the root of Rubia podantha Diels. Their structures were elucidated based on comprehensive spectroscopic analysis. All isolated compounds were tested for cytotoxic, antibacterial, and nitric oxide inhibitory activities. The results showed that 2, 4, and 5 possessed moderate cytotoxicity against MDA-MB-231 cells with the IC50 values of 19.14, 11.43, and 10.27 µM, respectively.

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli.

The clerodane and ent-kaurane diterpenoids are two typical categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol to reinforce the supply of IPP and DMAPP via two sequential phosphorylation reactions. Optimization of these constructs provided terpentetriene and ent-kaurene titers of 66 ± 4 mg/L and 113 ± 7 mg/L, respectively, in shake-flask fermentation. The truncated pathways to overproduce clerodane and ent-kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds.

Asiatic acid prevents renal fibrosis in UUO rats via promoting the production of 15d-PGJ2, an endogenous ligand of PPAR-γ.

Renal fibrosis is an inevitable outcome of all kinds of progressive chronic kidney disease (CKD). Recently, asiatic acid (AA), a triterpenoid compound from Chinese medicine Centella asiatica, has been found to attenuate renal fibrosis. In the current study, we explored the mechanisms underlying antifibrotic effect of AA on UUO model. SD rats and ICR mice were subjected to unilateral ureteral occlusion (UUO) surgery. Prior the surgery, rats were administered AA (10 mg·kg-1 per day, ig) for 7 days, whereas the mice received AA (15 mg·kg-1 per day, ig) for 3 days. UUO group displayed significant degree of renal dysfunction, interstitial fibrosis, oxidative stress, and activation of the TGF-ß/Smad and Wnt/ß-catenin signaling pathway in the kidney, these pathological changes were greatly ameliorated by pretreatment with AA. In addition, we found that co-treatment with GW9662, a selective PPAR-γ antagonist (1 mg·kg-1 per day, ip) for 7 days, abolished the protective effects of AA. We further revealed that AA pretreatment did not significantly change the expression levels of PPAR-γ in the kidney, but markedly increase the plasma levels of 15d-PGJ2, an endogenous ligand of PPAR-γ. In UUO mice, pretreatment with 15d-PGJ2 (24 µg·kg-1 per day, ip, for 7 days) produced similar protective effect as AA. Moreover, AA pretreatment upregulated the expression levels of active, nuclear-localized SREBP-1 (nSREBP-1), whereas fatostatin, a specific inhibitor of SREBP-1, decreased the expression of nSREBP-1, as well as the level of 15d-PGJ2. These results provide new insight into the antifibrotic mechanism of AA and endogenous metabolites might become a new clue for investigation of drug mechanism.

Colletopeptides A-D, Anti-inflammatory Cyclic Tridepsipeptides from the Plant Endophytic Fungus Colletotrichum sp. S8.

Four new hybrid peptide-polyketide cyclic tridepsipeptides, colletopeptides A-D (1-4), were isolated and characterized from the endophytic fungus Colletotrichum sp. S8 derived from the stems of Rubia podantha with the guidance of LC-UV-MS detection. Their structures were elucidated by extensive spectroscopic analysis and X-ray crystallography. Compounds 1-4 are rare natural 12-membered cyclic tridepsipeptides containing a 3,5,11-trihydroxy-2-methyl dodecanoic acid unit in their structures. 1-4 inhibited lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages with the IC50 values of 8.3, 38.7, 13.5, and 22.2 µM, respectively. 1 also inhibited the production of inflammatory factors IL-6 and TNF-α, and decreased the phosphorylation of NF-κB-associated proteins IκBα and p65.

Βeta-sitosterol enhances motor coordination, attenuates memory loss and demyelination in a vanadium-induced model of experimental neurotoxicity.

Environmental discharge of vanadium causes cognitive and behavioral impairments in humans and animals via production of reactive oxygen species leading to lipid peroxidation and alteration in antioxidant defence system. The current study was carried out to investigate the cognitive-enhancing ability of ß-sitosterol in vanadium-induced neurotoxicity. Forty eight mice were randomly assigned into 4 groups (A-D) with the following treatments: group A; distilled water, B; α-tocopherol + sodium metavanadate (NaO3V), C; ß-sitosterol + NaO3V and D; only NaO3V. NaO3V was administered intraperitoneally while other treatments were administered through gavage for 7 consecutive days. Neurobehavioral parameters measuring cognition, locomotion, anxiety and grip strength were evaluated at day 8. Following sacrifice, brain levels of catalase, superoxide dismutase, glutathione, malonaldehyde (MDA) and hydrogen peroxide (H2O2) were measured. Immunohistochemical expression of Myelin Basic Protein (MBP) in the brain was also investigated. The results showed that deficits in spatial learning, locomotor efficiency, and motor coordination, induced by acute vanadium neurotoxicity were mitigated by beta-sitosterol. Significantly (α ≤ 0.05) decreased in vivo antioxidant enzyme activities, increased brain levels of MDA and H2O2, structural damage to myelin sheaths and decreased expression of MBP were also observed in the NaO3V group (D), however, co-administration of ß-sitosterol reduced these pathologic features. It is concluded that ß-sitosterol alleviates vanadium-induced neurotoxicity by enhancing cognition and improving motor co-ordination via its antioxidant and myelo-protective activities.

Rubipodanin B, a New Cytotoxic Cyclopeptide from Rubia podantha.

Using the TLC cyclopeptide protosite detection method, a new cyclohexapeptide named rubipodanin B (1), together with 11 known Rubiaceae-type cyclopeptides (RAs), RA-X-OMe (2), RA-IV (3), RA-XI (4), RA-XIII-OMe (5), rubiyunnanin C (6), RA-I (7), RA-III (8), RA-V (9), RA-VII (10), RA-XII (11) and rubipodanin A (12), were obtained from the roots and rhizomes of Rubia podantha Diels. The structures were determined using various spectroscopic methods. Among them, 2 was firstly identified as a natural product, and 3-6 were firstly isolated from this species. Cytotoxicity and NF-κB signaling pathway activity of 1, 2, 4, 6, 7 and 9 were evaluated. All these compounds showed cytotoxic activities against three human tumor cell lines, MDA-MB-231, SW620 and HepG2, with the IC50 values between 0.015 and 10.27 µm, and only 7 and 9 possessed NF-κB inhibitory activities with the IC50 values of 2.42 and 0.046 µm, respectively, which demonstrated that 2-alanine amino acid plays a key role to maintain the RAs bioactivity.

[A new phenolic glycoside from honey-fried Eriobotrya japonica].

A total of twelve compounds were isolated from the ethyl acetate of the water extract of honey-fried Eriobotrya japonica through column chromatography over silica gel,Sephadex LH-20,RP-18,and preparative HPLC. Their structures were established by MS,1 D NMR and 2 D NMR data as japonicanoside A( 1),nerolidol-3-O-α-L-rhamnopyranosyl-( 1→2)-ß-D-glucopyranoside( 2),nerolidol-3-O-α-L-rhamnopyranosyl-( l→4)-α-L-rhamnopyranosyl-( 1 → 2)-[α-L-( 4-trans-feruloyl)-rhamnopyranosyl-( 1 → 6) ]-ß-D-glucopyranoside( 3),( +)-catechin( 4),(-)-epicatechin( 5),kaempferol 3-O-α-L-rhamnopyranoside( 6),quercitrin( 7),quercetin-3-O-ß-D-galactopyranoside( 8),quercetin-3-O-ß-glucopyranoside( 9),vanillin( 10),protocatechuic aldehyde( 11),and maltol( 12). Among them,1 is a new phenolic glycoside.

Design and synthesis of plant cyclopeptide Astin C analogues and investigation of their immunosuppressive activity.

To further investigate on the structure-activity relationships of immunosuppressive Astin C, seventeen analogues 1-17 were designed and synthetized via amino acid substitution strategy by the solid-phase peptide synthesis method for the first time. In comparison with Astin C (IC50 = 12.6 ±â€¯3.3 µM), only compounds 2 (IC50 = 38.4 ±â€¯16.2 µM), 4 (IC50 = 51.8 ±â€¯12.7 µM), 5 (IC50 = 65.2 ±â€¯15.6 µM), and 8 (IC50 = 61.8 ±â€¯12.4 µM) exhibited immunosuppressive activity in the Lymph node cells of mice. These results showed that the Astin C analogues containing D-amino acid residues, hydrophobic long-chain alkyl substituents, and aryl substituents performed better than those carrying hydrophilic amino acid residues and short-chain alkyl substituents. Moreover compounds 15, 16, and 17 had no immunosuppressive activity, which suggested that cis-3,4-dichlorinated proline played an important role in the immunosuppressive activity of Astin C.

[Chemical constituents from roots and rhizomes of Rubia oncotricha and their cytotoxic activities].

Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time. Cytotoxic and nematicidal activities of all these compounds were evaluated, and the results showed that only 4, 6, 11 and 12 exhibited cytotoxicities against A549, SGC-7901 and HeLa cancer cell lines. The IC50 of 6 were 19.42, 2.74, 8.07 µmol·L⁻¹, respectively.

[Chemical and cytotoxic constituents of Zanthoxylum nitidum].

Ten compounds were isolated from the methanol extract of Zanthoxylum nitidum through silica gel, Sephadex LH-20, RP-18 and HPLC chromatography techniques. Their structures were elucidated by the MS and NMR spectra as zanthonitidine B(1), cyclo-(Leu-Leu-Leu-Leu-Ile)(2),6S-10-O-demethylbocconoline(3), liriodenine(4), isoplatydesmine(5), 5, 5'-dimethoxylariciresinol(6), syringaresinol (7), episyringaresinol (8), marmesin (9) and syringaldehyde (10). Among them,1 is a new alkaloid,2 is a cyclopentapeptide isolated from plant kingdom for the first time, and 3 is from the genus Zanthoxylum for the first time. Compounds 3 and 4 exhibited cytoxoxicity against three human cancer cell lines HT29, A549 and MDA-MB-231 with IC58 values of 27.37, 24.10, 33.58 µmol·L⁻¹ and 9.12,6.05, 11.35 µmol·L⁻¹, respectively.

[Mass spectrometry guided strategy based on feature fragment ions for guided-separation on quinoline alkaloids from root barks of Dictamnus dasycarpus].

The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion m/z 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.

[Chemical constituents from root barks of Dictamnus dasycarpus and their cytotoxic activities].

Nineteen compounds, including kihadanin D (1), obacunone (2), kihadanin A (3), kihadanin B (4), kihadanin C (5), limonin (6), evodol (7), fraxinellone (8), furo[2,3-b]quinolin-4-ol (9), preskimmianine (10), ifflaiamine (11), dictamnol (12), naringenin (13), diosmetin (14), wogonin (15), scopoletin (16), cleomiscosin A (17), apocynin (18), and methyl pyroglutamate (19), were isolated from the methanol extract of the root barks of Dictamnus dasycarpus by using various column chromatographies. Their chemical structures were extensively determined on basis of UV, IR, NMR, MS, and CD spectroscopic data analyses. Among them, 1 is a new limonoid, 9 was isolated from plant kingdom for the first time, 11, 13-14 and 17-19 were obtained from the genus Dictamnnus for the first time. Cytotoxicities of compounds 1-18 were tested, and the results indicated that 1 exhibited cytotoxicities against three human cancer cell lines MDA-MB-231, A549 and HT29 with IC58 values of 16.22, 21.72 and 31.06 µmol·L⁻¹, respectively.

Phytochemical Analysis of a Cytotoxic Fraction of Quassia silvestris using LC-HR-ESI-MSn.

INTRODUCTION: The genus Quassia is a promising source of secondary metabolites with biological potential including antimalarial and cytotoxic activities. Limited data are available on the phytochemistry and pharmacology of Quassia silvestris Cheek & Jongkind, a Cameroonian medicinal plant used to treat various ailments. OBJECTIVES: To carry out the bioassay-guided fractionation and LC-HR-ESI-MS analyses of the leaves extract from Q. silvestris; to purify the active fractions and isolate the major compounds using different chromatographic and spectroscopic methods. The obtained compounds will be evaluated for their biological activity. MATERIAL AND METHODS: Following the cytotoxic screening and LC-HR-ESI-MS profiling of fractions obtained from partition of the methanolic extract of Q. silvestris leaves, the CH2 Cl2 -soluble fraction which exhibited the highest cytotoxicity was retained for further investigations. RESULTS: Sixteen squalene-derived metabolites were identified with oxasqualenoid derivatives being the most predominant. Among the isolates, structure elucidation of two new oxasqualenoids quassiols E (1) and F (2), were achieved by NMR (one-dimensional (1D) and two-dimensional (2D)) and MS methods. The newly characterised compounds 1 and 2, together with the known tetraol (3) and 3-oxo-oleanoic acid (16) displayed moderate cytotoxicity. CONCLUSION: The identification and structural characterisation of highly oxidised squalene derived metabolites from this plant may provide important insight data for further pharmacological investigations. The LC-HR-ESI-MSn method reported here could be developed as a rapid and efficient tool for the analyses of structurally related compounds in the genera Quassia, Simarouba, and Eurycoma of the subfamily Simarouboideae. Copyright © 2016 John Wiley & Sons, Ltd.

Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-κB signaling pathways.

Cyclopeptide RA-V has potent anti-tumor and anti-angiogenic activities, but its potential anti-metastatic activity is unknown. Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM), allowing them to migrate to adjacent tissues and ultimately metastasize. Hence, the present study aimed to investigate the effects of RA-V on cell adhesion, migration, invasion and matrix degradation, and its underlying mechanism in two human breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Our results demonstrated that RA-V (12.5 nM) can significantly inhibit breast cancer cell adhesion and migration via interfering cofilin signaling and chemokine receptors involved in cell migration. RA-V reduced the expressions of vascular intracellular adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), focal adhesion kinase (FAK) and integrins. The activities and expressions of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and urokinase-type of plasminogen activator (uPA) were also inhibited by RA-V. Furthermore, RA-V inhibits the expressions of EGFR, PI3K/AKT and NF-κB signaling molecules, and reduces the binding of ß-estradiol to ER via affecting binding ability of ER in MCF-7 cells. RA-V inhibits breast cancer cell migration, adhesion and ECM degradation in vitro, implying that RA-V is a potential anti-metastatic agent in breast cancer, and likely acts via PI3K/AKT and NF-κB signaling pathways in both ER-positive and ER-negative breast cancer cells.

Two New Cinnamyl Isovalerate Derivatives from Sabina gaussenii.

Chemical investigation of the 90% acetone extract of the branches and leaves of Sabina gaussenii led to the isolation of two new cinnamyl isovalerate derivatives (1-2) and eighteen known compounds (3-20). Their structures were determined mainly by means of MS, 1D- and 2D-NMR data, and this is the first time these compounds have been reported from this plant. The biological activity test results indicated that the 90% acetone extract showed cytotoxicity against the human lung adenocarcinoma (A549) cell line (IC50 = 0.98 ± 0.1 µg/mL), compound 6 showed cytotoxicities against human cervical carcinoma (HeLa) (IC50 = 0.4 ± 0.1 µM ) and human gastric carcinoma (BGC-823) (IC50 = 0.9 ± 0.2 µM) cancer cell lines, and compound 19 showed cytotoxicities against HeLa (IC50 = 1.5 ± 0.4 µM), BGC-823 (IC50 = 7.0 ± 0.8 µM ), and A549 (IC50 = 10.6 ± 1.5 µM ) cancer cell lines.

[Chemical constituents from Impatiens pritzllii var. hupehensis].

Eight compounds were isolated from the 50% ethanol extract of Impatiens pritzllii var.hupehensis through various column chromatography methods including silica gel, Sephadex LH-20, and preparative HPLC. Their structures were elucidated as 2,6-dimethyl-2-vinyl-2,3,4,7-tetrahydrooxepine(1), 1,3,6-trihydroxy-7-methyl-anthraquinone(2),4-hydroxybenzaldehyde(3),4-(3-methoxy-4-hydroxyphenyl)-2-butanone(4), podophyllotoxin(5),scopoletin(6), α-spinasterol(7) and 3-O-ß-D-glucopyranosyl-α-spinasterol(8) based on the NMR and MS spectral data. Compound 1 is new compound and compounds 2-8 are isolated from this plant for the first time.

Chemical constituents from stems and leaves of Micromelum integerrimum.

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.