Inhibitory Effect of Decoction of Perilla frutescens on Cultured Murine Mesangial Cell Proliferation and Quantitative Analysis of its Active Constituents

Abstract

The leaves of Perilla frutescens (perilla) are a common herb used in Japan for garnishing raw seafood. Previously, we reported that a decoction of perilla leaves had suppressive effects on the progression of glomerulonephritis in an animal model of spontaneous IgA nephropathy. The objective of the present study was to isolate anti-nephritic constituents in the perilla decoction under the guidance of its in vitro anti-proliferative activity on cultured murine mesangial cells, and to measure the contents of the active constituents in decoctions prepared from various perilla chemotypes, which differ in their composition of essential oils and/or pigments. DNA synthesis of cultured mesangial cells induced by 1 % fetal calf serum was significantly inhibited by the perilla decoction (IC₅₀ values, 8.8 μg/ml). Caffeic acid, luteolin 7-O-[β-glucuronosyl(1 š 2)β-glucuronide], apigenin 7-O-[β-glucuronosyl(1 š 2)β-glucuronide], scutellarin, and rosmarinic acid were isolated as active constituents. The contents of these phenolic compounds were not significantly different among chemotypes of P. frutescens. Considering the relation between the contents in the perilla decoction and the activities of these compounds, rosmarinic acid represents the in vitro anti-proliferative effect of perilla decoction.

Key words

Perilla frutescens - Labiatae - mesangial cell - caffeic acid - flavone glucuronides - rosmarinic acid

References

• 1 Yu  H C.. Perilla - The genus Perilla. . In: Yu HC, Kosuna K, Haga M, editors Harwood Academic Publishers, Amsterdam:; 1997: 1-8
• 2 Makino  T,, Ono  T,, Muso  E,, Honda  G,, Sasayama  H.. Suppressive effects of Perilla frutescens on spontaneous IgA nephropathy in ddY mice.  Nephron. 1999;;  83 40-6
• 3 Méne  P,, Simonson  M S,, Dunn  M.. Pathology of mesangial cell.  Physiol. Rev.. 1989;;  69 1347-424
• 4 Makino  T,, Ono  T,, Muso  E,, Honda  G.. Inhibitory effect of Perilla frutescens and its phenolic constituents on cultured murine mesangial cell proliferation.  Planta Medica. 1998;;  64 541-5
• 5 Koezuka  Y,, Honda  G,, Tabata  M.. Essential oil types of the local varieties and their F1 hybrids of Perilla frutescens. .  Shoyakugaku Zasshi. 1984;;  38 238-42
• 6 Koezuka  Y,, Honda  G,, Tabata  M.. Genetic control of anthocyanin production in Perilla frutescens. .  Shoyakugaku Zasshi. 1985;;  39 228-31
• 7 Yoshida  K,, Kameda  K,, Kondo  T.. Diglucuronoflavones from purple leaves of Perilla ocimoides. .  Phytochemistry. 1993;;  33 917-9
• 8 Wang  Y Q,, Matsuzaki  K,, Takahashi  K,, Okuyama  T,, Shibata  S.. Studies of the constituents of Scutellaria species. I. The flavonoid glucuronides of “Bo Ye Huang Chin”, Scutellaria ikonnikovii Juz.  Chem. Pharm. Bull.. 1988;;  36 3206-9
• 9 Mackay  K,, Striker  L J,, Elliot  S,, Pinkert  C A,, Brinster  R L,, Striker  G E.. Glomerular epithelial, mesangial, and endothelial cell lines from transgenic mice.  Kidney Int.. 1988;;  33 677-84
• 10 Mosmann  T.. Rapid colorimtric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J. Immunol. Methods. 1983;;  65 55-63
• 11 Kitasato  Institute.. Interferon inducers from Perilla frutescens. .  Jpn. Kokai Tokkyo Koho. 1987;;  87 5407
• 12 Asada  M,, Fukumori  Y,, Inoue  M,, Nakagomi  K,, Sugie  M,, Fujita  Y et al.. Glycoprotein derived from the hot water extract of mint plant, Perilla frutescens Britton.  J. Agric. Food Chem.. 1999;;  47 468-72
• 13 Nakazawa  T,, Osawa  K.. Metabolism of rosmarinic acid in rats.  J. Natl. Prod.. 1998;;  61 993-6
• 14 Makino  T,, Ono  T,, Nakamura  T,, Muso  E,, Honda  G,, Sasayama  S.. Suppressive effect of rosmarinic acid on mesangioproliferative glomerulonephritis in rats.  J. Am. Soc. Nephrol.. 1999;;  10 552A (Abstract)
• 15 Kim  D H,, Jung  E A,, Sohng  I S,, Han  J A,, Kim  T H,, Han  M J.. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities.  Arch. Pharm. Res.. 1998;;  21 17-23
• 16 Koezuka  Y,, Honda  G,, Tabata  M.. Genetic controls of the chemical composition of volatile oils in Perilla frutescens. .  Phytochemistry. 1986;;  25 859-63
• 17 Shirai  K,, Suzuki  M.. Pen-ts'ao kang mu translated into Japanese, Vol. 14,. Syun-yodo, Tokyo,; 1930: 634
• 18 Muso  E,, Yoshida  H,, Takeuchi  E,, Yashiro  M,, Matsushima  H,, Oyama  A et al.. Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice.  Kidney Int.. 1996;;  50 1946-57