Cinchonain Ia

The flavonoid-enriched extract from the root of Smilax china L. inhibits inflammatory responses via the TLR-4-mediated signaling pathway.[Pubmed:32222576]

J Ethnopharmacol. 2020 Jun 28;256:112785.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china L. has been used clinically to treat various inflammatory disorders with a long history. AIM OF THE STUDY: To investigate the mechanisms underlying anti-inflammatory action of the extract from the herb. MATERIALS AND METHODS: The extract was identified and quantified using the Ultra Performance Liquid Chromatography-Photo Diode Array-Mass Spectrometer method. The anti-inflammatory activities were examined in xylene-induced mouse ear edema and cotton ball-induced rat granuloma. The inflammatory mediators, pro-inflammatory cytokines and TLR-4-mediated signals in LPS-stimulated RAW264.7 macrophages were determined using ELISA, real-time PCR, Western blot and/or immunofluorescence, respectively. RESULTS: The extract was found to enrich flavonoids (44.3%, mainly astilbin, engeletin, isoastilbin, Cinchonain Ia, quercetin-3-O-a-L-rhamnopyranoside and chlorogenic acid). The flavonoid-enriched extract (FEE) inhibited xylene-induced mouse ear edema and cotton ball-induced rat granuloma, and suppressed LPS-induced over-release and/or overexpression of tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1beta and interleukin-6 in RAW264.7 macrophages. Mechanistically, FEE suppressed protein overexpression of TLR-4 and its downstream signals, MyD88 protein, phosphorylated inhibitory kappaB-alpha, NF-kappaB-P65 and MAPK p38, as well as phosphorylation of phosphoinositide 3-kinase (PI3K) p85alpha at Tyr(607) and Akt at Ser(473) in LPS-stimulated macrophages. The mode of the anti-inflammatory action of FEE was similar to that of TAK-242 (a selective TLR-4 inhibitor). CONCLUSIONS: The present results demonstrate that FEE inhibit inflammatory responses via the TLR-4-mediated signaling pathway. Our findings go a new insight into the mechanisms underlying anti-inflammatory action of the herb, and provide a better understanding of its use for inflammatory diseases.

Anti-Alzheimer's flavanolignans from Ceiba pentandra aerial parts.[Pubmed:32151639]

Fitoterapia. 2020 Jun;143:104541.

Four flavanolignans, ceibapentains A (1) and B (2) and cinchonains Ia (3) and Ib (4), were isolated for the first time from an ethyl acetate extract of Ceiba pentandra (L) (Bombacaceae) aerial parts. The ceibapentains A (1) and B (2) are new compounds and their structures, including the absolute configurations, were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism analyses, then compared with reported data. Compounds 1-4 were tested for their anti-Alzheimer's activity via an assessment of their inhibitory effect on amyloid beta42 aggregation using a thioflavin T assay. The results revealed that Cinchonain Ia (3) showed a higher inhibitory effect (91%) than the standard curcumin (70%). Compounds 1, 2, and 4 exhibited moderate activity, with inhibition ratios of 43%, 47%, and 58%, respectively. A molecular docking study on the binding mode of 3 and curcumin with an amyloid beta1-40 peptide fibril structure indicated a high affinity of cinchonain 1a (3) towards amyloid beta1-40 peptide, in agreement with the experimental results.

Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Triterpenes and Alkaloids from Psychotria nuda (Cham. & Schltdl.) Wawra.[Pubmed:30875889]

Molecules. 2019 Mar 15;24(6). pii: molecules24061026.

A phytochemical study of leaves and twigs of Psychotria nuda resulted in 19 compounds, including five indole alkaloids, N,N,N-trimethyltryptamine, lyaloside, strictosamide, strictosidine, and 5alpha-carboxystrictosidine; two flavonolignans, Cinchonain Ia and cinchonain Ib; an iridoid, roseoside; a sugar, lawsofructose; a coumarin, scopoletin; a diterpene, phytol; three triterpenes, pomolic acid, spinosic acid, and rotungenic acid; and five steroids, sitosterol, stigmasterol, campesterol, beta-sitosterol-3-O-beta-d-glucoside, and beta-stigmasterol-3-O-beta-d-glucoside. Some compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis and their ability to inhibit NO production by macrophages stimulated by lipopolysaccharide (LPS). The compounds pomolic acid, spinosic acid, strictosidine, and 5alpha-carboxystrictosidine displayed antimycobacterial activity with minimum inhibitory concentrations ranging from 7.1 to 19.2 microg/mL. These compounds showed promising inhibitory activity against NO production (IC50 3.22 to 25.5 mug/mL). 5alpha-carboxystrictosidine did not show cytotoxicity against macrophages RAW264.7 up to a concentration of 100 microg/mL. With the exception of strictosamide, this is the first report of the occurrence of these substances in P. nuda.

Chemical constituents from the rhizomes of Smilax glabra and their antimicrobial activity.[Pubmed:23698042]

Molecules. 2013 May 8;18(5):5265-87.

Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7-63 were isolated from the rhizomes of Smilax glabra. Their structures were elucidated on the basis of extensive spectroscopic analyses, as well as by comparison with literature data. Twenty-seven of these compounds were obtained from and identified in the genus Smilax for the first time. The absolute configuration of (2S)-1,2-O-di-trans-p-coumaroylglycerol (43) was determined for the first time using the exciton-coupled circular dichroism (ECCD) method. Thirty isolated compounds were evaluated for their antimicrobial activity against three Gram-negative bacteria, three Gram-positive bacteria and one fungus, and the corresponding structure-activity relationships were also discussed. Eighteen compounds were found to be antimicrobial against the microorganisms tested and the minimum inhibitory concentrations (MIC) were in the range of 0.0794-3.09 mM. Among them, compound 1 showed antimicrobial activity against Canidia albicans with MIC value of 0.146 mM, which was stronger than Cinchonain Ia with an MIC of 0.332 mM. Compounds 3 and 4 exhibited inhibitory activity against Staphylococcus aureus with MIC values of 0.303 and 0.205 mM, respectively. The results indicated that these antimicrobial constituents of this crude drug might be responsible for its clinical antimicrobial effect.

Triterpenoids and flavonoids from Cecropia schreberiana Miq. (Urticaceae).[Pubmed:23459662]

Biochem Syst Ecol. 2013 Jun 1;48:96-99.

Phytochemical investigation of the leaves of Cecropia schreberiana Miq. (Urticaceae) led to the isolation of four triterpenoids (1-4), three flavone C-glycosides (5-7), two flavan-3-ols (8, 9), two flavanolignans (10, 11), and two proanthocyanidins (12, 13). All compounds were isolated from C. schreberiana for the first time. This is the first report demonstrating the presence of arjunolic acid (4), Cinchonain Ia (10), and cinchonain Ib (11) in the Urticaceae family. The occurrence of flavanolignans within the family Urticaceae supports the likelihood that such compounds are more common within the class Magnoliopsida than previously thought.

Antioxidant phenylpropanoid-substituted epicatechins from Trichilia catigua.[Pubmed:18020420]

J Nat Prod. 2007 Dec;70(12):2010-3.

Two new phenylpropanoid-substituted epicatechins, namely, catiguanin A ( 1) and catiguanin B ( 2), were isolated from the bark of Trichilia catigua along with four known compounds, Cinchonain Ia ( 3), cinchonain Ib ( 4), cinchonain Ic ( 5), and cinchonain Id ( 6). The structures of 1 and 2 were elucidated by analysis of spectroscopic data and by comparison of their NMR data with those of previously reported cinchonains. The isolated compounds exhibited potent antioxidant activity in the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical scavenging test, with IC 50 values in the 2.3-9.4 microM range.

Flavan-3-ol-phenylpropanoid conjugates from Anemopaegma arvense and their antioxidant activities.[Pubmed:17642036]

Planta Med. 2007 Aug;73(10):1107-11.

One of the species of commercially available catuaba was identified as Anemopaegma arvense by comparison of its micromorphological characteristics and TLC profile with six species of authenticated plants that are commonly referred to as catuaba. The bioactivity-guided fractionation of the ethyl acetate extract of the stem bark of this catuaba sample resulted in the isolation of one new (1, catuabin A) and three known flavan-3-ol type phenylpropanoids, Cinchonain Ia (2), cinchonain IIa (3), and kandelin A1 (4) with antioxidant activities. The structures of these compounds were determined by a combination of spectroscopic techniques. Additionally, these compounds were tested for their anti-inflammatory, cytotoxicity, antimalarial, and antimicrobial activities, where no activity was observed.

Hepatoprotective effect of Apocynum venetum and its active constituents.[Pubmed:10763585]

Planta Med. 2000 Mar;66(2):127-33.

The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), Cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.