Zerumin

Anti-Inflammatory Terpenoids from the Rhizomes of Shell Ginger.[Pubmed:38126326]

J Agric Food Chem. 2024 Jan 10;72(1):424-436.

Shell ginger (Alpinia zerumbet) is a perennial ornamental plant of ginger native to East Asia, which can be used as a flavoring agent in food or beverage, as well as a traditional Chinese medicine. In this study, a total of 37 terpenoids, including 7 new compounds, Zerumin D1 to Zerumin D7 (2, 3, 28-30, 36, and 37), and 5 new naturally occurring compounds, Zerumin D10 to Zerumin D14 (9, 12, 15, 20, and 24), were isolated and identified from the rhizomes of shell ginger. Compound 3 was an unprecedented variant labdane diterpenoid featuring a unique 6/7/6/3 tetracyclic cyclic ether system in its side chain. The anti-inflammatory activities of the isolated terpenoids were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Compound 4 significantly inhibited the production of nitric oxide with an IC(50) value of 5.4 muM. Further investigation revealed that compounds 2 and 3 may inhibit the nuclear translocation of NF-kappaB, thus suppressing the expression of IL-6, IL-1beta, iNOS, and COX-2 to exert the anti-inflammatory effects.

Labdane-type diterpenoids and sesquiterpenes from Curcuma aromatica and their nitric oxide inhibitory activity in lipopolysaccharide-stimulated RAW264.7 macrophages.[Pubmed:37289576]

J Asian Nat Prod Res. 2024 Mar;26(3):387-393.

One new labdane-type diterpenoid, 3beta,15-dihydroxylabda-8(17),12E-dien-16,15-olide (1) named curcumatin and twelve known compounds, coronarin D (2), isocoronarin D (3), (E)-labda-8(17),12-diene-15,16-dial (4), Zerumin A (5), (E)-labda-8(17),12-dien-15,16-dioic acid (6), furanodiene (7), linderazulene (8), zedoarol (9), zedoarondiol (10), germacrone-1,10-epoxide (11), germacrone-4,5-epoxide (12), and zingiberenol (13) were isolated from the ethanol extract of the roots of Curcuma aromatica Salisb. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, and comparing with the NMR data reported in the literature. Compounds 2, 5, and 13 significantly inhibited the nitric oxide production effect in LPS-stimulated RAW 264.7 macrophages with IC(50) values of 8.8 +/- 1.7, 4.0 +/- 0.9, and 6.2 +/- 0.4 microM, respectively.

Anti-hyperglycaemic effect of labdane diterpenes isolated from the rhizome of Amomum maximum Roxb., an edible plant in Southwest China.[Pubmed:33759661]

Nat Prod Res. 2022 May;36(10):2570-2574.

Amomum maximum Roxb. rhizome is a fork medicine mainly used in South and Southeast Asia. In present study, the hypoglycaemic effects of the ethanolic extract of A. maximum rhizome were demonstrated both on alpha-glucosidase assay in vitro and streptozotocin (STZ)-induced postprandial hyperglycaemia in mice. Furthermore, six labdane diterpenes, amoxanthin A (1), ottensinin (2), coronarin D (3), coronarin D methyl ether (4), isocoronarin D (5), and Zerumin (6), were isolated from its ethyl acetate sub-fraction with the guidance of alpha-glucosidase inhibitory activity. Among these compounds, 2 and 6 exhibited significant inhibitory effect on alpha-glucosidase, as well as on STZ-induced high postprandial blood glucose levels in mice. Additionally, molecular docking analysis revealed that 2 and 6 could firmly bind to the active sites of alpha-glucosidase. These results suggest that compounds 2 and 6 are the main anti-hyperglycaemic agents present in A. maximum, which may demonstrate potential beneficial effects in diabetes management.

Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts.[Pubmed:33755281]

J Biochem Mol Toxicol. 2021 Jun;35(6):1-11.

Zerumin A (ZA) is one of the potential components of Curcuma amada rhizomes, and it has been shown to possess a variety of pharmacological activities. This study deals with the beneficial activity of ZA in lipopolysaccharide (LPS)-stimulated inflammation in H9c2 cardiomyoblasts. Herein, H9c2 cells were preincubated with ZA for 1 h and stimulated with LPS for 24 h. The cells were analyzed for the expression of various pro-inflammatory mediators and signaling molecules. Results showed that the cell viability was significantly improved and reactive oxygen species production was alleviated remarkably with ZA pretreatment. We also found that ZA pretreatment significantly suppressed the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein levels, and nitric oxide (NO) release in LPS-stimulated cells. In addition, ZA significantly ameliorated LPS-elicited overexpression of pro-inflammatory chemokines and cytokines such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF- alpha), interferon-gamma (IFN-gamma), and interleukin-1 (IL-1) in H9c2 cells, and it upregulated the synthesis of the anti-inflammatory cytokine interleukin-10 (IL-10). Moreover, pretreatment with ZA and the mitogen-activated protein kinases (MAPK) pathway inhibitors also reduced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK), and p38. ZA significantly inhibited IkB-a phosphorylation and nuclear factor (NF)-kB p65 subunit translocation into nuclei. Overall data demonstrated that ZA protects cardiomyocytes against LPS injury by inhibiting NF-kB p65 activation via the MAPK signaling pathway in vitro. These findings suggest that ZA may be a promising agent for a detailed study for the prevention or treatment of myocardial dysfunction in sepsis.

Chemical constituents from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae).[Pubmed:25751012]

Nat Prod Res. 2015;29(21):2030-2.

The chemical investigation of ethanolic extract from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae) has resulted in the isolation of eight compounds which were characterised as beta-sitosterol (1), beta-sitosterol beta-D-glucoside (2), bergapten (3), Zerumin A (4), (E)-labda-8(17),12-diene-15,16-dial (5), kaempferol (6), quercetin (7) and astragalin (8). All compounds were identified by spectroscopic and chemical methods. This paper describes the first phytochemical work on C. spicata.

Cytotoxic constituents from the rhizomes of Curcuma zedoaria.[Pubmed:25126594]

ScientificWorldJournal. 2014;2014:321943.

Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), Zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1-19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 +/- 1.0 and 9.3 +/- 0.3 mug/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer.

Phytochemical profiling of Curcuma kwangsiensis rhizome extract, and identification of labdane diterpenoids as positive GABAA receptor modulators.[Pubmed:24011802]

Phytochemistry. 2013 Dec;96:318-29.

An ethyl acetate extract of Curcuma kwangsiensis S.G. Lee & C.F. Liang (Zingiberaceae) rhizomes (100 mug/ml) enhanced the GABA-induced chloride current (IGABA) through GABAA receptors of the alpha1beta2gamma2S subtype by 79.0+/-7.0%. Potentiation of IGABA was measured using the two-microelectrode voltage-clamp technique and Xenopus laevis oocytes. HPLC-based activity profiling of the crude extract led to the identification of 11 structurally related labdane diterpenoids, including four new compounds. Structure elucidation was achieved by comprehensive analysis of on-line (LC-PDA-ESI-TOF-MS) and off-line (microprobe 1D and 2D NMR) spectroscopic data. The absolute configuration of the compounds was established by comparison of experimental and calculated ECD spectra. Labdane diterpenes represent a new class of plant secondary metabolites eliciting positive GABAA receptor modulation. The highest efficiency was observed for Zerumin A (maximum potentiation of IGABA by 309.4+/-35.6%, and EC50 of 24.9+/-8.8 muM).

Sesquiterpenes from the rhizomes of Curcuma heyneana.[Pubmed:23387824]

J Nat Prod. 2013 Feb 22;76(2):223-9.

Four new germacranes [heyneanones A-D (1-4)], three new guaianes [4,10-epizedoarondiol (5), 15-hydroxyprocurcumenol (6), 12-hydroxycurcumenol (7)], and two new spirolactones [curcumanolides C (8) and D (9)] were isolated from the rhizomes of Curcuma heyneana together with 13 known sesquiterpenes and two known labdane-type diterpenes. Among the isolated compounds, heyneanone A (1), heyneanone C (3), 4,10-epizedoarondiol (5), procurcumenol (16), aerugidiol (17), Zerumin A (23), and (E)-15,16-bisnorlabda-8(17),11-dien-13-one (24) inhibited protein tyrosine phosphatase 1B (PTP1B) with IC(50) values of 42.5, 35.2, 35.1, 45.6, 35.7, 10.4, and 14.7 muM, respectively.

Anti-angiogenic effects and mechanisms of zerumin A from Alpinia caerulea.[Pubmed:26434281]

Food Chem. 2012 May 1;132(1):201-8.

Alpinia caerulea (R.Br.) Bentham, a perennial herb growing in tropical and subtropical Australia, is used as a flavouring spice and a ginger substitute. Its fruit has been used as indigenous food among the aboriginal Australians; 95% ethanol extracts of the dried fruits, leaves, rhizomes and roots of this plant were investigated in a zebrafish model by quantitative endogenous alkaline phosphatase assay. Only the fruit extract showed potential anti-angiogenic effect, inhibiting vessel formation by 25% at 20mug/ml. Two diterpenoids were isolated and identified as Zerumin A and (E)-8(17),12-labdadiene-15,16-dial. Zerumin A, which had mainly accumulated in the fruits and bearing a carboxylic group, could dose-dependently inhibit vessel formation, in both wild-type and Tg(fli1a:EGFP)y1 zebrafish embryos. The semi-quantitative reverse transcription polymerase chain reaction assay on wild type zebrafish embryos suggested that Zerumin A affected multiple molecular targets related to angiogenesis. Further investigation, by human umbilical vein endothelial cell assays, revealed that Zerumin A specifically inhibited the proliferation and migration steps, to prevent angiogenesis progress.

Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes.[Pubmed:21629182]

Molecules. 2011 May 31;16(6):4539-48.

Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), Zerumin A (3), beta-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.

Synthesis of (+)-zerumin B using a regioselective singlet oxygen furan oxidation.[Pubmed:18247492]

J Org Chem. 2008 Mar 7;73(5):2021-3.

A short and efficient synthesis of the antitumor diterpenoid (+)-Zerumin B has been accomplished starting from (+)-sclareolide. At the heart of the synthetic strategy lies the regioselective formation of the alpha-substituted gamma-hydroxybutenolide moiety of Zerumin B. This was achieved by means of a [1,4] O-->C triisopropylsilyl migration followed by singlet oxygen (1 O 2) oxidation of the resulting 2-triisopropylsilyl-3-(alpha-hydroxy)alkylfuran.

Synthesis and stereochemistry of the antitumor diterpenoid (+)-zerumin B.[Pubmed:16901169]

J Org Chem. 2006 Aug 18;71(17):6670-3.

Starting from commercially available (+)-sclareolide, the first synthesis of Zerumin B was achieved by a concise, highly efficient pathway featuring stereoselective addition of a new silyloxyfuryltitanium reagent to an aldehyde intermediate and silyloxyfuran oxyfunctionalization as key steps. The synthesis established the relative and absolute configuration of Zerumin B along with its identity with a purportedly new diterpenoid isolated from the plant Renealmia alpinia.

A labdane diterpene glucoside from the rhizomes of Curcuma mangga.[Pubmed:16038556]

J Nat Prod. 2005 Jul;68(7):1090-3.

A new labdane diterpene glucoside, curcumanggoside (1), together with nine known compounds, including labda-8(17),12-diene-15,16-dial (2), calcaratarin A (3), Zerumin B (4), scopoletin, demethoxycurcumin, bisdemethoxycurcumin, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one, curcumin, and p-hydroxycinnamic acid, have been isolated from the rhizomes of Curcuma mangga. Their structures were determined using a combination of 1D (1H NMR, 13C NMR, DEPT) and 2D (COSY, HSQC, HMBC) NMR techniques. All diarylheptanoids and scopoletin showed significant antioxidant activity. Zerumin B, demethoxycurcumin, bisdemethoxycurcumin, and curcumin also exhibited cytotoxic activity against a panel of five human tumor cell lines.