The structure elucidation of three new alkaloids named isoformosaninol (1), formosaninol (2), and longiflorine (3), isolated from the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsdale, along with their biosynthetic pathways are discussed. Their absolute structures were determined through a combination of physical data interpretation and quantum chemical calculations using the time-dependent density functional theory (TDDFT) method.
The genus Uncaria belongs to the family Rubiaceae, which mainly distributed in tropical regions, such as Southeast Asia, Africa and Southeast America. Their leaves and hooks have long been thought to have healing powers and are already being tested as a treatment for asthma, cancer, cirrhosis, diabetes, hypertension, stroke and rheumatism. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of the genus Uncaria to support for further therapeutic potential of this genus. To better understanding this genus, information on the stereo-chemistry and structure-activity relationships in indole alkaloids is also represented.
Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1), 2,4-dihydroxybenzoic acid (2), 3,4-dihydroxybenzoic acid (3), scopoletin or 7-hydroxy-6-methoxy-coumarin (4), 3,4-dihydroxy-7-methoxycoumarin (5), quercetin (6), kaempferol (7), taxifolin (8), loganin (9) and β-sitosterol (10). Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR) spectral data and Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) spectroscopy and mass spectrometry (MS). In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3%) at a concentration of 1 mg/mL. The IC50 values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC50 values of 549 and 556 μg/mL compared to acarbose (IC50 580 μg/mL) while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus and the first report of the α-glucosidase inhibitory potential of 2,4-dihydroxybenzoic acid.
Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.
Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their cytoprotective and antioxidant activities with phenolic content was also determined.
Two new heteroyohimbine-type oxindole alkaloids, rauniticine-allo-oxindole B and rauniticinic-allo acid B, have been successfully isolated from the stems extract of Malaysian Uncaria longiflora var. pteropoda. The structures of the two new alkaloids were determined by spectroscopic analysis.