Coumarins in the Rutaceae

Over the past 150 years, since Vogel in 1820 isolated the parent oxygen heterocycle, coumarin (1) from Coumarouna odorata = Dipteryx odorata (1), coumarins have been recognized as widely distributed plant products. The vast majority carry an oxygen substituent at C-7; consequently 7-hydroxycoumarin [umbelliferone, (2)], one of the most widely distributed coumarins, is often regarded as the parent, in a structural sense and also biogenetically, of a large number of the structurally more complex coumarins. A number of review articles on natural plant coumarins have appeared (154, 302, 344, 420, 525, 541, 548) since the last in this series (153), the most comprehensive, albeit dealing solely with coumarins of the Umbelliferae, being that of Nielsen in 1970 (419).

Naturally Occurring Plant Coumarins

The naturally occurring coumarins.

A literature survey was conducted on herbs, their preparations and ingredients with reported liver protection activities, in which a total of 274 different species and hundreds of active ingredients have been examined. These ingredients can be roughly classified into two categories according to their activities: (1) the main ingredients, such as silybin, osthole, coumarin, glycyrrhizin, saikosaponin A, schisandrin A, flavonoids; and (2) supporting substances, such as sugars, amino acids, resins, tannins and volatile oil. Among them, some active ingredients have hepatoprotective activities (e.g. anti-inflammatory, anticancer, antioxidant, immunomodulating and liver cirrhosis-regulating effects). Calculation of physicochemical parameters indicates that the main ingredients with negative and positive Elumo values possibly display their hepatoprotective effects through different mechanisms, such as antioxidative, anti-inflammatory and immunomodulating effects. As the combination of herbs may achieve some treatment effects synergistically and/or additively, it is common in Chinese medicine to use mixtures of various medicinal herbs with pharmacologically active compounds to have synergistic and/or additive effects, or to reduce harmful effects of some pharmacologically active compounds. In particular, the active compounds with Clog P around 2 are suitable for passive transport across membranes and accessible to the target sites. Thus, Elumo and Clog P values are good indicators among the calculated parameters. Seven different physicochemical parameters (MW, Clog P, CMR, μ, Ehomo, Elumo and Hf) and four major biological activities (antioxidant, anti-inflammatory, antiviral/antitumor and immunomodulating) are discussed in this review. It is hoped that the discussion may provide some leads in the development of new hepatoprotective drugs.

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A survey of Chinese herbal ingredients with liver protection activities

Phytochemical investigation of leaves and stem bark extracts of Clausena anisata monitored by liquid chromatography high-resolution mass spectrometry (LC-HR-MS) analysis led to the isolation and characterization of twenty-one secondary metabolites: four carbazole alkaloids (1–4) including one new name clausamine H (1), fourteen coumarins (5–18), two porphyrin derivatives (19–20), and one limonoid (21). Crude extracts were analyzed first by LC-HR-MS, and target compounds were isolated by a multi-step separation procedure using column chromatography and preparative high-performance liquid chromatography (prep-HPLC) monitored by LC-HR-MS analysis. The structures of isolates were determined by means of spectroscopic and spectrometric data, as well as by comparison with literature values. The isolates showed weak to high antibacterial activities with imperatorin (14) being the most active one. Cytotoxic activities against HeLa and monkey Vero cells were also investigated, and murrayamine-A (4), 3-(1,1-dimethyl allyl) xanthyletin (5) gravelliferone (7), excavatin D (10), 7-[(E)-7-hydroxy-3,7-dimethylocta-2,5-dienyloxyl]-coumarin (13), phellopterin (15), and 1-O-methylclausenolide (21) were found active with LC50 values ranged from 1.14 to 3.26 µg/mL and a good selectivity index values (SI 38.20–231.58) against the HeLa cells. However, these compounds were non-toxic to normal cells indicating their high potential to be used as anticancer drug.

M.K. Bhan

Papers

A new coumarin in Boenninghausenia albiflora