Antimycobacterial Ergosterol-5,8-endoperoxide from Ajuga remota

Abstract

In a bioassay-guided search for antimycobacterial natural products from higher plants, we have chemically investigated the methanol extract of aerial parts of Ajuga remota Benth. (Labiatae) for its active constituent(s). Bioactive chromatographic fractions of the crude extract provided the known triterpene ergosterol-5,8-endoperoxide plus the diterpenes clerodin, ajugarin-I, and ajugarin-II, which had been previously isolated from A. remota. This is the first report on the isolation of ergosterol-5,8-endoperoxide from this plant. The above compounds were tested in a radiorespirometric bioassay for activity against Mycobacterium tuberculosis. Ergosterol-5,8-endoperoxide showed a minimum inhibitory concentration (MIC) of 1 microgram/ml, while ergosterol-5,8-endoperoxide acetate, ergosterol, and ergosta-5,7,9(11),22-tetraen-3 beta-ol gave MICs of 8 micrograms/ml, > 128 micrograms/ml, and 128 micrograms/ml, respectively. Clerodin, ajugarin-I, and ajugarin-II were inactive with MICs of > 128 micrograms/ml.

Antitubercular Activity and Inhibitory Effect on Epstein-Barr Virus Activation of Sterols and Polyisoprenepolyols from an Edible Mushroom, Hypsizigus marmoreus

“…Among the sterols tested, compounds 2-7 exhibited activity with MIC values of 1-51 mg/ml, among which ergosterol peroxide (2; MIC 1 mg/ml) 15) followed by cerevisterol (3; 6 mg/ml) and 6-epicerevisterol (4; 11 mg/ml) showed the most potent activity, although still being an order of magnitude less potent than the first-line antitubercular drug, ri- fampin (Table 1). From the limited data set, it appears that C6a,8a-epidioxidation (2), hydroxylation at both C-5a and C6a/b (3-6), or hydroxylation at C-7b accompanied with C5a,6a-epoxidation (7) gives rise to higher activity for the 3b-hydroxy sterols.…”

“…From the limited data set, it appears that C6a,8a-epidioxidation (2), hydroxylation at both C-5a and C6a/b (3-6), or hydroxylation at C-7b accompanied with C5a,6a-epoxidation (7) gives rise to higher activity for the 3b-hydroxy sterols. On the other hand, two compounds, hypsizprenol A 9 (8; MIC 15 mg/ml) and hypsiziprenol BA 10 (12; 44 mg/ml), showed potent antitubercular activity among the eight hypsiziprenols (8)(9)(10)(11)(12)(13)(14)(15) tested. There was no apparent correlation between the structures and antitubercular activity for the hypsiziprenols.…”

“…4) In the course of our studies on the bioactive principles of natural medicines and foodstuffs, 5,6) we evaluated the constituents of H. marmoreus for their antitubercular activity 7) as well as their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 5,6) In this paper, we describe the antitubercular activity against Mycobacterium tuberculosis of seven sterols (1-7) and eight polyisoprenepolyols, hypsiziprenols (8)(9)(10)(11)(12)(13)(14)(15), and inhibitory effects on the induction of EBV-EA by the TPA of seven sterols (1-7) and three hypsiziprenols (8, 10, 12) isolated from the non-saponifiable lipid (NSL) fraction of the extract of H. marmoreus.…”

Transformation of Ergosterol Peroxide to Cytotoxic Substances by Rat Intestinal Bacteria

“…4) EPO has significant cytotoxic activity. [5][6][7][8] Recent pharmacological studies have demonstrated that EPO also possesses immunosuppressive, 9) human T lymphocyte inhibitory, 10) anti-inflammatory, 11) phospholipase A 2 inhibitory, anti-atherosclerosis 12) apoptosis-inducing, 13) DNA topoisomerase inhibitory, 14,15) anticomplementary, 16) anti-viral, 17) anti-mycobacterial, 18) antibacterial, 19) sulfatase inhibitory, 20) and aldose reductase inhibitory 21) effects. Various mushrooms have been used as traditional or folk medicines for a long time.…”

Preventive and curative effect of the methanolic extract of Ajuga iva on collagen induced arthritis in rats

“…It has numerous beneficial effects such as panacea (cure-all), [10] gastrointestinal disorders, [11] hypertension, diabetes, [12] anthelmintic and antiinflammatory. [13] The plants of the genus Ajuga have been reported to have antifungal, antibacterial, [14][15] antimycobacterial, [16] antihypertensive, [17] antiplasmodial, [18] hypoglycaemic, [19] larvae and insect antifeedant activitis. [13,[20][21] Nevertheless, antiarthritic activities for Ajuga iva have never been proved.…”